Global Retinoblastoma Study Group IMPORTANCE Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.OBJECTIVES To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. DESIGN, SETTING, AND PARTICIPANTSA total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. MAIN OUTCOMES AND MEASURESAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTSThe cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI,, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI,). CONCLUSIONS AND RELEVANCEThis study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

BackgroundSeveral kinds of cancer surgeries with propofol-based total intravenous anesthesia (TIVA) have been shown to have better outcomes than those with sevoflurane-based inhalational anesthesia (INHA). However, the effects of this anesthetic technique have not been investigated in patients with gastric cancer. In this study, the authors retrospectively examined the link between the choice of anesthetic technique and overall survival in patients undergoing gastric cancer resection.MethodsWe conducted a retrospective analysis of the database of all patients undergoing gastric cancer resection for gastric cancer between 2007 and 2012. Patients who received TIVA or INHA were administered patient-controlled intravenous analgesia for 72–120 hours postoperatively. Survival was estimated using the Kaplan–Meier log-rank test, and associations between anesthetic technique and outcomes were analyzed using Cox proportional hazards regressions after propensity matching.ResultsA total of 2,856 anesthetics using INHA or TIVA were delivered in the study period. After propensity matching, 897 patients remained in each group. According to Kaplan–Meier analysis, the use of TIVA was associated with improved survival (P<0.001). TIVA was associated with a hazard ratio (HR) of 0.67 (95% confidence interval [CI]: 0.58–0.77) for death in univariate analysis and 0.65 (95% CI: 0.56–0.75) after a multivariate analysis of known confounders in the matched group. Cancer stage (HR =0.74, 95% CI: 0.64–0.86, P<0.001) and degree of differentiation (HR =1.28, 95% CI: 1.11–1.47, P<0.001) were also associated with survival in the univariate analysis in the matched group. In the multivariable Cox model, cancer stage (HR =0.72, 95% CI: 0.62–0.84, P<0.001) and degree of differentiation (HR =1.23, 95% CI: 1.07–1.42, P<0.001) were associated with survival in the matched group.ConclusionThese results indicate that TIVA may be associated with improved survival in gastric cancer patients who undergo resection.

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Epidermal growth factor receptor (EGFR) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and correlates with poor prognosis. EGFR has been demonstrated to be associated with cancer stem cell traits in HNSCC. However, the underlying molecular mechanism is far from elucidated. Here, SOX2, one of the most important stem cell markers, was identified as a binding partner and substrate of EGFR. EGFR signaling inhibition decreases SOX2 expression by promoting its autophagic degradation. Mechanistically, EGFR activation induces SOX2 phosphorylation at the Y277 site and reduces its ubiquitination, which inhibits its association with p62 and subsequent autophagic degradation. Gefitinib, an EGFR tyrosine kinase inhibitor, shows in vitro and in vivo protective effects against oral cancer cells that can be reversed through autophagy inhibition. Our study suggests that EGFR plays an important role in the development of cancer stem cells by stabilizing SOX2.Targeting EGFR in combination with conventional chemotherapy might be a promising strategy for the treatment of HNSCC through elimination of cancer stem cells. K E Y W O R D Sautophagy, gefitinib, oral cancer, P62, stemness SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.

