LBA-002Overall survival results from a phase III trial of trifluridine/tipiracil versus placebo in patients with metastatic gastric cancer refractory to standard therapies (TAGS)

Background: Trifluridine/tipiracil (FTD/TPI), an orally administered combination agent approved for patients with refractory metastatic colorectal cancer, demonstrated promising clinical activity in a refractory gastric cancer Japanese Phase II trial. Therefore, we initiated the TAGS study (NCT02500043) to evaluate the efficacy and safety of FTD/TPI in patients with heavily pretreated metastatic gastric cancer (mGC).

LBA-004Efficacy and safety results from IMblaze370, a randomised Phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer

Background: Patients with chemotherapy-refractory microsatellite stable (MSS) metastatic colorectal cancer (CRC) are a population with limited treatment options and relatively short survival. Atezolizumab (an anti–PD-L1 mAb) inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, leading to the re-invigoration of tumour-specific T-cell immunity. Cobimetinib inhibits MEK1/MEK2 in the MAPK pathway, and blocking the MAPK pathway has been shown to favourably alter the tumour, tumour microenvironment and T-cell responses to promote anti-tumour immune activity. We hypothesized that combining atezolizumab with cobimetinib may allow better immune recognition and generate greater anti-tumour effects than either agent alone in MSS/microsatellite instability-low (MSI-L) metastatic CRC. Here we report the primary analysis results from IMblaze370 (NCT02788279), a global, multi-centre, open-label, randomised Phase III trial comparing atezolizumab+cobimetinib and atezolizumab monotherapy with standard-of-care regorafenib in patients with previously treated, unresectable locally advanced or metastatic CRC.

LBA-001Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP) following first-line sorafenib: Pooled efficacy and safety across two global randomized Phase 3 studies (REACH-2 and REACH)

Background: Ramucirumab (RAM), a human IgG1 monoclonal antibody, inhibits ligand activation of VEGFR2. REACH and REACH-2 were two global, randomized, double-blind, placebo (PBO)-controlled multicenter, phase 3 studies of RAM vs PBO in patients with HCC after prior sorafenib. REACH-2 was designed to confirm the ramucirumab treatment benefit for patients with baseline AFP ≥400 ng/mL first observed in the prespecified subgroup of patients in REACH with AFP ≥400 ng/mL. The primary endpoint of REACH-2 was met demonstrating an improved overall survival (OS) compared to PBO, a result consistent with that in patients with AFP ≥400 ng/mL in REACH. Pooled analyses of patients from REACH-2 and REACH with baseline AFP ≥400 ng/mL was performed.

LBA-003Withdrawn

LBA-005KEYNOTE-061: Phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer

Background: Pembrolizumab showed promising antitumor activity and a manageable safety profile in patients with pretreated G/GEJ cancer in KEYNOTE-012 and KEYNOTE-059. KEYNOTE-061 (NCT02370498) was a global, open-label phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced G/GEJ adenocarcinoma that progressed after first-line chemotherapy containing platinum and fluoropyrimidine.

Author Index

Abada, Paolo   LBA-001

P-200Risk factors of colorectal cancer in Linxian, China: A nutrition intervention trial with 30 years follow-up

Introduction: Colorectal cancer (CRC) is one of the most common cancers in the world. Epidemiological and experimental studies have shown that some dietary factors and vitamins/minerals are associated with the risk of CRC. The Nutrition Intervention Trial (NIT) tested whether daily multivitamin/mineral supplements could reduce the incidence and mortality rate of esophageal/gastric cardia cancer. The current study evaluated the CRC risk factors at the NIT population.

P-233Trifluridine/tipiracil vs regorafenib as salvage-line treatment in patients with metastatic colorectal cancer: A multicenter retrospective study

Introduction: Trifluridine/tipiracil (TAS-102) and Regorafenib (REG) have shown promising activity in patients with heavily pretreated metastatic colorectal cancer (mCRC). The aim of this study was to compare the efficacy and safety of TAS-102 and REG alone in patients with mCRC refractory to standard chemotherapies.

