The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, ...as the current standard sequence for metastatic colorectal cancer patients.
Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence cetuximab ± irinotecan followed by regorafenib (C-R arm). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins.
One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS 95% confidence interval (CI) 0.39–0.96. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61–1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17–0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib.
The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.
Evidence of the association between chronic low-grade inflammation, as reflected by C-reactive protein (CRP) measurements, and cancer risk is equivocal. Specifically, few studies have examined this ...in uncommon cancers and Asian populations.
We utilised a case-cohort design consisting of multi-types of cancer (N = 3608), and a random subcohort (N = 4432) in a Japanese large population-based study, with a median follow-up time of 15.6 years, and measured baseline plasma CRP using high sensitivity assay. The hazard ratios (HRs) were estimated using weighted Cox proportional hazards methods.
The multivariable-adjusted HR (95% confidence interval) for the top quartile of CRP was 1.28 (1.11‒1.48) (P
< 0.001) for overall cancer compared to the bottom quartile of CRP. Among site-specific cancers, higher CRP levels were associated with an increased risk of colorectal, lung, breast, biliary tract, and kidney cancer, and leukaemia. These positive associations remained among participants after >3 years' follow-up. Furthermore, subgroup analyses for overall cancer robustly showed a positive association with CRP levels, regardless of sex and obesity.
Our consistent findings suggested that chronic low-grade inflammation measured by CRP is associated with the risk of cancer.
To evaluate the value of virtual monochromatic images (VMIs) at lower energy levels in fast-voltage-switching dual-energy computed tomography (DECT) for assessing pancreatic ductal adenocarcinoma ...(PDAC).
The institutional review board approved this prospective study. Written informed consent was obtained from all patients. Seventy-four consecutive patients with PDAC underwent dynamic contrast-enhanced DECT. Two radiologists reviewed eight energy levels (40, 45, 50, 55, 60, 65, 70, and 75 keV) of the pancreatic parenchymal phase VMIs. CT attenuation of the PDAC and pancreatic parenchyma, background noise, signal-to-noise ratio (SNR) of the pancreas, tumour-to-pancreas contrast-to-noise ratio (CNR), major and minor axes of PDAC, and qualitative tumour conspicuity were compared among the VMIs at eight energy levels.
CT attenuation of PDAC and pancreatic parenchyma, background noise, SNR, and CNR peaked on VMIs at 40 keV with statistically significant difference (p<0.0001) and gradually decreased with increasing energy levels. The reproducibility in measuring tumour size was better on VMIs at 40 keV (28.8 and 29.2 mm of major axis in readers 1 and 2, respectively) and tended to be overestimated at higher energy levels (29.8 and 30.9 mm of major axis at 75 keV in readers 1 and 2, respectively). Qualitative tumour conspicuity was also significantly superior on VMIs at 40 keV than at all other energy levels (p<0.0001).
VMIs at 40 keV demonstrated significantly increased SNR of the pancreas, CNR, and tumour conspicuity and high reproducibility in measuring tumour size for assessing PDAC.
•Dual-energy CT could be useful for assessing pancreatic ductal adenocarcinoma.•The best SNR and CNR was obtained using 40 keV images.•The reproducibility in measuring tumor size was better on 40 keV images.
Summary
Background
The aetiology for nonsteroidal anti‐inflammatory drug (NSAID)‐induced small intestinal injuries has not been well characterised.
Aim
To determine the risk factors of symptomatic ...NSAID‐induced small intestinal injuries, including diaphragm disease.
Methods
Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double‐balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5’‐nuclease assays.
Results
Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID‐induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID‐induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05–8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04–24.40, P = 0.002, respectively). The combination of aspirin and non‐aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34–1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55–108.36, P = 0.018, respectively).
Conclusion
The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.
To clarify the indispensable parameters for the multiple carbon nanofilaments (CNFs) growths, in other words, having a unique Octopus-like morphology consisting of the Marimo-like carbon (MC), we ...have systematically studied to synthesize the MC by the decomposition of methane using oxidized diamond-supported Ni–Cu bimetallic catalysts. We discovered that a Cu addition of 20 wt.% by weight and a growth temperature in the region of 550 °C to 600 °C resulted in many CNF forms from a single catalyst particle, specifically the "Octopus-like" morphology of CNFs. We also discovered that the several CNFs forms might occur from the carbon dissolved in the sintered catalyst particles. We described a model process of the unique structure formation. We expect that the Octopus-like CNFs growth gives enough space volume in the MC for a mass transfer, consequently, it should contribute to realizing a higher power generation performance of a polymer electrolyte fuel cell (PEFC) although under a higher-voltage generation region.
Optical tweezers are often applied to control the dynamics of objects by scanning light. However, there is a limitation that objects fail to track the scan when the drag exceeds the trapping force. ...In contrast, Laguerre-Gaussian (LG) beams can directly control the torque on objects and provide a typical model for nonequilibrium systems such as Brownian motion under external fields. Although stable "mid-water" trapping is essential for removing extrinsic hydrodynamic effects in such studies, three-dimensional trapping by LG beams has not yet been clearly established. Here we report the three-dimensional off-axis trapping of dielectric spheres using high-quality LG beams generated by a special holographic method. The trapping position was estimated as ~ half the wavelength behind the beam waist. These results establish the scientific groundwork of LG trapping and the technical basis of calibrating optical torque to provide powerful tools for studying energy-conversion mechanisms and the nonequilibrium nature of biological molecules under torque.
We measured the rotating ring-disk electrode (RRDE) voltammetry curves of a Pt catalyst supported on Marimo-like carbon (MC) to clarify the effect of carbon nanofilaments (CNFs) morphology and fine ...structures consisting of MC cathode material on the oxygen reduction reaction (ORR) activity for Polymer electrolyte fuel cells. The specific surface area and pore volume of MCs are influenced by their morphology and fine structures. MCs grown with Ni–Cu bimetal catalyst (represented as Ni80Cu20MC), having an octopus-like morphology, yielded four times larger total pore volume than that measured from the MC grown with Ni catalyst (Ni100MC). In the case of Ni80Cu20MC, coin-stacked graphenes perpendicular to the filament axis formed CNFs. Ni100MC consists of cup-stacked CNFs. The difference in the graphene stacked fine structure resulted in a different number of graphene edges covering the CNF surface; however, both supported Pt particle sizes and their distributions were similar. Linear sweep voltammetry with a RRDE revealed that the Pt/Ni80Cu20MC ORR onset potential was higher than that observed from the Pt/Ni100MC. This value is suggested to be correlates with the ORR activity. The origin of the ORR difference was discussed on the basis of the structural difference in the MCs.
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