Differences in lung injury after IMRT or proton therapy assessed by 18FDG PET imaging

Publication date: Available online 16 January 2018
Source:Radiotherapy and Oncology
Author(s): Nadya Shusharina, Zhongxing Liao, Radhe Mohan, Amy Liu, Andrzej Niemierko, Noah Choi, Thomas Bortfeld
Background and purposeTo compare lung injury among non-small cell lung cancer (NSCLC) patients treated with IMRT or proton therapy as revealed by ¹⁸F-FDG post-treatment uptake and to determine factors predictive for clinically symptomatic radiation pneumonitis.Material and methodsFor 83 patients treated with IMRT or proton therapy, planning CT and follow up ¹⁸F-FDG PET-CT were analyzed. Post-treatment PET-CT was aligned with planning CT to establish a voxel-to-voxel correspondence between PET and planning dose images. ¹⁸F-FDG uptake as a function of radiation dose to normal lung was obtained for each patient. PET image-derived parameters as well as demographic, clinical, treatment and dosimetric patient characteristics were correlated with clinical symptoms of pneumonitis.ResultsThe dose distributions for the two modalities were significantly different; V5 was higher for IMRT, whereas V60 was higher for protons. The mean lung dose (MLD) was similar for the two modalities. The slope of linear ¹⁸F-FDG-uptake – dose response did not differ significantly between the two modalities. The MLD, slope, and 95th percentile of SUV were identified as three major factors associated with radiation pneumonitis.ConclusionsDespite significantly different dose distributions for IMRT and for protons, the slope of the SUV–dose linear regression line previously shown to be associated with RP did not differ between IMRT and protons. Patients who developed radiation pneumonitis had statistically significantly higher MLD and higher slope regardless of treatment modality.



http://ift.tt/2DG2YCy

Monitoring early changes in rectal tumor morphology and volume during 5 weeks of preoperative chemoradiotherapy – An evaluation with sequential MRIs

Publication date: Available online 16 January 2018
Source:Radiotherapy and Oncology
Author(s): Doenja M.J. Lambregts, Ahmed Bani Yassien, Max J. Lahaye, Anja Betgen, Monique Maas, Geerard L. Beets, Uulke A. van der Heide, Baukelien van Triest, Regina G.H. Beets-Tan
PurposeTo assess early changes in rectal tumor volume and morphology on sequential MRIs performed during 5 weeks of chemoradiotherapy.Materials and methodsThirteen patients underwent weekly T2W-MRI during 5 weeks of preoperative radiotherapy (total 50 Gy), starting after the first week of radiation. Two radiologists visually evaluated tumor volume and morphology and one reader manually segmented tumors for each time point to quantitatively calculate tumor volumes. Evolution in tumor volume/morphology was assessed over time and compared between good responders (tumor regression grade (TRG) 1–2) and poor responders (TRG 3–5).ResultsTumor volumes decreased significantly during radiation. Early signs of response were also visually apparent: in the majority of good responders an early fibrotic transformation (week 2–3) as well as a visually estimated early volume reduction of >1/3 (week 1–2), was observed while these early changes only occurred in a minority of poor responders.ConclusionResults of this exploratory pilot study suggest that changes in rectal tumor morphology (fibrosis) and volume can already be observed early during radiation, both when measured quantitatively and when assessed visually. These changes appear to be indicative of the final treatment outcome.



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Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial

Publication date: Available online 11 January 2018
Source:Radiotherapy and Oncology
Author(s): Evelyn M. Monninkhof, Juliette W.L. van Loon, Marco van Vulpen, Linda G.W. Kerkmeijer, Floris J. Pos, Karin Haustermans, Laura van den Bergh, Sofie Isebaert, Gill M. McColl, Robert Jan Smeenk, Juus Noteboom, Iris Walraven, Petra H.M. Peeters, Uulke A. van der Heide
PurposeTo compare toxicity rates in patients with localized prostate cancer treated with standard fractionated external beam radiotherapy (EBRT) with or without an additional integrated boost to the macroscopically visible tumour.Material and methodsFLAME is a phase 3 multicentre RCT (NCT01168479) of patients with pathologically confirmed localized intermediate or high-risk prostate cancer. The standard treatment arm (n = 287) received a dose to the entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n = 284) received 77 Gy in 35 fractions to the entire prostate, with an integrated boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within the prostate. Treatment related toxicity was measured using the CTCAE version 3.0. Grade 2 or worse GU or GI events up to two years were compared between groups by presenting proportions and by Generalized Estimating Equations (GEE) analyses for repeated measures.ResultsNinety percent of the 571 men randomly assigned between September 2009 and January 2015 had high-risk disease (Ash 2000), of whom nearly 66% were prescribed hormonal therapy up to three years. Median follow-up was 55 months at the time of this analysis. Toxicity prevalence rates for both GI and GU increased until the end of treatment and regressed thereafter, with no obvious differences across treatment groups. Late cumulative GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group, respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses showed that both GU toxicity and GI toxicity (≥grade 2) up to two years after treatment were similar between arms (OR 1.02 95%CI 0.78–1.33p = 0.81 and (OR 1.19 95%CI 0.82–1.73p = 0.38), respectively.ConclusionsIn intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible.



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Perilesional edema in brain cancer: Independent prognosticator or epiphenomenon of biomolecular signature?

Publication date: Available online 10 January 2018
Source:Radiotherapy and Oncology
Author(s): Valerio Nardone, Claudia Vinciguerra, Antonio Federico, Alfonso Cerase, Luigi Pirtoli, Paolo Tini




http://ift.tt/2Efr484

Concurrent chemoradiotherapy alone is feasible for esophageal squamous cell carcinoma patients not suitable for surgery

Publication date: Available online 10 January 2018
Source:Radiotherapy and Oncology
Author(s): Yongshun Chen, Jun Wang




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Consolidation chemotherapy after definite concurrent chemoradiation in patients with non-operable esophageal cancer: Is it useful?

Publication date: Available online 10 January 2018
Source:Radiotherapy and Oncology
Author(s): Antoine Adenis, Florence Castan, Thierry Conroy




http://ift.tt/2EiUcv6

Liraglutide ameliorates palmitate-induced insulin resistance through inhibiting the IRS-1 serine phosphorylation in mouse skeletal muscle cells

Abstract

Objective

A reduction in insulin-stimulated glucose uptake in skeletal muscles is a characteristic of insulin resistance and type 2 diabetes mellitus (T2DM). The glucagon-like peptide (GLP)-1 agonist liraglutide can reduce blood glucose levels in individuals with T2DM. However, its effect on insulin-induced glucose metabolism in the skeletal muscle of insulin resistance is unknown. We investigated the effects and action mechanisms of liraglutide on insulin resistance (IR) in the skeletal muscle cells treatment with palmitic acid (PA).

Methods

The cell-surface GLUT4myc levels were determined by an antibody-coupled colorimetric assay. The phosphorylation levels of Akt, PI3K(p85α), AS160, IRS1, IKK, and JNK were determined by western blotting. The quantifications of mRNA levels of TNFα, IL-1β, and IL-6 were determined by real-time PCR. Analysis of variance was used for data analysis.

Results

PA elevated not only phosphorylation of JNK, IRS1 serines, and IKKα/β, but also the expression of IL-6, TNFα and IL-1β in C2C12–GLUT4myc cells. PA can reduce phosphorylation of IRS1 tyrosine. These effects of PA were reversed by liraglutide. In addition, liraglutide can reverse PA-decreased insulin-stimulated cell-surface GLUT4 levels, Akt, PI3K(p85α), and AS160 phosphorylation.

