Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this ...treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980–2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013.
The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis.
A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death HR = 0.64, 95% confidence interval (CI) 0.52–0.79, P < 0.0001 was observed with salvage chemotherapy.
When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40–0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56–0.90, P = 0.004) for docetaxel.
This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.
High-resolution postcontrast 3D T1WI is a widely used sequence for evaluating brain metastasis, despite the long scan time. This study aimed to compare highly accelerated postcontrast 3D T1-weighted ...sampling perfection with application-optimized contrasts by using different flip angle evolution by using wave-controlled aliasing in parallel imaging (wave-T1-SPACE) with the commonly used standard high-resolution postcontrast 3D T1-SPACE for the evaluation of brain metastases.
Among the 387 patients who underwent postcontrast wave-T1-SPACE and standard SPACE, 56 patients with suspected brain metastases were retrospectively included. Two neuroradiologists assessed the number of enhancing lesions according to lesion size, contrast-to-noise ratio
, contrast-to-noise ratio
, contrast ratio
, and overall image quality for the 2 different sequences.
Although there was no significant difference in the evaluation of larger enhancing lesions (>5 mm) between the 2 different sequences (
= .66 for observer 1,
= .26 for observer 2), wave-T1-SPACE showed a significantly lower number of smaller enhancing lesions (<5 mm) than standard SPACE (1.61 SD, 0.29 versus 2.84 SD, 0.47 for observer 1; 1.41 SD, 0.19 versus 2.68 SD, 0.43 for observer 2). Furthermore, mean contrast-to-noise ratio
and overall image quality of wave-T1-SPACE were significantly lower than those in standard SPACE.
Postcontrast wave-T1-SPACE showed comparable diagnostic performance for larger enhancing lesions (>5 mm) and marked scan time reduction compared with standard SPACE. However, postcontrast wave-T1-SPACE showed underestimation of smaller enhancing lesions (<5 mm) and lower image quality than standard SPACE. Therefore, postcontrast wave-T1-SPACE should be interpreted carefully in the evaluation of brain metastasis.
Summary
This study was performed to examine whether capsaicin, the main pungent ingredient of red peppers, exerts protective effects against testicular injuries induced by transient scrotal ...hyperthermia. Capsaicin (0.33 mg kg−1) was administered subcutaneously to mice one hour before heat stress (HS) in a 43°C water bath for 20 min. After 7 days, mice exposed to HS showed low testicular weight, severe vacuolisation of seminiferous tubules followed by loss of spermatogenic cells, and appearance of multinucleated giant cells and remarkable TUNEL‐positive apoptotic cells, as well as weak immunoreactivity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in spermatogenic cells. Levels of lipid peroxidation and heat shock 70‐kDa protein 1 (Hsp72) and BCL2‐associated X protein (Bax) mRNA were greatly increased, but PHGPx, manganese superoxide dismutase (MnSOD), and B‐cell lymphoma‐extra large (Bcl‐xL) mRNAs were significantly diminished in the testes by HS. However, capsaicin pre‐treatment significantly suppressed the spermatogenic cell death, oxidative stress (levels of MDA, PHGPx immunoreactivity, and Hsp72, PHGPx, and MnSOD mRNA) and apoptosis (levels of TUNEL‐positive cells, and Bcl‐xL and Bax mRNA) in testes by HS. These suggest that capsaicin has a protective effect against spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti‐apoptotic activities.
Background
National Health Insurance (NHI) claim records could provide valuable data for epidemiological studies of asthma in Korea. The aim of this study is to estimate the prevalence of adult ...asthma and to investigate asthma‐related healthcare use and prescription patterns in Korea over 5 years.
Methods
National Health Insurance claim records from January 1, 2006 to December 31, 2010 were analyzed in a retrospective, population‐based study. Outcome measures included asthma prevalence, healthcare use, and prescription patterns over time, by type of hospital, and by medical specialty. Additionally, we assessed differences in healthcare use between newly diagnosed and previously diagnosed patients in 2009.
Results
Over 5 years, the prevalence of asthma among Korean adults increased from 4944 to 5707 cases per 100 000 population (from 3760 to 4445 in men and from 6108 to 6951 in women). Asthma‐related outpatient visits decreased from 4.82 ± 8.02 to 3.44 ± 5.50. Approximately 3% of all patients were hospitalized and 2.4% received asthma‐related emergency treatment each year. Pulmonary function tests were performed in 10–11% of patients an average of 1.3 times per year. Newly diagnosed patients experienced fewer asthma‐related hospitalizations (1.78% vs 4.35%) and emergency department visits (0.80% vs 2.11%) than the previously diagnosed group. Prescriptions of inhaled corticosteroids‐based inhalers were maintained with about 20% of average of all types of hospitals.
Conclusions
The prevalence of asthma in Korea has increased over a recent 5‐year period, and asthma is still suboptimally controlled. Public health strategies are needed to improve the management of asthma in adults.
•First ever preparation of stacking fault energy maps (SFE maps) for the Cr-Ni-Mn-Fe MEA alloy system, applicable to various temperatures.•The most balanced tensile properties can be achieved by ...designing alloys with an SFE value adjacent to the TWIP-TRIP boundary line in the SFE maps.•Cr12Ni12Mn16Fe60 MEA possesses a combination of superior strength and good ductility at cryogenic temperatures, owing to the TWIP-TRIP effects.
