Ground-glass opacity nodules: histopathology, imaging evaluation, and clinical implications.
Ground-glass opacity (GGO) nodules noted at thin-section computed tomography (CT) scan have been shown to have a histopathologic relationship with atypical adenomatous hyperplasia, bronchioloalveolar carcinoma (BAC, or adenocarcinoma in situ), and adenocarcinoma with a predominant BAC component (minimally invasive adenocarcinoma). Patients harboring GGO nodules of BAC or adenocarcinoma with a predominant BAC component demonstrate negative results for malignancy at positron emission tomography. In peripheral adenocarcinoma of a part-solid (mixed GGO and solid attenuation) nodular nature, both the degree of disappearance of GGO area, when the lung window is changed to a mediastinal window image at CT scanning, and the maximum standardized uptake value at positron emission tomography correlate well with histopathologic BAC and non-BAC ratios. However, a high non-BAC ratio appears to be the only independent prognosis-determining factor. Epidermal growth factor receptor mutations are positively correlated with the GGO ratio at a thin-section CT scan in lung adenocarcinomas. As patients with a GGO nodule of BAC or adenocarcinoma with a predominant BAC component have a good prognosis, a wedge resection is recommended as a treatment option, in preference to lobectomy. Even for multiple malignant pure GGO nodules, minimally invasive surgery (including multiple resections) with the preservation of lung volume and adequate imaging follow-up studies are the recommended diagnostic and therapeutic measures.

title: Classification of Focal Prostatic Lesions on Transrectal Ultrasound (TRUS) and the Accuracy of TRUS to Diagnose Prostate Cancer
abstract: To improve the diagnostic efficacy of transrectal ultrasound (TRUS)-guided targeted prostatic biopsies, we have suggested the use of a new scoring system for the prediction of malignancies regarding the characteristics of focal suspicious lesions as depicted on TRUS.  A total of 350 consecutive patients with or without prostate cancer who underwent targeted biopsies for 358 lesions were included in the study. The data obtained from participants were randomized into two groups; the training set (n = 240) and the test set (n = 118). The characteristics of focal suspicious lesions were evaluated for the training set and the correlation between TRUS findings and the presence of a malignancy was analyzed. Multiple logistic regression analysis was used to identify variables capable of predicting prostatic cancer. A scoring system that used a 5-point scale for better malignancy prediction was determined from the training set. Positive predictive values for malignancy prediction and the diagnostic accuracy of the scored components with the use of receiver operating characteristic curve analysis were evaluated by test set analyses.  Subsequent multiple logistic regression analysis determined that shape, margin irregularity, and vascularity were factors significantly and independently associated with the presence of a malignancy. Based on the use of the scoring system for malignancy prediction derived from the significant TRUS findings and the interactions of characteristics, a positive predictive value of 80% was achieved for a score of 4 when applied to the test set. The area under the receiver operating characteristic curve (AUC) for the overall lesion score was 0.81.  We have demonstrated that a scoring system for malignancy prediction developed for the characteristics of focal suspicious lesions as depicted on TRUS can help predict the outcome of TRUS-guided biopsies.

title: New CT response criteria in non-small cell lung cancer: proposal and application in EGFR tyrosine kinase inhibitor therapy.
abstract: We aimed to devise new CT response criteria (new response criteria, NRC) in patients with non-small cell lung cancer (NSCLC) and to evaluate the efficacy of the criteria for stratifying patient responses and predicting patient survival compared to that of the traditional size-based criteria RECIST version 1.1. Our institutional review board approved this study with a waiver of informed consent. We enrolled 80 NSCLC patients as an experimental arm and treated them with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). Two blinded, independent radiologists assessed CT images for tumor response using the NRC, which were also validated in a separate arm (75 NSCLC patients). Tumor responses evaluated by RECIST 1.1 and the new criteria were compared from each other and correlated with patient survival. For statistical analyses, Kaplan-Meier method and kappa statistics were used. In the experimental arm (n=80), interobserver agreements for the assessment of patient response were excellent for both RECIST and NRC. Sixteen RECIST nonresponding patients achieved a designation of partial response according to NRC. In the validation arm (n=75), patients of optimal response (partial response) with the new criteria had median overall survival of 18.4 months compared with 8.5 months in patients with poor response (P=.04). However, RECIST failed to show survival difference between the two response groups. In NSCLC patients treated with EGFR-TKIs, new CT criteria reflecting additional morphological characteristics of target lesions are reproducible and have statistically significant association with overall survival.