Conclusions

Liraglutide can enhance insulin-induced GLUT4 translocation by inhibiting IRS1 serine phosphorylation in PA-treated muscle cells.

http://ift.tt/2GoHjAn

Dosimetric parameters predicting contralateral liver hypertrophy after unilobar radioembolization of hepatocellular carcinoma

Abstract

Purpose

This study aimed at identifying prior therapy dosimetric parameters using ^99mTc-labeled macro-aggregates of albumin (MAA) that are associated with contralateral hepatic hypertrophy occurring after unilobar radioembolization of hepatocellular carcinoma (HCC) performed with ⁹⁰Y–loaded glass microspheres.

Methods

The dosimetry data of 73 HCC patients were collected prior to the treatment with ⁹⁰Y–loaded microspheres for unilateral disease. The injected liver dose (ILD), the tumor dose (TD) and healthy injected liver dose (HILD) were calculated based on MAA quantification. Following treatment, the maximal hypertrophy (MHT) of an untreated lobe was calculated.

Results

Mean MHT was 35.4 ± 40.4%. When using continuous variables, the MHT was not correlated with any tested variable, i.e., injected activity, ILD, HILD or TD except with a percentage of future remnant liver (FRL) following the ⁹⁰Y–microspheres injection  (r = −0.56). MHT ≥ 10% was significantly more frequent for patients with HILD ≥ 88 Gy, (52% of the cases), i.e., in 92.2% versus 65.7% for HILD < 88 Gy (p = 0.032). MHT ≥ 10% was also significantly more frequent for patients with a TD ≥ 205 Gy and a tumor volume (VT) ≥ 100 cm³ in patients with initial FRL < 50%. MHT ≥10% was seen in 83.9% for patients with either an HILD ≥ 88 Gy or a TD ≥ 205 Gy for tumors larger than 100cm³ (85% of the cases), versus only 54.5% (p = 0.0265) for patients with none of those parameters. MHT ≥10% was also associated with FRL and the Child-Pugh score. Using multivariate analysis, the Child-Pugh score (p < 0.0001), FRL (p = 0.0023) and HILD (p = 0.0029) were still significantly associated with MHT ≥10%.

Conclusion

This study demonstrates for the first time that HILD is significantly associated with liver hypertrophy. There is also an impact of high tumor doses in large lesions in one subgroup of patients. Larger prospective studies evaluating the MAA dosimetric parameters have to be conducted to confirm these promising results.

http://ift.tt/2rIGkrz

Reply to ‘Single high dose versus repeated bone-targeted radionuclide therapy’

http://ift.tt/2GkYPWd

Incidental identification of osteoid osteoma by 68 Ga-PSMA PET/CT

http://ift.tt/2rQM2Ib

Is the whole larger than the sum of the parts? Integrated PET/MRI as a tool for response prediction

http://ift.tt/2GpNfJI

177 Lu-PSMA-617 radioligand therapy in mCRPC: ready for phase III trial?

http://ift.tt/2rKeuLB

FDG PET/CT radiomics for predicting the outcome of locally advanced rectal cancer

Abstract

Purpose

The aim of this study was to investigate the prognostic value of baseline ¹⁸F-FDG PET/CT textural analysis in locally-advanced rectal cancer (LARC).

Methods

Eighty-six patients with LARC underwent ¹⁸F-FDG PET/CT before treatment. Maximum and mean standard uptake values (SUVmax and SUVmean), metabolic tumoral volume (MTV), total lesion glycolysis (TLG), histogram-intensity features, as well as 11 local and regional textural features, were evaluated. The relationships of clinical, pathological and PET-derived metabolic parameters with disease-specific survival (DSS), disease-free survival (DFS) and overall survival (OS) were assessed by Cox regression analysis. Logistic regression was used to predict the pathological response by the Dworak tumor regression grade (TRG) in the 66 patients treated with neoadjuvant chemoradiotherapy (nCRT).

Results

The median follow-up of patients was 41 months. Seventeen patients (19.7%) had recurrent disease and 18 (20.9 %) died, either due to cancer progression (n = 10) or from another cause while in complete remission (n = 8). DSS was 95% at 1 year, 93% at 2 years and 87% at 4 years. Weight loss, surgery and the texture parameter coarseness were significantly associated with DSS in multivariate analyses. DFS was 94 % at 1 year, 86 % at 2 years and 79 % at 4 years. From a multivariate standpoint, tumoral differentiation and the texture parameters homogeneity and coarseness were significantly associated with DFS. OS was 93% at 1 year, 87% at 2 years and 79% after 4 years. cT, surgery, SUVmean, dissimilarity and contrast from the neighborhood intensity-difference matrix (contrast_NGTDM) were significantly and independently associated with OS. Finally, RAS-mutational status (KRAS and NRAS mutations) and TLG were significant predictors of pathological response to nCRT (TRG 3-4).

Conclusion

Textural analysis of baseline ¹⁸F-FDG PET/CT provides strong independent predictors of survival in patients with LARC, with better predictive power than intensity- and volume-based parameters. The utility of such features, especially coarseness, should be confirmed by larger clinical studies before considering their potential integration into decisional algorithms aimed at personalized medicine.

http://ift.tt/2GpBQt2

Head to head comparison of [ 18 F] AV-1451 and [ 18 F] THK5351 for tau imaging in Alzheimer’s disease and frontotemporal dementia

Abstract

Purpose

Tau accumulation is a core pathologic change in various neurodegenerative diseases including Alzheimer's disease and frontotemporal lobar degeneration-tau. Recently, tau positron emission tomography tracers such as [¹⁸F] AV-1451 and [¹⁸F] THK5351 have been developed to detect tau deposition in vivo. In the present study, we performed a head to head comparison of these two tracers in Alzheimer's disease and frontotemporal dementia cases and aimed to investigate which tracers are better suited to image tau in these disorders.

Methods

A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We recruited eight participants (two Alzheimer's disease, four frontotemporal dementia and two normal controls) who underwent magnetic resonance image, amyloid positron emission tomography with [¹⁸F]-Florbetaben and tau positron emission tomography with both THK5351 and AV-1451. To measure regional AV1451 and THK5351 uptakes, we used the standardized uptake value ratios by dividing mean activity in target volume of interest by mean activity in the cerebellar hemispheric gray matter.

Results

Although THK5351 and AV-1451 uptakes were highly correlated, cortical uptake of AV-1451 was more striking in Alzheimer's disease, while cortical uptake of THK5351 was more prominent in frontotemporal dementia. THK5351 showed higher off-target binding than AV-1451 in the white matter, midbrain, thalamus, and basal ganglia.

Conclusions

AV-1451 is more sensitive and specific to Alzheimer's disease type tau and shows lower off-target binding, while THK5351 may mirror non-specific neurodegeneration.

http://ift.tt/2rGoIwq

Striking lack of visualization of striatum on 18 F-FDG brain PET in chorea-acanthocytosis

http://ift.tt/2GnpNwq

18 F–fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment

Abstract

Purpose

Sorafenib, an oral multikinase inhibitor, is a recommended treatment option available for patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). This study aimed to evaluate the performance of ¹⁸F–fluorodeoxyglucose positron emission tomography (¹⁸F–FDG PET) for predicting tumour progression during sorafenib treatment.

Methods

We formed a retrospective cohort comprising patients treated with sorafenib for at least 30 days and undergoing ¹⁸F–FDG PET/CT within 1 month before treatment. For statistical analyses, the tumour-to-liver standardised uptake value (SUV) ratio (TLR) of the most hypermetabolic lesion was measured.

Results

Among a total of 35 patients, two obtained partial remission, and 11 showed stable disease after the first response evaluation. Patients with a TLR ≥ 2.9 (n = 17) had a median overall survival (OS) of 3.7 months after sorafenib treatment, whereas patients with a TLR < 2.9 (n = 18) had median OS of 12.2 months (P < 0.001), although the disease control rate was not significantly different between the two groups. Pretreatment TLR ≥ 2.9 (hazard ratio [HR] = 6.318, P = 0.002) and Child-Pugh class B (HR = 4.316, P = 0.044) were poor prognostic factors for OS, and a TLR ≥ 2.9 (HR = 2.911, P = 0.024) was the only poor prognostic factor for progression-free survival in a multivariate analysis.

