Molecular survey of Piroplasmida, Hepatozoon spp. and Anaplasmataceae in anemic and thrombocytopenic dogs from Uruguay.

Canine tick-borne diseases, such as babesiosis, rangeliosis, hepatozoonosis, anaplasmosis and ehrlichiosis, are of veterinarian relevance, causing mild or severe clinical cases that can lead to the death of the dog. The aim of this study was detecting tick-borne protozoan and rickettsial infections in dogs with anemia and/or thrombocytopenia in Uruguay. A total of 803 domestic dogs were evaluated, and 10% were found positive (detected by PCR) at least for one hemoparasite. Sequence analysis confirmed the presence of four hemoprotozoan species: Rangelia vitalii, Babesia vogeli, Hepatozoon canis and Hepatozoon americanum, and the rickettsial Anaplasma platys. The most detected hemoparasite was R. vitalii, followed by H. canis and A. platys. This is the first report of B. vogeli in Uruguay and the second report of H. americanum in dogs from South America. The results highlight the importance for veterinarians to include hemoparasitic diseases in their differential diagnosis of agents causing anemia and thrombocytopenia.

Low Cancer Incidence in Naked Mole-Rats May Be Related to Their Inability to Express the Warburg Effect.

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have a remarkably low cancer incidence. Most advanced cancers in mammals display increased production of lactic acid from glucose, irrespective of oxygen availability. This hallmark of cancer is known as the Warburg effect (WE). Most malignancies acquire this metabolic phenotype during their somatic evolution, as the WE benefits tumor growth in several ways. We propose that the peculiar metabolism of the NMR makes development of the WE inherently difficult, which might contribute to the extraordinarily low cancer rate in NMRs. Such an adaptation of NMRs to their subterranean environment may have been facilitated by modified biochemical responses with a stronger inhibition of the production of CO2 and lactic acid by a decreased extracellular pH. Since this pH-inhibition could be deeply hard-wired in their metabolic make-up, it may be difficult for malignant cells in NMRs to acquire the WE-phenotype that facilitates cancer growth in other mammals. In the present commentary, we discuss this idea and propose experimental tests of our hypothesis.

Early lactate and glucose kinetics following return to spontaneous circulation after out-of-hospital cardiac arrest.

OBJECTIVE: Lactate has been shown to be preferentially metabolized in comparison to glucose after physiological stress, such as strenuous exercise. Derangements of lactate and glucose are common after out-of-hospital cardiac arrest (OHCA). Therefore, we hypothesized that lactate decreases faster than glucose after return-to-spontaneous-circulation (ROSC) after OHCA. RESULTS: We included 155 OHCA patients in our analysis. Within the first 8 h of presentation to the emergency department, 843 lactates and 1019 glucoses were available, respectively. Lactate decreased to 50% of its initial value within 1.5 h (95% CI [0.2-3.6 h]), while glucose halved within 5.6 h (95% CI [5.4-5.7 h]). Also, in the first 8 h after presentation lactate decreases more than glucose in relation to their initial values (lactate 72.6% vs glucose 52.1%). In patients with marked hyperlactatemia after OHCA, lactate decreased expediently while glucose recovered more slowly, whereas arterial pH recovered at a similar rapid rate as lactate. Hospital non-survivors (N = 82) had a slower recovery of lactate (P = 0.002) than survivors (N = 82). The preferential clearance of lactate underscores its role as a prime energy substrate, when available, during recovery from extreme stress.

Model-based Prediction of Critical Illness in Hospitalized Patients with COVID-19.