P-267The prognostic impact of sidedness in RAS wild-type colorectal cancer

Introduction: Colorectal cancer (CRC) is a heterogeneous disease and sidedness [right colon (RC) vs. left colon (LC)] reflects different clinical, biological and molecular behaviors, which could have a significant prognostic impact. This study tried to evaluate the impact of sidedness on overall survival (OS) and progression-free survival (PFS) in RAS wild-type (RAS-WT) CRC patients treated with anti-EGFR antibodies in first line palliative chemotherapy.

PD-008Molecular characterization of immune microenvironment in colorectal cancers with microsatellite instability by digital RNA counting

Introduction: Alterations in the mismatch repair (MMR) mechanism in colorectal cancers (CRCs) lead to high levels of microsatellite instability (MSI-h) causing considerable endogenous immune anti-tumor response, counterbalanced by immune inhibitory signals. We evaluated the mRNA immune-profile of a series of MSI-h CRCs to identify new potential targets for future CRC immunotherapy trials by combining an extensive gene expression analysis and the clinicopathological characteristics such as presence of metastases, staging, genotype and primary tumor sidedness.

P-300Predictive value of circulating tumor-derived DNA (ctDNA) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CT-RT): Preliminary results

Introduction: In patients with LARC, neoadjuvant CT-RT followed by curative surgery is the standard of care. Risk-adopted treatment is based on MRI-predicting local T and N stage, radial margins and vascular involvement while no molecular predictive markers are available. In the present prospective study, we investigated the predictive role of serum ctDNA in patients with LARC.

P-217ABCG2 and TOP-1 as predictive biomarkers and targets for therapy in colon cancer

Introduction: There is a need for new and innovative solutions in the medical treatment of colon cancer since many of these patients eventually develop resistance to currently used drugs leading to untreatable cancer disease and death of the patients. We have by using our DEN50-R cell line based screening platform (isogenic pairs of drug sensitive and drug resistant human cancer cell lines), followed by testing in the PETACC-3 prospective randomized clinical study, identified ABCG2 and TOP1 mRNA expression as significant predictive biomarkers for irinotecan (a topoisomerase 1 inhibitor) resistance in the adjuvant treatment of colon cancer. Moreover, we have identified a new drug (SCO-101) that reverses irinotecan resistance in preclinical experiments (the DEN50-R platform). Here we present the clinical data with the biomarkers and data on SCO-101 including the clinical development plans for the drug.

P-251The prognostic ad predictive value of primary tumor sidedness in the mCRC pts

Introduction: The prognostic and predictive value of primary tumor sidedness in the pts with metastatic colorectal cancer (mCRC) is well known today. Right-sided primary was associated with high mutational burden, microsatellite instability, worse prognosis, more BRAF mutation rates and poor anti-EGFR response. We aimed to investigate the effects of tumor sidedness on survival, RAS-RAF mutation rates and responses to biologic agents in the pts with mCRC.

P-284Characteristics of colorectal cancer in the elderly patients about 60 cases

Introduction: Older people constitute a heterogeneous population, according to World Health Organization, the elderly person is defined as any individual with a chronological age equal to or higher than 60 years. In most cases, colorectal carcinoma is a disease of the elderly. Occurs mostly in the elderly people of more than 65 years and it poses public health problem. For several years geriatric evaluation has shown multiple benefits and we are witnessing a significant improvement in the oncological management of these patients.

P-316Is there any association of dose received by pelvic bone marrow in preoperative radiotherapy in rectal cancer with hematological toxicity of subsequent oxaliplatin-based chemotherapy?

Introduction: Preoperative radio(chemo)therapy in rectal cancer may irreversibly damage pelvic bone marrow (PBM) and impair the tolerance of subsequent chemotherapy. The aim of the study was to assess the association between irradiated volume of PBM and the tolerance of subsequent FOLFOX-4 chemotherapy in rectal cancer.

WITHDRAWN

O-001Efficacy of TAS-120, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in cholangiocarcinoma patients with FGFR pathway alterations who were previously treated with chemotherapy and other FGFR inhibitors

Introduction: TAS-120, an oral and highly selective, irreversible FGFR1-4 tyrosine kinase inhibitor, has demonstrated inhibition of cancer cell growth in human xenografts of tumors bearing FGFR aberrations. TAS-120 inhibited mutant and wild-type FGFR2 with similar IC50 (wild-type FGFR2, 0.9 nM; V5651, 1-3 nM; N550H, 3.6 nM; E566G, 2.4 nM) and has shown efficacy in cell lines with acquired resistance to FGFR inhibitors. In this Phase I study in patients with advanced solid tumors, TAS-120 was evaluated at 8-24 mg once daily (QD). 20 mg QD was determined as the maximum tolerated dose/recommended Phase II dose, while 24 mg QD had dose-limiting toxicity. Here we report results from cholangiocarcinoma (CCA) patients enrolled in this Phase I study.

