Estratificação de Risco e Avaliação da Atividade Simpática Cardíaca Utilizando Imagem Miocárdica com [123I] MIBG na Denervação Renal / Risk Stratification and Cardiac Sympathetic Activity Assessment Using Myocardial [123I] MIBG Imaging in Renal Denervation

Resumo A hiperativação do sistema nervoso simpático desempenha um papel central na fisiopatologia da hipertensão. O objetivo deste estudo foi avaliar a atividade simpática cardíaca e investigar o papel da cintigrafia miocárdica com metaiodobenzilguanidina com 123I ([123I] MIBG) na estratificação de risco cardiovascular de pacientes com hipertensão resistente tratados com denervação renal (DR). Dezoito pacientes foram incluídos neste estudo prospectivo (média de idade de 56 ± 10 anos, 27,8% mulheres). Ecocardiograma transtorácico, análise geral do sangue e cintilografia miocárdica com [(123I) MIBG] foram realizados antes e seis meses após a DR. Um paciente era considerado respondedor (R) se uma diminuição ≥ 5 mmHg na pressão arterial sistólica (PAS) média ambulatorial fosse observada no seguimento de seis meses. 66,7% dos pacientes foram R (diminuição na PAS de 20,6 ± 14,5 mmHg, vs. menos 8 ± 11,6 mmHg em não-respondedores (NR), p = 0,001). A relação coração-mediastino (RCM) inicial foi significativamente menor na linha basal no grupo R (1,6 ± 0,1 vs. 1,72 ± 0,1, p <0,02), mas semelhante em seis meses. Considerando os dois momentos no tempo, o grupo R teve valores iniciais de RCM mais baixos do que o grupo NR (p <0,05). Tanto o RCM tardio quanto a taxa de washout foram idênticos e nenhuma correlação significativa entre a resposta à DR ou qualquer índice de imagem com MIBG foi encontrada. A denervação renal efetivamente reduziu a pressão arterial na maioria dos pacientes, mas a imagem com [123I] MIBG não foi útil na previsão da resposta. Entretanto, houve evidência de overdrive do sistema nervoso simpático e, tanto a RCM inicial quanto tardia estavam reduzidas em geral, provavelmente colocando essa população em um risco maior de eventos adversos.

Abstract Hyperactivation of the sympathetic nervous system plays a central role in the pathophysiology of hypertension. The aim of this study was to assess cardiac sympathetic activity and investigate the role of myocardial123I-labelled meta-iodo benzyl guanidine ([123I] MIBG) scintigraphy in cardiovascular risk stratification of patients with resistant hypertension treated with renal denervation (RDN). Eighteen patients were included in this prospective study (mean age 56 ± 10 years old, 27.8% females). Transthoracic echocardiogram, general blood analysis and myocardial ([123I] MIBG scintigraphy were performed before and six-months after RDN. A patient was considered a responder (R) if a drop ≥ 5mmHg on mean systolic ambulatory blood pressure (BP) monitoring was observed at the six-month follow-up. 66.7% of patients were R (drop in systolic BP of 20.6 ± 14.5mmHg, vs minus 8 ± 11.6mmHg in non-responders (NR), p=0.001). Early heart-mediastinum ratio (HMR) was significantly lower at baseline in the R group (1.6 ± 0.1 vs 1.72 ± 0.1, p<0.02) but similar at six months. Considering both instants in time, the R group had lower early HMR values than the NR group (p<0.05). Both the late HMR and the washout rate were identical and no significant correlation between response to RDN or any MIBG imaging index was found. Renal denervation effectively lowered blood pressure in the majority of patients but [123I] MIBG was not useful in predicting the response. However, there was evidence of sympathetic overdrive and, both early and late HMR were overall reduced, probably putting this population at a higher risk of adverse events.

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.

