Cancer by Sfakianakis Alexandros: 06/03/17

Σάββατο 3 Ιουνίου 2017

Impact of comorbidity on survival by tumour location: Breast, colorectal and lung cancer (2000–2014)

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Oleguer Parés-Badell, Marta Banqué, Francesc Macià, Xavier Castells, Maria Sala
BackgroundTo assess the impact of comorbidity, measured by the Charlson Comorbidity Index (CCI), on survival in breast, colorectal and lung cancer.MethodsWe identified 3455 breast cancer, 3336 colorectal cancer and 2654 lung cancer patients through the Hospital del Mar cancer registry. The prevalence of comorbidities according to the CCI was calculated. Kaplan-Meier curves and the log-rank test were used to compare survival curves for each cancer location. Cox regression was used to calculate survival hazard ratios and 1-, 3- and 5-year mortality rate ratios adjusted by age, sex, CCI, place of first consultation, stage, treatment and period of diagnosis.ResultsThe overall unadjusted 5-year follow-up survival proportion was 82.6% for breast cancer, 55.7% for colorectal cancer, and 16.3% for lung cancer. Overall survival was associated with CCI≥3 in breast cancer (HR: 2.33 95%CI: 1.76–3.08), colorectal cancer (HR: 1.39; 95%CI: 1.13–1.70) and lung cancer (HR: 1.22; 95%CI: 1.06–1.40). In breast cancer, the higher the CCI, the higher the adjusted mortality rate ratio and differences were greater in 5-year than in 1-year follow-up survival.ConclusionsComorbidity is a significant predictor of overall survival in cancer patients; however, it has a stronger impact on survival in breast cancer than in colorectal and lung cancer.

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Impact of comorbidity on survival by tumour location: Breast, colorectal and lung cancer (2000–2014)

Retrospective Evaluation of Thromboembolism Risk in Ovarian Cancer Patients Treated with Bevacizumab

Abstract

Background

Bevacizumab is used in addition to standard, platinum-based chemotherapy to treat advanced-stage ovarian cancer patients. Thrombosis is a well-documented adverse effect of bevacizumab.

Objective

The aim of this study was to identify predictive parameters for thromboembolic events in ovarian cancer patients and to explain how bevacizumab increases the risk of these events.

Patients and Methods

Fifty-seven FIGO stage III ovarian cancer patients who underwent cytoreductive surgery and chemotherapy were identified and included in this retrospective study. Twenty-six patients were treated with carboplatin and paclitaxel (CP) only (control group), and 31 patients received CP with bevacizumab (study group). The two groups were compared with regard to thrombosis risk factors and laboratory parameters (total leukocytes, platelet count, hemoglobin, APTT, prothrombin time, INR, fibrinogen levels, D-dimer concentration) before treatment, after each course of chemotherapy, and during thromboembolic events.

Results

Only patients in the group receiving bevacizumab experienced venous thromboembolism (VTE) (p=0.03, χ² test). VTE occurred on average at the 13th cycle of chemotherapy. Patients who experienced VTE had increased BMI before chemotherapy as compared to patients with no thromboembolic event (27.2 vs. 23.3, p=0.005, Mann-Whitney test). D-dimer concentration before treatment was also elevated more in patients affected by VTE (3132.5) than in the non-VTE group (956.43) (p=0.0007, Mann-Whitney test). During the first four administrations of chemotherapy in patients with future VTE, there was a reduction in D-dimer concentration and an extension of APTT. A D-Dimer level higher than 485 ng/mL prior to first chemotherapy indicates for a risk of VTE with 94% sensitivity and 36% specificity.

Conclusions

An elevated D-dimer level and high BMI before chemotherapy are risk factors for VTE in ovarian cancer patients receiving bevacizumab. Bevacizumab possibly increases the risk for VTE.

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Retrospective Evaluation of Thromboembolism Risk in Ovarian Cancer Patients Treated with Bevacizumab

Abstract

Background

Bevacizumab is used in addition to standard, platinum-based chemotherapy to treat advanced-stage ovarian cancer patients. Thrombosis is a well-documented adverse effect of bevacizumab.

Objective

The aim of this study was to identify predictive parameters for thromboembolic events in ovarian cancer patients and to explain how bevacizumab increases the risk of these events.

Patients and Methods

Results

Conclusions

An elevated D-dimer level and high BMI before chemotherapy are risk factors for VTE in ovarian cancer patients receiving bevacizumab. Bevacizumab possibly increases the risk for VTE.

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Blood assessment of the expression levels of matrix metalloproteinase 9 ( MMP9 ) and its natural inhibitor, TIMP1 genes in Iranian schizophrenic patients

Abstract

Schizophrenia (SCZ) is the most severe chronic mental disorder characterized by abnormal social behavior and disrupted emotions and thought. Like other complex neuropsychological disease, SCZ is caused by a combination of genetic and environmental factors but with a high concordance rate. So far, different genetic factors are revealed to be associated with increased risk of developing SCZ. One of the best ways to investigate the genetic basis of the complex disease is to discover the genetic underlying mechanisms of the defective clinical aspects of the patients. In this regard, genes involved in the developmental mechanisms of the brain such as long-term potentiation (LTP) process that is the basis of synaptic plasticity, memory and learning are considered as strong candidates for SCZ. The aim of the present study was to evaluate the expression levels of two genes that are involved in the LTP regulation in the developing and adult brain, Matrix metallopeptidase9 (MMP9) and TIMP metallopeptidase inhibitor 1 (TIMP1) genes in a blood assessment of schizophrenic patients in comparison to healthy controls by means of quantitative real time PCR. The results of the study showed a significant difference in MMP9/TIPM1 ratio between SCZ patients and healthy controls (P = 0.01). However, no significant difference was detected in the expression level of individual MMP9 and TIMP1 genes in SCZ patients versus healthy controls either in total numbers of subject or in sex based subgroups. Considering the relatively small sample size of the current study, there is a need to replicate this study with further investigations about the mechanism of association of these genes and their functions in the pathogenesis of the SCZ.

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A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors [Research Briefs]

Larotrectinib, a selective TRK tyrosine kinase inhibitor (TKI), has demonstrated histology-agnostic efficacy in patients with TRK fusion-positive cancers. While responses to TRK inhibition can be dramatic and durable, duration of response may eventually be limited by acquired resistance. LOXO-195 is a novel, selective TRK TKI designed to overcome acquired resistance mediated by recurrent kinase domain (solvent front and xDFG) mutations identified in multiple patients who have developed resistance to TRK TKIs. Activity against these acquired mutations was confirmed in enzyme and cell-based assays and in vivo tumor models. As clinical proof of concept, the first two patients with TRK fusion-positive cancers that developed acquired resistance mutations on larotrectinib were treated with LOXO-195 on a first-in-human basis, utilizing rapid dose titration guided by pharmacokinetic assessments. This approach led to rapid tumor responses and extended the overall duration of disease control achieved with TRK inhibition in both patients.