BACKGROUND: Propofol is a common sedative-hypnotic drug traditionally used for inducing and maintaining general anesthesia. Recent studies have drawn attention to the nonanesthetic effects of propofol, but the potential mechanism by which propofol suppresses non–small-cell lung cancer (NSCLC) progression has not been fully elucidated. METHODS: For the in vitro experiments, we used propofol (0, 2, 5, and 10 µg/mL) to treat A549 cells for 1, 4, and 12 hours and Cell Counting Kit-8 (CCK-8) to detect proliferation. Apoptosis was measured with flow cytometry. We also transfected A549 cells with an microribonucleic acid-21 (miR-21) mimic or negative control ribonucleic acid (RNA) duplex and phosphatase and tensin homolog, deleted on chromosome 10 (PTEN) small interfering ribonucleic acid (siRNA) or negative control. PTEN, phosphorylated protein kinase B (pAKT), and protein kinase B (AKT) expression were detected using Western blotting, whereas miR-21 expression was examined by real-time polymerase chain reaction (RT-PCR). In vivo, nude mice were given injections of A549 cells to grow xenograft tumors; 8 days later, the mice were intraperitoneally injected with propofol (35 mg/kg) or soybean oil. Tumors were then collected from mice and analyzed by immunohistochemistry and Western blotting. RESULTS: Propofol inhibited growth (1 hour, P = .001; 4 hours, P ≤ .0001; 12 hours, P = .0004) and miR-21 expression (P ≤ .0001) and induced apoptosis (1 hour, P = .0022; 4 hours, P = .0005; 12 hours, P ≤ .0001) in A549 cells in a time and concentration-dependent manner. MiR-21 mimic and PTEN siRNA transfection antagonized the suppressive effects of propofol on A549 cells by decreasing PTEN protein expression (mean differences [MD] [95% confidence interval {CI}], –0.51 [–0.86 to 0.16], P = .0058; MD [95% CI], 0.81 [0.07–1.55], P = .0349, respectively), resulting in an increase in pAKT levels (MD [95% CI] = –0.82 [–1.46 to –0.18], P = .0133) following propofol exposure. In vivo, propofol treatment reduced NSCLC tumor growth (MD [95% CI] = –109.47 [–167.03 to –51.91], P ≤ .0001) and promoted apoptosis (MD [95% CI] = 38.53 [11.69–65.36], P = .0093). CONCLUSIONS: Our study indicated that propofol inhibited A549 cell growth, accelerated apoptosis via the miR-21/PTEN/AKT pathway in vitro, suppressed NSCLC tumor cell growth, and promoted apoptosis in vivo. Our findings provide new implications for propofol in cancer therapy and indicate that propofol is extremely advantageous in surgical treatment.

BackgroundEpidural use can provide a better short-term outcome and protect patients from the postoperative development of tumour recurrence and metastases. In this study, we sought to assess the effects of intra- and postoperative anaesthesia and analgesia choice on outcome after gastric cancer resection, searched for evidence of interaction between intra-and postoperative epidural use and outcomes of gastric cancer patients.MethodsFour thousand two hundred and eighteen cases of gastric cancer were identified from the Records of Hospital Patients. Patients who received only general anesthesia (GA group) or epidural anesthesia combined with general anesthesia (EGA group), were administered patient-controlled intravenous or epidural analgesia for 72-120 hours postoperatively. Flatus time, length of stay in hospital, incidence of nausea and vomiting, and visual analogue scale (VAS ) scores were collected for evaluating the short-outcome of the patients. A Kaplan-Meier log-rank test was used for a univariable analysis, and Cox proportional hazards regressions were used for a multivariable analysis of the survival time in both groups.ResultsThe VAS scores and incidence of nausea and vomiting in the EGA group were lower than the GA group. There was a significant association between intra-and postoperative epidural use and improved survival.ConclusionsThese results indicated that epidural anaesthesia combined with general anaesthesia and patient-controlled epidural analgesia may be associated with the improved overall survival in gastric cancer patients who underwent resection.

The presence of Th17 cells and IL-27 is observed in a variety of inflammatory associated cancers. However, there are some data on the role of Th17 cells and IL-27 in the regulation of immune reactions in non-small-cell lung cancer (NSCLC). The aim of this study is to assess the variation of Th17 cells and IL-27 in the peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The serum concentrations of IL-27 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of RORγt and IL-27 in the peripheral blood was examined by real-time quantitative polymerase chain reaction (QPCR). Expression of IL-27 was lower in NSCLC patients compared with normal controls. The frequency of Th17 cells was increased in NSCLC patients, accompanied by the upregulation of IL-17 and RORγt. IL-27 negatively correlated with the number of Th17 cells and the RORγt mRNA. Our results indicate that IL-27 might inhibit Th17 differentiation in NSCLC patients and better understanding of the regulatory effects of IL-27 on Th17 cells may shed light on potential new targets in cancer prevention and therapy.

Atypical hemolytic uremic syndrome (HUS) is a subtype of thrombotic microangiopathy associated with complement alternative pathway dysregulation. It is clinically characterized by a relapsing course and a poor prognosis. Multiple organ systems are commonly affected by thrombotic microangiopathy in pediatric atypical HUS; however, ocular involvement is rarely reported. The case of an 11-year-old girl diagnosed as having atypical HUS who presented with bilateral central retinal vein occlusions with macular subhyaloid hemorrhage during her initial onset and ophthalmoplegia, diplopia, and optic disc edema during her relapsing episode 1 year later is described. All ocular manifestations occurred in the convalescence phase of atypical HUS. No other extrarenal complications were found and full recovery was achieved following typical treatment for atypical HUS (ie, plasma infusion, steroid, and supportive therapy). This is thought to be the first reported case of recurrent ocular involvement in pediatric atypical HUS.