Escalated Photocurrent with Excitation Energy in Dual-Gated MoTe2.

Although van der Waals-layered transition metal dichalcogenides from transient absorption spectroscopy have successfully demonstrated an ideal carrier multiplication (CM) performance with an onset of nearly 2Eg, interpretation of the CM effect from the optical approach remains unresolved owing to the complexity of many-body electron-hole pairs. We demonstrate the escalated photocurrent with excitation photon energy by fabricating the dual-gate p-n junction of a MoTe2 film on a transparent substrate. Electrons and holes were efficiently extracted by eliminating the Schottky barriers in the metal contact and minimizing multiple reflections. The photocurrent was elevated proportionately to the excitation photon energy. The boosted quantum efficiency confirms the multiple electron-hole pair generation of >2Eg, consistent with CM results from an optical approach, pushing the solar cell efficiency beyond the Shockley-Queisser limit.

Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study.

The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post-hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal-IRI+5-FU/LV (n = 34) had significantly longer median OS versus 5-FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal-IRI+5-FU/LV versus 5-FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal-IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5-FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal-IRI+5-FU/LV versus 5-FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506).

Early venous thromboembolism at the beginning of palliative chemotherapy is a poor prognostic factor in patients with metastatic pancreatic cancer: a retrospective study.

BACKGROUND: This study investigated the prognostic effects of venous thromboembolism (VTE)-related factors in patients with metastatic pancreatic cancer receiving palliative chemotherapy. Predictive factors for VTE were also investigated. METHODS: A total of 216 patients diagnosed with metastatic pancreatic cancer who received gemcitabine-based palliative chemotherapy at our institution were retrospectively evaluated. RESULTS: VTE occurred in 51 (23.6%) patients during treatment and did not affect survival. However, patients who were diagnosed with VTE at the beginning of chemotherapy showed poor prognosis compared with patients diagnosed with VTE during chemotherapy: all patients (hazard ratio [HR] 1.897, p = 0.008); patients diagnosed with VTE (HR = 3.768, p = 0.001). Low serum sodium (Na) (< 135 mmol/L) and high Khorana score (≥3) were strong predictive factors of early VTE (odds ratio [OR] 5.109; 95% confidence interval [95% CI] = 1.010-25.845; p = 0.049 for Khorana score, OR 10.304; 95% CI = 1.036-102.466; p = 0.047) for hyponatremia). CONCLUSIONS: Our study demonstrated that occurrence and detection of VTE in the early period of chemotherapy was the most significant VTE-related prognostic factor in patients with metastatic pancreatic cancer receiving chemotherapy. Prediction using the Khorana score and serum Na levels would be helpful in early diagnosis of VTE.

Perceived social support and its impact on depression and health-related quality of life: a comparison between cancer patients and general population.

OBJECTIVE: It is well known that cancer patients' perception of social support is associated with their depressive symptoms and health-related quality of life. However, there have been little studies that compared the variates of cancer patients with the general population. We sought to compare differences in the level of perceived social support and the impact of perceived social support on depressive symptoms and health-related quality of life between cancer survivors and the general population. METHODS: Data were collected from 1818 cancer patients treated at the National Cancer Center and regional cancer centers in South Korea. The control group of the general population was composed of 2000 individuals without cancer from community. RESULTS: Cancer patients reported significantly higher level of perceived social support than the general population, while they reported lower health-related quality of life and were more susceptible to depression. The positive associations of higher perceived social support with lower depressive symptoms, as well as with higher health-related quality of life, were stronger among cancer patients than among the general population. CONCLUSIONS: The interaction effect suggests that the impact of social support would be stronger among cancer patients than the general public. Thus, it would be beneficial to pay attention to providing social support to cancer patients, particularly to those who are more vulnerable. Furthermore, investigation of the most effective and efficient methods to deliver social support interventions would be worthwhile.

Prognostic Factors and Skeletal-Related Events in Patients with Small Cell Lung Cancer with Bone Metastases at the Time of Diagnosis.