Conclusion

Pretreatment tumour metabolic activity assessed by ¹⁸F–FDG PET is an independent prognostic factor for survival in patients with BCLC-C stage HCC receiving sorafenib monotherapy, although it may not predict tumour response to the treatment.

http://ift.tt/2rKuBJc

Absolute number of new lesions on 18 F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab

Abstract

Purpose

Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of ¹⁸F-FDG PET/CT, using the patients' clinical response as reference.

Methods

The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent ¹⁸F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged ¹⁸F-FDG-avid lesions, as well as on the SUV changes after therapy.

Results

The median observation time of the patients after therapy was 21.4 months (range 6.3–41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged ¹⁸F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of ¹⁸F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT).

Conclusion

Our results show that a cut-off of four newly emerged ¹⁸F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical response. Validation of these results in larger cohorts of patients is warranted.

http://ift.tt/2Gr0qKm

Visualization of multiple organ amyloid involvement in systemic amyloidosis using 11 C-PiB PET imaging

Abstract

Purpose

To investigate the utility of Pittsburgh compound B (PiB) positron emission tomography (PET) imaging for evaluating whole-body amyloid involvement in patients with systemic amyloidosis.

Methods

Whole-body ¹¹C-PiB PET was performed in seven patients with systemic immunoglobulin light-chain (AL) amyloidosis, seven patients with hereditary transthyretin (ATTRm) amyloidosis, one asymptomatic TTR mutation carrier and three healthy controls. The correlations between clinical organ involvement, radiological ¹¹C-PiB uptake and histopathological findings were analysed for each organ.

Results

Organ involvement on ¹¹C-PiB PET imaging showed good correlations with the clinical findings for the heart and stomach. Abnormal tracer uptake was also observed in the spleen, lachrymal gland, submandibular gland, sublingual gland, lymph node, brain, scalp, extraocular muscles, nasal mucosa, pharynx, tongue and nuchal muscles, most of which were asymptomatic. Physiological tracer uptake was universally observed in the urinary tract (kidney, renal pelvis, ureter and bladder) and enterohepatic circulatory system (liver, gallbladder, bile duct and small intestine) in all participants. Most of the patients and one healthy control subject showed asymptomatic tracer uptake in the lung and parotid gland. The peripheral nervous system did not show any tracer uptake even in patients with apparent peripheral neuropathy. Histological amyloid deposition was confirmed in biopsied myocardium and gastric mucosa where abnormal ¹¹C-PiB retention was observed.

Conclusions

¹¹C-PiB PET imaging can be used clinically in the systemic evaluation of amyloid distribution in patients with AL and ATTRm amyloidosis. Quantitative analysis of ¹¹C-PiB PET images may be useful in therapy evaluation and will reveal whether amyloid clearance is correlated with clinical response.

http://ift.tt/2rLgPWH

Third-line treatment and 177 Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review

Abstract

Aims

There is a controversy as to the relative efficacy of ¹⁷⁷Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether ¹⁷⁷Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743).

Methods

The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model.

Results

Twelve studies including 669 patients reported ¹⁷⁷Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with ¹⁷⁷Lu-PSMA RLT. The treatment with ¹⁷⁷Lu-PSMA-617 and ¹⁷⁷Lu-PSMA for imaging and therapy (I&T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. ¹⁷⁷Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). ¹⁷⁷Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ² test). Median survival was longer after ¹⁷⁷Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for ¹⁷⁷Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ² test).

Conclusions

As for patients with mCRPC, treatment with ¹⁷⁷Lu-PSMA-617 RTL and ¹⁷⁷Lu-PSMA I&T gave better effects and caused fewer adverse effects than third-line treatment.

http://ift.tt/2DLvk2b

Founder of EJNM passed away

http://ift.tt/2GoYLVq

EANM/EARL FDG-PET/CT accreditation - summary results from the first 200 accredited imaging systems

Abstract

Purpose

From 2010 until July 2016, the EANM Research Ltd. (EARL) FDG-PET/CT accreditation program has collected over 2500 phantom datasets from approximately 200 systems and 150 imaging sites worldwide. The objective of this study is to report the findings and impact of the accreditation program on the participating PET/CT systems.

Methods

To obtain and maintain EARL accredited status, sites were required to complete and submit two phantom scans - calibration quality control (CalQC), using a uniform cylindrical phantom and image quality control (IQQC), using a NEMA NU2–2007 body phantom. Average volumetric SUV bias and SUV recovery coefficients (RC) were calculated and the data evaluated on the basis of quality control (QC) type, approval status, PET/CT system manufacturer and submission order.

Results

SUV bias in 5% (n = 96) of all CalQC submissions (n = 1816) exceeded 10%. After corrective actions following EARL feedback, sites achieved 100% compliance within EARL specifications. 30% (n = 1381) of SUVmean and 23% (n = 1095) of SUVmax sphere recoveries from IQQC submissions failed to meet EARL accreditation criteria while after accreditation, failure rate decreased to 12% (n = 360) and 9% (n = 254), respectively. Most systems demonstrated longitudinal SUV bias reproducibility within ±5%, while RC values remained stable and generally within ±10% for the four largest and ±20% for the two smallest spheres.

Conclusions

Regardless of manufacturer or model, all investigated systems are able to comply with the EARL specifications. Within the EARL accreditation program, gross PET/CT calibration errors are successfully identified and longitudinal variability in PET/CT performances reduced. The program demonstrates that a harmonising accreditation procedure is feasible and achievable.

http://ift.tt/2rFVjCs

Prospective evaluation of 18 F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial)

Abstract

Purpose

The purpose of this study was to evaluate ¹⁸F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa).

Methods

Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq ¹⁸F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV_max) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (V_T). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455.

Results

In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV_max and V_T of Gleason score (GS) >3 + 4 tumors were significantly (p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes.

Conclusions

Quantitative ¹⁸F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. ¹⁸F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.

http://ift.tt/2GoyUNF

Photodegradation of 2,4-dichlorophenol by supported Pd(X 2 ) catalyst (X = Cl, Br, N 3 ): a HOMO manipulating point of view

Abstract

Three different palladium(II) complexes with ligands containing nitrogenized aromatic rings were investigated theoretically as model to obtain the computational band gap energies. The results demonstrated promising possibility for designing palladium(II) complexes with photocatalytic properties at visible light irradiation. Deliberated products were synthesized via grafting on the silica-coated Fe₃O₄ magnetic nanoparticles (Fe₃O₄@SiO₂). Formation of complexes on the surface of Fe₃O₄@SiO₂, as insoluble and reusable photocatalysts, was proved by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric (TGA), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), transmission electron microscope (TEM), and scanning electron microscopy (SEM) analyses. The trend of the band gap energies of prepared structures was calculated via experimental and theoretical methods. The photocatalytic capability of these nanoparticles was investigated in degradation of 2,4-dichlorophenol by means of HPLC analysis. A tentative reaction mechanism for the formation of intermediates was proposed.