P-191Combined analysis of KRAS, NRAS, BRAF mutations and mismatch repair deficiency testing in Indian patients with metastatic colorectal carcinoma: A single centre experience

Introduction: Molecular evaluation of KRAS, NRAS and BRAF mutation has become an important part in colorectal carcinoma evaluation as their alterations determine the therapeutic response to anti-EGFR therapy and prognosis. MMR deficiency is important for identification of Lynch syndrome families and it has now become an important biomarker of response to immunotherapy in metastatic CRC. The aim of this study is to investigate the distribution of these mutations by tumor localization and to determine the prevalence of MMR deficiency in metastatic colorectal cancer.

P-208Autophagy (A) related proteins evaluation represents an independent survival factor of colorectal cancer (CRC) patients (pts)

Introduction: A holds a bimodal role during carcinogenesis. Before tumorigenesis, A promotes normal cells survival and suppress carcinogenesis, while after cancer development A induces cancer cells survival. The aim of this study is to assess the impact of A related proteins in the survival of CRC pts.

P-225The role of maintenance therapy in the first line treatment of metastatic colorectal cancer

Introduction: The first line of chemotherapy is decisive in the treatment of colorectal cancer. Choosing the right one allows you to increase PFS and improve long-term results. Surgical treatment and maintenance therapy (MT) increase PFS and OS, as they can be prescribed at any stage of treatment.

Restaurant oil and grease management in Hong Kong

Abstract

Oil and grease (O&G) in wastewater can be considered as two parts or proportion contained in emulsion which exceeded O&G standard. Most of oil becomes emulsified with water when they pass through grease trap and discharged in the effluents. Thus, it may indicate that either treatment of grease traps or standards for O&G content stipulated in technical memorandum of Water Pollution Control Ordinance (WPCO) do not reflect the actual situation. Existing grease traps should be upgraded to meet the requirements of WPCO. Alternative technologies need to be developed to tackle this unsolved problem. Good management and practices are also important to ensure proper collection and waste recycling rather than just disposing effluent into drains. Collected O&G content can be recycled as valuable products such as biofuel, flotation agent, or other derivatives. This approach not only protects the environment by improving water quality, it also encourages large flow restaurant operators to recycle oil and grease content towards cleaner production.

Characterization of As-polluted soils by laboratory X-ray-based techniques coupled with sequential extractions and electron microscopy: the case of Crocette gold mine in the Monte Rosa mining district (Italy)

Abstract

Arsenic concentration and distribution were studied by combining laboratory X-ray-based techniques (wavelength dispersive X-ray fluorescence (WDXRF), micro X-ray fluorescence (μXRF), and X-ray powder diffraction (XRPD)), field emission scanning electron microscopy equipped with microanalysis (FE-SEM-EDX), and sequential extraction procedure (SEP) coupled to total reflection X-ray fluorescence (TXRF) analysis. This approach was applied to three contaminated soils and one mine tailing collected near the gold extraction plant at the Crocette gold mine (Macugnaga, VB) in the Monte Rosa mining district (Piedmont, Italy). Arsenic (As) concentration, measured with WDXRF, ranged from 145 to 40,200 mg/kg. XRPD analysis evidenced the presence of jarosite and the absence of any As-bearing mineral, suggesting a high weathering grade and strong oxidative conditions. However, small domains of Fe arsenate were identified by combining μXRF with FE-SEM-EDX. SEP results revealed that As was mainly associated to amorphous Fe oxides/hydroxides or hydroxysulfates (50–80%) and the combination of XRPD and FE-SEM-EDX suggested that this phase could be attributed to schwertmannite. On the basis of the reported results, As is scarcely mobile, even if a consistent As fraction (1–3 g As/kg of soil) is still potentially mobilizable. In general, the proposed combination of laboratory X-ray techniques could be successfully employed to unravel environmental issues related to metal(loid) pollution in soil and sediments.

