Scope of practice of oculofacial plastic and reconstructive surgeons: a public perception survey.

PURPOSE: The purpose of this study is to determine the public's perception of the scope of practice for oculofacial plastic and reconstructive surgeons (OFPRS). METHODS: A 49-question survey was distributed by QualtricsⓇ to a panel similar to the US demographic composition. Responses collected underwent bivariate statistical analysis. RESULT: A total of 530 responses were obtained, with most respondents being white, female, over the age of 35, from the Midwest, and with at least a college education or above. Most respondents did not think ophthalmologists or optometrists were surgeons, and only 158 people (29.8%) knew the primary specialty of OFPRS was ophthalmology. Board certification was preferred by 98.87% of respondents, and 95.28% preferred ASOPRS-trained OFPRS. CONCLUSIONS: Our study highlights the gap in knowledge about OFPRS as a field, the qualifications and training required, and the scope of practice. Notably, even for OFPRS-specific procedures, PRS remained the leading subspecialist chosen for interventions such as orbital decompression (58.5% vs. 71.5%), orbital reconstruction (57.9% vs. 74.2%), enucleation/evisceration (48.1% vs. 53.4%), optic nerve-related surgery (39.8% vs. 43.4%), orbital cancer resection (42.8% vs. 46.8%), and tear duct surgery (41.9% vs. 52.5%). Additionally, most respondents did not feel that facial fillers, laser skin resurfacing, eyelid cancer removal, or cataract surgery were within the OFPRS scope of practice.

Psychosocial outcomes and quality of life among school-age survivors of retinoblastoma.

BACKGROUND: Retinoblastoma is the most common intraocular childhood cancer and is typically diagnosed in young children. With increasing number of survivors and improved medical outcomes, long-term psychosocial impacts need to be explored. Thus, the current study sought to assess functioning in school-aged survivors of retinoblastoma. PROCEDURE: Sixty-nine survivors of retinoblastoma underwent a one-time evaluation of psychosocial functioning. Survivors (Mage = 10.89 years, SD = 1.07 years; 49.3% male; 56.5% unilateral disease) and parents completed measures of quality of life (QoL; PedsQL) and emotional, behavioral, and social functioning (PROMIS [patient-reported outcome measurement information system] Pediatric Profile, BASC-2 parent report). Demographic and medical variables were also obtained. RESULTS: On the whole, both survivors and caregivers indicated QoL and behavioral and emotional health within the typical range of functioning. Survivors reported better physical QoL compared to both parent report and a national healthy comparison sample, whereas caregivers reported that survivors experienced lower social, school, and physical QoL than a healthy comparison. Regarding behavioral and emotional health, survivors indicated more anxiety than a nationally representative sample. Parents of female survivors endorsed lower adaptive scores than parents of male survivors. CONCLUSIONS: Results indicated that survivors of retinoblastoma reported QoL and behavioral and emotional health within normal limits, although parents appear to perceive greater impairment across several assessed domains. Understanding both survivor and parent reports remains important for this population. Future research should explore psychosocial functioning of these survivors as they transition to adolescence and early adulthood, given the increased independence and behavioral and emotional concerns during these developmental periods.

Metastasis of Conjunctival Melanoma to the Cardiac Atrium: A Case Report.

The authors present an unreported case of malignant conjunctival melanoma with metastasis to the right cardiac atrium. A 67-year-old woman with history of conjunctival melanoma of the OS presented with asymptomatic recurrence with new extension to the fornix. Surgical management was planned; however, the patient was admitted to the hospital with symptoms of heart and respiratory failure. She was found to have a large mass in the right atrium. The mass was resected and was found to be metastatic conjunctival melanoma. The patient received chemotherapy and her symptoms have improved. This case highlights the high recurrence rate of conjunctival melanoma and the importance of tumor surveillance.

Longitudinal Comparison of Orbital Volumes from Enucleated Eyes with Hydroxyapatite Orbital Implant in Unilateral Retinoblastoma Patients.