BACKGROUND/OBJECTIVE: The aim of this study was to evaluate the characteristics and prognostic factors of small cell lung cancer (SCLC) with bone metastases. We also investigated the characteristics and predictive factors of skeletal-related events (SREs) in these patients. MATERIALS AND METHODS: Sixty-one patients who were first diagnosed with SCLC with bone metastases at our institution were included in this retrospective analysis. RESULTS: The overall survival (OS) of patients with bone metastases was shorter than that of patients without bone metastases (4.13 vs. 6.17 months, p = 0.015). Poor Eastern Cooperative Oncology Group (ECOG) performance status (PS; ≥2) and higher serum alkaline phosphatase (ALP; above upper normal limit × 2) were independent poor prognostic factors (p = 0.027 for ECOG PS, p = 0.002 for ALP). More than 1 SRE occurred in 21 patients (34.4%). Cervical spine metastasis, thoracic spine metastasis, pelvic bone metastasis, more than 5 bone metastatic regions and higher serum lactate dehydrogenase were correlated with the occurrence of SREs. Thoracic spinal metastasis was a strong predictive factor for the occurrence of SREs (odds ratio = 5.475; 95% CI: 1.080-27.755). CONCLUSION: Our study demonstrates the poor prognosis of SCLC patients with bone metastases. Physicians should treat SCLC patients with bone metastases with caution.

Incidence and Predictors of Febrile Neutropenia among Early-Stage Breast Cancer Patients Receiving Anthracycline-Based Chemotherapy in Korea.

OBJECTIVE: This retrospective study was undertaken to assess the incidence of and risk factors for febrile neutropenia (FN) during adjuvant chemotherapy for early-stage breast cancer (ESBC). METHODS: A multicenter survey of three tertiary hospitals was conducted, with data extracted from the records of ESBC patients treated with adjuvant chemotherapy containing AC (doxorubicin, 60 mg/m2 and cyclophosphamide, 600 mg/m2 every 21 days). Assessments included clinical characteristics, chemotherapy dose modifications, and incidence of FN. RESULTS: A total of 610 patients were included for analysis. The incidence of grade 4 neutropenia and FN was 44.6 and 8.5%, respectively. Reduced relative dose intensity (RDI) less than 85% occurred in 11.0% of patients, and there were treatment delays in 12.6% of patients. Multivariate analysis identified several independent predictors for FN, including the presence of grade 4 neutropenia and pretreatment calculated estimated glomerular filtration rate less than 60 ml/min. CONCLUSION: Patients with ESBC are at substantial risk for FN and reduced RDI when treated with adjuvant AC chemotherapy. Predictive models based on risk factors identified in this study should enable the selective application of supportive measures in an effort to deliver the full dose of chemotherapy.

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

BACKGROUND: Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. CASE PRESENTATION: A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. CONCLUSIONS: Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

Comparison of the Efficacy between Pemetrexed plus Platinum and Non-Pemetrexed plus Platinum as First-Line Treatment in Patients with Wild-Type Epidermal Growth Factor Receptor Nonsquamous Non-Small Cell Lung Cancer: A Retrospective Analysis.

BACKGROUND: Despite the development of molecular research and targeted therapy, patients with wild-type epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) still receive platinum doublet chemotherapy as the standard first-line treatment. We investigated the efficacy of first-line regimens in patients with wild-type EGFR nonsquamous NSCLC. METHODS: We retrospectively analyzed the efficacy of various platinum doublet regimens as first-line treatments. Between 2007 and 2013, a total of 165 patients with wild-type EGFR nonsquamous NSCLC were included in this study. RESULTS: Seventy-one (43.0%) patients were treated with pemetrexed plus platinum (PP) and 94 (57.0%) with non-pemetrexed plus platinum (NPP). The overall response rate was not different between the PP- and NPP-treated groups (26.8 vs. 28.7%, respectively; p = 0.78). The median progression-free survival (PFS) and overall survival (OS) also showed no differences between the two treatment groups (p = 0.12 for PFS, p = 0.42 for OS). The median PFS and OS for the PP group were 4.6 months (95% CI, 3.8-5.4) and 18.7 months (95% CI, 11.7-25.8), respectively, and for the NPP group, they were 4.2 months (95% CI, 3.4-5.0) and 12.2 months (95% CI, 10.3-14.1), respectively. In the subgroup analysis, most subgroups showed no significant difference in PFS and OS between the two treatment groups. CONCLUSION: Our data showed that the efficacy of various platinum doublet regimens was similar in patients with wild-type EGFR nonsquamous NSCLC.

