Yoko Karube

Tumor-related gene expression levels in thymic carcinoma and Type B3 thymoma

BackgroundThymic carcinoma (TC) is a rare type of malignant neoplasm that develops in the anterior mediastinum and associated with poor prognosis. Type B3 thymoma (B3) occasionally demonstrates malignant tumor characteristics, especially in the advanced stage. We investigated the expressions of tumor-related genes in resected TC and B3 specimens.MethodsTC and B3 specimens resected from 1999 through 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg’s tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of cancer, data from lung cancer (LC) cases in our database were also examined.ResultsThe gene expression levels of thymidylate synthase were significantly higher in TC and B3 as compared to LC specimens (p < 0.02), while no difference were observed between TC and B3 tumors. The ratio of folypolyglutamyl synthase (FPGS) to gamma-glutamyl hydrolase (GGH) mRNA was significantly lower in TC than in B3 (p < 0.05), with lower FPGS/GGH in those tumors related to overall survival. Also, the gene expression of vascular endothelial growth factor (VEGF) was significantly higher in TC as compared to B3 (p = 0.04), with higher VEGF gene expression in TC and B3 specimens related to overall survival of affected patients. Epidermal growth factor receptor (EGFR) expression was significantly higher in B3 as compared to both TC and LC specimens (p < 0.01). However, there were no EGFR gene mutations detected in any of the specimens.ConclusionsThese results indicate that elevated expressions of the tumor-related genes FPGS/GGH and VEGF are correlated with malignancy of TC and B3 tumors. Additional examinations will be necessary to investigate their chemosensitivity.

Mitosis count and number of cancer cells in cases of primary pulmonary adenocarcinoma: Correlations among phosphorylated histone 3, number of cancer cells, nuclear grade, pathologic features and prognosis: Mitosis count in lung adenocarcinoma

Immunohistochemistry findings for the phosphorylated form of histone 3 (pHH3) have been shown to be a reliable mitosis‐specific marker. We evaluated the correlation between pHH3‐stained mitotic figures (PHMFs) and clinical outcome, and compared the results with findings for numbers of PHMFs and cancer cells. The primary tumor was obtained from 113 patients with pulmonary adenocarcinomas (≤2 cm maximum dimension). All specimens were stained with pHH3, then the number of cancer cells in each was determined. Cases with a cancer‐cell index ≥1000 showed worse recurrence‐free survival as compared to those with a value <1000 (P < 0.001). Also, cases with a pHH3 index ≥0.27 showed worse recurrence‐free survival as compared to <0.27 (P = 0.001) and cases with a pHH3/cancer‐cell index ≥0.001 showed worse recurrence‐free survival as compared to <0.001 (P = 0.002). Multivariate analysis demonstrated that pHH3/cancer‐cell index was significantly correlated with prognosis, but not Ki‐67 index. The number of cancer cells was also strongly correlated with progression of Noguchis classification and WHO pathologic type. pHH3/cancer‐cell index was correlated with prognosis, and those were useful for prognostic evaluation of pulmonary adenocarcinoma patients. Furthermore, cancer cell number was correlated with Noguchis classification and WHO pathologic type.

Advanced Lung Cancer Inflammation Index Predicts Outcomes of Patients with Pathological Stage IA Lung Adenocarcinoma Following Surgical Resection

Purpose: The correlation of advanced cancer with inflammation and/or nutrition factors is well known. Recently, the advanced lung cancer inflammation index (ALI) was developed as a new prognostic tool for patients with advanced lung cancer. In this study, we examined whether ALI results are correlated with prognosis of patients with early stage lung adenocarcinoma who undergo lung resection. Methods: From January 2009 to December 2014, 544 patients underwent lung resection due to primary lung cancer at Dokkyo Medical University Hospital, of whom 166 with pathological stage IA lung adenocarcinoma were retrospectively investigated in this study. ALI was calculated as follows: Body Mass Index (BMI; kg/m2) × albumin (g/dL)/neutrophil- to-lymphocyte ratio (NLR). Results: Multivariate analysis revealed that gender, red cell distribution width (RDW), NLR, and ALI were parameters significantly correlated with overall survival (OS). Patients with an ALI value less than 22.2 had an inferior 5-year OS rate as compared to those with a value of 22.2 or higher (p <0.001) as well as an inferior 5-year recurrence-free survival (RFS) rate (p <0.001). Conclusion: Low ALI was correlated with poor prognosis in patients with stage IA lung adenocarcinoma. Those with an ALI value less than 22.2 should be carefully followed regardless of cancer stage.

Association of Perioperative Redox Balance on Long-Term Outcome in Patients Undergoing Lung Resection

PURPOSE We examined whether redox balance during the perioperative period is associated with long-term survival of patients after undergoing lung resection. METHODS Patients who underwent surgery for lung cancer from January to June 2013 at our institution were investigated. Serum was collected during the operation, and on postoperative day (POD) 3 and 7, and the levels of derivatives of reactive oxygen metabolites (d-ROMs) and biologic antioxidant potential (BAP) were measured. RESULTS In all, 21 patients (69 ± 7 years old) were enrolled, of whom 9 underwent video-assisted thoracoscopic surgery. Comorbidities in the patients included chronic obstructive pulmonary disease in eight and idiopathic pulmonary fibrosis in five. d-ROM values on POD 3 and 7 were significantly increased as compared to those obtained during the operation (p <0.001), whereas BAP did not change after surgery. Patients with a value below a d-ROM cutoff value of 327 during the operation showed significantly superior 3-year overall survival as compared to those with a value above the cutoff (87.5% vs. 20.0%, p <0.001). CONCLUSION In the present patients, surgical stress caused an increase in d-ROM during the postoperative course. The d-ROM value obtained during the operation was correlated with long-term survival following resection for lung cancer.

Back-table procedure and auto-lung transplantation for locally advanced lung cancer: a case report

BackgroundTo avoid a pneumonectomy and preserve the lung parenchyma, a bronchovascular double-sleeve plasty including an extended sleeve lobectomy is a good choice for locally advanced lung cancer.Case presentationWe describe a case with lung adenocarcinoma enrolled in our new protocol for ex situ auto-lung transplantation following an en bloc pneumonectomy and back table procedure for central lung cancer. Following completion of the pneumonectomy, the excised lung was irrigated with a cold extracellular phosphate-buffered solution to protect the lung graft from ischemia-reperfusion injury during preparation of the graft of a right basal segment as a back-table procedure.ConclusionAlthough auto-lung transplantation is a complicated procedure, an en bloc pneumonectomy following a back table procedure makes preparation of the graft easy, while simultaneous mediastinal lymph node dissection by another surgeon shortens operation time.