Background The prognosis of hospitalized patients with severe coronavirus disease 2019 (COVID-19) is difficult to predict, and the capacity of intensive care units was a limiting factor during the peak of the pandemic and is generally dependent on a country's clinical resources. Purpose To determine the value of chest radiographic findings together with patient history and laboratory markers at admission to predict critical illness in hospitalized patients with COVID-19. Materials and Methods In this retrospective study, which included patients from March 7, 2020, to April 24, 2020, a consecutive cohort of hospitalized patients with real-time reverse transcription polymerase chain reaction-confirmed COVID-19 from two large Dutch community hospitals was identified. After univariable analysis, a risk model to predict critical illness (ie, death and/or intensive care unit admission with invasive ventilation) was developed, using multivariable logistic regression including clinical, chest radiographic, and laboratory findings. Distribution and severity of lung involvement were visually assessed by using an eight-point scale (chest radiography score). Internal validation was performed by using bootstrapping. Performance is presented as an area under the receiver operating characteristic curve. Decision curve analysis was performed, and a risk calculator was derived. Results The cohort included 356 hospitalized patients (mean age, 69 years ± 12 [standard deviation]; 237 men) of whom 168 (47%) developed critical illness. The final risk model's variables included sex, chronic obstructive lung disease, symptom duration, neutrophil count, C-reactive protein level, lactate dehydrogenase level, distribution of lung disease, and chest radiography score at hospital presentation. The area under the receiver operating characteristic curve of the model was 0.77 (95% CI: 0.72, 0.81; P < .001). A risk calculator was derived for individual risk assessment: Dutch COVID-19 risk model. At an example threshold of 0.70, 71 of 356 patients would be predicted to develop critical illness, of which 59 (83%) would be true-positive results. Conclusion A risk model based on chest radiographic and laboratory findings obtained at admission was predictive of critical illness in hospitalized patients with coronavirus disease 2019. This risk calculator might be useful for triage of patients to the limited number of intensive care unit beds or facilities. © RSNA, 2020 Online supplemental material is available for this article.

Neumonía intersticial linfoide en enfermedades del tejido conectivo / Lymphoid Interstitial Pneumonia in Connective Tissue Diseases

Mujer de 65 años, ex tabaquista de 20 p.y, ocupación ama de casa, antecedentes de artritis reumatoide y síndrome de Sjögren desde hace 44 años. Hace 14 años diagnóstico de neumonía intersticial linfoide (LIP, por sus siglas en inglés), por imágenes y clínica (tos seca, disnea); en tratamiento con corticoides, con buena respuesta a los mismos.

Síndrome combinado de fibrosis pulmonar y enfisema en artritis reumatoide / Combined pulmonary fibrosis syndrome and emphysema in rheumatoid arthritis

Caso clínico: Paciente de sexo masculino, de 72 años. Ingresa por un cuadro de disnea súbita mMRC 2-3, con progresión a disnea mMRC 4. Refiere tos crónica sin cambio en sus características. Niega fiebre. Antecedentes: Ex tabaquista (36 paquetes/año), con antecedentes de artritis reumatoidea, y fibrosis pulmonar. Examen físico: Saturación de oxígeno 88% aire ambiente, taquipneico. Con hipoventilación y crepitantes velcro hasta el tercio medio, bilaterales. Exámenes complementarios: Hemograma normal. La gasometría arterial revela alcalosis respiratoria compensada. La espirometría y los volúmenes pulmonares se encuentran dentro de los límites de referencia, se observa disminución severa de la capacidad de difusión pulmonar (DLCO). La tomografía computarizada torácica de alta resolución (TCAR) (Figuras 1 y 2) muestra enfisema en los lóbulos superiores, con fibrosis de predominio en lóbulos inferiores, no se observan signos indirectos de hipertensión pulmonar

Ischemic priapism as a model of exhausted metabolism.