Ramosetron Versus Ondansetron in Combination With Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Randomized Phase III Trial, KCSG PC10-21.

BACKGROUND: A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron's efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV. METHODS: Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was -15%. RESULTS: A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2-5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups. CONCLUSION: RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.

Fused aortic valve without an elliptical-shaped systolic orifice in patients with severe aortic stenosis: cardiac computed tomography is useful for differentiation between bicuspid aortic valve with raphe and tricuspid aortic valve with commissural fusion.

OBJECTIVE: The objective is to determine cardiac computed tomography (CCT) features capable of differentiating between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in severe aortic stenosis (AS) patients with fused cusp and without elliptical-shaped systolic orifices. METHODS: We retrospectively enrolled 53 patients who had severe AS with fused cusps and without an elliptical-shaped systolic orifice on CCT and who had undergone surgery. CCT features were analyzed using: 1) aortic valve findings including cusp size, cusp area, opening shape, midline calcification, fusion length, calcium volume score, and calcium grade; 2) diameters of ascending and descending aorta, and main pulmonary artery; and 3) rheumatic mitral valve findings. The variables were evaluated using univariate and multivariate logistic regression analyses. RESULTS: At surgery, 19 patients had BAV and 34 had TAV. CCT features including uneven cusp size, uneven cusp area, round-shaped systolic orifice, longer cusp fusion, and dilatation of ascending aorta were significantly associated with BAV (P < 0.05). In particular, fusion length (OR, 1.76; P = 0.001), uneven cusp area (OR, 10.46; P = 0.012), and midline calcification (OR, 0.08; P = 0.013) were strongly associated with BAV. CONCLUSION: CCT provides diagnostic clues that helps differentiate between BAV with raphe and TAV with commissural fusion in patients with severe AS. KEY POINTS: • Accurate morphologic assessment of the aortic valve is important for treatment planning. • It is difficult to differentiate BAV from TAV with a fused cusp. • CCT provides diagnostic clues for the differentiation of BAV and TAV.

Characteristics of aortic valve dysfunction and ascending aorta dimensions according to bicuspid aortic valve morphology.

OBJECTIVE: To characterize aortic valve dysfunction and ascending aorta dimensions according to bicuspid aortic valve (BAV) morphology using computed tomography (CT) and surgical findings. METHODS: We retrospectively enrolled 209 patients with BAVs who underwent transthoracic echocardiography (TTE) and CT. BAVs were classified as anterior-posterior (BAV-AP) or lateral (BAV-LA) orientation of the cusps and divided according to the presence (raphe+) or absence (raphe-) of a raphe. Ascending aortic dimensions were measured by CT at four levels. RESULTS: BAV-AP was present in 129 patients (61.7%) and raphe+ in 120 (57.4%). Sixty-nine patients (33.0%) had aortic regurgitation (AR), 70 (33.5%) had aortic stenosis (AS), and 58 (27.8%) had combined AS and AR. AR was more common in patients with BAV-AP and raphe+; AS was more common with BAV-LA and raphe-.Annulus/body surface area and tubular portion/body surface area diameters in patients with BAV-AP (17.1 ± 2.3 mm/m(2) and 24.2 ± 5.3 mm/m(2), respectively) and raphe+ (17.3 ± 2.2 mm/m(2) and 24.2 ± 5.5 mm/m(2), respectively) were significantly different from those with BAV-LA (15.8 ± 1.9 mm/m(2) and 26.4 ± 5.5 mm/m(2), respectively) and raphe- (15.7 ± 1.9 mm/m(2) and 26.2 ± 5.4 mm/m(2), respectively). CONCLUSION: The morphological characteristics of BAV might be associated with the type of valvular dysfunction, and degree and location of an ascending aorta dilatation. KEY POINTS: • The BAV-AP type had more frequent aortic regurgitation, raphe, and a larger aortic annulus. • BAV without raphe had more frequent aortic stenosis and mid-ascending aorta dilatation. • CT allows assessment of the morphological characteristics of BAV and associated aortopathy.

YKL-40 expression could be a poor prognostic marker in the breast cancer tissue.

