Obstrução lacrimal pós-tratamento oncológico: revisão de literatura / Lacrimal drainage system obstruction after cancer treatment: a literature review

RESUMO A obstrução de via lacrimal é uma possível complicação decorrente de tratamentos oncológicos sistêmicos e locais. A epífora crônica gera grande impacto na qualidade de vida desses pacientes, e, como a fibrose terminal da via lacrimal pode necessitar de procedimentos complexos para sua resolução, é importante estarmos atentos a esse efeito adverso, com o objetivo de reconhecê-lo e tratá-lo precocemente, ou mesmo preveni-lo. Nesta revisão da literatura, os autores analisam todos os agentes quimioterápicos e radioterápicos associados à obstrução lacrimal e descrevem os mecanismos, a frequência, os tratamentos e a profilaxia. Os tratamentos oncológicos associados à obstrução lacrimal foram: radioterapia em cabeça e pescoço (dosagem acima de 45 a 75Gy), radioiodoterapia (dosagem acima de 150mCi) e quimioterapia com 5-FU, S-1, capecitabine e docetaxel. A obstrução lacrimal pode ser irreversível, e a intubação profilática das vias lacrimais é uma possibilidade descrita de tratamento profilático em casos de radioterapia e uso do 5-FU, S-1 e docetaxel. O tratamento cirúrgico de todos os casos é a dacriocistorrinostomia.

ABSTRACT Lacrimal duct obstruction can be a side effect of systemic and/or local cancer treatments. Chronic epiphora has a great impact on the quality of life of oncological patients. Since terminal fibrosis of the lacrimal system may require complex procedures, it is important to be aware of this adverse effect in order to recognize and treat it, or even prevent it. A literature review was performed to identify all types of systemic cancer treatment associated with lacrimal obstruction and to describe the mechanisms, frequency, treatment, and prophylaxis. The oncological treatments associated with lacrimal obstruction were head and neck radiotherapy (dosage above 45-75 Gy), radioiodine therapy (dosage above 150 mCi), and chemotherapy with 5-FU, S-1, Capecitabine and Docetaxel. Depending on the dose, this complication may be irreversible. Prophylactic intubation of the lacrimal system is an option for prophylaxis in cases of radiotherapy, use of 5-FU, S-1, and Docetaxel. Final surgical treatment is dacryocystorhinostomy.

Disfunción tiroidea por I131-Metayodo Benzilguanidina en pacientes con neuroblastoma / Thyroid dysfunction due to 131I-metaiodobenzylguanidine in patients with neuroblastoma

Resumen: Introducción: El tratamiento del neuroblastoma en estadios avanzados incluye quimioterapia, cirugía y terapia con I131-Metayodo benzilguanidina (I131-MIBG). La disfunción tiroidea se reporta entre 12 y 85% a pesar de la protección tiroidea. Objetivo: Identificar la frecuencia de disfunción tiroidea en casos de neu roblastoma tratados con I131-MIBG. Pacientes y Método: Estudio transversal. Se incluyeron todos los casos con diagnóstico de neuroblastoma que recibieron I131-MIBG en el periodo de 2002-2015, a los cuales se les realizó antropometría completa, perfil de tiroides: hormona estimulante de tiroides (TSH), Triyodotironina total y libre (T3t y T3l), tiroxina total y libre (T4t, T4l), y anticuerpos antitiroglobulina y antiperoxidasa. Resultados: Se identificaron un total de 27 pacientes; once fallecieron (40%). De los 16 casos sobrevivientes, 9 (56%) presentaron disfunción tiroidea: 2 (13%) casos con hipotiroidismo subclínico y 7 (44%) casos con hipotiroidismo clínico (3 casos por retraso en el desa rrollo psicomotor y 4 por desaceleración del crecimiento). Los pacientes presentaron manifestaciones clínicas a los 16,1 meses (1,2-66,3 meses) de recibir el radiofármaco a una dosis acumulada de 142 mCi (96-391.5 mCi). No se logró evidenciar diferencias en la edad al diagnóstico, la edad al inicio del tratamiento con el I131-MIBG, la dosis acumulada del I131-MIBG y el tiempo trascurrido entre la dosis y el perfil tiroideo entre los casos con o sin disfunción tiroidea. Conclusiones: El 56% de los pacientes con neuroblastoma presentaron disfunción tiroidea. La mayoría de los casos con hipotiroidismo fue ron referidos cuando los datos de disfunción tiroidea eran clínicamente evidentes. Se propone en esta poblacion realizar perfil tiroideo semestral y valoración anual por un endocrinólogo pediatra durante los primeros 5 años posteriores al diagnóstico oncológico.

Abstract: Introduction: The treatment of advanced neuroblastoma includes chemotherapy, surgery, and radiotherapy with 131-I-Metaiodobenzylguanidine (131-I-MIBG). Despite strategies to protect thyroid function, its dysfunction is reported between 12 and 85%. Objective: To identify the frequency of thyroid dys function in cases of neuroblastoma treated with 131-I-MIBG. Patients and Method: Cross-sectional study. We included all the cases with neuroblastoma treated with 131-I-MIBG between 2002 and 2015, with complete somatometry, and complete thyroid profile (TSH, free and total T3 and T4, and anti-thyroglobulin and antiperoxidase antibodies). Results: 27 patients were identified out of which eleven died (40%). Out of the 16 surviving cases, 9 (56%) presented thyroid dysfunction: 2 (13%) cases with subclinical hypothyroidism and 7 (44%) cases with clinical hypothyroidism (3 cases due to psychomotor developmental delay and 4 due to growth deceleration). The patients presented cli nical manifestations at 16.1 months (1.2-66.3 months) after receiving the radiopharmaceutical at acumulative dose of 142 mCi (96-391.5 mCi). No differences were found in the age at diagnosis, age at the start of treatment with 131-I-MIBG, the cumulative dose of 131-I-MIBG, and the time elapsed between the dose and the thyroid profile among the cases with or without thyroid dysfunction. Con clusions: 56% of patients with neuroblastoma had thyroid dysfunction. Most of the cases with hypothyroidism were referred when thyroid dysfunction was clinically evident. A thyroid profile should be performed every 6 months, along with an annual endocrinological evaluation during the next 5 years in these patients.