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Blood assessment of the expression levels of matrix metalloproteinase 9 ( MMP9 ) and its natural inhibitor, TIMP1 genes in Iranian schizophrenic patients

Abstract

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ITV, mid-ventilation, gating or couch tracking – A comparison of respiratory motion-management techniques based on 4D dose calculations

Respiratory motion-management techniques (MMT) aim to ensure tumor dose coverage while sparing lung tissue. Dynamic treatment-couch tracking of the moving tumor is a promising new MMT and was compared to the internal-target-volume (ITV) concept, the mid-ventilation (MidV) principle and the gating approach in a planning study based on 4D dose calculations.

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Breast cancer electron intraoperative radiotherapy: assessment of preoperative selection factors from a retrospective analysis of 758 patients and review of literature

Abstract

Purpose

To report our experience with full-dose 21 Gy IORT in early breast cancer patients after breast-conserving surgery to define most important selection factors.

Methods

Seven hundred and fifty eight patients, subjected to conserving surgery and IORT, were retrospectively analyzed evaluating most important clinical outcomes.

Results

Median follow up was 5.2 years. Results from Cox analyses defined 2 groups of patients, "suitable" (age > 50 years, non lobular histology, tumour size ≤ 2 cm, pN0 or pNmic, ki67 ≤ 20%, non triple negative receptor status and G1-G2) and "unsuitable" for IORT, with a higher rate of breast related events moving from "suitable" to "unsuitable" group. The 5 year rate of IBR is 1.8% in suitable group with significant differences versus unsuitable (1.8 vs. 11.6%, p < 0.005). Same differences between two groups were evidenced in true local relapse (0.6 vs. 6.9%, p < 0.005) and in new ipsilateral BC (1.1 vs. 4.7%, p < 0.015).

Conclusions

In our current practice we consider the following preoperative factors to select patients suitable for IORT: age > 50 years, absence of lobular histology, tumor size ≤ 2 cm, pN0 or pNmic, according to APBI consensus statement, including also ki67 ≤ 20%, non triple negative receptor status and G1–G2.

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Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab

Abstract

Background

Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity.

Objective

We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck.

Patients and Methods

Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7 years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%).

Results

Sixty-nine patients received at least 7 cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade ≥ 3 dermatitis; grade ≥ 2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade ≥ 3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56 days (47–75) compared to 51 days (47–65) in patients who did not require toxicity-related radiation interruptions (p < 0.05). After a median follow-up of 17.5 months (1.3–107.6) for all patients, median overall survival was 17.9 months (95% CI: 12.7–23.2), and loco-regional control (LRC) was 9.2 months (95% CI: 3.9–14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade ≥ 2 were independent prognostic factors for LRC (p = 0.023 and p = 0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p = 0.048 and 0.052, respectively).

Conclusions

Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.

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Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab

Abstract

Background

Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity.

Objective

We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck.

Patients and Methods

Results

Conclusions

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Multiple supratentorial subependymomas causing obstructive hydrocephalus

Introduction

Subependymomas are benign intraventricular tumours that most often occur asymptomatically and are found incidentally on autopsy. Symptomatic examples requiring surgical intervention are exceedingly rare.

Case presentation

A 55-year-old man with no history of neurological symptoms presented with multiple episodes of loss of consciousness and increasing headaches. MRI revealed a lobulated intraventricular mass centred at the right Foramen of Monro. Obstructive hydrocephalus with localised midline shift and a second lesion were noted. Right frontal craniotomy with total removal via transcortical resection was performed.

Discussion

Symptomatic subependymomas generally present with signs of hydrocephalus due to obstruction of cerebrospinal fluid pathways. There is only one other reported case of multifocal subependymomas in a symptomatic patient. An example of multiple supratentorial subependymomas causing obstructive hydrocephalus has not been previously reported.

Conclusions

Multiple subependymomas are rare. Judicious surgical management with full excision led to symptomatic improvement in our patient.

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Multiple recurrent ischaemic strokes in a patient with cancer: is there a role for the initiation of anticoagulation therapy for secondary stroke prevention?

A 52-year-old woman with a medical history of cervical and thyroid cancer, hypertension, dyslipidaemia, uncontrolled diabetes and heavy smoking was diagnosed with a new metastatic cholangiocarcinoma. While undergoing palliative chemotherapy, she developed dysarthria and left-sided weakness. Imaging studies showed multiple bilateral ischaemic strokes. On hospital days 2 and 5, she developed worsening neurological symptoms and imaging studies revealed new areas of ischaemia on respective days. Subsequent workup did not revealed a clear aetiology for the multiple ischaemic events and hypercoagulability studies were only significant for a mildly elevated serum D-dimer level. Although guidelines are unclear, full-dose anticoagulation with low molecular weight heparin was initiated given her high risk of stroke recurrence. She was discharged to acute rehabilitation but, within a month, she experienced complications of her malignant disease progression and a new pulmonary thromboembolism. The patient died soon after being discharged home with hospice care.

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Corticosteroid treatment for traumatic acute subdural haematoma, maybe not such a good idea

Description

An 86-year-old woman with acute blunt head trauma (the patient's head was hit by a car) 10 days ago, associated with a right occipital fracture and an acute subdural haematoma (treated in the department of neurosurgery by oral prednisone 80 mg once a day) (figure 1), presented with focal left arm motor seizures. At that time, CT and MRI showed right cortical venous thrombosis (figure 1), absent on initial CT imaging. Corticosteroids were stopped and antiepileptic drugs and anticoagulation (warfarin) started. Three weeks later, CT showed complete resolution of the cortical venous thrombosis and spontaneous resorption of the subdural haematoma. Blood analyses in search of a prothrombotic state were negative in the absence of other blood test abnormalities (including normal metabolic profile).

Figure 1

Initial CT showing frontal (A) and temporal (B) acute subdural haematoma and right occipital fracture (C and D),...

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A 15-year-old Nepali boy with metastasised colorectal cancer

Nepal suffers from vast inequalities in modern healthcare. The low-income country wrestles with far-reaching insufficiencies in minimal preventative medicine, health awareness, limited infrastructure and difficult topography—all of which contribute to poor access and poor care-seeking behaviour. Our patient came from rural Nepal, where primary healthcare outposts are frequently understaffed and underequipped. He received supportive treatment in his village from the time symptoms presented until he was diagnosed 2 years later, at a tertiary medical centre, with colorectal cancer. An examination of the relevant literature indicates that younger patients often present in later stages of the disease due to initial misdiagnosis or overlooking colorectal cancer as a possibility. Beyond the rarity of the patient's condition, the logistical and financial obstacles he faced in Nepal, particularly outside of the capital of Kathmandu, deterred his access to a higher level of care and delayed his correct diagnosis and treatment.