Single-phase high-entropy alloys and medium-entropy alloys (MEAs) with face-centered-cubic (FCC) structures have attracted considerable attention owing to their exceptional strength and ductility at cryogenic temperatures by performing twinning and martensitic transformations. In this study, a series of novel MEAs were developed (Cr12Ni12MnxFe76−x, x = 12, 16, 20) based on a thermodynamic approach. The Cr12Ni12Mn16Fe60 MEA was discovered to possess a unique combination of excellent strength (~ 1050 MPa) and ductility (~ 86%) at cryogenic temperatures. Through experimental assessment and thermodynamic modeling, the strength–ductility synergy was quantitatively demonstrated to be derived from the interplay among a series of plasticity mechanisms. In addition, a model was proposed for evaluating the stacking fault energy of Cr-Ni-Mn-Fe MEAs at different temperatures. This work demonstrates an efficient and novel strategy for developing high-strength and high-ductility alloys with single-phase FCC structures.
Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst.
...Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%-80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated.
The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8-49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0-3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%-100.0%;
< .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic (
< .001) and cosmetic (
< .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient.
Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation.
Early detection of local recurrence is important to increase the chance of cure because local recurrence is the main cause of treatment failure in head and neck squamous cell carcinoma. We evaluated ...the added value of voxel-based color maps of dynamic contrast-enhanced MR imaging compared with conventional MR imaging alone for detecting local recurrence of head and neck squamous cell carcinoma.
We retrospectively enrolled 63 consecutive patients with head and neck squamous cell carcinoma after definitive treatment and posttreatment surveillance MR imaging studies that demonstrated focal enhancement at the primary site. Three independent readers assessed conventional MR imaging and a pair of color maps of initial and final 90-second time-signal intensity areas under the curve from dynamic contrast-enhanced MR imaging. The sensitivities, specificities, and accuracies of both conventional MR imaging alone and combined interpretation of conventional and dynamic contrast-enhanced MR imaging were assessed using the clinicopathologic diagnosis as the criterion standard. κ statistics were used to evaluate interreader agreement.
There were 28 patients with subsequently documented local recurrence and 35 with posttreatment change. Adding dynamic contrast-enhanced MR imaging to conventional MR imaging significantly increased the diagnostic accuracies for detecting local recurrence (48%-54% versus 87%-91%;
< .05), with excellent interreader agreement (κ = 0.8; 95% CI, 0.67-0.92 to κ = 0.81; 95% CI, 0.69-0.93). By all 3 readers, the specificities were also significantly improved by adding dynamic contrast-enhanced MR imaging to conventional MR imaging (22%-43% versus 87%-91%;
< .001) without sacrificing the sensitivities (68%-82% versus 86%-89%;
> .05).
Adding voxel-based color maps of initial and final 90-second time-signal intensity areas under the curve from dynamic contrast-enhanced MR imaging to conventional MR imaging increases the diagnostic accuracy to detect local recurrence in head and neck squamous cell carcinoma by improving the specificity without sacrificing the sensitivity.
Pancreatic ductal adenocarcinoma (PDAC) cells usually overexpress the epidermal growth factor receptor (EGFR); however, most are resistant to the anti-EGFR monoclonal antibody, cetuximab. In this ...study, we report that the molecular mechanism of resistance to cetuximab in PDAC cells is mediated by the overexpression of active integrin β1 with downstream Src-Akt activation; this triggers an EGFR ligand-independent proliferation signaling, bypassing EGFR-blocking effect. Knockdown of integrin β1 or inhibition of Src or Akt sensitized cetuximab-resistant (Ctx
) PDAC cells to cetuximab. We found that neuropilin-1 (NRP1) physically interacts with active integrin β1, but not inactive one, on the cell surface. To inhibit active integrin β1-driven signaling by targeting NRP1, while suppressing EGFR signaling, we generated an EGFR and NRP1 dual targeting antibody, Ctx-TPP11, by genetic fusion of the NRP1-targeting peptide, TPP11, to the C terminus of the cetuximab heavy chain (Ctx-TPP11). We demonstrate that Ctx-TPP11 efficiently inhibited the growth of Ctx
PDAC cells, in vitro and in vivo. The sensitization mechanism involved downregulating active integrin β1 levels through NRP1-coupled internalization mediated by the TPP11 moiety, leading to the inhibition of active integrin β1-driven bypass signaling. Our findings identify aberrant active integrin β1-driven Src-Akt hyperactivation as a primary resistance mechanism to cetuximab in PDAC cells and offer an effective therapeutic strategy to overcome this resistance using an EGFR and NRP1 dual targeting antibody.
S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, ...irinotecan and oxaliplatin.
Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m(-2) followed by oxaliplatin 85 mg m(-2) on day 1 and S-1 80 mg m(-2) per day from day 1 to 14 every 3 weeks. Polymorphisms in the UGT1A1, UGT1A6, UGT1A7 and CYP2A6 genes were analysed.
Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval: 53.4-81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of UGT1A6*2 or UGT1A7*3 and an improved tumour response was noted in those without variant alleles of CYP2A6 or UGT1A1*60.
The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.
Average load forecasting errors for the holidays are much higher than those for weekdays. So far, many studies on the short-term load forecasting have been made to improve the prediction accuracy ...using various methods such as deterministic, stochastic, artificial neural net (ANN) and neural network-fuzzy methods. In order to reduce the load forecasting error of the 24 hourly loads for the holidays, the concept of fuzzy regression analysis is employed in the short-term load forecasting problem. According to the historical load data, the same type of holiday showed a similar trend of load profile as in previous years. The fuzzy linear regression model is made from the load data of the previous three years and the coefficients of the model are found by solving the mixed linear programming problem. The proposed algorithm shows good accuracy, and the average maximum percentage error is 3.57% in the load forecasting of the holidays for the years of 1996-1997.
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