PURPOSE: To compare the orbital volume between enucleated and contralateral, uninvolved orbits over a 5-year period in patients with unilateral retinoblastoma who underwent enucleation with hydroxyapatite (HA) implant placement by a single surgeon. METHODS: A retrospective review was performed on the clinical records and radiographic images of unilateral retinoblastoma patients who underwent enucleation with primary HA implantation from 2003 to 2020 at a single institution. Bilateral orbital volume measurements were taken from the initial postoperative MRI scan and again at 1- and 5-years postenucleation. The main outcome measure was the longitudinal change in volume difference (∆𝑉). The implant size, age at enucleation, and sex were also evaluated. A linear mixed-effect model was used for analysis. RESULTS: A total of 124 patients (73 males) with HA implants following enucleation were included. Overall, the unaffected orbit trended toward having a greater volume compared with the enucleated orbit, but this was not statistically significant (ß = 0.003; p = 0.122). The mean age at enucleation was 2.4 years. The median time between enucleation and the initial, 1-year, and 5-year postoperative MRIs was 6 months, 17 months, and 55 months, respectively. There was no statistical correlation between age at enucleation, gender, implant size, or orbital volume at any time points (p > 0.05). CONCLUSIONS: Patients treated with enucleation and primary HA implant placement for unilateral retinoblastoma did not display significant asymmetry in orbital volume on 5-year postenucleation MRIs, suggesting that HA implants promote orbital growth comparable to a nonenucleated orbit in the pediatric population.

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma: A Multicenter, International Data-Sharing American Joint Committee on Cancer Study.

PURPOSE: To determine the value of clinical features for advanced intraocular retinoblastoma as defined by the eighth edition of the American Joint Committee on Cancer (AJCC) cT3 category and AJCC Ophthalmic Oncology Task Force (OOTF) Size Groups to predict the high-risk pathologic features. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Eighteen ophthalmic oncology centers from 13 countries over 6 continents shared evaluations of 942 eyes enucleated as primary treatment for AJCC cT3 and, for comparison, cT2 retinoblastoma. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between 2001 and 2013. High-risk pathologic features were defined as AJCC categories pT3 and pT4. In addition, AJCC OOTF Size Groups were defined as follows: (1) less than half, (2) more than half but less than two thirds, (3) more than two thirds of globe volume involved, and (4) diffuse infiltrating retinoblastoma. MAIN OUTCOME MEASURES: Statistical risk of high-risk pathologic features corresponding to AJCC cT3 subcategories and AJCC OOTF Size Groups. RESULTS: Of 942 retinoblastoma eyes treated by primary enucleation, 282 (30%) showed high-risk pathologic features. Both cT subcategories and AJCC OOTF Size Groups (P < 0.001 for both) were associated with high-risk pathologic features. On logistic regression analysis, cT3c (iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis) were predictive factors for high-risk pathologic features when compared with cT2a with an odds ratio of 2.3 (P = 0.002), 2.5 (P = 0.002), and 3.3 (P = 0.019), respectively. Size Group 3 (more than two-thirds globe volume) and 4 (diffuse infiltrative retinoblastoma) were the best predictive factors with an odds ratio of 3.3 and 4.1 (P < 0.001 for both), respectively, for high-risk pathologic features when compared with Size Groups 1 (i.e., < 50% of globe volume). CONCLUSIONS: The AJCC retinoblastoma staging clinical cT3c-e subcategories (glaucoma, intraocular hemorrhage, and aseptic orbital cellulitis, respectively) as well as the AJCC OOTF Size Groups 3 (tumor more than two thirds of globe volume) and 4 (diffuse infiltrative retinoblastoma) both allowed stratification of clinical risk factors that can be used to predict the presence of high-risk pathologic features and thus facilitate treatment decisions.