Variación de dosis de radioyodo en pacientes con cáncer diferenciado de tiroides post implementación de guías ATA 2015 / Variation of radioiodine dose in patients with differentiated thyroid cancer after implementation of the ATA 2015 guidelines

Introducción: El cáncer diferenciado de tiroides (CDT), es actualmente la neoplasia endocrina más frecuente. Su tratamiento estándar es la resolución quirúrgica, asociado a ablación con radioyodo (RI) según la clasificación propuesta por la American Thyroid Association (ATA). Las indicaciones y dosis de este último, han ido variando en los últimos años según avanzan las investigaciones en este ámbito. Objetivo: En el siguiente estudio se compararon las dosis de RI utilizadas previo y posterior a la implementación de las últimas guías de la ATA. Materiales y métodos: Estudio retrospectivo observacional de 70 pacientes con diagnóstico de CDT del Hospital Clínico de la Universidad de Chile entre 2012 y 2017. Se agruparon los pacientes en dos cohortes, los operados entre los años 2012-2015 y los 2016-2017 clasificándolos según riesgo ATA, TNM y riesgo de recurrencia. Se consignaron las dosis de RI utilizadas y se compararon entre las cohortes. Análisis estadístico: Mann Whithney. Resultados: Al comparar la dosis de RI entre ambas cohortes, según TNM y riesgo ATA, se obtuvo los siguientes resultados: los pacientes T1b de la cohorte 2012-2015 presentaron dosis de RI significativamente mayores que los de la cohorte 2016-2017; también se evidenció que en pacientes N0 hubo una diferencia estadísticamente significativa, mostrando una tendencia a disminuir la dosis de RI; además, en los pacientes de la cohorte 2012-2015 con riesgo ATA intermedio, se obtuvo que las dosis de RI fueron significativamente mayores que las utilizadas en la cohorte 2016-2017. Conclusión: Se concluye que las variaciones de las dosis de RI utilizadas en pacientes con CDT en un hospital universitario van acorde a las recomendaciones internacionales actuales, particularmente la publicación de la guía ATA 2015, aplicándose radioablación con menor dosis de RI. Dado este cambio, se ha evidenciado igualdad de efectos con dosis menores de RI y consecuentemente menos efectos adversos.

Introduction: Differentiated thyroid cancer (CDT) is currently the most frequent endocrine neoplasia. Its standard of care is surgical treatment, associated with radioiodine ablation (IR) according to the classification proposed by the American Thyroid Association (ATA). The indications and doses of the latter have changed in recent years as research in this area advances. Objective: In the following study, the doses of IR used before and after the implementation of the latest ATA guidelines were compared. Materials and methods: Retrospective observational study of 70 patients with a diagnosis of CDT from the Clinical Hospital of the University of Chile between 2012 and 2017. Patients were grouped into two cohorts, those surgically intervened between the years 2012-2015 and 2016-2017, classifying them according to ATA risk, TNM and recurrence risk. The IR doses used were reported and compared between the cohorts. Statistical analysis: Mann Whithney. Results: When comparing the IR dose between both cohorts, according to TNM and ATA risk, the following results were obtained: T1b patients in the 2012-2015 cohort had significantly higher IR doses than those in the 2016-2017 cohort; It was also evidenced that N0 patients showed a statistically significant tendency to decrease the IR dose; In addition, the 2012-2015 cohort with intermediate ATA risk, revealed IR doses significantly higher than those used in the 2016-2017 cohort. Conclusion: It is concluded that the variations in IR doses, used in patients with CDT in a university hospital, are in accordance with current international recommendations, particularly the publication of the ATA 2015 guidelines, applying radioablation with a lower dose of IR. Given this change, equality of effects has been evidenced with lower doses of IR and consequently fewer adverse effects.

Ultrasonography Echotexture as a surrogate for Sialadenitis secondary to 131I Radioiodine Therapy for differentiated Thyroid Cancer: a review and metaanalysis

To systematically review and analyze the medical literature to assess ultrasonography echotexture changes in thyroid cancer patients for the detection of chronic sialadenitis caused by radioiodine therapy. Methods: Sources were retrieved from PubMed, Scopus, EMBASE and LILACS through November 2018. All studies that assessed ultrasonographic features before 131I administration and at 12 months after 131I administration were selected. After data extraction, statistical analysis was performed by using Stata software. Results: From a total of 435 studies, 4 studies involving 665 patients were considered eligible, and echotexture heterogeneity was found with a significant difference. Conclusions: Ultrasound echotexture may detect chronic sialadenitis secondary to salivary radioiodine therapy.