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Two-staged en bloc excision of a retinal haemangioma

A 31-year-old man presented to us with diminution of vision in the right eye which he noticed since 10 days, with a visual acuity of hand motions only. On examination, festooned pupil and a complicated cataract were noted with no view of the retina. Ultrasonography of the right eye showed retinal detachment in all quadrants with suspected areas of traction and membranes in the vitreous. Left eye examination revealed a normal anterior and posterior segment. Intraoperatively, he underwent a pars plana lensectomy following which an inferior large retinal haemangioma was noted with dilated and tortuous feeder artery and draining vein. The haemangioma was managed by a two-staged procedure including ligature of the feeder artery in the first surgery and the en bloc excision of the angioma at the time of the second procedure after significant shrinkage in size of the tumour.

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An unusual position of retromandibular vein: a surgical challenge in parotid surgeries

A 44-year-old man presented with swelling in the left parotid region. The swelling was firm and Fine Needle Aspiration Cytology report proved pleomorphic adenoma. In the CT scan, the tumour was confined to the superficial lobe of parotid. So, left superficial parotidectomy was planned. Modified Wilson Blair's incision was used. On course of identifying the facial nerve, a large calibre vein was identified running vertically through the parotid substance. Assuming it as retromandibular vein, further dissection was carried out more meticulously. Marginal mandibularbranch of facial nerve was identified near the angle of mandible and retrograde dissection showed the cervicofacial division running medial to retromandibular vein with the main facial nerve trunk lying unusually medial and posterior to it. Adding to it, the temporofacial division was found 'forked' between the branches of retromandibular vein. These variations in head and neck venous channels are not that rare as we believe. All these variations have an embryological basis. Therefore, knowledge and understanding of this complex anatomy will help us preventing devastating complications like bleeding and facial nerve injury in such cases.

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Orbital myositis presenting with only unilateral orbital pain

Description

A 24-year-old woman developed sudden severe periorbital pain characterised by severe, unilateral, pounding, short-lived, repetitive pain. Consequently, she was diagnosed with paroxysmal haemicrania at the first visit. There was no history of diplopia or other ophthalmic symptoms. Her physical and other neurological findings were normal. Anti-thyroid and antinuclear antibodies were negative. IgG4, soluble interleukin-2 receptor, C-reactive protein and creatine kinase levels; cerebrospinal fluid analysis; and CT scan were normal. MRI revealed enlargement and increased signal in the left medial rectus muscle on gadolinium-enhanced T1-weighted imaging suggesting orbital myositis (OM) (figure 1A,B). The patient was treated with three cycles of intravenous methylprednisolone (IVMP) followed by oral prednisolone 30 mg/day, resulting in rapid resolution of the symptoms. There was no relapse after reducing the prednisolone dosage, and MRI findings were almost resolved after 2 months of steroid therapy (figure 1C,D). The most frequently used medication of OM...

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Rare Variant, Gene-Based Association Study of Hereditary Melanoma Using Whole-Exome Sequencing

Abstract

Background: Extraordinary progress has been made in our understanding of common variants in many diseases, including melanoma. Because the contribution of rare coding variants is not as well characterized, we performed an exome-wide, gene-based association study of familial cutaneous melanoma (CM) and ocular melanoma (OM).Methods: Using 11 990 jointly processed individual DNA samples, whole-exome sequencing was performed, followed by large-scale joint variant calling using GATK (Genome Analysis ToolKit). PLINK/SEQ was used for statistical analysis of genetic variation. Four models were used to estimate the association among different types of variants. In vitro functional validation was performed using three human melanoma cell lines in 2D and 3D proliferation assays. In vivo tumor growth was assessed using xenografts of human melanoma A375 melanoma cells in nude mice (eight mice per group). All statistical tests were two-sided.Results: Strong signals were detected for CDKN2A (P_min = 6.16 × 10^-8) in the CM cohort (n = 273) and BAP1 (P_min = 3.83 × 10^‐6) in the OM (n = 99) cohort. Eleven genes that exhibited borderline association (P < 10^‐4) were independently validated using The Cancer Genome Atlas melanoma cohort (379 CM, 47 OM) and a matched set of 3563 European controls with CDKN2A (P = .009), BAP1 (P = .03), and EBF3 (P = 4.75 × 10^‐4), a candidate risk locus, all showing evidence of replication. EBF3 was then evaluated using germline data from a set of 132 familial melanoma cases and 4769 controls of UK origin (joint P = 1.37 × 10^‐5). Somatically, loss of EBF3 expression correlated with progression, poorer outcome, and high MITF tumors. Functionally, induction of EBF3 in melanoma cells reduced cell growth in vitro, retarded tumor formation in vivo, and reduced MITF levels.Conclusions: The results of this large rare variant germline association study further define the mutational landscape of hereditary melanoma and implicate EBF3 as a possible CM predisposition gene.

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Rare Variant, Gene-Based Association Study of Hereditary Melanoma Using Whole-Exome Sequencing

Abstract

Trivalent Chromium Induces Autophagy by Activating Sphingomyelin Phosphodiesterase 2 and Increasing Cellular Ceramide Levels in Renal HK2 Cells

Abstract

In this study, we examined the role of autophagy in the initiation of lipid increases in renal epithelial HK2 cells. We found that trivalent chromium [Cr(III)] induced autophagy by activating sphingomyelin phosphodiesterase 2 (SMPD2). SMPD2 increases levels of ceramide and other lipids. Confocal immunofluorescence microscopy showed that signals of ceramide overlapped with LC3, suggesting that ceramide might play an important role in the formation of autophagosome. In conclusion, our data indicate that Cr(III) induces autophagy via structural aberration of organelle membrane, in particular by the increase of lipid compositions in addition to autophagy-associated proteins. This article is protected by copyright. All rights reserved

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Trivalent Chromium Induces Autophagy by Activating Sphingomyelin Phosphodiesterase 2 and Increasing Cellular Ceramide Levels in Renal HK2 Cells

Abstract

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EANO and palliative care: The Lancet Oncology: June 2, 2017

Martin Taphoorn outlines the importance of palliative care for patients with gliomas.

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ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS)

Abstract

Background

Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens.

Methods

This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research.

Discussion

This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG).

Trial registration

NCT01726452. Protocol 10-14. Date of registration 06/11/2012.