In vivo metabolic studies typically concern complex open systems. However, a closed system allows better assessment of the metabolic limits. Ischemic priapism (IP) constitutes a special model of the compartment syndrome that allows direct sampling from a relatively large blood compartment formed by the corpora cavernosa (CC). The purpose of our study was to measure metabolic changes and the accumulation of end products within the CC during IP. Blood gas and biochemical analyses of aspirates of the CC were analyzed over an 8-year period. Mean ± SD pH, pCO2 , pO2 , O2 -saturation, lactate, and glucose of the aspirated blood were determined with a point-of-care analyzer. Forty-seven initial samples from 21 patients had a pH of 6.91 ± 0.16, pCO2 of 15.3 ± 4.4 kPa, pO2 of 2.4 ± 2.0 kPa, and an O2 -saturation of 19 ± 24% indicating severe hypoxia with severe combined respiratory and metabolic acidosis. Glucose and lactate levels were 1.1 ± 1.5 and 14.6 ± 4.8 mmol/L, respectively. pH and pCO2 were inversely correlated (R2  = 0.86; P < 0.001), glucose and O2 -saturation were positively correlated (R2  = 0.83; P < 0.001), and glucose and lactate were inversely correlated (R2  = 0.72; P < 0.001). The positive correlation of CO2 and lactate (R2  = 0.69; P < 0.001) was similar to that observed in vitro, when blood was titrated with lactic acid. The observed combined acidosis underscores that IP behaves as a closed system where severe hypoxia and glycopenia coexist, indicating that virtually all energy reserves have been consumed.

The association of early combined lactate and glucose levels with subsequent renal and liver dysfunction and hospital mortality in critically ill patients.

BACKGROUND: The development of renal and liver dysfunction may be accompanied by initially subtle derangements in the gluconeogenetic function. Discrepantly low glucose levels combined with high lactate levels might indicate an impaired Cori cycle. Our objective was to examine the relation between early lactate and glucose levels with subsequent renal and liver dysfunction and hospital mortality in critically ill patients. METHODS: Over a 4-year period (2011 to 2014), all adult patients admitted to our adult 48-bed teaching hospital intensive care unit (ICU) for at least 12 h were retrospectively analyzed. Lactate and glucose were regularly measured with point-of-care analyzers in all ICU patients. Lactate and glucose measurements were collected from 6 h before to 24 h after ICU admission. Patients with fewer than four lactate/glucose measurements were excluded. Patients received insulin according to a computer-guided control algorithm that aimed at a glucose level <8.0 mmol/L. Renal dysfunction was defined as the development of acute kidney injury (AKI) within 7 days, and liver function was based on the maximal bilirubin in the 7-day period following ICU admission. Mean lactate and mean glucose were classified into quintiles and univariate and multivariate analyses were related with renal and liver dysfunction and hospital mortality. Since glucose has a known U-shaped relation with outcome, we also accounted for this. RESULTS: We analyzed 92,000 blood samples from 9074 patients (63% males) with a median age of 64 years and a hospital mortality of 11%. Both lactate quintiles (≤1.0; 1.0-1.3; 1.3-1.7; 1.7-2.3; >2.3 mmol/L) and glucose quintiles (≤7.0; 7.0-7.6; 7.6-8.2; 8.2-9.0; >9.0 mmol/L) were related with outcome in univariate analysis (p < 0.001). Acute Physiology and Chronic Health Evaluation (APACHE) IV, lactate, and glucose were associated with renal and liver dysfunction in multivariate analysis (p < 0.001), with a U-shaped relationship for glucose. The combination of the highest lactate quintile with the lowest glucose quintile was associated with the highest rates of renal dysfunction, liver dysfunction, and mortality (p < 0.001) with a significant interaction between lactate and glucose (p ≤ 0.001). CONCLUSIONS: Abnormal combined lactate and glucose measurements may provide an early indication of organ dysfunction. In critically ill patients a 'normal' glucose with an elevated lactate should not be considered desirable, as this combination is related with increased mortality.

[The Warburg effect and its role in tumour metabolism: opportunities for new cancer treatments]. / Het Warburg-effect en zijn rol in tumormetabolisme: Mogelijkheden voor nieuwe kankertherapie.