Short- and long-term effects of zinc treatment on lacrimal gland histopathology and tear functions tests in radioiodine-administered rats / Efeitos de curto e longo prazo do tratamento com zinco na histopatologia da glândula lacrimal e funções lacrimais em ratos que receberam iodo radioativo

ABSTRACT Purpose: To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. Methods: A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage. All rats underwent tear function tests before and 1 week after RAI administration. About 1 week after irradiation, half of the animals in each group were sacrificed and the extraorbital lacrimal glands were removed for histopathological examination. The remaining animals of the groups underwent the same procedures at 8 weeks after irradiation. Results: In the RAI and zinc groups, the mean tear production was 3.75 ± 1.55 and 3.65 ± 1.53 mm at baseline, 2.10 ± 1.07 and 3.30 ± 1.34 mm at week 1 (p=0.004), and 3.22 ± 1.48 and 3.50 ± 1.78 mm at week 8, respectively; further, the mean corneal fluorescein staining scores were 4.65 ± 2.16 and 4.80 ± 2.21 points at baseline, 7.85 ± 1.90 and 5.45 ± 2.06 points at week 1 (p=0.001), and 5.44 ± 2.13 and 4.90 ± 2.08 at week 8, respectively. The histopathological changes in rat lacrimal glands at weeks 1 and 8 were consistent with the tear function test results. Conclusions: Zinc treatment seems to be protective against RAI-induced lacrimal gland damage of rats, particularly in the acute period.

RESUMO Objetivo: Investigar se o tratamento com zinco tem efeito protetor, no curto prazo (1 semana) e longo prazo (8 semanas), sobre os danos induzidos na glândula lacrimal por iodo radiotativo (RAI) em ratos. Métodos: Quarenta ratos foram divididos em dois grupos. No grupo RAI (n=20) foi administrada uma única dose de 3 mCi 131I e 1 cc de solução salina fisiológica durante 7 dias, por gavagem gástrica. O grupo zinco (n=20) recebeu uma dose única de 3 mCi 131I e 1 cc de solução salina fisiológica contendo sulfato de zinco na concentração de 10 mg/kg durante 7 dias por gavagem gástrica. Os testes de função lacrimal foram realizadas para todos os animais antes e após uma semana da administração da RAI. Em seguida, após 1 semana da administração, metade dos animais de cada grupo foi sacrificada e as glândulas lacrimais extraorbitais foram removidas para exame histopatológico. Os animais remanescentes dos grupos foram submetidos aos mesmos procedimentos após 8 semanas a radiação. Resultados: As médias de produção lacrimal foram de 3,75 ± 1,55 e 3,65 ± 1,53 mm na linha de base, 2,10 ± 1,07 e 3,30 ± 1,34 mm na 1a semana (p=0,004), e 3,22 ± 1,48 e 3,50 ± 1,78 mm na 8a semana, para os grupos RAI e zinco, respectivamente. As pontuações médias de coloração fluoresceína foram 4,65 ± 2,16 e 4,80 ± 2,21 no início do estudo, 7,85 ± 1,90 e 5,45 ± 2,06 na primeira semana (p=0,001), 5,44 ± 2,13 e 4,90 ± 2,08 pontos na 8a semana, para os grupos RAI e zinco, respectivamente. As alterações histopatológicas das glândulas lacrimais em 1 e 8 semanas foram consistentes com os testes de função lacrimal resultados. Conclusões: O tratamento de zinco parece ser protetor sobre os danos glândula lacrimal induzidos por RAI em ratos, especialmente no período agudo.

Long term outcome and side effects in patients receiving low-dose I125 brachytherapy: a retrospective analysis

ABSTRACT Objectives: To retrospectively evaluate the disease free survival (DFS), disease specific survival (DSS),overall survival (OS) and side effects in patients who received low-dose rate (LDR) brachytherapy with I125 stranded seeds. Materials and methods: Between july 2003 and august 2012, 274 patients with organ confined prostate cancer were treated with permanent I125 brachytherapy. The median follow-up, age and pretreatment prostate specific antigen (iPSA) was 84 months (12-120), 67 years (50-83) and 7.8 ng/mL (1.14-38), respectively. Median Gleason score was 6 (3-9). 219 patients (80%) had stage cT1c, 42 patients (15.3%) had stage cT2a, 3 (1.1%) had stage cT2b and 3 (1.1%) had stage cT2c. The median D90 was 154.3 Gy (102.7-190.2). Results: DSS was 98.5%.OS was 93.5%. 13 patients (4.7%) developed systemic disease, 7 patients (2.55%) had local progression. In 139 low risk patients, the 5 year biochemical freedom from failure rate (BFFF) was 85% and 9 patients (6.4%) developed clinical progression. In the intermediate risk group, the 5 year BFFF rate was 70% and 5 patients (7.1%) developed clinical progression. Median nPSA in patients with biochemical relapse was 1.58 ng/mL (0.21 – 10.46), median nPSA in patients in remission was 0.51 ng/mL (0.01 – 8.5). Patients attaining a low PSA nadir had a significant higher BFFF (p<0.05). Median D90 in patients with biochemical relapse was 87.2 Gy (51 – 143,1). Patients receiving a high D90 had a significant higher BFFF (p<0.05). Conclusion: In a well selected patient population, LDR brachytherapy offers excellent outcomes. Reaching a low PSA nadir and attaining high D90 values are significant predictors for a higher DFS.