Transcutaneous CO2 monitoring as indication for inpatient non-invasive ventilation initiation in patients with amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by profound muscle weakness, including diaphragmatic weakness resulting in hypercapnic respiratory failure. While non-invasive ventilation (NIV) is usually initiated in the home, patients presenting with hypercapnic respiratory failure may be at high risk of adverse outcomes with delays in treatment. We aim to describe the clinical utility of transcutaneous CO2 (TCO2 ) to assess the need for inpatient initiation of NIV. METHODS: Eight patients from the University of Michigan Pranger ALS clinic were directly admitted to the hospital for urgent initiation of NIV between May 2020-May 2021. A retrospective review of electronic medical records, including pre-hospital pulmonary function assessments, hospitalization blood gases, and NIV use metrics was performed. RESULTS: All eight patients had symptoms of respiratory insufficiency at time of admission, although not all patients had forced vital capacity (FVC) measurements that would identify need for NIV. All patients had measured TCO2 > 45 mmHg. Seven of eight patients had worsening hypercapnia after admission, indicating advanced respiratory failure. All patients were titrated to tolerance of continuous nocturnal NIV while in the hospital, with an average length of stay of 6.5 days (range, 3-8). All patients demonstrated compliance with NIV, >4 h, at post-hospital follow-up. DISCUSSION: Many current ambulatory measurements underestimate, or incompletely evaluate, respiratory dysfunction, and arterial blood gases are not typically readily available. Outpatient TCO2 measurements can serve as a useful screening tool to identify ALS patients who would benefit from inpatient initiation and titration of NIV.

Light Therapy for QoL/Depression in AYA With Cancer: A Randomized Trial.

OBJECTIVE: Secondary outcomes from a published feasibility and acceptability trial were examined to explore the effect of bright white light (BWL) on quality of life (QoL) and depressive symptoms compared to dim red light (DRL) control in adolescents and young adults (AYAs) receiving cancer-directed therapy. METHODS: Fifty-one AYAs (12-22 years, 51% male) newly diagnosed with cancer were randomized to receive 8 weeks of BWL (n = 26) or DRL (n = 25). The CDI-2 (total score, negative mood/physical symptoms, interpersonal problems, ineffectiveness, and negative self-esteem) and parent- and self-report PedsQL (total score and subscales of physical, emotional, social, and school QoL) were completed at multiple timepoints. RESULTS: BWL produced improvements in self-reported total depression (d = -.64; 95% confidence interval [CI] = -1.26, -0.01), negative self-esteem (d = -.80; 95% CI = -1.43, -.14), negative mood/physical symptoms (d = -.73; 95% CI = -1.36, -0.08), ineffectiveness (d = -.43; 95% CI = -1.04, .19), total self-reported QoL (d = .41; 95% CI = -.16, .96), emotional (d = .78; 95% CI = .19, 1.37), school functioning (d = .48; 95% CI = -.09, 1.04), and parent-reported school functioning (d = .66; 95% CI = 0.02, 1.33). BWL reported a greater rate of improvement than DRL for total depression (ß = .49, p < .05) and self-esteem (ß = .44, p < .05), and parent-reported school functioning (ß = -1.68, p < .05). CONCLUSIONS: BWL improved QoL and depressive symptoms for AYAs with cancer. These findings will inform larger randomized controlled trials.

Long-acting opioid prescribing patterns of ophthalmic plastic surgeons in the medicare Part D database.

PURPOSE: To assess extended release/long acting (ER/LA) opioid prescribing patterns among ophthalmic plastic surgeons in the Centers for Medicare and Medicaid Services (CMS) Part D database. METHODS: A retrospective observational cohort study was conducted on oculoplastic surgeons in the CMS Part D database who prescribed ER/LA opioids from 2013 to 2017. American Society of Ophthalmic Plastics and Reconstructive Surgery (ASOPRS) and non-ASOPRS surgeons were analyzed as groups. Prescribers were also analyzed based on gender and practice experience. RESULTS: Oculoplastic surgeons (64 ASOPRS and 78 non-ASOPRS) were responsible for 1,177 ER/LA opioid prescriptions from 2013 to 2017. ASOPRS members accounted for 4.6% and non-ASOPRS members accounted for 7.5% of all ER/LA opioids prescribed by ophthalmologists over the study period (p= .02). The total number of ASOPRS and non-ASOPRS members prescribing ER/LA opioids decreased by 52% (p= .10) and 58% (p= .07) from 2013 to 2017 respectively. CONCLUSION: ER/LA opioids are indicated for treatment of chronic pain and may be appropriately prescribed by the oculoplastic surgeon in certain circumstances, however due to the higher risk of overdose injury, those circumstances must be defined and justified. While a relatively small number of oculoplastic surgeons (10.6% ASOPRS and 19.6% non-ASOPRS) prescribed ER/LA opioids from 2013 to 2017, non-ASOPRS oculoplastic surgeons wrote 23.5% more ER/LA opioid prescriptions over the study period. Over the 5-year study period there was a general decline in the prescribing of ER/LA opioids by oculoplastic surgeons. Reviewing the prescribing practices of oculoplastic specialists, regardless of professional affiliation, is necessary to understand the role of ER/LA opioids for all of ophthalmology.