Topical Application of Photofrin® for Photodynamic Diagnosis of Malignant Cutaneous Neoplasms

The prognosis of patients suffering from malignant cutaneous neoplasms can be improved by early diagnosis. Exact demarcation of tumor margins could contribute to optimum results in surgical excision and reconstruction. The purpose of our study is to evaluate Photofrin® with a new diagnostic procedure, photodynamic diagnosis (PDD), for the detection of Bowen's disease (squamous cell carcinoma in situ), squamous cell carcinoma (SCC), and basal cell carcinoma (BCC).

Clindamycin anaphylaxis confirmed by in vivo and in vitro testing

Publication date: Available online 22 June 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Didier G. Ebo, Christel Mertens, Marissa Braes, Isabel Mennes, Chris H. Bridts, Vito Sabato

Trimethoprim-sulfamethoxazole induces acute pancreatitis associated with drug-specific cytotoxic T lymphocytes

Publication date: Available online 22 June 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Minyoung Jung, Jihyun Kim, Ji Young Lee, Minji Kim, Seung-Hyun Kim, Kangmo Ahn

Control of the incorporation and release of guest molecules by photodimerization in liposomes

Publication date: Available online 23 June 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Ryo Shimokawa, Masafumi Ueda, Kouta Sugikawa, Atsushi Ikeda
In a drug-delivery system using liposomes, the use of guest molecules bearing hydrophilic moieties results in some leakage from lipid membranes. We suppressed the leakage of coumarins (used as model guest molecules in a drug-delivery system) from lipid membranes by photodimerization at 365 nm. The reason for this phenomenon could be ascribed to an increase in the hydrophobicity of the dimers of the coumarins. The formation of the dimers was detected by ¹H NMR, UV–vis absorption, and mass spectra and the leakage percentages of the coumarins were determined by ¹H NMR spectra based on the peak intensities. In contrast, when the dimer reverted to a monomer by ultraviolet (254 nm) irradiation, the resulting monomer was released from liposomes.

Graphical abstract

Detecting urine metabolites related to training performance in swimming athletes by means of Raman spectroscopy and principal component analysis

Publication date: Available online 22 June 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Letícia Parada Moreira, Landulfo Silveira, Marcos Tadeu Tavares Pacheco, Alexandre Galvão da Silva, Debora Dias Ferraretto Moura Rocco
Raman spectroscopy (RS) is a vibrational technique that is suitable for performing biochemical analyses in human tissues and fluids. This work has investigated the identification of biochemical markers due to physical performance in the urine of swimming athletes. This was achieved by means of the Raman features that were found before and after the swimming training compared to the sedentary control subjects. These particular biochemical marker identifications refer to and infer the physiological status of individuals. The urine samples (single stream) were collected before and after the training (velocity, middle distance and distance) of professional swimmers, as well as from sedentary subjects (control). The urine samples were submitted to RS (830 nm excitation, 350 mW, 400–1800 cm⁻¹ spectral range, 2 cm⁻¹ resolution) and the spectra after the training were compared to the spectra before training, and subsequently, to the control subjects. The principal component analysis (PCA) was employed in order to identify the biochemicals that were responsible for the spectral differences. The Raman features of the urine samples after training showed peaks that were related to common urine metabolites, such as urea and creatinine. PCA analysis also revealed Raman features that were attributed to other metabolites, such as creatine, ketone bodies, phosphate and nitrogenous compounds in the swimmers after training. RS was a rapid and reliable technique for the evaluation of urine metabolites that were related to the physical performance of high-level swimmers, which then allowed for an accurate assessment and a control of their physiological efficiencies.

Graphical abstract

Identification of differentially expressed proteins in Ostrinia furnacalis adults after exposure to ultraviolet A

Abstract

Ultraviolet A (UVA), the major component of solar UV irradiation, is an important environmental factor inducing damage to insects including cell death, photoreceptor damage, and oxidative stress. In order to improve understanding of the adaptation mechanisms of insect after UVA exposure, a comparative proteomic analysis was carried out to reveal differential protein expression in Ostrinia furnacalis. Three-day-old adults were treated with UVA for 1 h. Total proteins of control and UVA-treated insects were examined using two-dimensional electrophoresis (2-DE). 2-DE analysis demonstrated that 19 proteins were increased and 18 proteins were decreased significantly in O. furnacalis after UVA exposure, respectively. Thirty differentially expressed proteins were successfully identified by mass spectrometry. The identified proteins were involved in diverse biological processes, such as signal transduction, transport processing, cellular stress, metabolisms, and cytoskeleton organization. Our results reveal that the response patterns of O. furnacalis to UVA irradiation are complex and provide novel insights into the adaptation response to UVA irradiation stress.