Eficacia y seguridad de sorafenib en el tratamiento de pacientes con diagnóstico de carcinoma de tiroides diferenciado, metastásico, irresecable, refractario a tratamiento con yodo radioactivo / Efficacy and safety of sorafenib in the treatment of patients with differentiated, metastatic, unresectable thyroid carcinoma refractory to treatment with radioactive iodine

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar el uso e la seguridad y eficacia de sorafenib en el tratamiento de pacientes con diagnóstico de carcinoma de tiroides, metastásico, irresecable, refractario a tratamiento con yodo radioactivo detnro del sistema de EsSalud, indicación actualmente no contempla en el petitorio de medicamentos.Generalidades: El cáncer de tiroides es la neoplasia endocrin más frecuente, representando más del 90% de todas las neoplasias endocrinas. Se estima que a nível mundial la incidencia de cáncer de tiroides es mayor en los países desarrollados que en los países en desarrrollo, específicamente 11.1 casos por cada 100 000 habitantes y 4.7 casos por cada 100 000 habitantes, respectivamente. Sin embargo, la mortalidad por cáncer de tiroides es menos en los países desarrollados que en los países en desarrollo, específicamente 0.4 muertes por cada 100 000 habitantes y en 0.7 muertes por cada 100 000 habitantes, respectivamente. Tecnología Sanitaria de Interés: Sorafenib: Sorafenib es un compuesto sintético, inhibidor de quinasas múltiple con capacidad de inhibir tanto los VEGFR-1, VEGFR-2, VEGFR-3 y el receptor beta del factor de crecimiento derivado de las plaquetas, así como la expresión de los genes RET (incluyendo la translocación RET/PTC), RAF (incluyendo la mutación BRAFV600E, C-RAF y B-RAF), c-kit y Flt-3 (25,26).Desde el punto de vista farmacológico, sorafenib alcanza concentraciones séricas máximas a las 2.5-12-5 horas post administración oral, pero se asocia con una biodisponibilidad del 38%-49% que disminuye significativamente con la ingesta de grasas. METOLOGÍA: Estrategia de Búsqueda: La presente evaluación de tecnología fue preparada y revisada por el equipo técnico del IETSI. Las siguientes fuentes ha sido revisadas y consultadas con la intención de buscar la mejor evidencia disponible que directamente responda a la pregunta PICO de esta evaluación. American Thyroid Association (ATA) de los Estados Unidos, British Thyroid Association (ETA) del Reino Unido, Canadian Agency for Drugs and Technologies in Health (CADTH), Cochrane Library, Canadian Agency for Drugs and Technologies in Helath (CADTH), Cochrane Library, Cumulative Index to Nursing and Allied Health Literatura (CINAHL), Embase, European Society of Medical Oncology (ESMO) de Europa, European Thyroid Association (ETA) de Europa, Institute for Health Technology Assessment Ludwing Boltzmann Gelsellschaft (LBIHTA) de Austria, Medline/Pubmed, National Guideline Clearinghouse (NGC) de los Estados Unidos, National Institute for Health Research (NIHR) del Reino Unido, Scopus, Scopus, Scottihs Medicines Consortium (SMC), Translating Research into Practice (TRIP Database)Web of Science. RESULTADOS: Luego de revisar un total de 853 referencias resultados de nuestra búsqueda bibliográfica, logramos filtrar 166 referencias relevantes para nuestra pregunta PICO de interés, de los cuales sólo 21 referencias fueron finalmente selecionadas para nuestro análisis, toda vez que constituían referencias que respondían a la pregunta PICO de interés de este dictamen, incluyendo tres guias de práctica clínica, tres meta-análisis, una evaluación de tecnología y 14 referencias todas procedentes de un ensayo clínico de fase III. CONCLUSIONES: A la fecha no se dispone de evidencia que sustente de maera consistente un beneficio neto de sorafenib como alternativa de tratamiento más eficaz, segura en el manejo de pacientes con diagnóstico carcinoma de tiroides, metastásico, irresecable, refractario a tratamiento con yodo radioactivo. La evidencia disponible, sugiere que sorafenit tiene una ventaja relativa sobre el placebo solo en términos de desenlaces intermedios como la sobrevida libre de progresión y tasa de respuesta parcial, pero no se tiene evidencia que éstas se traduzcan en un beneficio en cuanto a desenlaces clínicos finales de alta relevancia desde la perspectiva del paciente, como la sobrevida global y la calidad de vida; es más, existe evidencia consistente que sorafenib conctituye un riesgo mayor eventos adversos serios y evidencia que sugiere que este medicamento puede incrementar el riesgo muerte por cualquier causa durante el lapso de seguridad del tratamiento. El hecho que la evidencia al momento existente establece que las ganancias atribuibles al sorafenib se da solo en desenlaces clínicos intermedios de relativo significado clínico desde la perspectiva del paciente (como la sobrevida livre de progresión y tasa de respuesta), que no se traducen en otros desenlaces de alta relevancia para el paciente (como la sobrevida global y la calidad de vida), y que ocurre a costa de un mayor riesgo (con evidencia bastante consistente incluso proveniente de meta-análisis) de muerte por culquier causa y de eventos adversos serios, limita seriamente la posibilidad de recomendar el uso de este medicamento algún beneficio neto para estos pacientes.El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI, no aprueba el uso de sorafenib en Pacientes adultos con carcinoma de tiroides diferenciado, metastásico, irresecable, refractario a tratamiento con yodo radioactivo.

Radioiodine-induced oxidative stress in patients with differentiated thyroid carcinoma and effect of supplementation with vitamins C and E and selenium (antioxidants)

ABSTRACT Objective The objective of this study, in addition to confirming that therapy with 131I causes oxidative stress, was to evaluate the effect of supplementation with vitamins C and E and selenium on this phenomenon by measuring plasma 8-epi-PGF2a, a marker of lipid peroxidation. Subjects and methods Forty patients with thyroid cancer submitted to thyroidectomy, who received 3.7 GBq 131I after levothyroxine withdrawal, were selected; 20 patients did not receive (control group) and 20 patients received (intervention group) daily supplementation consisting of 2000 mg vitamin C, 1000 mg vitamin E and 400 µg selenium for 21 days before 131I. Plasma 8-epi-PGF2a was measured immediately before and 2 and 7 days after 131I. Results A significant increase in plasma 8-epi-PGF2a after 131I was observed in the two groups. The concentrations of 8-epi-PGF2α were significantly higher in the control group before and 2 and 7 days after 131I. The percentage of patients with elevated 8-epi-PGF2α was also significantly higher in the control group before and after 131I. Furthermore, the increase (percent) in 8-epi-PGF2α was significantly greater in the control group (average of 112.3% versus 56.3%). Only two patients (10%) reported side effects during supplementation. Conclusions Ablation with 131I causes oxidative stress which can be minimized by the use of antioxidants.