title: Diagnostic Efficacy of PET/CT Plus Brain MR Imaging for Detection of Extrathoracic Metastases in Patients with Lung Adenocarcinoma
abstract: We aimed to evaluate prospectively the efficacy of positron emission tomography (PET)/computed tomography (CT) plus brain magnetic resonance imaging (MRI) for detecting extrathoracic metastases in lung adenocarcinoma. Metastatic evaluations were feasible for 442 consecutive patients (M:F=238:204; mean age, 54 yr) with a lung adenocarcinoma who underwent PET/CT (CT, without IV contrast medium injection) plus contrast-enhanced brain MRI. The presence of metastases in the brain was evaluated by assessing brain MRI or PET/CT, and in other organs by PET/CT. Diagnostic efficacies for metastasis detection with PET/CT plus brain MRI and with PET/CT only were calculated on a per-patient basis and compared from each other. Of 442 patients, 88 (20%, including 50 [11.3%] with brain metastasis) had metastasis. Regarding sensitivity of overall extrathoracic metastasis detection, a significant difference was found between PET/CT and PET/CT plus brain MRI (68% vs. 84%; P=0.03). As for brain metastasis detection sensitivity, brain MRI was significantly higher than PET/CT (88% vs. 24%; P<0.001). By adding MRI to PET/CT, brain metastases were detected in additional 32 (7% of 442 patients) patients. In lung adenocarcinoma patients, significant increase in sensitivity can be achieved for detecting extrathoracic metastases by adding dedicated brain MRI to PET/CT and thus enhancing brain metastasis detection.

title: Molecularly Targeted Therapy Using Bevacizumab for Non-Small Cell Lung Cancer: a Pilot Study for the New CT Response Criteria
abstract: We wanted to compare the efficacy of the new CT response evaluation criteria for predicting the tumor progression-free survival (PFS) with that of RECIST 1.1 in non-small cell lung cancer (NSCLC) patients who were treated with bevacizumab.  Sixteen patients (M:F = 11:5; median age, 57 years) treated with bevacizumab and combined cytotoxic chemotherapeutic agents were selected for a retrospective analysis. The tumor response was assessed by four different methods, namely, by using RECIST 1.1 (RECIST), RECIST but measuring only the solid component of tumor (RECISTsolid), the alternative method reflecting tumor cavitation (the alternative method) and the combined criteria (the combined criteria) that evaluated both the changes of tumor size and attenuation. To evaluate the capabilities of the different measurement methods to predict the patient prognosis, the PFS were compared, using the log rank test, among the responder groups (complete response [CR], partial response [PR], stable disease [SD] and progressive disease [PD]) in terms of the four different methods.  The overall (CR, PR or SD) response rates according to RECIST, RECISTsolid, the alternative method and the combined criteria were 81%, 88%, 81% and 85%, respectively. The confirmed response rates (CR or PR) were 19%, 19%, 50% and 54%, respectively. Although statistically not significant, the alternative method showed the biggest difference for predicting PFS among the three response groups (PR, SD and PD) (p = 0.07). RECIST and the alternative method showed a significant difference for predicting the prognosis between the good (PR or SD) and poor overall responders (p = 0.02).  The response outcome evaluations using the three different CT response criteria that reflect tumor cavitation, the ground-glass opacity component and the attenuation changes in NSCLC patients treated with bevacizumab showed different results from that with using the traditional RECIST method.

title: Volume-Based Parameter of 18F-FDG PET/CT in Malignant Pleural Mesothelioma: Prediction of Therapeutic Response and Prognostic Implications
abstract: BackgroundTo evaluate the importance of assessing volume-based parameter of 18F-FDG PET/CT in patients with malignant pleural mesothelioma (MPM) for the prediction of response and patient outcome early in the course of treatment.Materials and MethodsPatients (n = 13; M:F = 9:4, mean age, 54 years) with histopathologically proven MPM, all of whom were scheduled to undergo curative extrapleural pneumonectomy (EPP) or palliative chemotherapy, were included in this study. They were evaluated using integrated 18F-FDG PET/CT at baseline. Maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using PET/CT data. Relationships between tumor progression and PET parameters were statistically analyzed.ResultsOf the 13 patients, 8 (62%) developed disease recurrence after surgery or tumor progression after chemotherapy (median follow-up, 329 days; range, 28–536 days). Between subgroups with and without tumor progression, significant differences were noted in MTV (P = 0.045). On ROC curve analysis, MTV (AUC = 0.850, 95% confidence interval [95% CI] 0.550–0.977) and TLG (AUC = 0.800, 95% CI 0.494–0.960) showed good predictive performance for tumor progression. Multivariate analysis adjusted for treatment modality showed that MTV (HR 1.003, P = 0.025) and TLG (HR 1.001, P = 0.031) were independent factors associated with tumor progression. Time to tumor progression was shorter in patients with a high volume-based parameter of PET than in those with a low value.ConclusionsVolume-based parameters of 18F-FDG PET/CT have the potential to provide prognostic information in MPM patients who are receiving surgery or palliative chemotherapy.