Cancer cells are characterised by altered metabolism compared to healthy tissue. Ninety years ago, the German medical doctor and biochemist Otto Warburg discovered that tumours--when compared to healthy tissue--convert considerably more glucose into lactate, regardless of oxygen presence. This phenomenon is known as the Warburg effect; it is a hallmark of most cancer types and can be well understood by the process of somatic evolution. The Warburg effect explains the significance of the PET scan and may offer opportunities for new treatments of cancer.

Rotura del septo interventricular después infarto agudo de miocardio con apertura y cierre intermitentes / Interventricular septal rupture after acute myocardial infarction with intermittent opening and closing

La rotura del septo interventricular es una grave complicación en pacientes que sufren infarto agudo de miocardio. Se presenta aproximadamente en el 1 % de los pacientes infartados, su mortalidad es elevada y el tratamiento de elección es la reparación quirúrgica. Se presenta un paciente anciano que ingresó en la Unidad de Cuidados Intensivos por infarto agudo de miocardio de cara anterior, que recibió tratamiento trombolítico con estreptokinasa recombinante cubana y 24 horas más tarde, presentó deterioro hemodinámico con cambios electrocardiográficos y aparición de soplo sistólico en la punta. Se realizó una ecocardiografía que mostró un defecto del septo interventricular con apertura y cierre intermitentes. Horas más tarde el paciente falleció por insuficiencia cardiocirculatoria, a pesar del tratamiento. Se presentan las imágenes ecocardiográficas y la pieza anatómica. Lo inusual del presente caso fue la apertura y el cierre intermitentes del defecto interventricular. No se encontró ningún informe similar a en las bases de datos bibliográficas consultadas(AU)

Plaque radiotherapy for juxtapapillary choroidal melanoma: tumor control in 650 consecutive cases.

PURPOSE: To evaluate treatment of juxtapapillary choroidal melanoma with plaque radiotherapy and to investigate the role of supplemental transpupillary thermotherapy (TTT). DESIGN: Retrospective, comparative case series. PARTICIPANTS: We included 650 consecutive eyes with juxtapapillary choroidal melanoma within 1 mm of the optic disc. METHODS: Eyes with juxtapapillary choroidal melanoma receiving plaque radiotherapy over a 31-year period from October 1974 to November 2005 were included in the study. The TTT and no TTT groups were analyzed separately and compared. MAIN OUTCOME MEASURES: Local tumor control, metastasis, and tumor-related mortality. RESULTS: The median basal tumor diameter was 10 mm (range, 1.5-21) and median thickness was 3.5 mm (range, 0.5-14.8). In 481 eyes (74%), the tumor was directly adjacent to the optic disc and in 169 eyes (26%) the posterior tumor margin was between 0.1 and 1.0 mm from the optic disc. The circumpapillary extent of the tumor was <4 clock-hours in 321 eyes (50%), 4-8 clock-hours in 250 eyes (38%), and >8 clock-hours in 79 eyes (12%). Plaque radiotherapy using iodine-125 in 616 eyes (95%), cobalt-60 in 19 eyes (3%), iridium-192 in 12 eyes (2%), and ruthenium-106 in 3 eyes (<1%) delivered a median radiation dose of 8000 cGy (range, 3600-15 500) to the tumor apex and adjunctive TTT was used in 307 eyes (56%). Kaplan-Meier estimates for tumor recurrence, metastasis, and death were 14%, 11%, and 4% at 5 years and 21%, 24%, and 9% at 10 years, respectively. Eyes treated with additional TTT showed slight (statistically nonsignificant) reduction in recurrence and metastasis. Using multivariable analysis, factors predictive of tumor recurrence included foveolar tumor requiring TTT (hazard ratio, 5.07; P<0.001) and greater tumor thickness (hazard ratio, 1.29 per mm increase; P<0.001). Factors predictive of metastasis included greater tumor base (hazard ratio, 1.21 per mm increase; P<0.001) and increasing intraocular pressure (hazard ratio, 1.11 per mmHg increase; P = 0.020). CONCLUSIONS: Plaque radiotherapy for juxtapapillary melanoma provides local tumor control in approximately 80% of eyes at 10 years. In subjects who received TTT, there was slight but nonsignificant improved local tumor control and lower metastatic rate.

