Surgical Ophthalmic Oncology

Designed as an easy-to-use, practical guide to tumors of the eye, lids, and orbit, this open access book comprehensively addresses surgical treatment and management of diseases related to ophthalmic oncology. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is an ideal reference for general ophthalmologists, surgeons, fellows and trainees around the world who encounter these diseases in the care of their patients. Notably, this book includes considerations for those ophthalmologists offering subspecialty care in environments with limited access to advanced technology and instrumentation. Individual chapters address diagnostic indications, pre-operative and post-operative concerns, and provide detailed explanations of surgical techniques required to manage various eye cancer ailments with help of ample illustrations. High-quality videos included throughout the book provide readers with the opportunity to review surgical steps in real-time as a learning tool. Chapters thoroughly cover tumors of eyelid, cornea and conjunctiva, orbit as well as intraocular tumors, while later chapters discuss ophthalmic radiation therapy. The book concludes with a section on ophthalmic pathology which details essential guidelines on relevant aspects from specimen collection and transport, to interpretation of the pathology report. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is a unique and necessary valuable resource for ophthalmologists, trainees, and related medical professionals working in underserved areas in providing quality care for patients suffering from ocular cancers

Patients presenting with metastases : stage IV uveal melanoma, an international study

Objective To analyse ocular and systemic findings of patients presenting with systemic metastasis. Methods and analysis It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. Results Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. Conclusions Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.Peer reviewe

Multicenter, International Assessment of the Eighth Edition of the American Joint Committee on Cancer Cancer Staging Manual for Conjunctival Melanoma

This case series assesses whether the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual can be used to accurately estimate mortality rates of conjunctival melanoma. Key PointsQuestionCan the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for conjunctival melanoma be used to accurately estimate metastasis and mortality rates? FindingsIn this case series of 288 patients, there was a significantly higher cumulative mortality rate among patients with cT2 and cT3 conjunctival melanoma compared with those presenting with cT1 conjunctival melanoma. MeaningHigher T-staged tumors were associated with both an earlier and greater incidence of metastasis; therefore, the results from this multicenter, international registry study support the use of the eighth edition AJCC staging system for conjunctival melanoma. ImportanceEye cancer staging systems used for standardizing patient care and research need to be validated. ObjectiveTo evaluate the accuracy of the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual in estimating metastatis and mortality rates of conjunctival melanoma. Design, Setting, and ParticipantsThis international, multicenter, registry-based case series pooled data from 10 ophthalmic oncology centers from 9 countries on 4 continents. A total of 288 patients diagnosed with conjunctival melanoma from January 1, 2001, to December 31, 2013, were studied. Data analysis was performed from July 7, 2018, to September 11, 2018. InterventionsTreatments included excision biopsy, cryotherapy, topical chemotherapy, radiation therapy, enucleation, and exenteration. Main Outcomes and MeasuresMetastasis rates and 5-year and 10-year Kaplan-Meier mortality rates according to the clinical T categories and subcategories of the eighth edition of the AJCC Cancer Staging Manual. ResultsA total of 288 eyes from 288 patients (mean [SD] age, 59.7 [16.8] years; 147 [51.0%] male) with conjunctival melanoma were studied. Clinical primary tumors (cT) were staged at presentation as cT1 in 218 patients (75.7%), cT2 in 34 (11.8%), cT3 in 15 (5.2%), and cTx in 21 (7.3%). There were no T4 tumors. Pathological T categories (pT) were pTis in 43 patients (14.9%), pT1 in 169 (58.7%), pT2 in 33 (11.5%), pT3 in 12 (4.2%), and pTx in 31 (10.8%). Metastasis at presentation was seen in 5 patients (1.7%). Metastasis during follow-up developed in 24 patients (8.5%) after a median time of 4.3 years (interquartile range, 2.9-6.0 years). Of the 288 patients, 29 died (melanoma-related mortality, 10.1%) at a median time of 5.3 years (interquartile range, 1.8-7.0 years). The cumulative rates of mortality among patients with cT1 tumors were 0% at 1 year, 2.5% (95% CI, 0.7%-7.7%) at 5 years, and 15.2% (95% CI, 8.1%-27.4%) at 10 years of follow-up; among patients with cT2 tumors, 0% at 1 year, 28.6% (95% CI, 12.9%-58.4%) at 5 years, and 43.6% (95% CI, 19.6%-77.9%) at 10 years of follow-up; and among patients with cT3 tumors, 21.1% (95% CI, 8.1%-52.7%) at 1 year of follow-up and 31.6% (95% CI, 13.5%-64.9%) at 5 years of follow-up. Patients with cT2 and cT3 tumors had a significantly higher cumulative mortality rate compared with those presenting with cT1 tumors (log-rank PPeer reviewe