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Progressive resistance training in head and neck cancer patients during concomitant chemoradiotherapy -- design of the DAHANCA 31 randomized trial

Abstract

Background

Head and neck cancer patients undergoing concomitant chemoradiotherapy (CCRT) frequently experience loss of muscle mass and reduced functional performance. Positive effects of exercise training are reported for many cancer types but biological mechanisms need further elucidation. This randomized study investigates whether progressive resistance training (PRT) may attenuate loss of muscle mass and functional performance. Furthermore, biochemical markers and muscle biopsies will be investigated trying to link biological mechanisms to training effects.

Methods

At the Departments of Oncology at Herlev and Aarhus University Hospitals, patients with stage III/IV squamous cell carcinoma of the head and neck, scheduled for CCRT are randomized 1:1 to either a 12-week PRT program or control group, both with 1 year follow-up. Planned enrollment is 72 patients, and stratification variables are study site, sex, p16-status, and body mass index. Primary endpoint is difference in change in lean body mass (LBM) after 12 weeks of PRT, assessed by dual-energy X-ray absorptiometry (DXA). The hypothesis is that 12 weeks of PRT can attenuate the loss of LBM by at least 25%. Secondary endpoints include training adherence, changes in body composition, muscle strength, functional performance, weight, adverse events, dietary intake, self-reported physical activity, quality of life, labor market affiliation, blood biochemistry, plasma cytokine concentrations, NK-cell frequency in blood, sarcomeric protein content in muscles, as well as muscle fiber type and fiber size in muscle biopsies. Muscle biopsies are optional.

Discussion

This randomized study investigates the impact of a 12-week progressive resistance training program on lean body mass and several other physiological endpoints, as well as impact on adverse events and quality of life. Furthermore, a translational approach is integrated with extensive biological sampling and exploration into cytokines and mechanisms involved. The current paper discusses decisions and methods behind exercise in head and neck cancer patients undergoing concomitant chemoradiotherapy.

Trial registration

Approved by the Regional Ethics Committee for the Capital Region of Denmark (protocol id: H-15003725) and registered retrospectively at ClinicalTrials.gov (NCT02557529) September 11th 2015.

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ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS)

Abstract

Background

Methods

Discussion

Trial registration

NCT01726452. Protocol 10-14. Date of registration 06/11/2012.

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Progressive resistance training in head and neck cancer patients during concomitant chemoradiotherapy -- design of the DAHANCA 31 randomized trial

Abstract

Background

Methods

Discussion

Trial registration

Approved by the Regional Ethics Committee for the Capital Region of Denmark (protocol id: H-15003725) and registered retrospectively at ClinicalTrials.gov (NCT02557529) September 11th 2015.

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Differentiating perforated from non-perforated appendicitis on contrast-enhanced magnetic resonance imaging

Abstract

Background

The role of magnetic resonance imaging (MRI) in pediatric appendicitis is increasing; MRI findings predictive of appendiceal perforation have not been specifically evaluated.

Objective

To assess the performance of MRI in differentiating perforated from non-perforated appendicitis.

Materials and methods

A retrospective review of pediatric patients undergoing contrast-enhanced MRI and subsequent appendectomy was performed, with surgicopathological confirmation of perforation. Appendiceal diameter and the following 10 MRI findings were assessed: appendiceal restricted diffusion, wall defect, appendicolith, periappendiceal free fluid, remote free fluid, restricted diffusion within free fluid, abscess, peritoneal enhancement, ileocecal wall thickening and ileus. Two-sample t-test and chi-square tests were used to analyze continuous and discrete data, respectively. Sensitivity and specificity for individual MRI findings were calculated and optimal thresholds for measures of accuracy were selected.

Results

Seventy-seven patients (mean age: 12.2 years) with appendicitis were included, of whom 22 had perforation. The perforated group had a larger mean appendiceal diameter and mean number of MRI findings than the non-perforated group (12.3 mm vs. 8.6 mm; 5.0 vs. 2.0, respectively). Abscess, wall defect and restricted diffusion within free fluid had the greatest specificity for perforation (1.00, 1.00 and 0.96, respectively) but low sensitivity (0.36, 0.25 and 0.32, respectively). The receiver operator characteristic curve for total number of MRI findings had an area under the curve of 0.92, with an optimal threshold of 3.5. A threshold of any 4 findings had the best ability to accurately discriminate between perforated and non-perforated cases, with a sensitivity of 82% and specificity of 85%.

Conclusion

Contrast-enhanced MRI can differentiate perforated from non-perforated appendicitis. The presence of multiple findings increases diagnostic accuracy, with a threshold of any four findings optimally discriminating between perforated and non-perforated cases. These results may help guide management decisions as MRI assumes a greater role in the work-up of pediatric appendicitis.

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Differentiating perforated from non-perforated appendicitis on contrast-enhanced magnetic resonance imaging

Abstract

Background

The role of magnetic resonance imaging (MRI) in pediatric appendicitis is increasing; MRI findings predictive of appendiceal perforation have not been specifically evaluated.

Objective

To assess the performance of MRI in differentiating perforated from non-perforated appendicitis.

Materials and methods

Results

Conclusion

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The critical role of EGF-β-catenin signaling in the epithelial-mesenchymal transition in human glioblastoma

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First international consensus conference on standardization of oncoplastic breast conserving surgery

Abstract

Purpose

To obtain consensus recommendations for the standardization of oncoplastic breast conserving surgery (OPS) from an international panel of experts in breast surgery including delegates from the German, Austrian and Swiss societies of senology.

Methods

A total of 52 questions were addressed by electronic voting. The panel's recommendations were put into context with current evidence and the report was circled in an iterative open email process until consensus was obtained.

Results

The panelists considered OPS safe and effective for improving aesthetic outcomes and broadening the indication for breast conserving surgery (BCS) towards larger tumors. A slim majority believed that OPS reduces the rate of positive margins; however, there was consensus that OPS is associated with an increased risk of complications compared to conventional BCS. The panel strongly endorsed patient-reported outcomes measurement, and recommended selected scales of the Breast-Q™-Breast Conserving Therapy Module for that purpose. The Clough bi-level classification was recommended for standard use in clinical practice for indicating, planning and performing OPS, and the Hoffmann classification for surgical reports and billing purposes. Mastopexy and reduction mammoplasty were the only two recognized OPS procedure categories supported by a majority of the panel. Finally, the experts unanimously supported the statement that every OPS procedure should be tailored to each individual patient.

Conclusions

When implemented into clinical practice, the panel recommendations may improve safety and effectiveness of OPS. The attendees agreed that there is a need for prospective multicenter studies to optimize patient selection and for standardized criteria to qualify and accredit OPS training centers.