title: Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis.
abstract: Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt activation in vivo, as measured by immunohistochemistry and immunoblotting, and statistically significantly reduced NNK/BaP-induced lung tumor multiplicity, volume, and load in A/J mice, as monitored by microcomputed tomography image analysis, with no detectable toxicity. These results indicate that deguelin warrants consideration as a chemopreventive agent for early-stage lung carcinogenesis in a clinical lung cancer chemoprevention trial.

title: Time to follow up after an abnormal finding in organized gastric cancer screening in Korea
abstract: BackgroundThe prognosis for an abnormal medical finding is affected by both early detection and adherence to the presecribed schedule for follow-up examinations. In this study, we examined the time to follow up after an abnormal finding and determined the risk factors related to delays in follow up in a population-based screening program.MethodsThe study population consisted of patients who were newly diagnosed with gastric cancer through a gastric cancer screening program sponsored by the National Cancer Screening Program (NCSP) in 2005. Due to the skewed nature of the distribution of time to follow up, medians and interquartile ranges (IQR) are presented, and we analyzed the number of days preceding the follow-up time as a binary variable (≤90 days or >90 days). We used logistic regression analyses to evaluate the risk factors for a long delay.ResultsThe median number of days to follow-up initiation after an abnormal finding was 11 (IQR 7–27); 13.9% of the patients with gastric cancer obtained their follow-up evaluation more than 90 days. Age, type of health insurance, screening method, and screening results were risk factors for delays in follow up.ConclusionsThis study examined delays from the time of the discovery of an abnormal finding to time of the follow-up evaluation. Because inadequate follow up of abnormal exam results undermines the potential benefits of cancer screening, it is important to organize services that minimize delays between cancer screening and treatment.

title: Cardio–renal protection with aliskiren, a direct renin inhibitor, in the ASPIRE HIGHER program
abstract: Aliskiren is the first in a new class of orally effective direct renin inhibitors. Initial results of clinical efficacy studies have demonstrated at least equivalent or superior blood pressure-lowering efficacy when compared with existing drugs, and a favorable side-effect profile either as monotherapy or as a component of combination therapy. This report aims to introduce and provide a critical appraisal of the initial results of the ASPIRE HIGHER program, evaluating the potential cardio–renal protective effects of aliskiren.

title: Response of Non–Small Cell Lung Cancer Cells to the Inhibitors of Phosphatidylinositol 3-Kinase/Akt- and MAPK Kinase 4/c-Jun NH2-Terminal Kinase Pathways: An Effective Therapeutic Strategy for Lung Cancer
abstract: We previously showed that phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways cooperate to promote non–small cell lung cancer (NSCLC) cell proliferation in vitro. This study was designed to explore whether inhibition of these pathways effectively inhibits NSCLC tumor growth in vivo.  The effects of PI3K/Akt inhibitors {LY294002, adenoviruses expressing dominant-negative mutant of the p85α adaptor subunit of PI3K (Ad-dnp85α), dominant-negative Akt [Ad-HA-Akt(KM)], or PTEN (Ad-PTEN)}, MKK4/c-jun NH2-terminal kinase (JNK) inhibitor [SP600215, adenovirus expressing dominant-negative MKK4, Ad-MKK4(KR)], and their combinations on proliferation and apoptosis in NSCLC cells were tested in vitro and in vivo using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, a flow cytometry-based terminal deoxynucleotidyl transferase–mediated nick-end labeling assay, Western blot and immunohistochemical analyses, and an NSCLC xenograft tumor model.  Ad-dnp85α significantly inhibited proliferation of a subset of NSCLC cell lines used in our study. Intratumoral injection of Ad-dnp85α induced a significant decrease in the growth of H1299 NSCLC xenograft tumors. Concurrent inhibition of the PI3K/Akt and MKK4/JNK pathways showed enhanced antiproliferative effects on H1299 cells in vitro and in vivo by increasing apoptosis.  PI3K/Akt and MKK4/JNK pathways cooperate to stimulate NSCLC cell proliferation by maintaining cell survival, suggesting that simultaneously targeting these two pathways might be an effective therapeutic strategy against NSCLC.

title: Primary acinic cell carcinoma of the lung with lymph node metastasis.
abstract: We report the case of a 30-year-old woman who presented with a subpleural mass in the lower lobe of the right lung, which was found incidentally on a routine chest radiograph. A wedge biopsy followed by lobectomy and lymph node staging revealed an acinic cell carcinoma with involvement of a hilar lymph node. The subcarinal and mediastinal lymph nodes were free of tumor. Perineural invasion was identified at the periphery of the tumor. There was no evidence of origin from salivary gland or involvement of any other organ. The patient was well 12 months postoperatively. To our knowledge, this is the second case report featuring lymph node metastasis in an acinic cell carcinoma of the lung and the first to demonstrate perineural invasion.