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. (C) 2022 by the American Academy of Ophthalmology.Peer reviewe

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% but 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 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. (C) 2022 by the American Academy of Ophthalmology.Peer reviewe

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 KaplaneMeier 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 KaplaneMeier 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. (C) 2020 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND licensePeer reviewe

Retinoblastoma seeds : impact on American Joint Committee on Cancer clinical staging

Aim To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. Methods Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. Results Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; pPeer reviewe

XTE J1946+274 = GRO J1944+26: An Enigmatic Be/X-ray Binary

XTE J1946+274 = GRO J1944+26 is a 15.8 s Be/X-ray pulsar discovered simultaneously in 1998 September with the Burst and Transient Source Experiment (BATSE) on the Compton Gamma Ray Observatory (CGRO) and the All-Sky Monitor (ASM) on the Rossi X-ray Timing Explorer (RXTE). Here we present new results from BATSE and {\em RXTE} including a pulse timing analysis, spectral analysis, and evidence for an accretion disk. Our pulse timing analysis yielded an orbital period of 169.2 days, a moderate eccentricity of 0.33, and implied a mass function of 9.7 M_sun. We observed evidence for an accretion disk, a correlation between measured spin-up rate and flux, which was fitted to obtain a distance estimate of 9.5 +/- 2.9 kpc. XTE J1946+274 remained active from 1998 September - 2001 July, undergoing 13 outbursts that were not locked in orbital phase. Comparing RXTE PCA observations from the initial bright outburst in 1998 and the last pair of outbursts in 2001, we found energy and intensity dependent pulse profile variations in both outbursts and hardening spectra with increasing intensity during the fainter 2001 outbursts. In 2001 July, optical Halpha observations indicate a density perturbation appeared in the Be disk as the X-ray outbursts ceased. We propose that the equatorial plane of the Be star is inclined with respect to the orbital plane in this system and that this inclination may be a factor in the unusual outburst behavior of the system.Comment: 18 pages, 15 figures, To appear in ApJ v584, Feb 20, 2003 issu

Probing stellar winds and accretion physics in high-mass X-ray binaries and ultra-luminous X-ray sources with LOFT

This is a White Paper in support of the mission concept of the Large Observatory for X-ray Timing (LOFT), proposed as a medium-sized ESA mission. We discuss the potential of LOFT for the study of high-mass X-ray binaries and ultra-luminous X-ray sources. For a summary, we refer to the paper.Comment: White Paper in Support of the Mission Concept of the Large Observatory for X-ray Timing. (v2 few typos corrected

A Puzzling Paucity of Double Peaked X-ray Pulsars

Accretion powered pulsars exhibit a variety of lightcurves. In this paper we propose to classify the observed lightcurves as single or double pulsed.We analyze the lightcurves of 86 accretion powered pulsars and assign them to these classes. We present three datasets: first in which the classification can be easily done, second for which the classification is more difficult and not certain, and third for which we were unable to classify the pulsar because of lack of published data. We analyze a simple model in which the angles between the magnetic and rotation axis $\beta$, and between the rotation axis and the line of sight $\theta$ are random, and show that it is inconsistent with the data. We also present a model in whichthe angle between the magnetic axis and rotation axis is restricted and compare it with the data. This leads to an upper limit on the angle $\beta < 40^\circ$. We conclude that there must be a mechanism that leads to alignment of the magnetic and spin axis in X-ray pulsars.Comment: submitted to A&