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[Evaluation of multidisciplinary team meeting; the example of gynecological mammary cancers in a tertiary referral center in Morocco].

[Evaluation of multidisciplinary team meeting; the example of gynecological mammary cancers in a tertiary referral center in Morocco].

Bull Cancer. 2017 May 29;:

Authors: Chaouki W, Mimouni M, Boutayeb S, Hachi H, Errihani H, Benjaafar N

Abstract
The multidisciplinary team meeting has become a standard medical practice in oncology. However, no evaluation of this activity was carried out in Morocco. The aim of this study was to evaluate the multidisciplinary team meeting of gynecological mammary cancers in a National Tertiary Referral Center. The study was carried out by retrospective analysis of 207 cases of patients randomly selected among the 1190 cases recruited during the year 2015. Completeness and quality criteria were evaluated. The global completeness rate of passage in multidisciplinary team meeting is 38%. According to the therapeutic specialities, the completeness of passage in multidisciplinary team meeting is 68% of surgery, 35% of medical oncology and 19% of radiotherapy. As far as localizations are concerned, the completeness of passage in multidisciplinary team meeting is 43% for the breast and only 19% for the cervix. A quorum was met 100% of the cases. In 96% of cases the treatment performed is in accordance with the decision of the multidisciplinary team meeting. Eighty-four percent of cases performed multidisciplinary team meeting within less than one month. This analysis shows that the completeness of the transition to multidisciplinary team meeting has not reached the 100% planned by our institution. However, the requirements for conducting the multidisciplinary team meeting were generally met. This study shows an organizational evolution of our structure based on collective and multidisciplinary medical decision. The national obligation measure of multidisciplinary team meeting is necessary.

PMID: 28571842 [PubMed - as supplied by publisher]

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Real-World Impact of Cardiovascular Disease and Anemia on Quality of Life and Productivity in Patients with Non-Dialysis-Dependent Chronic Kidney Disease

Abstract

Introduction

Patients with chronic kidney disease (CKD) have an increased risk of comorbid conditions, including cardiovascular disease (CVD). Anemia is prevalent in the CKD population and worsens as kidney function declines, resulting in a diminished quality of life and increased morbidity/mortality. The purpose of this secondary analysis was to determine the real-world prevalence of CVD among patients with non-dialysis-dependent CKD (NDD-CKD), with and without comorbid anemia, and to assess the impact of these conditions on quality of life (QoL) and work productivity.

Methods

Data were drawn from the Adelphi CKD Disease-Specific Programme, conducted in France, Germany, Italy, Spain, and the UK (2012). Anonymized data were collected via patient record forms and patient-completed questionnaires. Patient data were stratified by anemic status and the presence of CVD comorbidity.

Results

Data were collected by physicians for 1993 patients, of whom 867 completed a patient-completed questionnaire. A total of 61.4% of patients had anemia, and the prevalence of anemia increased with CKD stage. Patients with anemia had a higher mean number of cardiovascular comorbidities than non-anemic patients (1.27 vs 0.95, respectively; P < 0.001). The presence of cardiovascular conditions was associated with a significantly reduced QoL (EuroQol EQ-5D-3L visual analog scale: coefficient, −5.68 in anemic patients; P = 0.028) and work productivity and activity impairment (WPAI activity impairment: coefficient, +8.04 in anemic patients; P = 0.032), particularly among anemic patients.

Conclusions

The presence of anemia in this cohort of NDD-CKD patients was high. The presence of concomitant cardiovascular conditions was more common in NDD-CKD patients with comorbid anemia, and was associated with reduced QoL and work productivity outcomes.

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Monitoring for and Characterizing Crizotinib Progression: A Chart Review of ALK -Positive Non-Small Cell Lung Cancer Patients

Abstract

Introduction

Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance. With the recent approval of second-generation ALK inhibitors, this study assessed how physicians monitor for and diagnose progression and how they alter treatment following progression on crizotinib.

Methods

A panel of oncologists from the United States were surveyed regarding their monitoring practices and criteria for diagnosing progression on crizotinib. The physicians also retrospectively provided data (March–June 2016) from the medical charts of their adult patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib after the approval (April 2014) of the first second-generation ALK inhibitor, ceritinib.

Results

A total of 28 physicians responded to the survey. Data was abstracted on 74 patients. In the physician survey, most physicians (71%) reported monitoring for radiographic progression every 3–4 months. When new lesions were detected, physician response varied. Following a symptomatic isolated lesion, most physicians (75%) would add local therapy and resume crizotinib. Following multiple symptomatic lesions, 96% and 64% of physicians would switch to a new therapy depending on whether the lesions were extracranial or isolated to the brain, respectively. For the patient cohort, physician-defined progression on crizotinib was diagnosed after a median of 10 months, and within 30 days of diagnosis, 86% of patients discontinued crizotinib. Among all patients who discontinued crizotinib, 77% switched to ceritinib, 14% to chemotherapy, and 1% to alectinib. The remaining 7% did not receive additional systemic antineoplastic therapy.

Conclusion

The findings from this physician survey and retrospective chart review study suggest that physician response to the development of new lesions in crizotinib-treated ALK-positive NSCLC patients varies with location and extent of the lesions. Once patients were considered to have progressed, most of them were immediately switched to ceritinib.

Funding

Novartis Pharmaceuticals Corporation.

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Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer’s disease using functional laser speckle contrast imaging

Abstract

Increasing evidence from epidemiological, clinical, and experimental studies indicates that cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including both vascular cognitive impairment (VCI) and Alzheimer's disease. Vascular contributions to cognitive impairment and dementia (VCID) include impairment of neurovascular coupling responses/functional hyperemia ("neurovascular uncoupling"). Due to the growing interest in understanding and pharmacologically targeting pathophysiological mechanisms of VCID, there is an increasing need for sensitive, easy-to-establish methods to assess neurovascular coupling responses. Laser speckle contrast imaging (LSCI) is a technique that allows rapid and minimally invasive visualization of changes in regional cerebromicrovascular blood perfusion. This type of imaging technique combines high resolution and speed to provide great spatiotemporal accuracy to measure moment-to-moment changes in cerebral blood flow induced by neuronal activation. Here, we provide detailed protocols for the successful measurement in neurovascular coupling responses in anesthetized mice equipped with a thinned-skull cranial window using LSCI. This method can be used to evaluate the effects of anti-aging or anti-AD treatments on cerebromicrovascular health.