Global Retinoblastoma Treatment Outcomes: Association with National Income Level.

PURPOSE: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. METHODS: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. MAIN OUTCOME MEASURES: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). RESULTS: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001). CONCLUSIONS: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.

Chemoreduction with topotecan and vincristine: Quantifying tumor response in bilateral retinoblastoma patients.

BACKGROUND: Evaluate the efficacy of two courses of vincristine and topotecan (VT) neoadjuvant intravenous chemotherapy in reducing retinoblastoma tumor volumes. METHODS: Twenty-seven patients with previously untreated, bilateral advanced retinoblastoma who were enrolled on a prospective treatment protocol (NCT00186888). Patients underwent high-resolution ophthalmic imaging at diagnosis and were reimaged following treatment with two cycles of VT. Tumor height and diameter were measured before and after treatment, and tumor volumes were calculated. Statistical methods for dependent samples were used. RESULTS: Imaging was completed for 75 tumors in 23 patients (43 eyes). After two cycles of VT, median decrease in tumor height was 47% and median decrease in tumor diameter was 22%. Median decrease in estimated tumor volume was 74%. Sixty-one of 75 tumors demonstrated >50% reduction in tumor volume. Distance from the optic nerve (=0 vs >0), age (<4 vs >4 months), macular location (within vs outside), and time (pre- and posttreatment) were found significantly associated with log-transformed tumor volume adjusting for the repeated effect of patient eye using generalized estimating equations to estimate the parameters of a generalized linear model (P < .0001 [ ß : 1.95, CI: 1.53-2.36], P = .0031 [ ß : 1.49, CI: 0.57-2.41], P < .0001 [ ß : .94, CI: 0.54-1.35], and P < .0001 [ ß : 1.43, CI: 1.15-1.71]). CONCLUSION: Chemoreduction was achieved in all patients and most retinoblastoma tumors following two cycles of VT. Reduction in tumor dimensions was comparable to that reported with platinum-based chemotherapy. Tumor location, distance from the optic nerve, and age at diagnosis were significant predictors of treatment response.

Response criteria for intraocular retinoblastoma: RB-RECIST.

Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid Tumors (RECIST) provide radiological standards for assessment of solid tumors. However, no such guidelines exist for the evaluation of intraocular cancer, and ocular oncology clinical trials have largely relied on indirect measures of therapeutic response-such as progression-free survival-to evaluate the efficacy of treatment agents. Herein, we propose specific criteria for evaluating treatment response of retinoblastoma, the most common pediatric intraocular cancer, and emphasize a multimodal imaging approach for comprehensive assessment of retinoblastoma tumors in clinical trials.

Noninvasive ventilation: An important option in the management of hemidiaphragm paralysis.

Hemidiaphragm paralysis (HP) is a potential complication of cardiac surgery. While most patients are either asymptomatic or have mild symptoms, some are at risk of developing life-threatening hypercapnia. We present a case of a patient who developed HP after tricuspid valve replacement. Diaphragm plication was deferred due to underlying comorbidities, but over time she developed severe hypercapnic respiratory failure requiring intensive care unit admission. Chronic noninvasive ventilation therapy (NIV) was initiated, which improved her symptoms and hypercapnia and prevented further hospitalizations. For patients with iatrogenic HP unable to undergo diaphragm plication, Pulmonology referral for initiation of NIV should be strongly considered.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part I: Metastasis-Associated Mortality.

PURPOSE: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. MAIN OUTCOME MEASURES: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. RESULTS: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P < 0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P < 0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease. CONCLUSIONS: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part II: Treatment Success and Globe Salvage.