CyberKnife radiosurgery for the treatment of intraocular and periocular lymphoma.

OBJECTIVES: To evaluate efficacy, patient tolerance, and adverse effects of CyberKnife radiosurgery for the treatment of intraocular and periocular lymphoma. METHODS: Retrospective case series of 13 patients who underwent CyberKnife radiosurgery was conducted. RESULTS: Fourteen eyes of 13 patients were included. The tissue location of the lymphoma was orbit (7 eyes), conjunctiva (3 eyes), choroid (2 eyes), and retina (2 eyes). The lymphoma type was classified as extranodal marginal zone B-cell lymphoma in 7 eyes (50%), diffuse large B-cell lymphoma in 3 eyes (21%), follicular lymphoma in 2 eyes (14%), and benign reactive lymphoid hyperplasia in 2 eyes (14%). The mean treatment dose was 1718 centigrays (cGy) (range, 1350-2250 cGy) given over a mean of 5 days (range, 3-5 days) with a mean dose rate of 320 cGy per fraction. Complete tumor resolution without local recurrence over a mean follow-up of 23 months was documented in all cases. Radiation-associated adverse effects included mild dry eye in 2 patients and cataract in 1 patient with conjunctival lymphoma. There was no radiation retinopathy or papillopathy, and visual acuity was preserved or improved in 13 eyes and decreased in 1 eye due to the presence of cataract. CONCLUSIONS: CyberKnife radiosurgery is a well-tolerated technique for the treatment of intraocular and periocular lymphoma, allowing for local resolution of the lesions. An important benefit is that treatment was completed over 5 days.

Plaque radiotherapy for juxtapapillary choroidal melanoma overhanging the optic disc in 141 consecutive patients.

OBJECTIVE: To evaluate tumor control with plaque radiotherapy for juxtapapillary choroidal melanoma that overhangs the optic disc. METHODS: Retrospective medical record review of 141 consecutive patients with data on complications of treatment, final visual acuity, visual loss, enucleation, tumor recurrence, metastasis, and death. RESULTS: The median patient age was 61 years. Presenting symptoms included reduced visual acuity in 72 eyes (51%), photopsia in 14 (10%), and visual field defect in 18 (13%); 35 patients (25%) were asymptomatic. The median tumor basal diameter was 11 mm and the median thickness was 5.2 mm. The tumor overhung 50% or less of the disc in 88 eyes (62%) and more than 50% of the disc in 53 eyes (38%). In 19 cases (13%), the tumor overhung the entire disc. All patients were treated with plaque radiotherapy, using a notched design in 126 eyes (89%) and a round design in 14 eyes (10%), with iodine 125 in 132 eyes (94%) and cobalt 60 in 9 eyes (6%). The median radiation dose to the tumor apex was 8500 cGy. Adjuvant transpupillary thermotherapy was used in 54 eyes (39%). During a mean follow-up of 56 months, complications included nonproliferative retinopathy in 61 eyes (51%), proliferative retinopathy in 26 (22%), maculopathy in 44 (37%), papillopathy in 57 (48%), neovascular glaucoma in 23 (19%), and vitreous hemorrhage in 48 (40%). A final visual acuity of 20/200 or worse was measured in 72 eyes (77%), and visual loss of more than 5 Snellen lines occurred in 59 eyes (63%). Enucleation was necessary in 27 eyes (23%). Tumor recurrence was found in 12 eyes (10%). Metastasis developed in 15 patients (13%) and death in 4 cases (3%). CONCLUSIONS: Using plaque radiotherapy for choroidal melanoma overhanging the optic disc, local tumor control was achieved in 90% of cases. Tumor and radiation effects led to poor visual acuity in 77% of eyes. The metastatic rate was 13% and the mortality rate was 3%.