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Real-World Impact of Cardiovascular Disease and Anemia on Quality of Life and Productivity in Patients with Non-Dialysis-Dependent Chronic Kidney Disease

Abstract

Introduction

Methods

Results

Conclusions

http://ift.tt/2s3WD19

Monitoring for and Characterizing Crizotinib Progression: A Chart Review of ALK -Positive Non-Small Cell Lung Cancer Patients

Abstract

Introduction

Methods

Results

Conclusion

Funding

Novartis Pharmaceuticals Corporation.

http://ift.tt/2qKDxJx

The beneficial effects of HMG-CoA reductase inhibitors in the processes of neurodegeneration

Abstract

Statins, cholesterol lowering drugs, have been demonstrated to exert beneficial effects in other conditions such as primary and progressing neurodegenerative diseases beyond their original role. Observation that statins ameliorate the neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and cerebral ischemic stroke, the neuroprotective effects of these drugs are thought to be linked to their anti-inflammatory, anti-oxidative, and anti-excitotoxic properties. Despite the voluminous literature on the clinical advantages of 3-hydroxy-3-methylglutaryl Co-enzyme A reductase (HMGCR) inhibitors (statins) in cardiovascular system, the neuroprotective effects and the underlying mechanisms are little understood. Hence, the present review tries to provide a critical overview on the statin-induced neuroprotection, which are presumed to be associated with the ability to reduce cholesterol, Amyloid-β and apolipoprotein E (ApoE) levels, decrease reactive oxygen and nitrogen species (ROS and RNS) formation, inhibit excitotoxicity, modulate matrix metalloproteinases (MMPs), stimulate endothelial nitric oxide synthase (eNOS), and increase cerebral blood perfusion. This review is also aimed to illustrate that statins protect neurons against the neuro-inflammatory processes through balancing pro-inflammatory/anti-inflammatory cytokines. Ultimately, the beneficial role of statins in ameliorating the development of PD, AD, MS and cerebral ischemic stroke has been separately reviewed.

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Apocynin Alleviates Renal Ischemia/Reperfusion Injury Through Regulating the Level of Zinc and Metallothionen

Abstract

The purpose of this research was to evaluate the protective effects of apocynin on renal ischemia/reperfusion (I/R) injury (RI/RI) in rats. Rats preconditioned with apocynin were subjected to renal I/R. Zinc levels in serum and renal tissues, blood urea nitrogen (BUN), and serum creatinine (Scr) were detected. We further measured the activity of superoxide dismutase (SOD); the content of malondialdehyde (MDA), IL-4, IL-6, IL-10, and TNF-α; and the expression of metallothionein (MT) in the renal tissues. Results indicated that the levels of MDA, IL-4, IL-6, IL-10, TNF-α, and MT in the kidney tissue and serum BUN and Scr levels in RI/RI group were significantly higher than those in sham-operated group, while the levels of serum Zn and kidney Zn and SOD were reduced in RI/RI group. Apocynin treatment further decreased the levels of MDA, IL-6, TNF-α, and serum BUN and Scr, whereas it significantly increased the levels of Zn, SOD, IL-4, IL-10, and MT in the kidney tissue and serum Zn. These findings suggest that apocynin might play a protective role against RI/RI in rats through regulating zinc level and MT expression involving in oxidative stress.

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Nanoselenium Supplementation of Heat-Stressed Broilers: Effects on Performance, Carcass Characteristics, Blood Metabolites, Immune Response, Antioxidant Status, and Jejunal Morphology

Abstract

An experiment was conducted to investigate the effects of dietary nanoselenium supplementation at 0, 0.6 and 1.2 mg/kg of diet on growth performance, serum biochemical parameters, immune response, antioxidant capacity, and jejunal morphology of 29-d-old male broilers subjected to heat stress at 37 ± 1°C for 14 d. Broilers were fed for 42 d on the experimental diets. The results showed that nanoselenium supplementation had no effect on growth performance, but it supplementation at the rate of 1.2 mg/kg diet decreased the serum concentration of cholesterol prior to the heat exposure. Further, dietary nanoselenium supplementation linearly increased the high-density lipoprotein cholesterol concentration, while linearly decreased those of low-density lipoprotein cholesterol and aspartate aminotransferase in the serum before applying heat stress. Compared with thermoneutral temperature, heat stress reduced body mass gain, feed intake, percentages of carcass, breast, leg, abdominal fat, bursa of Fabricius, thymus, antibody response against sheep red blood cells, serum concentration of protein, erythrocyte activities of glutathione peroxidase and superoxide dismutase, jejunal villus height, and villus height to crypt depth ratio, while increased feed conversion ratio, percentages of liver, gizzard, pancreas, gallbladder, heart, and the concentrations of aspartate aminotransferase and malondialdehyde. Dietary supplementation of nanoselenium linearly reduced the abdominal fat and liver percentages, while linearly increased the activity of glutathione peroxidase and villus height in heat-stressed broilers. Furthermore, the lower level of nanoselenium decreased the percentages of gizzard and heart in broilers under heat stress. The diet supplemented with 1.2 mg/kg nanoselenium improved feed conversion ratio and increased antibody response against sheep red blood cells, activity of superoxide dismutase, and villus height to crypt depth ratio, but decreased the serum concentrations of cholesterol, low-density lipoprotein cholesterol, and malondialdehyde in heat-stressed broilers. The results suggest that supplemental nanoselenium improved growth performance, internal organs health, immune response, and jejunal morphology by alleviating the oxidative stress induced by heat stress.

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Influence of Selenium on the Production of T-2 Toxin by Fusarium poae

Abstract

The objective of this study was to investigate the effects of selenium on the production of T-2 toxin by a Fusarium poae strain cultured in a synthetic medium containing different concentrations of selenium. The T-2 toxin contents in fermentative products were evaluated by a high performance liquid chromatography (HPLC). The results showed that the production of T-2 toxin was correlated with the concentration of selenium added to the medium. In all three treatments, the addition of 1 mg/L selenium to the medium resulted in a lower toxin yield than the control (0 mg/L); the yield of the toxin began to increase when selenium concentration was 10 mg/L, while it decreased again at 20 mg/L. In summary, T-2 toxin yield in the fermentative product was affected by the addition of selenium to the medium, and a selenium concentration of 20 mg/L produced the maximum inhibitory effect of T-2 toxin yield in the fermentative product of F. poae.

