Impact of insulin-like growth factor-1 receptor and amphiregulin expression on survival in patients with stage II/III gastric cancer enrolled in the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer

Background

Exploratory biomarker analysis was conducted to identify factors related to the outcomes of patients with stage II/III gastric cancer using data from the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer, which was a randomized controlled study comparing the administration of an orally active combination of tegafur, gimeracil, and oteracil with surgery alone.

Methods

Formalin-fixed paraffin-embedded surgical specimens from 829 patients were retrospectively examined, and 63 genes were analyzed by quantitative real-time RT-PCR after TaqMan assay-based pre-amplification. Gene expression was normalized to the geometric mean of GAPDH, ACTB, and RPLP0 as reference genes, and categorized into low and high values based on the median. The impact of gene expression on survival was analyzed using 5-year survival data. The Benjamini and Hochberg procedure was used to control the false discovery rate.

Results

IGF1R and AREG were most strongly correlated with overall survival, which was significantly worse in high IGF1R patients than low IGF1R patients, but better in high AREG patients than low AREG patients. The hazard ratio for death in the analysis of overall survival (S-1 vs. surgery alone) was reduced in the high IGF1R group compared with the low IGF1R group and in the low AREG group compared with the high AREG group. There were no significant interaction effects.

Conclusion

IGF1R gene expression was associated with poor outcomes after curative resection of stage II/III gastric cancer, whereas AREG gene expression was associated with good outcomes. No significant interaction effect on survival was evident between S-1 treatment and gene expression.

     

Phase II Study of the EGFR-TKI Rechallenge With Afatinib in Patients With Advanced NSCLC Harboring Sensitive EGFR Mutation Without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line therapy for patients with EGFR-mutated non–small-cell lung cancer (NSCLC) have shown a significantly better objective response rate and progression-free survival than platinum doublet therapy. However, acquired resistance often occurs within 12 months. One of the potential strategies for treating acquired resistance in NSCLC is the readministration of EGFR-TKIs, a strategy that has mainly been evaluated using gefitinib or erlotinib. The aim of the present study is to investigate the efficacy and safety of EGFR-TKI readministration with afatinib in patients with advanced NSCLC harboring activating EGFR mutations without T790M. The primary endpoint is progression-free survival. The secondary endpoints include the objective response rate, disease control rate, overall survival, toxicity, and quality of life. A total of 12 patients will be enrolled in this trial.     

Perioperative nutrition management as an important component of surgical capacity in low‐ and middle‐income countries

Needs for surgical care are growing in low‐ and middle‐income countries. Existing surgical care capacity indicators, focusing on the availability of equipment, personnel, and operation and anaesthetic skills, are not intended to evaluate perioperative nutrition management, which influences surgical outcomes. In this narrative review, we describe the prevalence of malnutrition and its clinical consequences among surgical patients in low‐ and middle‐income countries, suggest potential measures to improve nutrition management and discuss the necessity of considering nutrition management as a component of surgical care capacity.     

Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension

This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker. The primary end point was the mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks. An efficacy analysis was performed in 195 patients (98 in the eplerenone group and 97 in the thiazide group). Systolic and diastolic blood pressures at 48 weeks were similar in the two groups. The mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks was similar in the two groups (P=.804). In the safety analysis, the withdrawal rates for adverse events were similar in both groups. The antialbuminuric effects and safety of eplerenone therapy were similar to those of thiazide diuretics when combined with an angiotensin II receptor blocker in patients with hypertension and albuminuria.     

Liquid biopsy in patients with pancreatic cancer: Circulating tumor cells and cell-free nucleic acids

Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called "liquid biopsy" has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field.     