Incidência de rouquidão em alunos do último ano dos cursos de licenciatura / Incidence of hoarseness in students of the last year of degree courses

Introdução: Os professores representam um dos grupo mais freqüentemente acometido por alterações vocais, sob a pena do surgimento de sintomas disfônicos, prejudiciais ao prosseguimento do magistério. Objetivo: Avaliar a ocorrência de rouquidão em alunos do último ano dos cursos de licenciatura de uma Instituição de Ensino Superior. Método: Realizou-se estudo prospectivo, individuado, observacional e transversal, entrevistando-se 100 alunos quanto a aspectos clínicos, pessoais e profissionais,através de questionário próprio. Resultados: Dos 100 alunos 65% já lecionam em pelo menos uma instituição de ensino. Do total dos alunos que já lecionam 83,08% apresentam algum tipo de sintoma relacionado ao uso inadequado da voz. Dentre os alunos que já lecionam em instituições, apenas 26,15% relatam manter habitualmente algum cuidado com a voz enquanto 73,85% dizem não ter esse hábito. 83,33% dos estudantes ao apresentarem algum sintoma relacionado a voz não buscam atendimento médico. Dentre as queixas a tríade: dor ou irritação (27,33%), pigarro (21,33%) e rouquidão (21,33%) foram constatados como as de maior freqüência. A sintomatologia foi de 27% nos que usam pouca água, contrastando com os 8% dos que fazem o uso de muita água. Conclusão: Mais da metade dos alunos pesquisados já trabalhavam como professor e apresentavam queixa de rouquidão. É fundamental que orientações vocais sejam fornecidas durante esses cursos de graduação

Introduction: Teachers are the group most affected by vocal problems, under penalty of the appearance of dysphonia symptoms, more or less early, damaging the continuation of the teaching. Aim: The authors intended to assess the occurrence of hoarseness in the last year students of the degrees courses. Method: Prospective, individual, observational and cross study, interviewed 100 students collecting clinical, personal and business information. Results: Among the 100 students 65% already teaches in at least one institution of education. Of the total of students who already teaches 83.08% have some type of symptom related to the misuse of the voice. Among the students who already teaches, only 26.15% reported usually maintain some care with the voice, while 73.85% do not have.83.33% of the students when present a symptom related to the voice do not look for medical attention. Among the complaints the triad:pain or irritation (27.33%), hawk (21.33%) and hoarseness (21.33%) were identified as those of higher frequency.The symptoms was 27% for that one who usually drink less water, contrasting with 8% of those who drink more. Conclusion: More than half of students surveyed had been working as a teacher and presented complaints of hoarseness. It is essential that guidelines are provided vocal during those courses for graduation.

Taponamiento cardíaco por rotura de infarto de aurícula derecha

Se presenta un paciente con antecedentes de hipertensión arterial y de cardiopatía isquémica que presentó una parada cardíaca por hemopericardio masivo secundario a rotura de infarto de aurícula derecha no diagnosticado. Se realiza revisión de la literatura(AU)

Conjunctival melanoma 3 years after radiation and chemotherapy for retinoblastoma.

An 8-month-old infant with advanced bilateral retinoblastoma was managed with enucleation of the right eye and chemotherapy and radiotherapy of the left eye. Three years after treatment, an ill-defined, nonpigmented mass was noted in the anophthalmic right socket. Excisional biopsy revealed an amelanotic melanoma of the conjunctiva with superficial orbital invasion. There has been no tumor recurrence during 20 months of follow-up.

Plaque radiotherapy for choroidal melanoma encircling the optic disc (circumpapillary choroidal melanoma).

