Tomohiro Haruki

Identification of Early T1b Lung Adenocarcinoma Based on Thin-Section Computed Tomography Findings

Introduction: The aim of this study was to radiologically identify early lung adenocarcinoma in clinical T1bN0M0 lung cancer, based on pathological findings and long-term prognosis. Methods: In this study, we reviewed lung nodules findings on thin-section computed tomography in 173 patients with clinical T1bN0M0 lung adenocarcinoma who underwent surgery between 2003 and 2007. The ratio of the size of solid attenuation to the maximum tumor dimension (consolidation/tumor [C/T] ratio) was calculated. We defined two groups of patients by C/T ratio cutoff levels of 0.00, 0.25, 0.50, 0.75, and 1.00 and compared the rates of pathological nonaggressive lung adenocarcinoma, overall survival, and recurrence rates between the groups. The percentages of predominant histological subtypes were compared between two groups divided by the optimal cutoff level. Various clinical factors were analyzed by univariate and multivariate analyses to predict pathological lymph node involvement. Results: The median follow-up period was 62 months. All patients with C/T ratios of 0.5 or less were diagnosed as having pathological nonaggressive adenocarcinomas, and there was no recurrence; their 5-year overall survival rate was 97.4%, which was significantly better than that for patients with C/T ratios of greater than 0.5 (76.2%). None of the ground-glass opacity–predominant tumors were predominantly solid adenocarcinoma with mucin. The C/T ratio of 0.5 or more was an independent predictor of lymph node involvement. Conclusion: In patients with clinical T1bN0M0 disease, the C/T ratio of 0.5 or less identified early lung adenocarcinoma. In patients with the identified early disease, a feasibility study of limited surgery may be warranted.

Small cell lung cancer tumors and preclinical models display heterogeneity of neuroendocrine phenotypes

BackgroundnSmall cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with variant morphology which did not express some NE markers and exhibited more aggressive growth.nnnMethodsnTo quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models. We identified high and low NE subtypes of SCLC in all of our sample types, and characterized their properties.nnnResultsnWe found that 16% of human SCLC tumors and 10% of SCLC cell lines were of the low NE subtype, as well as cell lines from the GEM model. High NE SCLC lines grew as non-adherent floating aggregates or spheroids while Low NE lines had morphologic features of the variant subtype and grew as loosely attached cells. While the high NE subtype expressed one of the NE lineage master transcription factors ASCL1 or NEUROD1, together with NKX2-1, the entire range of NE markers, and lacked expression of the neuronal and NE repressor REST, the low NE subtype had lost expression of most NE markers, ASCL1, NEUROD1 and NKX2-1 and expressed REST. The low NE subtype had undergone epithelial mesenchymal transition (EMT) and had activated the Notch, Hippo and TGFβ pathways and MYC oncogene . Importantly, the high and low NE group of SCLC lines had similar gene expression profiles as their SCLC tumor counterparts.nnnConclusionsnSCLC tumors and cell lines can exhibit distinct inter-tumor heterogeneity with respect to expression of NE features. Loss of NE expression results in major alterations in morphology, growth characteristics, and molecular properties. These findings have major clinical implications as the two subtypes are predicted to have very different responses to targeted therapies.

Thin-section computed tomography findings of lung adenocarcinoma with inherent metastatic potential.

PurposeThe solid component of lung ground-glass nodules on thin-section computed tomography (TSCT) reflects cancer cell progression and invasiveness. The purpose of this study was to clarify the cut-off value of preoperative TSCT findings in treating a lesion suspected of being adenocarcinoma and to recognize the timing of surgical resection for lung nodules.MethodsWe reevaluated the TSCT findings in 392 patients with clinical stage IA lung adenocarcinoma who underwent surgical resection between 2003 and 2007. We identified the clinical parameters that were most useful for predicting recurrence and identified a cut-off level for each parameter.ResultsRecurrence was observed in 75 (19xa0%) of 392 patients (median follow-up: 7xa0years). The size of internal consolidation of a lung nodule (SCL) and the ratio of the SCL to the maximum tumor diameter (C/T ratio) were extracted as independent factors that predicted recurrence. Only 1 (0.3xa0%) patient each with a lung nodule C/T ratio ≤0.5 and SCLxa0≤10xa0mm recurred. These conditions were associated with a significantly better overall survival and recurrence-free survival.ConclusionIn patients with clinical stage I lung adenocarcinoma with a C/T ratio ≤0.5 and/or SCLxa0≤10xa0mm on TSCT, surgery is extremely likely to achieve a cure.