Long-term results of visual function in posterior uveal melanoma patients treated with I125 episcleral brachytherapy in a Spanish referral Ocular Oncology Unit / Resultados de longo prazo da função visual em pacientes com melanoma uveal posterior tratados com braquiterapia epiescleral com I125 em uma unidade de referência em Oncologia Oftalmológica na Espanha

ABSTRACT Purposes: We analyzed patient, tumor and dosimetric characteristics of subjects in a Spanish population diagnosed with uveal melanoma treated with iodine 125 (I125) episcleral brachytherapy, who presented with post-treatment loss of useful visual acuity and global evolution of visual acuity. Methods: A single historic observational cohort study was undertaken. Patients with uveal melanoma were recruited between September 1995 and June 2015. Clinical, tumor and dosimetric data collection and visual acuity evaluations were performed under everyday practice conditions based on a useful visual acuity >0.1 on the decimal scale. The baseline analysis was performed using descriptive and survival analyses according to Kaplan-Meier curves. Results: A total of 286 of the 665 patients diagnosed with uveal melanoma received episcleral brachytherapy, and 198 were included in the study. The mean follow-up time was 75.3 months (95% CI = 68.0-82.6). Patients with post-treatment useful visual acuity loss (n=94, 47%) presented the following characteristics: visual symptoms (n=80, p-value = 0.001); iris color (brown n=33, hazel green n=49, p-value = 0.047); Collaborative Ocular Melanoma Study size (medium n=80, p-value = 0.159); tumor, node, metastasis stage (T2: n=38, T3: n=38, p=0.012); shape (nodular n=67, mushroom-shaped n=26, p=0.001); posterior pole involvement (n=47, p=0.04); recurrence (n=10, p=0.001); and dose administered in the fovea, optic nerve and center of the eye (p<0.002). Using Kaplan-Meier analysis, the mean overall survival of useful visual acuity was 90.19 months, and the probability of preserving useful visual acuity was 66% for one year, 45% for five years and 33% for ten years. Conclusion: Patients most likely to present with visual acuity loss were those with the following profile: elderly males with dark irises who were diagnosed with visual symptoms and exhibited a medium/large melanoma with a mushroom shape in the posterior pole (near the fovea and/or optic nerve). All patients treated with episcleral brachytherapy are likely to present with visual acuity loss, which is more pronounced in the first few years following treatment.

RESUMO Objetivo: Analisar características individuais, tu morais e dosimétricas de pacientes diagnosticados com melanoma uveal, tratados através de braquiterapia epiescleral com iodo-125 (I125), que apresentaram perda da acuidade visual útil após o tratamento e analisar a evolução global da acuidade visual em uma população da Espanha. Métodos: Este é um estudo observacional de coorte histórica considerando pacientes com melanoma uveal diagnosticados entre setembro de 1995 e junho de 2015. Foram coletados dados clínicos, tumorais e dosimétricos e medida a acuidade visual em condições de prática clínica diária, considerando uma acuidade visual útil superior a 0,1 na escala decimal. A análise de base foi efetuada por curvas Kaplan-Meier descritivas de sobrevivência Resultados: Um total de 286 dos 665 pacientes diagnosticados com melanoma uveal recebeu braquiterapia epiescleral e 198 deles foram incluídos no estudo. O tempo médio de acompanhamento foi de 75,3 meses (IC 95%: 68,0-82,6). Os pacientes com perda da acuidade visual útil após o tratamento (n=94, 47%) apresentaram as seguintes características: sintomas visuais (n=80, p=0,001), cor da íris (castanha: n=33, castanho-esverdeada: n=49; p=0,047), tamanho de acordo com o Collaborative Ocular Melanoma Study (tamanho médio: n=80, p=0,159), tumor, nódulo, estágio de metástase (T2: n=38, T3: n=38, p=0,012), forma (nodular: n=67, em forma de cogumelo: n=26, p=0,001), envolvimento do polo posterior (n=47, p=0,04), recorrência (n=10, p=0,001) e dose administrada na fóvea, no nervo óptico e no centro do olho (p<0,002). Na análise de Kaplan-Meier, o tempo médio de sobrevivência geral da acuidade visual útil foi de 90,19 meses e a probabilidade de preservação da acuidade visual útil foi de 66% por um ano, 45% por 5 anos e 33% por 10 anos. Conclusão: O perfil de paciente com maior probabilidade de perda da acuidade visual útil é o de homem idoso com íris escura, diagnosticado com sintomas visuais e melanoma de tamanho médio a grande, em forma de cogumelo no polo posterior (próximo à fóvea, ao nervo óptico ou a ambos). Todos os pacientes tratados com braquiterapia epiescleral terão perda da acuidade visual, mais pronunciada nos primeiros anos após o tratamento.