Improving the concordance of mammography assessment and management recommendations

PURPOSE: To retrospectively compare the concordance of initial and final assessment categories for mammograms with management recommendations made before and after the final rules of the Mammography Quality Standards Act (MQSA) were in effect for screening and diagnostic mammography. MATERIALS AND METHODS: The study included mammograms from 1996 to 2001 from the seven mammography registries of the Breast Cancer Surveillance Consortium (BCSC). The authors defined the pre-MQSA period as January 1, 1996-April 27, 1999, and the post-MQSA period as April 28, 1999-December 31, 2001 (2470151 screening and 194199 diagnostic mammograms). Assessment was cross-classified according to management recommendation. Changes in concordance between assessment and recommendation were evaluated by year and by period (before and after MQSA) for computer-linked data and for all data by using Pearson chi(2) test to evaluate differences. Mantel-Haenszel chi(2) test was used to measure change in concordance over time. Each registry and the BCSC Statistical Coordinating Center had a Federal Certificate of Confidentiality and approval from each institution's review board for protection of human subjects to collect and send data to coordinating center and conduct research with these data. Active consent was required at only one site in this HIPAA-compliant study. RESULTS: Concordance increased significantly in the post-MQSA period for Breast Imaging Reporting and Data System categories 3-5 assessments at both screening and diagnostic mammography. The most substantial improvements were in the use of the management recommendation for "additional imaging," which decreased from 41% in 1996 to 15% in 2001 for screening mammograms with an initial assessment of category 4 (P < .001). Recommendation for short-interval follow-up in women with screening mammograms with a category 3 final assessment increased from 51% in 1996 to 76% in 2001 (P < .001). Concordance for diagnostic mammograms assigned category 0 improved from 65% in the pre-MQSA period to 81% in the post-MQSA period (P < .001). CONCLUSION: This analysis demonstrates that over a relatively short period of time, major improvement in radiology reporting has occurred.     

Performance evaluation of computed tomography with equivalent resolution images

A method of evaluating the performance of computed tomography (CT) with equivalent resolution images was investigated. Generally, in performance evaluations of CT, the resolution property is measured by the wire method, and the noise property is measured from noise images of a cylindrical water phantom. The signal-to-noise ratio (SNR) is then calculated for the integrated evaluation. Our proposed method enabled perceptual integrated evaluation by using equivalent resolution images created with frequency processing. The frequency-processing factor was calculated from the ratio of the modulation transfer factors of two models of CT, and the image of one of the two was processed by the factor. Because these processed images have resolution equivalent to images of the other CT, the perceptual evaluation with noise images becomes effective. In this investigation, images of a water phantom and a middle contrast resolution phantom were employed. Perceptual comparison of the amount of noise with equivalent resolution images could be performed easily, and effective performance evaluation was achieved. Therefore, our proposed method is useful for noise property and performance evaluation of CT.     

Evaluation of pathological features of hepatocellular carcinoma by contrast-enhanced ultrasonography: comparison with pathology on resected specimen

Features of hepatocellular carcinoma (HCC) observed by contrast-enhanced ultrasonography (CEUS) were compared to pathological features of corresponding resected HCC specimens, to evaluate the ability of CEUS to depict the pathological features of HCC. We investigated 50 HCC nodules that were treated by surgical resection. All nodules had been examined by CEUS with intravenous contrast agent (Levovist) before surgery. CEUS findings were divided into three phases for evaluation and classification of enhancement patterns: two vascular phases (arterial phase and portal venous phase) and the delayed phase. Pathological examination focused on differentiation and on the presence or absence of a tumor capsule, intratumoral septum, and intratumoral necrosis. All 21 nodules that showed a linear or annular vessel around the tumor margin in the arterial phase had capsular formation. Of the 27 nodules that showed heterogeneous perfusion in the portal venous phase, 21 (77.8%) had an intratumoral septum and 23 (85.2%) showed intratumoral necrosis. All nodules that were depicted as a defect with an unclear margin in the delayed phase were well-differentiated HCCs, whereas all nodules that were depicted as a defect with a clear margin were moderately or poorly differentiated HCCs. From our observations, the arterial, portal venous, and delayed phases of CEUS could reflect different pathological aspects of HCC. Some pathological characteristics of HCC might be evaluated preoperatively and non-invasively, by means of combined analysis of three phases of CEUS findings.