YKL-40 is a glycoprotein involved in cellular growth, migration, and the inflammatory process. Elevation in serum levels of YKL-40 has been associated with worse prognosis in various cancers, including breast cancer. Given that the clinical significance of YKL-40 expression in breast cancer tissue is unclear, we aimed to determine the prognostic value of YKL-40 expression in breast cancer tissue using immunohistochemistry. We performed tissue microarray (TMA) analysis of 425 breast cancer tissues collected during operation. Immunohistochemical staining was performed to measure expression of YKL-40 and several breast cancer biomarkers, such as aldehyde dehyadrogenase1, TGF-beta, and Gli-1 as well as hormonal receptor and Her-2/neu status. Statistical analysis of the relationship of YKL-40 expression with clinicopathological characteristics was performed for 390 TMA samples. YKL-40 was expressed to varying degrees in 84.9% of breast cancer tissues. YKL-40 expression was correlated with estrogen receptor and progesterone receptor negativity and was positively correlated with TGF-beta and Gli-1 expression. Strong YKL-40 expression was associated with a larger proportion of Her-2/neu-enriched and basal-like tumors. The results of this study demonstrate that YKL-40 expression in breast cancer tissues is associated with hormone receptor negativity and Her-2/neu-enriched molecular subtypes of breast cancer, and therefore could be considered a poor prognostic predictor.

Prognostic Factors for the Selection of Patients Eligible for Second-Line Chemotherapy in Advanced Biliary Tract Cancer.

BACKGROUND: The efficacy of second-line chemotherapy (CT2) after the failure of first-line chemotherapy (CT1) for advanced biliary tract cancer (BTC) has not been established. We investigated the favorable prognostic factors for CT2 to determine which patients could be expected to benefit from CT2. METHODS: From a total of 168 patients who were treated with chemotherapy at our institution between January 2003 and December 2012, we retrospectively reviewed 50 patients who received CT2. Patients were treated with various chemotherapeutic combinations as CT1 and CT2. RESULts: The median overall survival (OS) of patients who received and CT2 was 10.2 and 5.5 months, respectively. Good performance status (PS), a serum albumin level >3.5 g/dl and metastasis to only 1 organ were independent prognostic factors that affected the OS of the patients who received CT2. Patients who had only 1 metastastic organ, a good PS and a serum albumin level >3.5 g/dl at the beginning of CT2 demonstrated prolonged survival compared to patients who did not exhibit these 3 factors (9.5 vs. 4.3 months, p < 0.005). CONCLUSIONS: CT2 should be considered for patients with advanced BTC, especially for those who have only 1 metastatic organ and remain in generally good medical condition after the failure of CT1.

The relationship between preeclampsia, pregnancy-induced hypertension and maternal risk of breast cancer: a meta-analysis.

BACKGROUND: It has long been recognized that some human breast cancers are hormone dependent. Preeclampsia is a syndrome of pregnancy defined by the onset of hypertension and proteinuria and characterized by dysfunction of the maternal endothelium. Many hormonal changes occur with preeclampsia, and we hypothesize that these changes may influence the risk of maternal breast cancer. We also analyzed the relation between pregnancy-induced hypertension (PIH) and maternal risk of breast cancer. METHODS: Among 13 relevant publications about preeclampsia and six relevant publications about PIH, some studies find preeclampsia associated with a lower risk of breast cancer, but others did not. Therefore, these results are inconclusive. We conducted meta-analysis to evaluate more precisely the relationship between preeclampsia, PIH and maternal risk of breast cancer. RESULTS: The pooled estimate of the hazard ratio (HR) associated with preeclampsia was 0.86 (95% CI 0.73-1.01), and that associated with PIH was 0.83 (0.66-1.06), both based on the random effects model. CONCLUSION: Some suggestive but not entirely consistent nor conclusive evidence was found on the association between the history of preeclampsia or PIH with the subsequent risk of breast cancer.

