Summary
Background
Gastric cancer is the fourth most common cancer worldwide. Surgery in combination with multimodal therapy provides the only curative therapy until now. The importance of targeted ...therapy became clear over the last few years. Due to the implication of HER2 and angiogenesis-directed targeted therapies major advances in the treatment of gastric cancer could be reached. Nevertheless, benefits in survival remain unsatisfactory and the development of resistance to monoclonal antibodies is arising.
Methods
A comprehensive and comparative literature research was performed to evaluate the status of HER2 and angiogenesis-directed targeted therapy in gastric cancer.
Results
Up to now, trastuzumab and ramucirumab are the only agents showing remarkable benefits in the therapy for the patients suffering from gastric cancer. The limitations of targeted therapies in gastric cancer are mainly associated with the development of secondary resistance.
Conclusion
Addition of targeted therapy in second-line treatment is beneficial when compared with chemotherapy alone. Nevertheless, results in first-line treatment remain modest. Therefore, new therapeutic agents and combinations in the first-line treatment of gastric cancer are urgently needed and remain to be validated in clinical trials.
Different extensions of the standard model of particle physics, such as braneworld or mirror matter models, predict the existence of a neutron sterile state, possibly as a dark matter candidate. This ...Letter reports a new experimental constraint on the probability p for neutron conversion into a hidden neutron, set by the STEREO experiment at the high flux reactor of the Institut Laue-Langevin. The limit is p<3.1×10^{-11} at 95% C.L. improving the previous limit by a factor of 13. This result demonstrates that short-baseline neutrino experiments can be used as competitive passing-through-walls neutron experiments to search for hidden neutrons.
As endocrinological parameters such as thyroid hormones modulate proliferative, metabolic, and angiogenic pathways, it is surmised that their levels can be associated with cancer development and ...progression. Most patients with gastroesophageal cancer are diagnosed very late and have a poor prognosis, yet the association with endocrinological parameters has not been addressed so far. The aim of this study was to correlate hormones with the outcome, so new prognostic and potentially therapeutic markers can be defined. We analyzed clinical and endocrinological parameters including history of thyroid disorders and laboratory analyses of thyroid hormones and correlated these with the overall survival in a large European cohort of patients with inoperable locally advanced or metastatic gastroesophageal cancer treated between 2002 and 2018 at the Vienna General Hospital, Austria. In total, the survival outcome of 258 patients was evaluated. Higher levels of fT4 (
p
= 0.041, HR = 2.202) and lower levels of T3 (
p
= 0,003, HR = 0,141) were associated with significantly shorter survival. However, the overall survival of patients with known thyroid disorders did not differ significantly from euthyroid patients (euthyroid, 283 days; hyperthyroid, 354 days; hypothyroid, 284 days;
p
= 0.472). Elevated fT4 levels are associated with poorer overall survival of patients with gastroesophageal cancer in advanced stages. Since data on the correlation of endocrinological parameters and gastroesophageal cancer are scarce, this analysis is an important impulse for further studies concerning the impact of thyroxine on patients with cancer of the upper GI tract.
Background
Obesity and gastroesophageal reflux disease (GERD) are major health problems showing an inconstant relationship in the literature. Therefore, anthropometric parameters which are predictive ...and can simply be assessed at first patient presentation may lead to a better patient selection for ambulatory reflux monitoring. We aimed to examine the association of body mass index (BMI) and waist to hip ratio (WHR) with gastroesophageal reflux activity during 24 hour‐pH‐impedance monitoring.
Methods
Seven hundred and seventy‐one patients with GERD symptoms underwent 24 hour‐pH‐impedance monitoring and high resolution manometry off proton pump inhibitors. Patients with known primary motility disorders of the esophagus and pre‐existing endoscopic or operative procedure on esophagus or stomach were excluded from the study. Reflux parameters and anthropometric and demographic data from our prospectively gathered database were analyzed. We performed univariate and multivariate regression analysis to evaluate the associations of BMI and WHR with reflux parameters measured with 24 hour‐pH‐impedance monitoring.
Key Results
WHR showed a significantly stronger association with esophageal acid exposure than BMI (P<.001). Our data show that 6.9% of the percentage of endoluminal pH<4 in the distal esophagus is attributable to WHR. Furthermore, an association of WHR with impaired esophageal acid clearance was observed. Additionally, we observed an inverse relationship between lower esophageal sphincter integrity (P=.05) and esophageal acid exposure.