Is radioactive iodine- 131 treatment related to the occurrence of non-synchronous second primary malignancy in patients with differentiated thyroid cancer?

Objective Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs . 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors.

Incidencia de patología salival sintomática aleada en pacientes tratados con yodo radioactivo por cáncer diferenciado de tiroides / Incidence of sympthomatic salivary disease in patients with differentiated thyroid cancer treated with radioactive iodine

Background: The radioactive iodine therapy for differentiated thyroid cancer can produce severe and frequent salivary symptoms, during the treatment or later. Aim: To analyze the incidence, severity and charactheristics of the salivary signs and symptoms in these patients. Patients and Method: Retrospective and descriptive analisis of 106 patients with confirmed diagnosis of differentiated thyroid cancer, treated with surgery and radioactive iodine, that completed a telephonic survey for the evaluation of salivary symptoms. Results: 26 (24.52 percent) patients presented with salivary symptoms or signs after the radioactive iodine therapy (mean 5 months). The average doses of I 131 was 128,5 mCi. Xerostomy, pain, xeroftalmy, inflammation, sialoadenitis and dysgeusia, were the most frequent clinical symptoms. Conclusions: After radioactive iodine therapy the salivary symptoms and signs incidence is high. We conclude that the indication for this treatment must be selective, but in accordance with the oncological risk of each patient.

Introducción: El tratamiento con yodo radioactivo en el tratamiento del cáncer diferenciado de tiroides puede originar síntomas alejados de origen salival. Éstos pueden llegar a ser intensos y frecuentes. Objetivo: Conocer la incidencia, características e intensidad de dichos síntomas. Material y Método: Revisión retrospectiva y análisis descriptivo de 106 pacientes con diagnóstico definitivo y anatomopatológico de cáncer diferenciado de tiroides, tratados con yodo radioactivo, que contestaron una encuesta telefónica especialmente diseñada para evaluación de patología salival. Resultados: Veintiséis (24,52 por ciento) pacientes presentaron y consultaron por síntomas y/o signos alejados (promedio 5 meses) de la terapia ablativa, de origen salival. La dosis promedio fue de 128,5 mCi de I 131. Los síntomas más frecuentes fueron xerostomía, dolor, xeroftalmia, inflamación, sialoadenitis y alteración del gusto. Discusión: La incidencia de signos y síntomas salivales alejados en pacientes tratados con I 131 es alta y justificaría a nuestro juicio su indicación selectiva, de acuerdo a los riesgos de recurrencia tumoral de cada paciente.

Obstrução da via lacrimal após radioiodoterapia: relato de caso e conduta / Lacrimal duct obstruction after radioiodine therapy: case report and treatment

Iodoterapia representa a terapia com iodo radioativo. A radiação beta emitida pelo iodo radioativo são partículas que irão se armazenar no tecido da tireóide destruindo as células cancerígenas que ainda restaram após a cirurgia (tireoidectomia). É importante enfatizar este possível efeito deletério da terapêutica, a qual afeta a mucosa da via lacrimal, sendo o resultado do processo de inflamação e cicatrização vascular, produzindo transtornos hipovasculares, hipocelulares e hipóxicos.

Iodotherapy represents the radioactive iodine therapy. The beta radiation emitted by radioactive iodine are particles that will be stored in the thyroid tissue destroying cancer cells that were left after surgery (thyroidectomy). It is important to emphasize a possible deleterious effect of therapy which affects the mucosa of the lacrimal system which results in a process of vascular inflammation and scarring producing disorders hypovascular, hypocellular and hypoxic.

Avaliação do surgimento de comorbidades em pacientes com doença de Graves tratados com iodo radioativo em acompanhamento por mais de 10 anos / Emerging comorbidities in Graves' disease patients treated with radioiodine with more than 10 years of follow-up

OBJETIVOS: Avaliar o surgimento de comorbidades cardiovasculares e/ou neoplásicas e a taxa de mortalidade nos pacientes com hipertireoidismo em decorrência da doença de Graves tratados com iodo radioativo há mais de 10 anos. MATERIAIS E MÉTODOS: Estudo retrospectivo com análise de prontuários do Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, entre janeiro de 1981 e novembro de 1999. RESULTADOS: Foram avaliados 107 pacientes (93 mulheres e 14 homens), com uma mediana de idade de 54 anos. Comparando o grupo de pacientes que receberam iodo radiativo com grupo de pacientes eutireoidianos pós-tratamento com drogas antitireoidianas (DAT), foi observado aumento significativo no surgimento de hipertensão arterial (HAS) e dislipidemia, mas não na taxa de mortalidade. CONCLUSÃO: Para avaliar a real influência da terapêutica com iodo radioativo no surgimento dessas comorbidades e na taxa de mortalidade, é necessário um tempo maior de acompanhamento. A idade e o tempo de exposição aos efeitos do hipertireoidismo parecem influenciar no surgimento dessas comorbidades.