Evolution in the dark: unifying our understanding of eye loss

Abstract

The evolution of eye loss in subterranean, deep sea and nocturnal habitats has fascinated biologists since Darwin wrestled with it in On the Origin of Species. This phenomenon appears consistently throughout the animal kingdom, in groups as diverse as crustaceans, salamanders, gastropods, spiders and the well-known Mexican cave fish, but the nature, extent and evolutionary processes behind eye loss remain elusive. With the advantage of new imaging, molecular, and developmental tools, eye loss has once again become the subject of intense research focus. To advance our understanding of eye loss as a taxonomically widespread and repeated evolutionary trajectory, we organized a cross-disciplinary group of researchers working on the historic question, 'how does eye loss evolve in the dark?'. The resulting set of papers showcase new progress made in understanding eye loss from the diverse fields of molecular biology, phylogenetics, development, comparative anatomy, paleontology, ecology and behaviour in a wide range of study organisms and habitats. Through the integration of these approaches, methods and results, common themes begin to emerge across the field. For the first time, we hope researchers can exploit this new synthesis to identify the broader challenges and key evolutionary questions surrounding eye evolution and so-called regressive evolution and collectively work to address them in future research.

Dim light at night: physiological effects and ecological consequences for infectious disease

Abstract

Light pollution has emerged as a pervasive component of land development over the past century. Several detrimental impacts of this anthropogenic influence have been identified in night shift workers, laboratory rodents, and a plethora of wildlife species. Circadian, or daily, patterns are interrupted by the presence of light at night and have the capacity to alter rhythmic physiological or behavioral characteristics. Indeed, biorhythm disruption can lead to metabolic, reproductive, and immunological dysfunction depending on the intensity, timing, duration and wavelength of light exposure. Light pollution, in many forms and by many pathways, is thus apt to affect the nature of host-pathogen interactions. However, no research has yet investigated this possibility. The goal of this manuscript is to outline how dim light at night (dLAN), a relevant and common form of light pollution, may affect disease dynamics by interrupting circadian rhythms and regulation of immune responses as well as opportunities for host-parasite interactions and subsequent transmission risk including spillover into humans. We close by proposing some promising interventions including alternative lighting methods or vector control efforts.

Science in the Public Eye: Leveraging Partnerships—An Introduction

Abstract

With stories of struggle and dramatic breakthroughs, science has incredible potential to interest the public. However, as the rhetoric of outrage surrounds controversies over science policy there is an urgent need for credible, trusted voices that frame science issues in a way that resonates with a diverse public. A network of informal educators, park rangers, museum docents and designers, and zoo and aquarium interpreters are prepared to do so during millions of visits a year; just where science stories are most meaningfully told—in the places where members of the public are open to learning. Scientific researchers can benefit from partnerships with these intermediaries who are accorded status for their trustworthiness and good will, who have expertise in translating the science using language, metaphors, encounters, and experiences that are appropriate for non-experts. In this volume, we describe and probe examples wherein scientists work productively with informal educators and designers, artists, staff of federal agencies, citizen scientists, and volunteers who bring science into the public eye.

Risques de conjonctivite avec le dupilumab (Dupixent®)

Publication date: Available online 22 June 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Schmutz

Degradation of nitrobenzene wastewater in an acidic environment by Ti(IV)/H 2 O 2 /O 3 in a rotating packed bed