PURPOSE: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. MAIN OUTCOME MEASURES: Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). RESULTS: Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001). CONCLUSIONS: Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

Acute kidney injury is common with intravenous abuse of extended-release oral oxymorphone and delayed renal recovery rates are associated with increased KDIGO staging.

AIM: Prescription opioid abuse poses a serious problem in the United States, representing 615 per 100 000 deaths annually. Extended-release oxymorphone (Opana-ER) is an oral opioid pain medication that has recently been found to cause thrombotic microangiopathy when intravenously abused. In this retrospective study, we attempted to determine the prevalence and outcomes of acute kidney injury (AKI) among patients intravenously abusing extended-release oral oxymorphone. METHODS: A query of electronic medical records for 'drug abuse' at an academic medical centre during January 2012 to December 2015 was performed and yielded 2350 patients. Patients were further identified by documented intravenous abuse of extended-release oxymorphone. Patients were stratified based on multiple renal indices and outcomes. Potential confounders were also identified. RESULTS: One hundred and sixty-five patients were found to have a documented history of intravenous abuse of extended-release oral oxymorphone. Prevalence of AKI in this population was a 47.8%. KDIGO stage-I patients consisted of 17.8% of patients with AKI, 40.5% were classified as KDIGO stage-II AKI, and 41.8% were classified as KDIGO stage-III AKI. Among patients with AKI, average age was found to be 37.5 years, 59.4% experienced renal recovery, 56.9% required intensive care unit admission, 13.9% progressed to end-stage renal disease (ESRD), and 7.6% expired during admission. CONCLUSION: Clinicians should be educated to help recognize intravenous abuse of extended-release oral oxymorphone and its associated effects. Our data suggests AKI is common in these patients; higher KDIGO staging appears to be associated with slower rates of renal recovery, increased comorbidities and progression to both CKD and ESRD.

Inhibition of MMP-2 and MMP-9 decreases cellular migration, and angiogenesis in in vitro models of retinoblastoma.

BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis. Two such targets are matrix metalloproteinases-2 and -9 (MMP-2, -9), which degrade extracellular matrix as a prerequisite for cellular invasion and have been shown to be involved in other types of cancer metastasis. Cancer Clinical Trials with an anti-MMP-9 therapeutic antibody were recently initiated, prompting us to investigate the role of MMP-2, -9 in Rb metastasis. METHODS: We compare MMP-2, -9 activity in two well-studied Rb cell lines: Y79, which exhibits high metastatic potential and Weri-1, which has low metastatic potential. The effects of inhibitors of MMP-2 (ARP100) and MMP-9 (AG-L-66085) on migration, angiogenesis, and production of immunomodulatory cytokines were determined in both cell lines using qPCR, and ELISA. Cellular migration and potential for invasion were evaluated by the classic wound-healing assay and a Boyden Chamber assay. RESULTS: Our results showed that both inhibitors had differential effects on the two cell lines, significantly reducing migration in the metastatic Y79 cell line and greatly affecting the viability of Weri-1 cells. The MMP-9 inhibitor (MMP9I) AG-L-66085, diminished the Y79 angiogenic response. In Weri-1 cells, VEGF was significantly reduced and cell viability was decreased by both MMP-2 and MMP-9 inhibitors. Furthermore, inhibition of MMP-2 significantly reduced secretion of TGF-ß1 in both Rb models. CONCLUSIONS: Collectively, our data indicates MMP-2 and MMP-9 drive metastatic pathways, including migration, viability and secretion of angiogenic factors in Rb cells. These two subtypes of matrix metalloproteinases represent new potential candidates for targeted anti-metastatic therapy for Rb.

A longitudinal investigation of parenting stress in caregivers of children with retinoblastoma.