OBJECTIVE: To report results of plaque radiotherapy for choroidal melanoma that completely encircles the optic disc (circumpapillary melanoma). METHODS: Retrospective medical record review over a 31-year period of 37 consecutive patients. The main outcome measures were treatment complications, long-term visual acuity, enucleation, tumor recurrence, metastasis, and death. RESULTS: The median patient age at treatment was 69 years (range, 20-86 years). The presenting complaint was visual loss in 19 eyes (51%), photopsia in 5 (14%), and visual field loss in 3 (8%). All tumors touched and encircled the optic disc for 360 degrees . The quadrantic location of the main tumor epicenter was superior in 8 eyes (22%), nasal in 10 (27%), inferior in 9 (24%), and temporal in 10 (27%). The median tumor basal diameter was 11 mm (range, 4.8-20 mm) and median tumor thickness was 3.6 mm (range, 1.8-14.8 mm). The optic disc was obscured to some extent by overhanging tumor in 19 cases (52%). The most commonly used isotope for plaque radiotherapy was iodine 125 (n = 34 cases; 92%), and a notched plaque design was used in 34 cases (92%). Planned adjunctive treatment included transpupillary thermotherapy in 17 cases (49%) and argon laser photocoagulation in 6 of 35 cases (17%) with follow-up. Of the 28 eyes with more than 5 months' follow-up (mean, 52 months; median, 46 months; range, 5-234 months), treatment complications included nonproliferative and proliferative retinopathy in 11 (39%) and 7 eyes (25%); maculopathy in 7 (25%); papillopathy in 9 eyes (32%); neovascular glaucoma in 5 (18%); and vitreous hemorrhage in 13 (46%). Pars plana vitrectomy was required in only 2 of 13 eyes (15%) with persistent vitreous hemorrhage. Long-term visual acuity of 20/200 or worse was observed in 13 eyes (62%), and 12 eyes (57%) lost more than 5 Snellen visual acuity lines, excluding 7 cases (25%) in which enucleation was necessary. Recurrence was noted in 4 cases (14%), of which 3 were treated with enucleation and 1 with transpupillary thermotherapy. Systemic metastasis occurred in 1 patient (4%) and there were no melanoma-specific deaths during the study period. CONCLUSIONS: Custom-designed plaque radiotherapy is a potential treatment for selected patients with circumpapillary choroidal melanoma. We found satisfactory local tumor control, and globe retention was achieved in 75% of eyes with more than 5 months' follow-up.

Custom-designed plaque radiotherapy for nonresectable iris melanoma in 38 patients: tumor control and ocular complications.

PURPOSE: To evaluate plaque radiotherapy for iris melanoma. DESIGN: Prospective noncomparative interventional case series. METHODS: For 38 patients, custom-designed plaque radiotherapy using iodine 125 isotope was applied overlying the cornea with a tumor apex dose of 80 Gy. The main outcome measures were tumor control and ocular complications using Kaplan-Meier estimates and Cox proportional hazards regression analysis. RESULTS: In all cases, the melanoma was nonresectable owing to large or discohesive tumor. The tumor configuration was nodular in 24 cases (63%) and flat (diffuse) in 14 (37%). The mean tumor basal diameter was 9 mm (range 4 to 13 mm). Solid tumor extended into the anterior chamber angle in 36 eyes (95%). Tumor seeds were noted on the iris stroma for a mean of 7 clock hours and in the anterior chamber angle for a mean of 4 clock hours. Five-year follow up revealed tumor metastasis in 0% and tumor recurrence in 8% of patients. Visual acuity of 20/200 or worse was found in 16% at 5 years. Radiation-related complications at 5 years included corneal epitheliopathy (9%), cataract (70%), and neovascular glaucoma (8%). No patients developed corneal necrosis, scleral necrosis, retinopathy, or papillopathy. After treatment, the combined incidence of tumor-related and radiation-related elevated intraocular pressure at 5 years was 33%. Enucleation was necessary in 13% at 5 years, for tumor recurrence (n = 3) and patient preference (n = 1). CONCLUSIONS: Plaque radiotherapy is a useful alternative to enucleation for eyes with nonresectable iris melanoma. Tumor control is 92% at 5 years, but related complications, especially cataract and elevated intraocular pressure, should be anticipated.

Plaque radiotherapy for selected orbital malignancies: preliminary observations: the 2002 Montgomery Lecture, part 2.