Abrogation of Gli3 expression suppresses the growth of colon cancer cells via activation of p53.

p53, the major human tumor suppressor, appears to be related to sonic hedgehog (Shh)-Gli-mediated tumorigenesis. However, the role of p53 in tumor progression by the Shh-Gli signaling pathway is poorly understood. Herein we investigated the critical regulation of Gli3-p53 in tumorigenesis of colon cancer cells and the molecular mechanisms underlying these effects. RT-PCR analysis indicated that the mRNA level of Shh and Gli3 in colon tumor tissues was significantly higher than corresponding normal tissues (P<0.001). The inhibition of Gli3 by treatment with Gli3 siRNA resulted in a clear decrease in cell proliferation and enhanced the level of expression of p53 proteins compared to treatment with control siRNA. The half-life of p53 was dramatically increased by treatment with Gli3 siRNA. In addition, treatment with MG132 blocked MDM2-mediated p53 ubiquitination and degradation, and led to accumulation of p53 in Gli3 siRNA-overexpressing cells. Importantly, ectopic expression of p53 siRNA reduced the ability of Gli3 siRNA to suppress proliferation of those cells compared with the cells treated with Gli3 siRNA alone. Moreover, Gli3 siRNA sensitized colon cancer cells to treatment with anti-cancer agents (5-FU and bevacizumab). Taken together, our studies demonstrate that loss of Gli3 signaling leads to disruption of the MDM2-p53 interaction and strongly potentiate p53-dependent cell growth inhibition in colon cancer cells, indicating a basis for the rational use of Gli3 antagonists as a novel treatment option for colon cancer.

Awareness of incurable cancer status and health-related quality of life among advanced cancer patients: a prospective cohort study.

BACKGROUND: Many patients near death report an interest in knowing their prognoses. Patients' awareness of disease status may lead to more appropriate care and maintained or improved quality of life. However, it is not known whether advanced cancer patients' awareness of disease status is associated with patients' quality of life. AIM: We aimed to examine the effect of patients' awareness of disease status on the health-related quality of life (HRQOL) among advanced cancer patients undergoing palliative chemotherapy. DESIGN: In this prospective cohort study, patients were followed-up at 4-6 weeks and 2-3 months after the initial palliative chemotherapy. Patients' awareness of disease status, and demographic and clinical characteristics were assessed at baseline, and depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) and HRQOL using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were assessed three times. SETTING / PARTICIPANTS: In total, 100 patients with advanced cancer starting palliative chemotherapy were recruited from two tertiary university hospitals and from the Korea National Cancer Center. RESULTS: Patients with advanced cancer undergoing palliative chemotherapy experienced deteriorated HRQOL. Of these, the patients who were aware of their disease status as incurable had significantly higher role (p=0.002), emotional (p=0.025), and social functioning (p=0.002), and lower fatigue (p=0.008), appetite loss (p=0.039), constipation (p=0.032), financial difficulties (p=0.019), and anxiety (p=0.041) compared with patients unaware of disease status. CONCLUSION: Our findings demonstrate the importance of patients' awareness of disease status to HRQOL.

Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study.

BACKGROUND: Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a standard treatment for patients with advanced biliary-tract cancer. Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits. Therefore, we aimed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer. METHODS: In this open label, randomised, phase 3 trial, we randomly assigned patients (in a 1:1 ratio) with metastatic biliary-tract cancer (cholangiocarcinoma, gallbladder cancer, or ampulla of Vater cancer) to receive either first-line treatment with chemotherapy alone (gemcitabine 1000 mg/m(2) on day 1 and oxaliplatin 100 mg/m(2) on day 2) or chemotherapy plus erlotinib (100 mg daily). Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects. Randomisation was done centrally (stratified by participating centre and presence of measurable lesion). The primary endpoint was progression-free survival. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01149122. FINDINGS: 133 patients were randomly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group. The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group (96 [71%] patients vs 84 [63%]). Median progression-free survival was 4·2 months (95% CI 2·7-5·7) in the chemotherapy alone group and 5·8 months (95% CI 4·6-7·0) in the chemotherapy plus erlotinib group (hazard ratio [HR] 0·80, 95% CI 0·61-1·03; p=0·087). Significantly more patients had an objective response in the chemotherapy plus erlotinib group than in the chemotherapy alone group (40 patients vs 21 patients; p=0·005), but median overall survival was the same in both groups (9·5 months [95% CI 7·5-11·5] in the chemotherapy alone group and 9·5 months [7·6-11·4] in the chemotherapy plus erlotinib group; HR 0·93, 0·69-1·25; p=0·611). All-cause deaths within 30 days of random assignment occurred in one (1%) of the patients in the chemotherapy alone group and in four (3%) of those in the chemotherapy plus erlotinib group. The most common grade 3-4 adverse event was febrile neutropenia (eight [6%] patients in the chemotherapy alone group and six [4%] in the chemotherapy plus erlotinib group). No patient died of treatment-related causes during the study. Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma, the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival (5·9 months [95% CI 4·7-7·1] for chemotherapy plus erlotinib vs 3·0 months [1·1-4·9] for chemotherapy alone; HR 0·73, 95% CI 0·53-1·00; p=0·049). INTERPRETATION: Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma. FUNDING: None.