Graphical abstract

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Air quality and acute myocardial infarction in adults during the 2016 Hangzhou G20 summit

Abstract

To fulfill its commitment to a successful Hangzhou G20 summit (4 to 5 September 2016), the Chinese government implemented a series of measures to improve the air quality in Hangzhou. We report findings on air quality and acute myocardial infarction (AMI) hospital admissions in adults during the Hangzhou G20 summit. Three study periods were defined. The first period was pre-G20 (28 July to 27 August: limited restrictions on industrial emissions). The second period was G20 (28 August to 6 September) when there were further restrictions on industrial emissions and increased transportation restrictions. The third period was post-G20 (7 September to 6 October) when restrictions were relaxed again. The mean number of AMI admissions per day was, respectively, 8.2 during G20, 13.3 during pre-G20, and 15.1 during post-G20. We used time-series Poisson regression models to estimate the relative risk (RR) for AMI associated with pollution levels. Our results suggest that the air quality improvement can reduce the number of hospital admissions for AMI.

http://ift.tt/2DHNuBY

Organic fertilizer application increases the soil respiration and net ecosystem carbon dioxide absorption of paddy fields under water-saving irrigation

Abstract

Quantifying carbon sequestration in paddy soil is necessary to understand the effect of agricultural practices on carbon cycles. The objective of this study was to assess the effect of organic fertilizer addition (MF) on the soil respiration and net ecosystem carbon dioxide (CO₂) absorption of paddy fields under water-saving irrigation (CI) in the Taihu Lake Region of China during the 2014 and 2015 rice-growing seasons. Compared with the traditional fertilizer and water management (FC), the joint regulation of CI and MF (CM) significantly increased the rice yields and irrigation water use efficiencies of paddy fields by 4.02~5.08 and 83.54~109.97% (p < 0.05). The effects of organic fertilizer addition on soil respiration and net ecosystem CO₂ absorption rates showed inter-annual differences. CM paddy fields showed a higher soil respiration and net CO₂ absorption rates during some periods of the rice growth stage in the first year and during most periods of the rice growth stage in the second year. These fields also had significantly higher total CO₂ emission through soil respiration (total R_soil) and total net CO₂ absorption compared with FC paddy fields (p < 0.05). The total R_soil and net ecosystem CO₂ absorption of CM paddy fields were 67.39~91.55 and 129.41~113.75 mol m⁻², which were 27.66~135.52 and 12.96~31.66% higher than those of FC paddy fields. The interaction between water and fertilizer management had significant effects on total net ecosystem CO₂ absorption. The frequent alternate wet–dry cycles of CI paddy fields increased the soil respiration and reduced the net CO₂ absorption. Organic fertilizer promoted the soil respiration of paddy soil but also increased its net CO₂ absorption and organic carbon content. Therefore, the joint regulation of water-saving irrigation and organic fertilizer is an effective measure for maintaining yield, increasing irrigation water use efficiency, mitigating CO₂ emission, and promoting paddy soil fertility.

http://ift.tt/2ninzFO

Corrigendum to “Hodgkin Lymphoma Cell Lines Are Characterized by a Specific miRNA Expression Profile.” Neoplasia 2009, Feb;11(2):167-176

Publication date: February 2018
Source:Neoplasia, Volume 20, Issue 2
Author(s): J.H. Gibcus, L.P. Tan, G. Harms, R.N. Schakel, D. de Jong, T. Blokzijl, P. Möller, S. Poppema, B.J. Kroesen, A. van den Berg




http://ift.tt/2GqOuYT

c-RAF Ablation Induces Regression of Advanced Kras/Trp53 Mutant Lung Adenocarcinomas by a Mechanism Independent of MAPK Signaling

Publication date: Available online 27 January 2018
Source:Cancer Cell
Author(s): Manuel Sanclemente, Sarah Francoz, Laura Esteban-Burgos, Emilie Bousquet-Mur, Magdolna Djurec, Pedro P. Lopez-Casas, Manuel Hidalgo, Carmen Guerra, Matthias Drosten, Monica Musteanu, Mariano Barbacid
A quarter of all solid tumors harbor KRAS oncogenes. Yet, no selective drugs have been approved to treat these malignancies. Genetic interrogation of the MAPK pathway revealed that systemic ablation of MEK or ERK kinases in adult mice prevent tumor development but are unacceptably toxic. Here, we demonstrate that ablation of c-RAF expression in advanced tumors driven by Kras^G12V/Trp53 mutations leads to significant tumor regression with no detectable appearance of resistance mechanisms. Tumor regression results from massive apoptosis. Importantly, systemic abrogation of c-RAF expression does not inhibit canonical MAPK signaling, hence, resulting in limited toxicities. These results are of significant relevance for the design of therapeutic strategies to treat K-RAS mutant cancers.

Graphical abstract

Teaser

Sanclemente et al. generate oncogenic Kras mice that allow inducible deletion of Raf1, encoding c-RAF, and/or Braf in established Kras^G12V or Kras^G12V;Trp53^−/− lung tumors. They show that systemic c-RAF ablation has limited toxicity and leads to significant tumor regression without having an impact on MAPK activity.


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Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma

Publication date: Available online 27 January 2018
Source:Cancer Cell
Author(s): Markus Eberl, Doris Mangelberger, Jacob B. Swanson, Monique E. Verhaegen, Paul W. Harms, Marcus L. Frohm, Andrzej A. Dlugosz, Sunny Y. Wong
Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh⁺/Notch⁺ suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh⁺⁺⁺/Notch⁻ basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions. Altogether, these findings suggest that the three-dimensional architecture of BCCs establishes a natural hierarchy of drug response in the tumor and that this hierarchy can be overcome, for better or worse, by modulating Notch.

Graphical abstract

Teaser

Eberl et al. show that in mouse basal cell carcinoma models, interior Hh⁺/Notch⁺ suprabasal cells undergo apoptosis in response to vismodegib, whereas peripheral Hh⁺⁺⁺/Notch⁻ basal cells survive throughout treatment. Modulating Notch overcomes the drug response hierarchy established by tumor architecture.


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Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation

Publication date: Available online 27 January 2018
Source:Chem
Author(s): Sourav P. Mukherjee, Beatrice Lazzaretto, Kjell Hultenby, Leon Newman, Artur F. Rodrigues, Neus Lozano, Kostas Kostarelos, Per Malmberg, Bengt Fadeel
Understanding the biological interactions of graphene-based materials is important for the safe use of these materials. Previous studies have explored the interaction between graphene oxide (GO) and macrophages but not the impact of GO on neutrophils, key cells of the immune system. Here, we synthesized GO sheets with differing lateral dimensions and showed by using an array of analytical and imaging techniques, including transmission and scanning electron microscopy, confocal microscopy, and time-of-flight secondary ion mass spectroscopy (ToF-SIMS), that GO elicited the formation of neutrophil extracellular traps (NETs). ToF-SIMS revealed pronounced perturbations of plasma membrane lipids, including a decrease in cholesterol and increased levels of oxidized cholesterol species. The induction of NETs was size dependent and associated with the production of mitochondrial reactive oxygen species and calcium influx. Importantly, antioxidant treatment reduced the production of NETs. These studies provide evidence that a previously undescribed biological effect of GO manifests through direct effects on membrane lipids.

Graphical abstract

Teaser

Graphene oxide (GO) is a promising material for a variety of biomedical and other applications. The increasing use of GO necessitates careful assessment of potential health hazards. Using primary neutrophils as a model, Mukherjee et al. show that GO elicits neutrophil extracellular traps. Furthermore, by using ToF-SIMS, the authors noted pronounced perturbations of plasma membrane lipids in cells exposed to GO.


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Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil

Background/Aim: The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF). Patients and Methods: The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed. Results: Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUV_max) after induction DCF therapy and small decreases in SUV_max from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis. Conclusion: Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUV_max DCF therapy are associated with early disease relapse and death.

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Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis

Background: In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. Materials and Methods: The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. Results: The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). Conclusion: GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC.