OBJECTIVES: To evaluate the occurrence of cardiovascular disease and malignant tumors and the mortality rate in patients who received radioiodine treatment for hyperthyroidism due to Grave's disease with at least ten years of follow-up. MATERIALS AND METHODS: The medical records of all patients who were treated with I131 for Graves' disease at Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, were reviewed retrospectively, between January, 1981 and November, 1999. RESULTS: Data from 107 patients (14 men and 93 women), with median age of 54 years were analyzed. Comparing the group of patients who were treated with I131 therapy with a group of euthyroid patients post-treatment with antithyroid drugs, a significant increase in the occurrence of hypertension and dyslipidemia was observed, but not in mortality rate. CONCLUSION: To evaluate the real influence of the treatment with radioactive iodine in the occurrence of these comorbidities and the mortality rate, we need a longer follow-up. The age and time of exposure to the effects of hyperthyroidism seem to influence the occurrence of these comorbidities.

Estudio gammagráfico de la disfunción de las glándulas salivales en pacientes con cáncer diferenciado de tiroides tratados con yodo radiactivo I-131 en el Hospital Guillermo Almenara Lima-Perú Julio del 2012 a Diciembre del 2012 / Scintigraphic study of the dysfunction of the salivary glands in patients with differentiated thyroid cancer treated with I-131 radioactive iodine in the Hospital Guillermo Almenara Lima-Peru July 2012 to December 2012

Introducción: El presente trabajo de investigación realizado en el servicio de Medicina Nuclear del Hospital Guillermo Almenara, tiene como finalidad demostrar que el uso de yodo radioactivo en el tratamiento de cáncer de tiroides, tiene como consecuencias el daño de las glándulas salivales. Situación que se tiene que tomar en cuenta al aplicar este tipo de terapia. Objetivos: Determinar la utilidad del estudio gammagráfico en la disfunción de glándulas salivales en los pacientes que reciben yodo radiactivo por cáncer tiroideo. Material y Metodología: Se trata de un estudio observacional, prospectivo, de una sola cohorte, en la que se evaluó el grado de disfunción tiroidea estimado gammagráficamente en relación a la dosis de yodo radioactivo recibido como tratamiento de cáncer de tiroides. Resultados: Se realizaron gammagrafía de glándulas salivales a 30 sujetos antes de la terapia con yodo radiactivo y una gammagrafía a los 6 meses después del tratamiento, de los cuales 24 (80 por ciento) fueron mujeres y 6 (20 por ciento) varones. La dosis usada tuvo un rango de entre 80 a 200mCi, con una media de 100mCi, una mediana de 100mCi, y una desviación estándar de 23,03. Solamente una paciente recibió la dosis más alta de la cohorte (200mCi). En cuanto a las dosis recibidas en ambos sexos, no existieron diferencias entre varones y mujeres, habiendo recibido en promedio 103mCi en varones y 98mCi en mujeres. Conclusiones: Se concluye que la dosis de yodo radioactivo utilizada en el tratamiento del cáncer diferenciado tiroideo no guarda relación con la severidad de la afectación de las glándulas salivales, es decir, que a mayor dosis de iodo radioactivo no cabe esperar una disfunción más severa de la función de las glándulas salivales, y que posiblemente otros factores estén relacionados con dicha severidad.

Aplicaciones clínicas del radioyodo 131 (I131) en las enfermedades del tiroides / Clinical applications of radioiodine 131 (I131) in the thyroid diseases

El radioyodo 131 es un isótopo radioactivo que se emplea exitosamente en el diagnóstico y tratamiento de las enfermedades benignas y malignas del tiroides. Su propiedad de integrarse selectivamente al metabolismo del tiroides y emitir una señal, le permite describir el funcionamiento glandular mediante estudios de captación, y delimitar la morfología y localización de los tejidos que capten yodo, a través de la gammagrafía. Es además una radioterapia sencilla, segura y coste-efectiva, usada como primera línea terapéutica en el control del hipertiroidismo, cuya dosis y momento de aplicación debería individualizarse según la etiología y la clínica de cada paciente. El radioyodo 131 ofrece una alternativa eficaz para reducir el tamaño del bocio no tóxico; además, respalda el tratamiento quirúrgico del carcinoma diferenciado del tiroides, y destruye a dosis ablativa los restos tisulares y las lesiones metastásicas que puede identificar durante el seguimiento gammagráfico. El empleo de radioyodo 131 está sujeto al cumplimiento de regulaciones de protección contra la radioactividad(AU)

Radioiodine 131 is a radioactive isotope that is successfully used for the diagnosis and the treatment of benign and malignant thyroid diseases. Its quality of selectively integrating to the thyroid metabolism and emitting a signal allows it to describe the gland functioning through capture studies, and to delimit the morphology and location of the tissues that capture iodine by means of gammagraphy. It is also a simple, safe and cost-effective radiotherapy used as first-line therapeutics in the control of hyperthyroidism. The dose and right time of application should be individualized according to the etiology and the clinic of each patient. Radioiodine 131 offers an efficient alternative to reduce the size of non-toxic goiter in addition to supporting the surgical treatment of the differentiated thyroid carcinoma and destroying with ablative doses the tissular remains and the metastatic lesions that can be detected during the gammagraphic follow-up. Radioiodine 131 depends on the fulfillment of safety regulations against radioactivity(AU)

Obstrução de vias lacrimais associada ao tratamento radioiodoterápico de carcinoma de tireoide / Lacrimal drainage system obstruction associated to radioactive iodine therapy for thyroid carcinoma