Resultados a corto plazo del tratamiento con 131I en el bocio multinodular: valor adicional de la estimulación previa con rhTSH / Short-term results of treatment with 131I in multinodular goiter: additional value of previus stimulation with Recombinant human thyrotropin

OBJETIVO: El yodo radiactivo (131I) es una opción terapeútica segura y eficaz cuando se utiliza solo o con la estimulación previa de TSH recombinante humana (rhTSH) en el tratamiento del bocio multinodular (BMN). En espera de ensayos clínicos que determinen la dosis óptima, demuestren seguridad y confirmen la eficacia, diferentes protocolos se utilizan para aplicar la dosis de 131I. Analizamos la respuesta al tratamiento con una dosis calculada por protocolo mixto (dosis fijas y cálculo por porcentaje de captación) en pacientes con BMN toxico y no toxico en nuestro hospital, en el periodo 2010-2013. MATERIALES Y MÉTODOS: Estudio prospectivo en pacientes con BMN no quirúrgico (BMNNQ) que requerían reducción del volumen glandular y/o tratamiento del hipertiroidismo. Se evaluaron 134 pacientes, 14 cumplieron con los criterios de inclusión (13mujeres) de edad media 71.08 años. Un grupo con BMN toxico, otro grupo con BMN no toxico, un tercer grupo con BMN no toxico estimulado con 0,1 mg de rhTSH previo a la dosis. Se evaluó, función tiroidea, captación tiroidea de 99ᵐTc, volumen tiroideo y síntomas compresivos. Se siguió a los pacientes durante 12 meses. RESULTADOS: Se aplicaron dosis entre 15 y 30 mCi de 131I. Remitió el hipertiroidismo en 6 de 7 pacientes. Hubo una reducción del volumen glandular (p<0.01).Los pacientes con estímulo de 0,1 mg rhTSH, aumentaron el porcentaje de captación de 99ᵐTc a las 24 h en un 32.43±10.61 permitiendo aplicar menor dosis de 131I. La tasa de aparición de hipotiroidismo fue de 7.41 por cada 100 pacientes.mes, mayor en pacientes con BMN toxico tratados con dosis bajas (p-=0.03). Hubo una mejoría subjetiva de la clínica compresiva en todos los pacientes. No hubo eventos adversos. CONCLUSIONES: Una dosis de 131I calculada por protocolo mixto es efectiva y segura para la reducción del volumen glandular y control del hipertiroidismo asociado. La estimulación con rhTSH logra el mismo efecto con una menor dosis administrada.

OBJECTIVE: Radioactive iodine (131I) is a safe and effective therapeutic option when used alone or with prior stimulation of recombinant human Thyrotropin (rhTSH) in the treatment of multinodular goiter (MNG). In absence of clinical trials that determine the optimal dose, demonstrate safety and confirm efficacy, different protocols are used to apply the dose of 131I. We analyze the response to treatment with a dose calculated by mixed protocol (fixed doses and calculation by percentage of uptake) in patients with toxic and non-toxic MNG in our hospital, in the period 2010-2013. MATERIALS AND METHODS: Prospective study in patients with non-surgical MNG that required glandular volume reduction and / or treatment of hyperthyroidism. 134 patients were evaluated, 14 met the inclusion criteria (13 women) of average age 71.08 years. One group with toxic MNG, another group with non-toxic MNG and a third with non-toxic multinodular goiter stimulated with 0.1 mg of rhTSH prior to the dose. Patients were followed for 12 months. Upon following, we assessed Thyroid function, 99ᵐTc thyroid uptake, thyroid volume and compressive symptoms. RESULTS: Doses between 15 and 30 mCi of 131I were applied. We observed hyperthyroidism remission in 6 of 7 patients. There was a reduction in glandular volume (p <0.01) considering all patients. Patients with a stimulus of 0.1 mg rhTSH, increased the percentage of uptake of 99ᵐTc at 24 h by 32.43 ± 10.61, allowing a lower dose of 131I to be applied. The rate of onset of hypothyroidism was 7.41 per 100 patients-month, and was higher in patients with toxic MNG treated with low doses (p = 0.03). There was a subjective improvement of the compression clinic in all patients. No adverse events were observed. CONCLUSIONS: A dose of 131I calculated by a mixed protocol is effective and safe for achieving glandular volume reduction and associated hyperthyroidism control. Stimulation with rhTSH produces the same effect with a lower administered dose.