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Tandem Affinity Purification and Nano HPLC-ESI-MS/MS Reveal Binding of Vitamin D Receptor to p53 and other New Interaction Partners in HEK 293T Cells

While nuclear cofactors that contribute to vitamin D receptor (VDR)-mediated gene transcription, including retinoid X receptors, nuclear co-activators and co-repressors, have been extensively investigated, little is known about cytoplasmic VDR-binding partners and the physiological relevance of their interaction. To gain new insight into this topic, we isolated whole-cell protein extracts of 1,25-dihydroxyvitamin D₃ stimulated and UV-B-irradiated vs. non-irradiated HEK 293T cells transfected with a plasmid called pURB VDR C-Term TAP tag. VDR complex was purified by tandem affinity purification (TAP). The nuclear tumor-suppressor protein p53 and its negative regulator novel INHAT repressor (NIR), in addition to 43 other nuclear or cytoplasmatic VDR binding partners, were identified using nano high-performance liquid chromatography–electrospray ionization tandem mass spectrometric analysis. VDR binding to p53 was confirmed by western blot analysis. Future studies are required to further elucidate the functional significance of these interactions.

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Effects of Combined Treatment with Vitamin D and COX2 Inhibitors on Breast Cancer Cell Lines

Background: Vitamin D is known for its anticancer potential. Prostaglandin E₂ (PGE₂) is a proliferative and inflammation-activating agent. The production of PGE₂ is dependent on the activity of cyclooxygenase-2 (COX2). A link between vitamin D and PGE₂ metabolism was shown recently. Materials and Methods: In MDA-MB-231 and MCF-7 breast cancer cell lines, we investigated the influence of calcitriol and the COX2 inhibitor celecoxib on cell growth via the MTT test, as well as on the protein and mRNA expression of COX2 using western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Results: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX2 inhibitor celecoxib and even more strongly by their combination. Moreover, calcitriol inhibited COX2 protein expression in MDA-MB-231 cells, as well as COX2 mRNA expression in both cell lines. Conclusion: The combination of calcitriol and celecoxib demonstrated a synergistic growth-inhibitory effect in breast cancer cell lines.

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Partial Body UV Exposure in Chronic Kidney Disease and Extrarenal Vitamin D Metabolism

Background/Aim: Exposure of the skin to sunshine is the major natural source of vitamin D. In order to imitate this natural production of vitamin D for patients with chronic kidney disease, hemodialysis patients were exposed three times a week to radiation of the front part of both legs to normalize the vitamin D status. Patients and Methods: Partial body UVB irradiation was performed during the routine dialysis session. Twenty-two patients took part, with a mean age of 61.7 (range=35-81) years. Results: Serum levels of 25(OH)D₃ and 1,25(OH)₂D₃ increased into the mid normal range. Intact parathyroid hormone decreased by 25% and osteocalcin by 45%. 24-Hour blood-pressure monitoring demonstrated decreases in systolic and diastolic blood pressure. Conclusion: Partial body exposure to UVB radiation normalized not only the serum level of 25(OH)D₃, but also that of 1,25(OH)₂D₃, which resulted in a significant decrease in parathyroid hormone, osteocalcin levels, and also in blood pressure. Sunshine imitating UVB exposure utilizes the capacity of the skin to convert extrarenally vitamin D₃ to 25(OH)D₃ and 1,25(OH)₂D₃.

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Vitamin D Status, Supplementation and Cardiovascular Disease

This review was conducted to assess the dose–response relationship between vitamin D and cardiovascular disease (CVD) outcomes in humans: Prospective cohort studies indicate a multivariable-adjusted non-linear increase in CVD events at levels of circulating 25-hydroxyvitamin D [25(OH)D] of less than 50 nmol/l. However, Mendelian randomization studies do not support these findings. Although meta-analyses of randomized controlled trials (RCTs) do not rule out small beneficial vitamin D effects on surrogate parameters of CVD risk, such as arterial stiffness, at vitamin D doses equivalent to 1,000-5,333 IU daily, other meta-analyses of RCTs show no reduction in CVD events by vitamin D supplementation. Notably, some cohort studies and a recent RCT provide evidence for harmful effects of vitamin D on CVD outcomes at 25(OH)D levels in excess of 100 nmol/l. In conclusion, more studies in individuals with a deficient 25(OH)D level (i.e. <30 nmol/l) are needed, but caution is necessary regarding supplementation with vitamin D doses achieving a 25(OH)D level which exceeds 100 nmol/l.

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The Winding Path Towards an Inverse Relationship Between Sun Exposure and All-cause Mortality

For a long time, skin cancer has been known to be related to extensive UV exposure. New emerging data have, however, shown low UV exposure/low vitamin D levels to be related to increased mortality rate due to skin cancer. In addition, low sun exposure habits in regions of low solar intensity have been shown to be a major risk factor for all-cause mortality in the same range as that for smoking. This is mainly due to lower all-cause mortality due to cardiovascular disease (CVD) and non-CVD/non-cancer disease among women with active sun exposure. Women with active sun exposure habits were estimated to have a 1- to 2-year longer life-expectancy during the Melanoma in Southern Sweden study interval. These findings are in line with those to be expected from an evolutionary perspective and research findings, but in opposition to present guidelines and recommendations.

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Solarium Use and Risk for Malignant Melanoma: Meta-analysis and Evidence-based Medicine Systematic Review

Background: There is an ongoing debate whether solarium use (indoor tanning/artificial UV) may increase the risk for primary cutaneous malignant melanoma. Aim: A systematic literature search was conducted using MEDLINE and ISI Web of Science. Included studies were critically assessed regarding their risk of bias, and methodological shortcomings. Levels of evidence and grades of recommendation were determined according to guidelines of the Oxford Centre for Evidence-Based Medicine. Summary risk estimates and 95% confidence intervals for four different outcomes (ever exposure, exposure at younger age, high/low exposure vs. non-exposure) were derived from random-effects meta-analyses to account for possible heterogeneity across studies. Results: Two cohort and twenty-nine case–control studies were eligible. Overall, quality of included studies was poor as a result of severe limitations, including possible recall and selection bias, and due to lack of interventional trials. Summary risk estimates suggested a weak association (odds ratio (OR)=1.19, 95% confidence interval (CI)=1.04-1.35, p=0.009) for ever-exposure to UV radiation from a solarium with melanoma risk. However, sensitivity analyses did not show an association for studies from Europe (OR=1.10; 95%CI=0.95-1.27, p=0.218), studies with low risk of bias (OR=1.15; 95%CI=0.94-1.41, p=0.179), and studies conducted after 1990 (OR 1.09; 95%CI=0.93-1.29, p=0.295). Moreover, moderate associations were found for first exposure to UV radiation from a solarium at younger age (<25 years) and high exposure (>10 sessions in lifetime) with melanoma risk. However, for all outcomes analyzed, overall study quality and resulting levels of evidence (3a–) and grades of recommendation (D) were low due to lack of interventional studies and severe limitations including unobserved or unrecorded confounding. Conclusion: Current scientific knowledge is mainly based on observational studies with poor quality data, which report associations but do not prove causality. At present, there is no convincing evidence that moderate/responsible solarium use increases melanoma risk.

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Xeroderma Pigmentosum - Facts and Perspectives

Ultraviolet (UV)-induced DNA lesions are almost exclusively removed by the nucleotide excision repair (NER) pathway, which is essential for prevention of skin cancer development. Patients with xeroderma pigmentosum (XP) are extremely sun sensitive due to a genetic defect in components of the NER cascade. They present with first signs of premature skin aging at an early age, with a considerably increased risk of developing UV-induced skin cancer. XP belongs to the group of DNA repair defective disorders that are mainly diagnosed in the clinic and in hindsight confirmed at the molecular level. Unfortunately, there are no causative treatment options for this rare, autosomal-recessive disorder, emphasizing the importance of an early diagnosis. Subsequently, UV-protective measures such as the reduction of exposure to environmental UV and regular skin cancer screenings should be undertaken to substantially improve prognosis as well as the disease course.