OBJETIVO: Descrever uma série de pacientes portadores de obstrução do sistema lacrimal associado à radioiodoterapia para tratamento de carcinoma de tireoide, revisar os dados clínicos e a resposta ao tratamento cirúrgico desta rara complicação. MÉTODOS: Foi realizada uma análise retrospectiva dos achados oftalmológicos de pacientes com histórico de carcinoma de tireoide previamente submetidos à tireoidectomia e à RIT que foram encaminhados para cirurgia de vias lacrimais. RESULTADOS: Dezessete pacientes com carcinoma de tireoide tratados com tireoidectomia e RIT apresentaram obstrução do ducto nasolacrimal sintomática após período médio de 13,2 meses do tratamento do câncer. Onze pacientes tiveram epífora bilateral, 8 com mucocele de saco lacrimal. A idade dos pacientes variou entre 30 e 80 anos, sendo 10 com idade menor ou igual a 49 anos. A dose cumulativa média de radioiodo administrada foi de 571 mCi (variação entre 200-1200 mCi). Sintomas de obstrução nasal e aumento de glândulas salivares ocorreram em 53% dos pacientes. Todos os pacientes foram submetidos à dacriocistorrinostomia. Observou-se ainda que nos 3 pacientes mais jovens houve maior sangramento intraoperatótio e dilatação de saco lacrimal. A resolução completa da epífora e da dacriocistite ocorreu em 82,4%, e foi parcial em 17,6% (3 pacientes mantiveram queixa unilateral após a correção da obstrução bilateralmente). O seguimento médio foi de 6 meses (intervalo: 2-24 meses). CONCLUSÕES: Alta dose cumulativa de radioiodo, disfunção nasal e de glândulas salivares estão associadas à obstrução das vias lacrimais. Observa-se uma maior porcentagem de pacientes mais jovens apresentando quadro de dacriocistite quando comparado à dacrioestenose idiopática. A absorção de iodo radioativo pela mucosa do ducto nasolacrimal com subsequente inflamação, edema e fibrose parece ter relação direta com a obstrução do ducto nasolacrimal. O conhecimento desta complicação é importante para o estudo e abordagem correta desses pacientes.

PURPOSE: To report the finding of nasolacrimal drainage system obstruction associated with radio iodine therapy and to review clinical data and the surgical treatment outcome of this rare complication. METHODS: We retrospectively analyzed ophthalmological data of patients with history of thyroid carcinoma that underwent radioactive iodine I-131 therapy and were referred to lacrimal surgery. RESULTS: 17 patients with thyroid cancer treated with thyroidectomy and radioactive iodine I-131 therapy presented symptomatic nasolacrimal duct obstruction after 13.2 months following cancer treatment. 11 patients presented bilateral epiphora, 8 had lacrimal sac mucocele. Age range was 30 to 80 years, 10 patients had less than or equal to 49 years. The mean cumulative dose of radioiodine was 571mCi (range: 200-1200 mCi). Nasal obstruction symptoms and increased salivary glands were also present in 53% of patients. All subjects underwent dacryocystorhinostomy. Dilation of the lacrimal sac and increased intraoperative bleeding was also observed in 3 younger patients. Complete epiphora and dacryocystitis resolution after surgery occurred in 82.4%, and partial in 17.6% (3 patients that still presented unilateral relapse after correction of bilateral obstruction). Mean follow-up was 6 months (range: 2-24 months). CONCLUSIONS: Cumulative high dose of radioidine, nasal and salivary gland dysfunction are associated with lacrimal drainage obstruction. We observed a great percentage of younger patients presenting dacryocystitis when compared to the idiopathic dacryostenosis. Radioactive iodine uptake by nasolacrimal duct mucosa with subsequent inflammation, edema and fibrosis seems to have a relationship to lacrimal duct obstruction. The knowledge of this complication is important for the study and proper management of these patients.

A atividade dos profissionais de medicina nuclear com o Iodo-131: um estudo em psicodinâmica do trabalho / The activity of nuclear medicine professionals with Iodine-131: a study of the psychodynamics of work

As muitas incertezas presentes no trabalho dos profissionais de Medicina Nuclear que lidam com o I podem gerar riscos de exposição às radiações ionizantes. É imprescindível aproximar as normas e regulamentos da realidade complexa das atividades, na medida em que as normas, embora importantes, não as recobrem totalmente. A proposta deste estudo é buscar formas alternativas nos processos de trabalho na prática com o I que auxiliem na redução de riscos de exposição às radiações ionizantes para os trabalhadores. Baseando-se noreferencial teórico da Psicodinâmica do Trabalho, estabeleceu-se os pressupostos de que os profissionais percebem os perigos da sua função e que eles não só se defendem contra o medo referente aos riscos, por mecanismos defensivos individuais e estratégias defensivas coletivas,mas também contra os próprios riscos, de forma concreta, recorrendo a procedimentos específicos eficazes para minimizar a exposição ocupacional à radiação. Um estudo de caso foi conduzido com 15 profissionais que lidam com o 131I para diagnósticos ou tratamento, numa instituição pública de saúde. As técnicas empregadas consistiram numa entrevistaindividual semi-estruturada e a observação direta assistemática. Analisou-se o discurso destestrabalhadores pelas técnicas de análise de conteúdo, segundo Bardin e pela análise da enunciação, segundo D’Unrug. Com a finalidade de verificar as diferenças entre a organização do trabalho real e a organização do trabalho prescrito, realizou-se uma pesquisa documental em relação às normas e regulamentos, nacionais e internacionais, sobre esta fonteradioativa, para comparar os dados da pesquisa documental com os dados provenientes das entrevistas. Os resultados identificaram contradições entre os modelos prescritivos das normas e o que é vivenciado pelos trabalhadores na atividade. O medo em relação aos riscos fez com que se defendessem, modificando os modos operatórios prescritos, em virtude de mecanismos de defesa individuais, como a racionalização e a negação do risco, e de estratégias defensivas coletivas, levando-os a um maior enfrentamento do risco como defesa. Observou-se também o papel defensivo das ideologias da profissão. Algumas categorias profissionais recorreram a procedimentos específicos a partir de conhecimentos tácitos aprendidos no ofício, contra os próprios riscos, denominados de saberes-fazer de prudência, capazes de minimizar aexposição à radiação. Em contrapartida aos discursos tradicionais sobre a prevenção, os trabalhadores percebem os perigos do seu trabalho, e os saberes-fazer de prudência, ao invés de serem abolidos pelos especialistas, devem ser reconhecidos e incorporados aogerenciamento de riscos para que este possa ser realmente eficaz.