The relationship between twin births and maternal risk of breast cancer: a meta-analysis.

Women who undergo a greater number of menstrual cycles may be at increased risk of breast cancer, possibly due to cumulative exposure to ovarian hormones. Pregnancy reduces the lifetime number of menstrual cycles and also influences the levels of ovarian hormones. Twin pregnancies differ from singleton pregnancies in both hormone levels and perinatal changes. To date, a meta-analysis on the effects of twin birth on the risk of maternal breast cancer has not been conducted. Among 17 relevant publications identified in a systematic search, some suggest that twin births may be associated with lower breast cancer risk but others do not; therefore, the results are inconclusive. Although our pooled results of all 17 published studies did not show a reduced maternal risk of breast cancer for twin births (HR 0.94; 95% CI = 0.87-1.02; P = 0.127), a trend toward reduced maternal risk of breast cancer was identified in a subgroup analysis of cohort studies (HR 0.91; 95% CI = 0.83-1.01; P = 0.068). The results of this meta-analysis suggest that twin pregnancy does not significantly decrease the maternal risk of breast cancer.

Flexible field emission from thermally welded chemically doped graphene thin films.

Flexible field-emission devices (FEDs) based on reduced graphene oxide (RGO) emitters are fabricated by the thermal welding of RGO thin films onto a polymeric substrate. The RGO edges are vertically aligned relative to the substrate as a result of cohesive failure in the RGO layer after thermal welding. Even at large bending angles, excellent electron emission properties, such as low turn-on and threshold fields, a high emission current density, a high field enhancement factor, and long-term stability of the emission properties of RGO emitters, arise from the uniform distribution and high density of the extremely sharp RGO edges, as well as the high interfacial strength between the RGO emitters and the substrate. Al- and Au-doped RGO emitters are fabricated by introducing a dopant solution to the RGO emitters, and the resulting field-emission characteristics are discussed. The proposed approach is straightforward and enables the practical use of high-performance RGO flexible FEDs.

How does inhibition of the renin-angiotensin system affect the prognosis of advanced gastric cancer patients receiving platinum-based chemotherapy?.

BACKGROUND: The renin-angiotensin system (RAS) is related to the regulation of cell proliferation, angiogenesis, and tumor progression. PATIENTS AND METHODS: We retrospectively analyzed the effect of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 63 patients with advanced gastric cancer (AGC) with platinum-based chemotherapy. All patients analyzed had received medications for hypertension at the diagnosis of AGC. Patients were divided into two groups: an ACEI/ARB group (n = 30) and a non-ACEI/ARB group (n = 33). RESULTS: Patient characteristics were not different between patients with and without ACEI/ARB. The response rate for all patients was 25.4% and the disease control rate was 77.8%. The median progression-free survival (PFS) for first-line chemotherapy was 5.5 months (95% CI 3.71-7.29) in the ACEI/ARB group and 4.3 months (95% CI 2.39-6.21) in the non-ACEI/ARB group (p = 0.506). There was a significant difference in overall survival (OS) in the ACEI/ARB group compared to the non-ACEI/ARB group (median OS: 8.2 vs. 13.9, p = 0.0095). In multivariate analysis, the use of ACEI/ARB was a significant independent prognostic factor for OS (p = 0.039) but not for PFS. CONCLUSION: ACEI/ARB in combination with standard chemotherapy might improve survival in patients with AGC and hypertension. These results support further investigation into the anticancer effects of ACEL/ARB.