Conclusions and Inferences
WHR is a better predictor for esophageal acid exposure than BMI. Biomechanical and metabolic mechanisms of central fat distribution may influence reflux parameters in 24 hour pH impedance monitoring, which may affect patient selection for ambulatory reflux monitoring.
WHR is associated with the mean clearance time of acid from the distal esophagus (lct, logarithm of mean acid clearance time; hwr, waist to hip ratio)
Background. A number of studies have revealed that inflammation-based prognostic scores, such as Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein and ...albumin ratio (C/A ratio), are associated with poor outcome in cancer patients. However, until now, no study has investigated the role of these prognostic scores in a cohort of neoadjuvant-treated esophageal adenocarcinomas (nEAC) and squamous cell carcinomas (nESCC). Methods. Patients had laboratory measurements within three days before resection. GPS, mGPS, and C/A ratio were tested together with established clinicopathological factors in simple and multiple Cox regression analysis of overall survival (OS) and disease-free survival (DFS). Results. A total of 283 patients (201 EAC and 82 ESCC) with locally advanced esophageal cancer were enrolled. 167 patients received neoadjuvant treatment (59.0%). Simple analysis revealed that there were significant differences in cancer-specific survival in relation to elevated C-reactive protein (p=0.011), lymph node status (p<0.001), UICC stage (p<0.001), and nEAC (p=0.005). mGPS (p=0.024) showed statistical significance in simple analysis. No statistical significance could be found for GPS (p=0.29), mGPS (p=0.16), and C/A ratio (p=0.76) in multiple analysis. Conclusion. The investigated prognostic scores should be used and interpreted carefully, and established factors like histology, including tumor size and differentiation, lymph node involvement, and status of resection margin remain the only reliable prognostic factors for patients suffering from resectable EC.
.
The STEREO experiment measures the electron antineutrino spectrum emitted in a research reactor using the inverse beta decay reaction on H nuclei in a gadolinium loaded liquid scintillator. The ...detection is based on a signal coincidence of a prompt positron and a delayed neutron capture event. The simulated response of the neutron capture on gadolinium is crucial for the comparison with data, in particular in the case of the detection efficiency. Among all stable isotopes,
155
Gd and
157
Gd have the highest cross sections for thermal neutron capture. The excited nuclei after the neutron capture emit gamma rays with a total energy of about 8MeV. The complex level schemes of
156
Gd and
158
Gd are a challenge for the modeling and prediction of the deexcitation spectrum, especially for compact detectors where gamma rays can escape the active volume. With a new description of the Gd (n,
γ
) cascades obtained using the FIFRELIN code, the agreement between simulation and measurements with a neutron calibration source was significantly improved in the STEREO experiment. A database of ten millions of deexcitation cascades for each isotope has been generated and is now available for the user.
Attempts for identifying targeted therapy strategies in metastatic gastric and gastroesopheal junction cancer (upper-GI) revealed that the inhibition of human epidermal growth factor receptor-2 ...(HER2) by monoclonal antibody trastuzumab improves survival of these patients. Hence, adding trastuzumab to doublet chemotherapy has become the standard treatment in this setting. Although the patient survival is extended among clinical trials, the knowledge on the real-time setting is limited. With this retrospective, single center analysis of the patient data of the Medical University of Vienna, we sought to investigate the clinical characteristics and outcome of patients, who received trastuzumab-based chemotherapy for metastatic upper-GI tumor. All patients, who received trastzumab at least once were included to the analysis. Clinical and pathological data were recorded. This search revealed 33 patients. The demographic data was comparable with that of the previous clinical trials. Progression free survival (PFS) was 11 months, whereas overall survival (OS) was 21 months. OS was significantly associated with initially favorable response to treatment. Thirteen patients (39%) received trastuzumab as maintenance treatment with a median cycle number of 6. Toxicity profile was acceptable with only one patient detected to have cardiotoxicity. Taken together, trastuzumab based treatment induced a considerable PFS and OS in metastatic or advanced upper-GI tumors with acceptable toxicity profile. The maintenance therapy with trastuzumab was safe and effective in patients who had initially a favorable response to chemotherapy. The optimal duration of the maintenance therapy should be tested in future clinical trials.
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