Radioactive iodine and radioactive cesium: two important radio-hazard elements in post nuclear power plant crisis

The present nuclear leakage crisis from Japan is a topic to be discussed in present public health. In radiology, the leaked radioactive elements are considered hazard. Here, the author briefly reviews and discusses on two important radio-hazard elements in post nuclear power plant crisis, radioactive iodine and radioactive cesium. Based on previous similar nuclear crisis in Russia, it is evidenced that the increased incidence of some cancers in post-crisis period is due to exposure to these two important radioactive elements

Carotid artery rupture following radioiodine therapy for differentiated thyroid carcinoma / Ruptura de carótida pós-iodoterapia em carcinoma diferenciado de tireoide

INTRODUCTION: Radioiodine therapy for patients with differentiated thyroid cancer aims at reducing tumor recurrence by eradicating residual macro- and microscopic foci. Side effects are generally rare, tenuous and transient, with little clinical significance. OBJECTIVE: To report a rare case of differentiated thyroid carcinoma presenting a large expansive solid mass at the base of the skull, with invasion of the left masticatory muscle and adjacent subcutaneous tissue, and without invasion of the carotid space, which evolved to carotid artery rupture following radioiodine therapy. DISCUSSION: Side effects are uncommon after radioiodine therapy and when present, have mild intensity. Serious adverse events are very rare, especially those arising from structures not directly invaded by metastatic tissue with radioiodine uptake, as occurred in this case. This occurrence serves to raise awareness of the need for increased care when using radioiodine therapy on high-avidity masses located close to important structures.

INTRODUÇÃO: Iodoterapia em pacientes com carcinoma diferenciado da tireoide tem o objetivo de reduzir a recorrência tumoral erradicando focos residuais macro e microscópicos. Os efeitos colaterais, em geral, são raros, tênues e transitórios, com pouca repercussão clínica. OBJETIVO: Relatar um caso raro de carcinoma diferenciado da tireoide apresentando grande massa sólida expansiva na base do crânio, com invasão da musculatura mastigatória esquerda e do tecido subcutâneo adjacente, sem invasão do espaço carotídeo que evoluiu com ruptura de carótida pós-iodoterapia. DISCUSSÃO: Os efeitos colaterais pós-iodoterapia são pouco frequentes e, quando presentes, de intensidade discreta. Os eventos adversos graves são muito raros, em especial, aqueles decorrentes de estruturas não invadidas diretamente pelo tecido metastático iodocaptante, como nesse caso, alertando também para a necessidade do aumento dos cuidados na terapia de grandes massas ávidas pelo radioiodo próximas às estruturas nobres.

Transient cytotoxicity of 131I beta radiation in hyperthyroid patients treated with radioactive iodine.

Background & objectives: Radioiodine (131I) or radioactive iodine in low doses is used worldwide as the first line of management in the treatment of hyperthyroidism. Information is available on the extent and severity of cell damage after a high dose radioiodine (131I) therapy for thyroid cancer, but information is scanty on its cellular effects, its extent and severity of cell damage after a low dose 131I therapy. The present investigation was aimed to study the cytotoxic effects of a low dose 131I therapy in varying doses as is normally being used in routine clinical practice in the treatment of various forms of hyperthyroidism. Methods: Peripheral blood lymphocytes were analyzed in 32 hyperthyroid patients. All of them received 131I in the form of sodium iodide solution orally. Blood lymphocytes were studied for the presence of chromosomal aberrations (CA) and micro nucleus (MN) using micronucleus assay. Blood samples of these patients were drawn prior to the treatment, on 7 thand 30 thdays after the treatment. Results: The results indicated a positive relationship between 131I dose, CA and MN frequency. A statistically significant increase in CA and MN frequency in day 7 post- therapy and a decrease in mean levels of CA and MN on day 30 post-therapy were observed when compared to pre-therapy. Interpretation & conclusions: This study showed that the cytogenetic damage induced by 131I in low doses i.e., less than 555MBq was minimal and reversible. Patients can be motivated to undertake this safe and easy procedure as a first line of therapy in the treatment of hyperthyroidism.

Radioiodine therapy for hyperthyroidism

Radioiodine therapy is the safest, simplest, least expensive and most effective method for treatment of hyperthyroidism. The method employed in this research was a systematic bibliographic review, in which only valid studies or the clinically detailed enough open-labeled studies using validated scales were used. Iodine-131 [I-131] acts by the destructive effect of short-range beta radiation on thyroid cells. Indications for radioiodine therapy include toxic nodules [in which I-131 is the first choice of treatment], recurrent hyperthyroidism after antithyroid treatment or surgery, intolerance to antithyroid therapy due to side-effects and patient preference. Due to difficulties in previous methods for dose determination, fixed dose method of I-131 is now considered the best practical method for radioiodine therapy in primary hyperthyroidism. Absolute contraindications for radioiodine treatment are pregnancy and lactation. In pediatric patients, radioiodine therapy can be used, but is mainly considered in recurrent toxic goiter and when antithyroid medication is ineffective. There is no clear evidence indicative of carcinogenic or teratogenic effect of this agent