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The Influence of the Dietary Cu-Glycine Complex on the Histomorphology of Cancellous Bone, Articular Cartilage, and Growth Plate as well as Bone Mechanical and Geometric Parameters Is Dose Dependent

Abstract

Copper (Cu) is required for all basic biochemical and physiological processes. The objective of this study was to compare the effect of two different chemical forms (sulfates and glycinate chelates also below the recommended dose) of Cu administered to adult rats on the biomechanical and morphometric properties of femur. Male rats at the age of 12 weeks were used in the 12-week experiment. The control diet provided the required Cu level from sulfate (S-Cu), and the other diets were supplemented with Cu-glycine complex. The Cu-Gly-treatment, irrespective of its concentration, did not influence the bone mass and length. The Cu-Gly-treatment in 100 and 75% of daily demand increased mechanical endurance. The Cu-Gly-treatment (regardless of its concentration) increased the real bone volume in epiphysis and decreased the total thickness and zone I of the articular cartilage compared to the control group supplemented with S-Cu. The Cu-Gly-treatment enhanced the content of proteoglycans (except the OG50 group). Dietary Cu given to adult rats in the Cu-Gly complex covering the daily demand in 75% exerted a positive effect on bone metabolism and appeared to be the most effective among the investigated doses of the organic form.

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Erratum to: How Trace Element Levels of Public Drinking Water Affect Body Composition in Turkey

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Nickel Oxide Nanoparticles Induce Oxidative DNA Damage and Apoptosis in Kidney Cell Line (NRK-52E)

Abstract

Increasing use of nickel oxide (NiO) nanoparticles in different applications results in high occupational and environmental exposure to them. However, the effect of NiO nanoparticles on human health is still poorly documented. It was aimed to investigate the toxic potentials of NiO nanoparticles on NRK-52E kidney epithelial cells. The following assays were used: the nanoparticle characterization by transmission electron microscopy (TEM) and dynamic light scattering (DLS); the determination of cellular uptake and morphologic changes by TEM and inductively coupled plasma-mass spectrometry (ICP-MS); MTT and neutral red uptake (NRU) assays for cytotoxicity; comet assay for genotoxicity; the determination of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), protein carbonyl (PC) and glutathione (GSH) levels by enzyme-linked immune sorbent assays (ELISA) for the potential of oxidative damage; and Annexin V-FITC apoptosis detection assay with propidium iodide (PI) for apoptosis. The nanoparticles were taken up by the cells and induced dose-dependent DNA damage by comet assay and oxidative damage evidenced by increasing levels of MDA, 8-OHdG, PC and depletion of GSH. At ≥294.0 μg/mL concentration, NiO nanoparticles caused 50% inhibition in cell viability by the cytotoxicity assays. Also, they showed apoptotic/necrotic effects on the cells as well as some morphological changes. We have indicated that their cellular damage effects should raise concern about the safety associated with their applications in consumer products.

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The Effect of Ketogenic Diet on Serum Selenium Levels in Patients with Intractable Epilepsy

Abstract

The aim of the present study was to evaluate serum selenium levels in children receiving olive oil-based ketogenic diet (KD) for intractable seizures for at least 1 year. Out of 320 patients who were initiated on KD, patients who continued receiving KD for at least 12 months were enrolled. Sixteen patients who had selenium deficiency at the time of starting KD were excluded. Finally, a total of 110 patients (mean age 7.3 ± 4.2 years) were included. Serum selenium levels were measured at baseline and at 3, 6, and 12 months after treatment initiation by using atomic absorption spectroscopy. Selenium deficiency was defined as a serum selenium level <48 μg/L at each visit. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. Mean duration of KD was 15.3 ± 4.3 months. Mean serum selenium levels were significantly lower at 6 and 12 months of KD treatment (66.2 ± 23.3 and 57.2 ± 16.2 μg/L, respectively) compared to pre-treatment levels (79.3 ± 25.7 μg/L) (p = 0.001). On the other hand, selenium levels did not show any significant difference at 3 months of KD treatment (70.0 ± 21.2 μg/L) compared to baseline levels (p = 0.076). A total of 54 patients (49.1%) were diagnosed with selenium deficiency, and oral selenium medication was initiated for these patients. No relevant clinical findings were detected, and echocardiographic findings were normal in all patients. The decline of the serum selenium concentrations after 6 and 12 months of ketogenic diet suggests that patients on this highly prescriptive dietary treatment need close monitoring of this trace element.

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Increased Serum Al Levels in Hemodialysis Patients Kept Enhanced during a 2-Year Prospective Study

Abstract

The regulation of mineral homeostasis is altered in hemodialysis patients with renal insufficiency, producing increased risk for secondary diseases like cardiovascular ones. We hypothesized that risen serum aluminum (Al) concentration in hemodialysis patients kept enhanced during a 2-year longitudinal study is associated with enhanced cardiovascular risk and influenced by medical treatments. This study reports the prospective monitoring of serum Al levels in six-monthly samplings over 2 years in 116 hemodialysis patients and a control group of 50 healthy adults. The influence of other factors like sex, age, kidney transplant, disease etiology, and drug consumption was also considered. At each sampling, serum Al levels were significantly higher in the patients than in the healthy controls (P < 0.05). Levels in the patient group were statistically significantly lower at the third and fourth versus first and second samplings, which may be related to Al accumulation in tissues. Increased Al levels in patients were positively and significantly related to serum calcium (Ca) and uric acid levels. Serum Al concentrations were significantly lower in patients receiving vasodilators and diuretics. Higher serum Al levels in hemodialyzed patients administered with phosphate binders or anti-hyperkalemics are attributable to their usual Al salt content. The consumption of antianemic drugs increases Al absorption by forming more bioavailable complexes with the compounds in these drugs. In conclusion, this is the first study to indicate that cardiovascular problems associated with elevated serum Al levels in hemodialysis patients may be in part mitigated by administrating vasodilators and diuretics, which reduce these levels.

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Effects of Chromium-Loaded Chitosan Nanoparticles on Glucose Transporter 4, Relevant mRNA, and Proteins of Phosphatidylinositol 3-Kinase, Akt2-Kinase, and AMP-Activated Protein Kinase of Skeletal Muscles in Finishing Pigs

Abstract

The study was conducted to evaluate the effects of chromium-loaded chitosan nanoparticles (Cr-CNP) on glucose transporter 4 (GLUT4), relevant messenger RNA (mRNA), and proteins involved in phosphatidylinositol 3-kinase (PI3K), Akt2-kinase, and AMP-activated protein kinase (AMPK) of skeletal muscles in finishing pigs. A total of 120 crossbred barrows (BW 65.00 ± 1.26 kg) were randomly allotted to four dietary treatments, with three pens per treatment and 10 pigs per pen. Pigs were fed the basal diet supplemented with 0, 100, 200, or 400 μg/kg of Cr from Cr-CNP for 35 days. After the feeding trials, 24 pigs were slaughtered to collect longissimus muscle samples for analysis. Cr-CNP supplementation increased GLUT4 messenger RNA (mRNA) (quadratically, P < 0.01) and total and plasma membrane GLUT4 protein contents (linearly and quadratically, P < 0.001) in skeletal muscles. Glycogen synthase kinase 3β (GSK-3β) mRNA was decreased linearly (P < 0.001) and quadratically (P < 0.001). Supplemental Cr-CNP increased insulin receptor (InsR) mRNA quadratically (P < 0.01), Akt2 total protein level linearly (P < 0.01) and quadratically (P < 0.001), and PI3K total protein was increased significantly (P < 0.05) in 200 μg/kg treatment group. The mRNA of AMPK subunit gamma-3 (PRKAG3) and protein of AMPKα₁ was significantly increased (P < 0.001) with the addition of Cr-CNP. The results indicate that dietary supplementation of Cr-CNP may promote glucose uptake by leading to recruitment of GLUT4 to the plasma membrane in skeletal muscles, and these actions may be associated with the insulin signal transduction and AMPK.

