Molecularly Targeted Therapy Using Bevacizumab for Non-Small Cell Lung Cancer: a Pilot Study for the New CT Response Criteria
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: 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: Mucinous versus nonmucinous solitary pulmonary nodular bronchioloalveolar carcinoma: CT and FDG PET findings and pathologic comparisons.
abstract: We aimed to evaluate the CT, PET, and pathologic findings of solitary pulmonary nodular mucinous and nonmucinous bronchioloalveolar carcinomas (BACs). From August 2003 to March 2008, we saw 24 patients with solitary pulmonary nodular mucinous (n=6) or nonmucinous (n=18) BACs that were resected. CT and PET findings of the lesions were assessed in terms of size, solidity, morphologic characteristics, attenuation and maximum standardized uptake value (mSUV). All nonmucinous BACs appeared as a pure ground-glass opacity (GGO) nodule, whereas mucinous BACs appeared as solid (n=4) or part-solid (n=2) nodules. CT attenuation values were significantly higher for mucinous BACs (-21.0 HU+/-4.9) than for nonmucinous BACs (-491.8 HU+/-172.5) (P<.001). Mean mSUVs were 2.3+/-1.9 for mucinous BACs and 0.5+/-0.8 for nonmucinous BACs (P=.007), but mSUVs were not statistically different after size adjustment (r=0.371, P=.081). Mucinous BACs appear as solid or part-solid nodules at CT, whereas nonmucinous BACs present as pure GGO nodules. Both subtypes of tumors show scant FDG uptake at PET.

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: Primary postpartum hemorrhage: outcome of pelvic arterial embolization in 251 patients at a single institution.
abstract: To evaluate the safety and efficacy of pelvic arterial embolization (PAE) for the treatment of primary postpartum hemorrhage (PPH) and to determine the factors associated with clinical outcomes.



This retrospective single-center study was institutional review board approved, and informed consent was waived. Outcomes were analyzed in 251 patients who underwent PAE for primary PPH between January 2000 and February 2011. Mode of delivery, causes of bleeding, detailed laboratory and treatment records, and clinical outcomes were recorded. Clinical success was defined as cessation of bleeding after initial session of PAE without the need for additional PAE or surgery. Univariate and multivariate analyses were performed to determine the factors related to clinical outcomes.



The clinical success rate was 86.5% (217 of 251). Among the 34 failed cases, 12 underwent repeat PAE, 16 underwent additional surgery, and three recovered with conservative management. Overall bleeding control was achieved in 98.0% (246 of 251) of the patients. Overall mortality was 2% (five of 251) after the first (n = 3) or second (n = 1) session of PAE or additional surgery (n = 1). Among the 113 patients with long-term follow-up, 110 (97.3%) maintained a regular menstrual cycle and 11 had successful pregnancies. Univariate analysis showed that cesarean section delivery, disseminated intravascular coagulation (DIC), and massive transfusion of more than 10 red blood cell units were related to failed PAE. Multivariate analysis showed that DIC (odds ratio, 0.36; P = .04) and massive transfusion (odds ratio, 0.10; P < .001) were significantly related to clinical failure.



PAE is safe and effective for managing primary PPH. Patients with DIC and massive transfusion were likely to have poor results after PAE.

title: Z-Shaped Microcatheter Tip Shaping for Embolization of Aneurysms at the Proximal A1 Segment of the Anterior Cerebral Artery: A Technical Note
abstract: Embolization of an aneurysm at the proximal A1 segment of the anterior cerebral artery (ACA) is technically challenging. We treated four consecutive patients with unruptured aneurysms at the proximal portion of the A1 segment of the ACA. We tested various microcatheter tip shapes before we successfully embolized a lesion with a zigzag-shaped microcatheter tip, which was made by steam shaping. The shape of this microcatheter tip resembled the letter "Z", had a relatively long distal straight segment and was helpful in prompt catheterization of the aneurysm sac and stable placement of the catheter and delivery of coils.

title: Multiple forms of secretory phospholipase A2 in plants.
abstract: Multiple secretory phospholipase A2 (sPLA2) genes have been identified in plants and encode isoforms with distinct regulatory and catalytic properties. Elucidation of this genetic and biochemical heterogeneity has provided important clues to the regulation and function of the individual enzymes. An increasing body of evidence shows that their lipid products, lysophospholipids and free fatty acids, mediate a variety of cellular responses, including plant growth, development, and responses to stress and defense. This review discusses the newly-acquired information on plant sPLA2s including the molecular and biochemical characteristics, and signaling functions of each isoform.

title: Phase IV, 8-week, multicenter, randomized, active treatment-controlled, parallel group, efficacy, and tolerability study of high-dose candesartan cilexetil combined with hydrochlorothiazide in Korean adults with stage II hypertension.
abstract: The objective of this study was to evaluate the efficacy and tolerability of high-dose (32 mg) candesartan in Asians.