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Photocarcinogenesis and Skin Cancer Prevention Strategies: An Update

UV radiation is acknowledged as the primary cause of photocarcinogenesis and therefore contributes to the development of skin cancer entities such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. Typical DNA photoproducts and indirect DNA damage caused by reactive oxygen species are the result of UV radiation. UV-induced DNA damage is repaired by nucleotide excision repair, which consequently counteracts the development of mutations and skin carcinogenesis. Tumour-suppressor genes are inactivated by mutation and growth-promoting pathways are activated leading to disruption of cell-cycle progression. Depending on the skin cancer entity, some genes are more frequently affected than others. In BCC mutations in Patched or Smoothened are common and affect the Sonic hedgehog pathway. In SCC, cell regulator protein p53 (TP53) mutations are prevalent, as well as mutations of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 2A (CDKN2A), Rat sarcoma (RAS), or the tyrosine kinase Fyn (FYN). UV-induced mutations in TP53 and CDKN2A are frequent in melanoma. UV-induced inflammatory processes also facilitate photocarcinogenesis. Recent studies showed a connection between photocarcinogenesis and citrus consumption, phytochemicals, alcohol consumption, hormone replacement therapy, as well as oral contraceptive use. Preventative measures include adequate use of sun protection and skin cancer screening at regular intervals, as well as the use of chemopreventative agents.

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The Impact of UV-dose, Body Surface Area Exposed and Other Factors on Cutaneous Vitamin D Synthesis Measured as Serum 25(OH)D Concentration: Systematic Review and Meta-analysis

Background/Aim: To optimize public health campaigns concerning UV exposure, it is important to characterize factors that influence UV-induced cutaneous vitamin D production. This systematic review and meta-analysis investigated the impact of different individual and environmental factors including exposed body surface area (BSA), UVB dose and vitamin D status, on serum 25(OH)D concentration. Materials and Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses, and Meta-analysis of Observational studies in Epidemiology guidelines, a systematic literature search was conducted (MEDLINE; 01/1960-07/2016) investigating the impact of these factors on vitamin D status after artificial UV exposure as main outcome measure. Summary mean differences [and 95% confidence interval (CI)] were derived from random-effects meta-analysis to account for possible heterogeneity across studies. Meta-regression was conducted to account for impact of UVB dose, baseline 25(OH)D level and BSA. Results: We identified 15 studies, with an estimated mean 25(OH)D rise per standard erythema dose (SED) of 0.19 nmol/l (95% CI 0.11-0.26 nmol/l). Results from meta-regression suggest a significant impact of UV dose and baseline 25(OH)D concentration on serum 25(OH)D level (p<0.01). Single UVB doses between 0.75 and 3 SED resulted in the highest rise of serum 25(OH)D per dose unit. BSA exposed had a smaller, non-proportional, not significant impact. Partial BSA exposure resulted in relatively higher rise compared to whole-body exposure (e.g. exposure of face and hands caused an 8-fold higher rise of serum 25(OH)D concentration/SED/1% BSA compared to whole-body exposure). Our findings support previous reports, estimating that the half-life of serum 25(OH)D varies depending on different factors. Conclusion: Our results indicate that partial BSA exposure (e.g. 10%) with moderate UV doses (e.g. 1 SED) is effective in generating or maintaining a healthy vitamin D status. However, due to limitations that include possible confounding factors such as skin type, which could not be considered, these findings should be interpreted with caution.

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Analytical Methods for Quantification of Vitamin D and Implications for Research and Clinical Practice

A plethora of contradictory research surrounds vitamin D and its influence on health and disease. This may, in part, result from analytical difficulties with regard to measuring vitamin D metabolites in serum. Indeed, variation exists between analytical techniques and assays used for the determination of serum 25-hydroxyvitamin D. Research studies into the effects of vitamin D on clinical endpoints rely heavily on the accurate assessment of vitamin D status. This has important implications, as findings from vitamin D-related studies to date may potentially have been hampered by the quantification techniques used. Likewise, healthcare professionals are increasingly incorporating vitamin D testing and supplementation regimens into their practice, and measurement errors may be also confounding the clinical decisions. Importantly, the Vitamin D Standardisation Programme is an initiative that aims to standardise the measurement of vitamin D metabolites. Such a programme is anticipated to eliminate the inaccuracies surrounding vitamin D quantification.

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A Review of the Evidence Supporting the Vitamin D-Cancer Prevention Hypothesis in 2017

The vitamin D–cancer prevention hypothesis has been evaluated through several types of studies, including geographical ecological studies related to indices of solar ultraviolet-B (UVB) dose (the primary source of vitamin D for most people), observational studies related to UVB exposure or serum 25-hydroxyvitamin D [25(OH)D] concentrations, laboratory studies of mechanisms, and clinical trials. Each approach has strengths and limitations. Ecological studies indirectly measure vitamin D production and incorporate the assumption that vitamin D mediates the effect of UVB exposure. Findings from observational studies with long follow-up times are affected by changing 25(OH)D concentrations over time. Most clinical trials have been poorly designed and conducted, based largely on guidelines for pharmaceutical drugs rather than on nutrients. However, three clinical trials do support the hypothesis. In general, the totality of the evidence, as evaluated using Hill's criteria for causality in a biological system, supports the vitamin D–cancer prevention hypothesis.

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Vitamin D: Current Guidelines and Future Outlook

Vitamin D is of public health interest because its deficiency is common and is associated with musculoskeletal diseases, as well as extraskeletal diseases, such as cancer, cardiovascular diseases, and infections. Several health authorities have reviewed the existing literature and published nutritional vitamin D guidelines for the general population. There was a wide consensus that serum 25-hydroxyvitamin D [25(OH)D] concentration should be used to assess vitamin D status and intake, and that musculoskeletal, and not extraskeletal, effects of vitamin D should be the basis for nutritional vitamin D guidelines. Recommended target levels for 25(OH)D range from 25 to 50 nmol/l (10 to 20 ng/ml), corresponding to a vitamin D intake of 400 to 800 International Units (10 to 20 μg) per day. It is of concern that significant sections of the general population do not meet these recommended vitamin D levels. This definitely requires action from a public health perspective.

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Is Ki-67 of Diagnostic Value in Distinguishing Between Partial and Complete Hydatidiform Moles? A Systematic Review and Meta-analysis

Background/Aim: To demonstrate the value of Ki-67 in distinguishing between partial and complete hydatidiform moles. Materials and Methods: We searched electronic databases included Medline, WOK, Cochrane Library and CNKI, through January 24, 2015. Experts were consulted, and references from related articles were examined. The meta-analysis was conducted with RevMan5.3, according to the PRISMA guidelines. Mantel-Haenszel estimates were calculated and pooled under a random effect model, with data expressed as odds ratio (OR) and 95% confidence interval (CI). Results: We analyzed eight trials with a total of 337 participants who underwent uterine curettage and met the inclusion criteria. A significantly higher expression of Ki-67 was observed in complete than in partial hydatidiform moles (OR=3.28; 95%CI=1.80-5.96; p<0.0001). Conclusion: The Ki-67 expression was higher in complete than in partial hydatidiform moles. Therefore, Ki-67 may be of diagnostic value in distinguishing between partial and complete hydatidiform moles. However, the present study had only a limited number of samples, so investigation of a greater number of cases is needed to confirm this conclusion.

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Fibrinogen Levels Are Associated with Lymph Node Involvement and Overall Survival in Gastric Cancer Patients

Background/Aim: Combination of perioperative chemotherapy with gastrectomy with D2 lymphadenectomy improves long-term survival in patients with gastric cancer. The aim of this study was to investigate the predictive value of preoperative levels of CRP, albumin, fibrinogen, neutrophil-to-lymphocyte ratio and routinely used tumor markers (CEA, CA 19-9, CA 72-4) for lymph node involvement. Materials and Methods: This retrospective study was conducted in 136 patients who underwent surgery between 2007 and 2015. Bivariable and multivariable analyses were performed in order to identify important characteristics associated with the risk of lymph node involvement. Kaplan-Meier survival curves and log-rank tests were used to compare overall survival. Results: Lymph node involvement was significantly affected by preoperative fibrinogen (p=0.008) and albumin (p=0.023). Poor clinical condition, T and N staging and fibrinogen level above 3.5 g/l were significantly associated with worse overall survival. Conclusion: Preoperative fibrinogen and albumin levels are significantly associated with lymphoid metastases in patients with gastric cancer.