PURPOSE: To describe the principles and preliminary results of plaque brachytherapy for selected orbital malignancies. METHODS: A custom-designed Iodine-125 plaque, designed to deliver a target dose of 50 Gray, was placed surgically in the region from which an orbital malignancy was partially resected. The mean dose to the target area was 50 Gray. The initial and follow-up patient data were reviewed. RESULTS: Of the 8 patients, the diagnosis was adenoid cystic carcinoma of the lacrimal gland (4 cases), orbital invasion by basal cell carcinoma (2), orbital extension of conjunctival melanoma (1), and metastatic carcinoma (1). Of the 4 with adenoid cystic carcinoma, there was microscopic residual tumor after excision and orbital exenteration was considered. Three have tumor control with follow-up of 1, 3, and 6 years. One patient required exenteration for recurrence separate from the field of brachytherapy and is free of tumor after 10 years. All 4 patients are alive and well with tumor control. Of the 2 patients with orbital extension of basal cell carcinoma, tumor control without recurrence has been achieved in both after 2 years. The patient with orbital metastasis responded to plaque radiotherapy, with no orbital recurrence, but died of systemic metastasis. The patient with orbital melanoma had local orbital recurrence separate from the area of irradiation and is currently being treated for systemic metastasis. CONCLUSIONS: Based on preliminary observations, plaque radiotherapy appears to be a reasonable alternative to exenteration and external irradiation for selected orbital malignancies.

Plaque radiotherapy for large posterior uveal melanomas (> or =8-mm thick) in 354 consecutive patients.

OBJECTIVE: To assess treatment complications and tumor control after plaque radiotherapy for large posterior uveal melanomas measuring 8 mm or greater in thickness. DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: Three hundred fifty-four patients each of whom had a posterior uveal melanoma measuring 8 mm or greater in thickness treated with plaque radiotherapy. MAIN OUTCOME MEASURES: The four endpoints included (1) poor final visual acuity (20/200 or worse), (2) enucleation, (3) local tumor recurrence, and (4) metastasis. The clinical data regarding patient features, tumor features, and radiation parameters were analyzed for their impact on the four main outcomes using Cox proportional hazards regression models. RESULTS: Using Kaplan-Meier estimates, final visual acuity was poor in 57% at 5 years and 89% at 10 years follow-up. Using multivariate analysis, the most important risk factors for poor visual acuity included retinal invasion by melanoma, increasing patient age, iodine 125 (I(125)) isotope, and <2 mm distance to the optic disc. Treatment-related complications at 5 years included proliferative retinopathy (25%), maculopathy (24%), papillopathy (22%), cataract (66%), neovascular glaucoma (21%), vitreous hemorrhage (23%), and scleral necrosis (7%). Enucleation was necessary in 24% at 5 years and 34% at 10 years follow-up. Using multivariate analysis, the risk factors for enucleation included left eye, peripheral tumor margin anterior rather than posterior to the equator, increasing tumor thickness, and ruthenium 106 (Ru(106)) isotope. Using Kaplan-Meier estimates, local tumor recurrence was found in 9% at 5 years and 13% at 10 years follow-up. Using multivariate analysis, risk factors for tumor recurrence included Ru(106) radioisotope and ciliary body involvement with tumor. Tumor-related metastases were found in 30% at 5 years and 55% at 10 years follow-up. Using multivariate analysis, risk factors for metastases included inferotemporal meridian, anterior extension of the tumor to the iris root, increasing tumor base, and posterior margin < 2 mm from the optic nerve. CONCLUSIONS: Plaque radiotherapy provided tumor control at 10 years in 87% of patients with selected large posterior uveal melanomas (>8 mm thick) that otherwise would have been managed with enucleation. The large intraocular mass and associated features and radiation complications led to poor visual acuity in most patients. At 10 years follow-up, enucleation was necessary in 34% of patients, and metastasis developed in 55% of patients.