In Korean adult patients with stage II hypertension, we evaluated the efficacy and tolerability of candesartan 16 mg/hydrochlorothiazide (HCT) 12.5 mg and candesartan 32 mg/HCT 12.5 mg compared with candesartan 16-mg and 32-mg monotherapy, respectively. This Phase IV, 8-week, multicenter, randomized, active treatment-controlled, parallel group, efficacy, and tolerability study, named CAESAR (Candesartan Effect in Second Stage Arterial Hypertension), enrolled 253 patients with stage II hypertension. Treatment started with either candesartan 16 mg or candesartan 16 mg/HCT 12.5 mg. After 4 weeks, the candesartan dose was forced titrated to 32 mg in both groups. The primary and secondary objectives were to compare the blood pressure (BP) changes after 4 weeks and 8 weeks between candesartan-HCT combination therapy and candesartan monotherapy. The proportion of patients achieving target BP (systolic blood pressure [SBP] <140 mm Hg, but <130 mm Hg for patients with diabetes mellitus or chronic kidney disease; diastolic blood pressure (DBP) <90 mm Hg, but <80 mm Hg for those with diabetes mellitus or chronic kidney disease) after 4 and 8 weeks of therapy was also evaluated. Adverse events were investigated both by spontaneous report by the patient and by the investigators' evaluations in each visit. Laboratory tests were performed at the end of the study to evaluate drug tolerability.



Study patients were all Asians, mostly male (65.7%), with a mean (SD) age of 49.4 (10.6) years and a mean body weight of 68.9 (12.1) kg; there were no between-group variances in demographic profiles except that the mean age in the candesartan-HCT group (51.0 [10.2] years) was about 3.2 years higher than that in the candesartan monotherapy group (47.8 [10.7] years; P = 0.02) despite random allocation. A total of 80.4% of the study patients had not been treated before, whereas 19.6% were previously treated and enrolled after 2 weeks of washout period. Baseline sitting systolic/diastolic BPs (SBP/DBP) were 160.7 (13.0)/104.6 (9.5) mm Hg. After 4 weeks, patients treated with candesartan 16 mg/HCT 12.5 mg showed significant decreases in SBP/DBP of 28.7 (17.5)/17.8 (10.2) mm Hg, and those in the candesartan 16 mg monotherapy group showed decreases of 20.5 (14.5)/14.1 (10.1) mm Hg (P < 0.01 between treatments for both SBP and DBP). After forced titration of candesartan from 16 mg to 32 mg at week 8, there was an additional reduction in SBP/DBP of 4.1 (12.7)/3.8 (8.3) mm Hg in the candesartan-HCT combination therapy group and 4.0 (11.6)/2.0 (8.5) mm Hg in the candesartan monotherapy group (P < 0.001 for SBP and DBP in both groups compared with values at week 4). A greater proportion of patients (70.6%) attained the target BP in the candesartan-HCT combination therapy group than in the candesartan monotherapy group (53.2%, P = 0.014). A total of 32 mg of candesartan was well tolerated both in combination therapy with HCT and in monotherapy. Dizziness was the most common adverse event in both groups (5 and 2 patients, respectively).



The candesartan-HCT combination was associated with a statistically significant lowering of BP compared with candesartan monotherapy.

title: Assessment of participant satisfaction with upper gastrointestinal endoscopy in South Korea.
abstract: To measure the perceived satisfaction with gastric cancer screening as part of the National Cancer Screening Program (NCSP) in South Korea.



Data were derived from the participants in a satisfaction survey of the Quality Evaluation of National Cancer Screening in 2009. This is a population-based nationwide telephone survey of participants who were screened by the NCSP between May and October 2009. This study included 4412 participants who provided full sets of data and who had upper endoscopies for the purpose of gastric cancer screening.



The negative appraisal percentages for each of the seven questions were as follows: explanation in preparation for the upper endoscopy, 12.3%; explanation about the process and procedure of the upper endoscopy, 13.8%; explanation about any pain or discomfort related to the upper endoscopy, 27.5%; level of pain during the procedure, 30.3%; physical environment, 16.2%; manner of the staff, 11.2%, and privacy protection, 8.8%.



The critical issues identified by the Pareto analysis include the adequacy of the explanation about any pain or discomfort associated with the upper endoscopy and the level of pain experienced during the procedure.