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A Critical Appraisal of the Recent Reports on Sunbeds from the European Commission's Scientific Committee on Health, Environmental and Emerging Risks and from the World Health Organization

The European Commission's Scientific Committee on Health, Environmental and Emerging Risks and the World Health Organization recently published reports which concluded that a large proportion of melanoma and non-melanoma skin cancer is attributable to sunbed use, and that there is no need to use sunbeds as there are no health benefits and they are not needed to achieve an optimal vitamin D level. The overall conclusion from both bodies was that there is no safe limit for UV irradiance from sunbeds. We are, however, deeply concerned that these assessments appear to be based on an incomplete, unbalanced and non-critical evaluation of the literature. Therefore, we rebut these conclusions by addressing the incomplete analysis of the adverse health effects of UV and sunbed exposure (what is 'safe'?) and the censored representation of beneficial effects, not only but especially from vitamin D production. The stance taken by both agencies is not sufficiently supported by the data and in particular, current scientific knowledge does not support the conclusion sunbed use increases melanoma risk.

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Image Quality Assessment of 2D versus 3D T2WI and Evaluation of Ultra-high b-Value (b=2,000 mm/s2) DWI for Response Assessment in Rectal Cancer

Aim: The purpose of this IRB-approved, retrospective study was to compare image quality between 2D and high-resolution 3D, T2-weighted (T2WI) magnetic resonance imaging (MRI) sequences and to investigate the additional value of ultra-high b-value diffusion-weighted imaging (DWI; b=2,000 mm/s²) for both rectal cancer staging and evaluating treatment response. Materials and Methods: From 12 February to 24 August 2016, 26 consecutive patients (22 males, four females; mean age: 61.9±14.0 years) with histologically-proven rectal cancer. In total 31 examinations [12 prior to and 19 after chemoradiation (CRT)] were included. The patients underwent pelvic MRI on a 3.0-T scanner (Magnetom Skyra, Erlangen, Germany). Three radiologists (3, 4, and 5 years of experience in MRI, respectively) independently assessed all images and rated the image quality of DWI (b=800 mm/s²), apparent diffusion coefficient map, DWI (b=2,000 mm/s²), 3D sagittal T2WI, 3D axial T2WI, 2D sagittal T2WI, and 2D axial T2WI of each patient, respectively. In addition, signal intensity ratios (SIR) were calculated between rectal cancer and obturator internus muscle (background) in all patients after CRT on DWI (b=2,000 mm/s²) and correlated with histopathological regression grade (RG). Results: Tumor delineation was significantly better by 2D T2WI than 3D T2WI both before and after CRT (before CRT: Z=–3.2, p=0.02; after CRT: Z=–4.408, p<0.001; all: Z=–5.192; p<0.001) and was the preferred method, although image quality ratings were not significantly different (3D sagittal: 4.00±0.48; 2D sagittal: 4.03±0.34, p=0.713; 3D axial: 3.85±0.61, 2D axial: 3.78±0.64, p=0.537). Independent t-test showed significantly higher SIR between those with RG 1 or 2 (moderate response: mean score=2.02) and those with RG 3+4 (good response: mean score=0.8) (t=3.044, p=0.011). In those with RG 4 (complete response), SIR of b2000 was 0.946 compared to a 1.41 average of the whole cohort. In two patients, tumor was invisible on b2000 following CRT (RG 3 and 4, respectively). Interobserver agreement was mostly good (≥0.6) regarding image quality assessment, except for poor agreement (=0.4) in DWI (b2000) between the two less-experienced readers. Conclusion: In conclusion, 3D T2WI might be useful for evaluating response to neoadjuvant therapy in a comprehensive, cost-effective protocol, where 2D imaging seems to be preferable. In addition, DWI (b2000) may be beneficial in assessing both the primary and the residual tumor after CRT in rectal cancer and SIR may be helpful in assessing response to CRT.

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Prognostic Significance of NSCLC and Response to EGFR-TKIs of EGFR-Mutated NSCLC Based on PD-L1 Expression

Background/Aim: Recent clinical trials have shown that immune checkpoint blockades that target either PD-1 or PD-L1 yield remarkable responses in a subgroup of patients with non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively examined, by immunohistochemical analysis, 211 NSCLC samples. Using 32 independent samples, we also evaluated PD-L1 expression in NSCLC patients with EGFR gene mutations treated by EGFR-TKIs. Results: Overall survival of PD-L1-positive stages I-III NSCLC and stage I NSCLC and stages I-III squamous cell carcinoma (SQ) were significantly shorter than those of PD-L1-negative NSCLC (p<0.01 and p=0.02 and p=0.01, respectively). In stage I NSCLC and stages I-III SQ, PD-L1 expression was found to be independent predictor of death after multivariate analysis. Response to EGFR-TKIs was not significantly different between PD-L1-positive and PD-L1-negative NSCLC patients with EGFR mutations. Conclusion: PD-L1 expression was a significant independent predictor of poor outcome in NSCLC patients.

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Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report

Background/Aim: It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters. Materials and Methods: For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern – as homogenous and heterogenous. Results: Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008). Conclusion: Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information.

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Loop-Mediated Isothermal Amplification test for the diagnosis of pertussis in Japan

Publication date: 1 February 2018
Source:Vaccine, Volume 36, Issue 6
Author(s): Nobutoshi Nawa




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Response to the letter by Dr. Nawa, Loop-Mediated isothermal amplification test for the diagnosis of pertussis in Japan

Publication date: 1 February 2018
Source:Vaccine, Volume 36, Issue 6
Author(s): Hideyuki Ikematsu, Naoki Kawai, Shigehiro Yajima




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Editorial Board/Aims and Scope

Publication date: 1 February 2018
Source:Vaccine, Volume 36, Issue 6





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Self-assembling protein nanoparticles with built-in flagellin domains increases protective efficacy of a Plasmodium falciparum based vaccine

Publication date: 1 February 2018
Source:Vaccine, Volume 36, Issue 6
Author(s): Stephen A. Kaba, Christopher P. Karch, Labdhi Seth, Karen M.B. Ferlez, Casey K. Storme, Danielle M. Pesavento, Paige Y. Laughlin, Elke S. Bergmann-Leitner, Peter Burkhard, David E. Lanar
To eliminate the problems associated with the use of extraneous adjuvants we have designed a Self-Assembling Protein Nanoparticle (SAPN) containing epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) (designated FMP014) and portions of the TLR5 agonist flagellin (designated FMP014D0D1) as an intrinsic adjuvant. By combining different molar ratios of FMP014 to FMP014D0D1 monomers before self-assembly, we generated multiple nanoparticles and investigated their biophysical characteristics, immunogenicity and protective efficacy. Immunization with the construct formulated with the ratio 58:2 of FMP014 to FMP014D0D1 had the highest protective efficacy against a challenge with a transgenic P. berghei sporozoite expressing PfCSP. Increasing the proportion of flagellin per particle resulted in an inverse relationship with levels of both antibody titers and protection. The cytokine profiles of the various immunization groups were evaluated and quantitative amounts of the cytokines IL-2, IFN-γ, IL-12/p70 (Th1); IL4, IL5 (Th2); TNF-α, IL1β, IL-6, KC/GRO (pro-inflammatory), and IL-10 (immunomodulatory) were measured. The relationship of the cytokines to each other revealed a strong immunomodulatory effect depending on the proportion of flagellin in the construct. Our results demonstrate that SAPNs with flagellin may be a promising strategy for the development and delivery of a safe vaccine for infectious diseases.