Abstract

The rotating packed bed (RPB) as a continuous flow reactor performs very well in degradation of nitrobenzene wastewater. In this study, acidic nitrobenzene wastewater was degraded using ozone (O₃) combined with hydrogen peroxide and titanium ions (Ti(IV)/H₂O₂/O₃) or using only H₂O₂/O₃ in a RPB. The degradation efficiency of nitrobenzene by Ti(IV)/H₂O₂/O₃ is roughly 16.84% higher than that by H₂O₂/O₃, and it reaches as high as 94.64% in 30 min at a H₂O₂/O₃ molar ratio of 0.48. It is also found that the degradation efficiency of nitrobenzene is significantly affected by the high gravity factor, H₂O₂/O₃ molar ratio, and Ti(IV) concentration, and it reaches a maximum at a high gravity factor of 40, a Ti(IV) concentration of 0.50 mmol/L, a pH of 4.0, a H₂O₂/O₃ molar ratio of 0.48, a liquid flow rate of 120 L/h, and an initial nitrobenzene concentration of 1.22 mmol/L. Both direct ozonation and indirect ozonation are involved in the reaction of O₃ with organic pollutants. The indirect ozonation due to the addition of different amounts of tert-butanol (·OH scavenger) in the system accounts for 84.31% of the degradation efficiency of nitrobenzene, indicating that the nitrobenzene is dominantly oxidized by ·OH generated in the RPB-Ti(IV)/H₂O₂/O₃ process. Furthermore, the possible oxidative degradation mechanisms are also proposed to better understand the role of RPB in the removal of pollutants.

Graphical abstract

ᅟ

Identification of Genomic and Molecular Traits that Present Therapeutic Vulnerability to HGF-targeted therapy in Glioblastoma

Abstract

Background

Cancer is a complex disease with profound genomic alterations and extensive heterogeneity. Recent studies on a large-scale genomics have shed lights on the impact of core oncogenic pathways which are frequently dysregulated in a wide spectrum of cancer types. Aberrant activation of hepatocyte growth factor (HGF) signaling axis has been associated with promoting various oncogenic programs during tumor initiation, progression, and treatment resistance. As a result, HGF-targeted therapy has emerged as an attractive therapeutic approach. However, recent clinical trials involving HGF-targeted therapies have demonstrated rather disappointing results. Thus, an alternative, in-depth assessment of new patient stratification is necessary to shift the current clinical course.

Methods

To address such challenges, we have evaluated therapeutic efficacy of YYB-101, a HGF neutralizing antibody, in a series of primary glioblastoma stem cells (GSCs) both in vitro and in vivo. Furthermore, we performed genome and transcriptome analysis to determine genetic and molecular traits that exhibit vulnerability to HGF-mediated therapy.

Results

We have identified differentially expressed genes, including MET, KDR, and SOX3 which are associated with tumor invasiveness, malignancy, and unfavorable prognosis in glioblastoma patients. We also demonstrated HGF-MET signaling axis as a key molecular determinant in GSC invasion and also discovered that a significant association in HGF expression existed between mesenchymal phenotype and immune cell recruitment.

Conclusions

Up-regulation of MET and mesenchymal cellular state are essential in generating HGF-mediated therapeutic responses. Our results provide an important framework for evaluating HGF-targeted therapy in future clinical settings.

Selenium in Graves Hyperthyroidism and Orbitopathy

Purpose: To review the in vitro and in vivo studies supporting a role of selenium for the treatment of mild Graves orbitopathy. Methods: Review of the current literature on the role of selenium in the management of Graves orbitopathy. Results: Graves orbitopathy (GO) is a disfiguring and disabling disorder usually observed in patients with Graves hyperthyroidism, and more rarely in patients with hypothyroid autoimmune thyroiditis or in the absence of overt thyroid dysfunction. Noninvasive treatments include intravenous glucocorticoids and orbital radiotherapy and are generally offered to patients with moderately severe GO. In contrast, patients with mild GO are generally treated only with local measures. Thus, the benefits of intravenous glucocorticoids in mild GO are limited and do not justify the risks that the treatment carries. However, a medical treatment for mild GO is heavily wanted, as a relevant proportion of patients have a significant decrease in their quality of life, and GO can progress into more severe forms. Because of the role of oxidative stress in the pathogenesis of GO, an antioxidant approach has been proposed and the antioxidant agent selenium has been shown to be effective for GO. Conclusion: Studies have shown that a 6-month course of sodium selenite can improve the course of mild GO and prevent deterioration when compared with placebo. Accepted for publication March 19, 2018. Claudio Marcocci received research grants from IBSA Italia and is consultant/speaker for Abogen Pharma and SHIRE. All other authors have no conflicts of interest. Address correspondence and reprint requests to Claudio Marcocci, M.D., Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy. E-mail: claudio.marcocci@med.unipi.it © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.