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N-Acetyl-L-Cysteine Protects Liver and Kidney Against Chromium(VI)-Induced Oxidative Stress in Mice

Abstract

Acute hexavalent chromium [Cr(VI)] compound exposure may lead to hepatotoxic and nephrotoxic effects. Cr(VI) reduction may generate reactive intermediates and radicals which might be associated with damage. We investigated effects of N-acetyl-l-cysteine (NAC) pre- or post-treatment on oxidative stress and accumulation of Cr in liver and kidney of Cr(VI)-exposed mice. Intraperitoneal potassium dichromate injection (20 mg Cr/kg) caused a significant elevation of lipid peroxidation in both tissues as compared to control (p < 0.05). Significant decreases in non-protein sulfhydryl (NPSH) level, as well as enzyme activities of catalase (CAT) and superoxide dismutase (SOD) along with significant accumulation of Cr in the tissues (p < 0.05) were of note. NAC pre-treatment (200 mg/kg, ip) provided a noticeable alleviation of lipid peroxidation (p < 0.05) in both tissues, whereas post-treatment exerted significant effect only in kidney. Similarly, Cr(VI)-induced NPSH decline was restored by NAC pre-treatment in both tissues (p < 0.05); however, NAC post-treatment could only replenish NPSH in liver (p < 0.05). Regarding enzyme activities, in liver tissue NAC pre-treatment provided significant restoration on Cr(VI)-induced CAT inhibition (p < 0.05), while SOD enzyme activity was regulated to some extent. In kidney, SOD activity was efficiently restored by both treatments (p < 0.05), whereas CAT enzyme alteration could not be totally relieved. Additionally, NAC pre-treatment in both tissues and post-treatment in liver exerted significant tissue Cr level decreases (p < 0.05). Overall, especially NAC pre-treatment seems to provide beneficial effects in regulating pro-oxidant/antioxidant balance and Cr accumulation caused by Cr(VI) in liver and kidney. This finding may be due to several mechanisms including extracellular reduction or chelation of Cr(VI) by readily available NAC.

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The beneficial effects of HMG-CoA reductase inhibitors in the processes of neurodegeneration

Abstract

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A prognostic model for resectable acral melanoma patients on the basis of preoperative inflammatory markers.

Acral melanoma is a rare disease, but is common in Asia. Knowledge of its prognostic indicators is limited. Growing evidence indicates that inflammation plays a critical role in the development and progression of acral melanoma. We developed a novel prognostic model on the basis of preoperative inflammatory markers and examined its prognostic value in a cohort of patients. This retrospective study included 232 acral melanoma patients who underwent radical surgical resection between 2000 and 2010 at the Sun Yat-sen University Cancer Center. Significant predictive factors were identified by multivariate Cox regression analyses, and a prognostic model on the basis of these variables was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. Multivariate analyses showed that C-reactive protein, albumin/globulin ratio, age, lactic dehydrogenase, and lymph node positivity were related independently to survival. After analyzing these variables, we classified patients into three risk groups. The new prognostic model identified three categories of patients with different prognoses (P

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Single-stage excision and sentinel lymph node biopsy in cutaneous melanoma in selected patients: a retrospective case-control study.

Sometimes, diagnostic excision of a primary melanoma would already necessitate skin grafting or transposition skin flaps, especially in areas with an esthetic or functional importance. The utility of sentinel lymph node biopsy (SLNB) after skin reconstruction is controversial. We carried out a single-institution retrospective case-control study. In patients with a wide primary lesion at high clinical-dermatoscopic suspicion for invasive melanoma in anatomical region in which a reconstruction with a skin graft or a flap is required, we proposed the performance of a confocal microscopy examination and an incisional biopsy of the primary lesion. If these diagnostic methodologies confirmed the suspicion of melanoma, lymphatic mapping was performed before the wide excision (WE) of the primary lesion, and WE and SLNB were performed during the same operative procedure. The database evaluation showed 496 patients who had undergone a previous complete local excision and a subsequent SLNB (two-stage group), whereas 61 patients underwent WE and SLNB during the same surgical time (one-stage group). Histological results of the excisional biopsy confirmed the diagnosis of melanoma in all patients of the one-stage group. The false-negative rate was lower in the one-stage group (5.5%) than in the two-stage group (16.7%). Patients of the two groups showed a similar recurrence-free and overall survival period even when corrected for clinic-demographical variables. The concomitant execution of SLNB and WE after confocal microscopy examination and incisional biopsy appears to be a safe and accurate procedure in patients with a wide primary melanoma that requires a skin flaps or a skin graft to cover the residual defect. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Development of a biclonal cutaneous T-cell lymphoproliferative process during treatment with immune checkpoint inhibitors for metastatic melanoma.

The immune checkpoint inhibitors targeting cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and the programmed death protein 1 (PD-1)/PD-L1 pathway have recently shown promising therapeutic results in patients with metastatic melanoma. Dermatologic side effects of these agents occur in ~30-40% of cases. Here, we report the development of a biclonal cutaneous T-cell lymphoproliferative disorder in a patient being treated with ipilimumab (a CTLA-4 inhibitor) for metastatic melanoma. Nivolumab (a PD-1 inhibitor) had also been administered to him previously. An 8 mm reddish papule appeared on the skin of the left forearm. A biopsy of that lesion showed an atypical population of predominantly CD4-positive, CD30-positive T-cells that also expressed PD-1 and PD-L1 immunohistochemically. PCR studies for T-cell receptor rearrangements showed the presence of two distinct clonal T-cell populations. The lesion was completely excised and the patient had no local recurrences. There was also no subsequent evidence of a systemic lymphoproliferative process. Although the development of a lymphoid skin lesion in our patient may have only been coincidentally related to his treatment, immunostimulatory drugs could theoretically cause clonal expansion of a population of lymphocytes that leads to a lymphoproliferative disorder. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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