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Vascular Reconstruction in a Neonate after Iatrogenic Injury during Cardiac Catheterization

Summary: As technology and interventional techniques continue to evolve, both the volume and complexity of cardiac catheterizations will increase, leading to a rise in the number of complications. One of the most morbid complications of cardiac catheterization is vascular injury. We report the case of a 31-day-old, 3.0-kg infant with hypoplastic left heart syndrome who experienced a left common iliac artery disruption during cardiac catheterization resulting in a retroperitoneal hemorrhage. The extent of the vascular injury combined with the vessel caliber posed a technically challenging surgical scenario. Ultimately, the vascular supply to the left lower extremity was reconstructed by the plastic surgery team with a reverse autologous vein graft. To our knowledge, this multidisciplinary approach with the involvement of plastic surgery represents a unique case.

http://ift.tt/2DF87KS

No Vertical Scar Breast Weight Transfer

Summary: Women desire beautiful breasts that are functional, pain free, and without foreign material. Vertical scars, insufficient elevation, inadequate upper pole fullness, nipple numbness, and loss of breast feeding are undesirable. Relieving pain attributed to enlarged breasts has required significant tissue removal. Software analysis of chest images, physical measurements, and desires are combined to generate a surgical blueprint. The breast is divided horizontally into two components preserving the neurovascular supply and major lactiferous ducts. The skin flap cephalad to the areola provides external coverage. The areola remains attached to a deepithelialized mound, which is rotated into a cone. Dermal straps originating from the base of the cone are looped through the pectoralis major muscle and the cone repeatedly. Weight transfer to the pectoralis major muscles eliminates pain in 54% and decreases pain in 38%. Incisions are concealed at the areola cutaneous junction and in the shadow of the breast. Upper pole fullness increased in 86% without implants or fat transfer. Nipple sensation was increased in 37% and unchanged in 44%. Overall results were excellent in 50% and good in 36%. Complications consisted of dog-ears, periareolar infection, and fat necrosis. No patient required a return to the operation room. Combing computer-aided design with plastic surgical principles creates beautiful, functional breasts without foreign material. Vertical scars are avoided, and weight transfer relieves pain.

http://ift.tt/2EdzuNp

Short Takes

Publication date: Available online 17 January 2018
Source:Pediatric Neurology
Author(s): Steven G. Pavlakis




http://ift.tt/2rEI19o

Cosmetics, Vol. 5, Pages 15: Development of a Natural Anti-Age Ingredient Based on Quercus pubescens Willd. Leaves Extract—A Case Study

Cosmetics, Vol. 5, Pages 15: Development of a Natural Anti-Age Ingredient Based on Quercus pubescens Willd. Leaves Extract—A Case Study

Cosmetics doi: 10.3390/cosmetics5010015

Authors: Hortense Plainfossé Pauline Burger Stéphane Azoulay Anne Landreau Grégory Verger-Dubois Xavier Fernandez

Consumers pay more and more attention not just to the safety and health aspects of ingredients entering their cosmetics' formulations, but also to their potency, origin, processing, ethical value and environmental footprint. Sustainability of the supply chain, preservation of biodiversity, as well as greener extraction techniques are hence very popular with consumers. Consumers are primarily concerned by the efficacy of the cosmetic products they use and continuously scrutinize product labels, so marketing arguments need to be based on rigorous testing and reliable results to support claims (anti-age, anti-pollution, etc.) displayed on the product's packaging. As a result, the increasing demand for natural ingredients with assessed bioactivities has profoundly modified the strategies adopted by cosmetic professionals to innovate in terms of actives. Sourcing and developing new natural cosmetic actives is a long-term procedure that is thoroughly described in the present paper, via the example of the design of both liquid and solid ingredients based on Quercus pubescens Willd. leaves extract, for which anti-age properties were assessed by a combination of in vitro assays.

http://ift.tt/2rI3iPL

Scholar : These new articles for Spanish Journal of Finance and Accounting / Revista Española de Financiación y Contabilidad are available online

The online platform for Taylor & Francis Online content New for Spanish Journal of Finance and Accounting / Revista Española de Financiación y Contabilidad and online now on Taylor & Francis Online: Article Does corporate governance affect the valuation of Spanish IPOs? The role of ownership structure and the board of directors Susana Álvarez-Otero & Félix J. López-Iturriaga Pages: 1-28 | DOI: 10.1080/02102412.2018.1429556 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Activities, Adaptation & Aging are available online

The online platform for Taylor & Francis Online content New for Activities, Adaptation & Aging and online now on Taylor & Francis Online: Original Articles Older adult Internet super-users: counsel from experience Mark Tyler, Veronika Simic & Linda De George-Walker Pages: 1-12 | DOI: 10.1080/01924788.2018.1428472 Routledge Psychology 2017 sponsor of BPS #PsychCrunch podcasts. Access 25 journal articles: http://bit.ly/psychcrunch2017 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Journal of Museum Education, Volume 43, Issue 1, March 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Journal of Museum Education, Volume 43, Issue 1, March 2018 is now available online on Taylor & Francis Online. Interpreting Trauma, Memory, and Lived Experience in Museums and Historic Sites This new issue contains the following articles: Editorial From the Editor-in-Chief Cynthia Robinson Pages: 1-3 | DOI: 10.1080/10598650.2018.1426902 From the Guest Editor Interpreting Trauma, Memory, and Lived Experience in Museums and Historic Sites Lauren Zalut Pages: 4-6 | DOI: 10.1080/10598650.2017.1419412 Creating Safe(r) Spaces for Visitors and Staff in Museum Programs Mark Katrikh Pages: 7-15 | DOI: 10.1080/10598650.2017.1410673 A Balancing Act: Interpreting Tragedy at the 9/11 Memorial Museum Noah Rauch Pages: 16-21 | DOI: 10.1080/10598650.2017.1407909 Sharing Lived Experience with Incarceration to Encourage Visitor Empathy: A Case Study Through Conversation Marvin Robinson & Lauren Zalut Pages: 22-34 | DOI: 10.1080/10598650.2017.1410672 Tools, Frameworks, and Case Studies Mindfulness in Art Contemplation. The Story of a Rothko Experience Fernando Echarri & Carmen Urpi Pages: 35-46 | DOI: 10.1080/10598650.2017.1384977 "Blending" Docent Learning: Using Google Forms Quizzes to Increase Efficiency in Interpreter Education at Fort Henry Michael P. A. Murphy Pages: 47-54 | DOI: 10.1080/10598650.2017.1396435 STEAM-y Partnerships: A Case of Interdisciplinary Professional Development and Collaboration Molly L. Kelton & Patti Saraniero Pages: 55-65 | DOI: 10.1080/10598650.2017.1419772 What the Research Says Can Sensory Gallery Guides for Children with Sensory Processing Challenges Improve Their Museum Experience? Tina S. Fletcher, Amanda B. Blake & Kathleen E. Shelffo Pages: 66-77 | DOI: 10.1080/10598650.2017.1407915 Conference Review The Annual Ecsite Conference: An Engagement and Education Forum for Science Museums Joseph Roche, Nicola Davis, Jessica Stanley & Mairéad Hurley Pages: 78-82 | DOI: 10.1080/10598650.2017.1407908 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Aphasiology are available online

The online platform for Taylor & Francis Online content New for Aphasiology and online now on Taylor & Francis Online: Original Articles Receiving aphasia intervention in a virtual environment: the participants' perspective Ana Amaya, Celia Woolf, Niamh Devane, Julia Galliers, Richard Talbot, Stephanie Wilson & Jane Marshall Pages: 1-21 | DOI: 10.1080/02687038.2018.1431831 Routledge Psychology 2017 sponsor of BPS #PsychCrunch podcasts. Access 25 journal articles: http://bit.ly/psychcrunch2017 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.