BACKGROUND: Retinoblastoma is typically diagnosed in young children and may present unique parenting challenges. Qualitative research suggests that parents experience distress related to the initial diagnosis and treatment that subsequently resolves. The objectives were to systematically assess parenting stress over time in parents of young children with retinoblastoma and to examine associations between parenting stress and child outcomes. PROCEDURES: Parents of children with retinoblastoma completed the Parenting Stress Index (PSI) during serial psychological assessments scheduled based on the child's age (6 months to 5 years). Caregivers of 92 patients (85.9% mothers) completed the assessments. Child outcomes included developmental functioning and parent-reported adaptive functioning. RESULTS: At baseline and age 5, all subscales on the PSI were within normal limits, and most were significantly below normative means (i.e., demonstrating low levels of stress). All domains remained relatively stable over time. Associations between parenting stress and child outcomes were much stronger at age 5 than at baseline. Child-directed parenting stress was a small but significant contributor to declines in child functioning over time. CONCLUSIONS: Parents of children with retinoblastoma report normal levels of parenting stress while their children are young. However, baseline parenting stress appears to contribute to changes in child functioning over time. Future studies should assess illness-related aspects of adjustment to further understand the parenting experience of young children with cancer and/or having a visually impaired child.

Analysis of Intensive Care Unit Admission and Sequelae in Patients Intravenously Abusing Extended-Release Oral Oxymorphone.

OBJECTIVES: Prescription drug abuse is a major public health problem in the United States, with the rate of opioid-related deaths nearly quadrupling between 2000 and 2014. Extended-release oral oxymorphone hydrochloride (Opana ER) is a long-acting opioid prescribed for chronic pain; however, it also has the potential to be abused via intravenous injection. This retrospective review sought to analyze specific complications and sequelae requiring intensive care unit resources for patients intravenously abusing extended-release oral oxymorphone. METHODS: We retrospectively reviewed the medical records of patients identified for drug abuse between January 2012 and December 2015, identifying patients who intravenously abused extended-release oral oxymorphone. Medical charts were reviewed to identify associated sequelae and patients requiring an intensive care unit level of care. RESULTS: We identified 53 patients who required treatment in an intensive care unit setting as a consequence of intravenously abusing extended-release oral oxymorphone. Twenty-eight patients (52.8%) required endotracheal intubation with mechanical ventilation for either acute hypoxic respiratory failure or protection of airway. Acute kidney injury developed in 48 patients (90.6%); 28.3% of these patients failed to regain renal function and required renal replacement therapy. Bacteremia was diagnosed in 36 patients (67.9%) and 30 patients (56.6%) were diagnosed as having acute infective bacterial endocarditis. CONCLUSIONS: Our patients demonstrated a great need for critical care resources and severe sequelae related to intravenous drug abuse. Clinicians should be vigilant for the possibility for clinical decompensation when initially evaluating patients reporting intravenous abuse of extended-release oral oxymorphone.

Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy-related toxicities.

BACKGROUND: A total of 5-10% of patients with retinoblastoma (RB) harbor deletion of the long arm (q) chromosome 13 (13q-). The treatment-related toxicities in this population have not been described. METHODS: Sixty-eight RB patients on a single institutional protocol (RET5) from 2005 to 2010 were reviewed. Genetic screening identified 11 patients (seven female) with 13q-. Patients with early (Reese-Ellsworth [R-E] group I-III) disease (6/23 with 13q-) received eight courses of vincristine/carboplatin (VC). Patients with advanced (R-E group IV-V) bilateral disease (2/27 with 13q-) received two courses of vincristine/topotecan (VT) followed by nine courses of alternating VT/VC. Patients undergoing upfront enucleation received histopathology-based chemotherapy: intermediate risk (2/8 with 13q-) or high risk (1/10 with 13q-). Dose reductions were mandated for >7 day delay in two consecutive courses following hematologic toxicity. Grades 3 and 4 hematologic, infectious, and gastrointestinal toxicities were compared between RET5 patients with and without 13q-. RESULTS: Demographics were similar between groups. When present, prolonged neutropenia (median 7 days, range 0-14 days) delayed chemotherapy and resulted in more frequent dose reductions among 13q- patients (5/11) than non-13q- patients (4/57) (P < 0.01). GI toxicity was similar between groups (5/11 13q- vs. 13/57 non-13q-; P = 0.14), but halted chemotherapy in one 13q- patient. Infectious complications and disease outcomes were similar between groups. At follow-up, all patients are alive (median 6.1 years, range 7.6 months-9.5 years). CONCLUSIONS: 13q- RB patients had a higher incidence of neutropenia requiring chemotherapy dose reductions, but did not have increased treatment failure.