In properly selected patients with differentiated thyroid cancer, antithyroglobulin antibodies decline after thyroidectomy and their sole presence should not be an indication for radioiodine ablation

ABSTRACT Objective Our objective was to evaluate the trend of antithyroglobulin antibodies (TgAb) during follow-up of patients with differentiated thyroid cancer (DTC) treated without RAI, as well as their role in the risk of recurrence. Subjects and methods This was a prospective, descriptive study. A total of 152 consecutive patients with DTC treated in a single institution undergoing total thyroidectomy without RAI and followed for a median of 2.3 years (0.5-10.3) were divided in two groups: TgAb(-) (n = 111) and TgAb(+) (n = 41). Patients were classified according to AJCC 7th and 8th editions, as well as to their risk of recurrence and response to treatment categories. Results Both groups, TgAb(-) and TgAb(+), were similar regarding patient and tumor characteristics. At the end of follow-up, 90 (59.2%), 57 (37.5%), 3 (2%) and 2 (1.3%) patients achieved excellent, indeterminate, biochemically incomplete and structurally incomplete response, respectively. The risk of structural recurrence was similar in both groups (TgAb[-] 0.9% vs. TgAb[+] 2.4%, p = 0.46). In the TgAb(+) group, TgAb became negative in 10 (24.4%), decreased ≥ 50% without negativization in 25 (60.9%), decreased < 50% in 4 (9.8%) and remained stable or increased in 2 (4.9%) cases. The only incomplete structural response had increasing TgAb during follow-up. Conclusions In properly selected patients with DTC, TgAb concentration immediately after total thyroidectomy should not mandate RAI ablation, and their trend during follow-up may impact the risk of recurrence.

Tratamiento con radioyodo endovenoso y estimulación con TSH recombinante humana en paciente con cáncer de tiroides extenso: caso clínico / Intravenous radioiodine and recombinant human TSH in a patient with extensive thyroid cáncer: report of one case

Abstract: We report a 72-years-old male patient with extensive differentiated thyroid cancer (DTC), who required a tracheostomy and gastrostomy. Considering his clinical condition, risk of aspiration and management of the ostomies, radioiodine (131I) was administered intravenously, using recombinant human thyrotropin (rhTSH) and levothyroxine. The procedure was successful, both clinically and in terms of radioprotection.

Clinical outcomes of low and intermediate risk differentiated thyroid cancer patients treated with 30mCi for ablation or without radioactive iodine therapy

ABSTRACT Objective To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). Subjects and methods A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. Results From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). Conclusions Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

Radioyodo como tratamiento de hipertiroidismo en un paciente en hemodiálisis: Caso clínico / Treatment of hyperthyroidism with radioiodine during hemodialysis: Report of one case

Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.

Recombinant human TSH versus thyroid hormone withdrawal in adjuvant therapy with radioactive iodine of patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central compartment (cN1b)

ABSTRACT Objective To compare the short- and long-term outcomes of adjuvant therapy with radioactive iodine (RAI) preceded by the administration of recombinant human TSH (rhTSH) versus thyroid hormone withdrawal (THW) in patients with papillary thyroid carcinoma and clinically apparent lymph node metastases not limited to the central neck compartment (cN1b). Subjects and methods The sample consisted of 178 cN1b patients at intermediate risk who underwent total thyroidectomy with apparently complete tumor resection [including postoperative ultrasonography (US) without anomalies] and who received adjuvant therapy with RAI (30-100 mCi) preceded by the administration of rhTSH (n = 91) or THW (n = 87). Results One year after RAI, the rates of excellent response to therapy, i.e., nonstimulated thyroglobulin (Tg) ≤ 0.2 ng/mL with negative antithyroglobulin antibodies and negative neck US, and of structural disease were similar for the two preparations (84% and 4.5%, respectively, in both groups). During follow-up (median 66 months), the rate of structural or biochemical (nonstimulated Tg > 1 ng/mL, with increment) recurrence was also similar in the two groups (4.5%). In the last assessment, the percentage of patients without evidence of disease, i.e., nonstimulated Tg < 1 ng/mL and no evidence of structural disease, was similar for the two preparations [92.3% in the rhTSH group and 97.7% in the THW group (p = 0.17)]. Conclusion Preparation with rhTSH was equally effective (short- and long-term) as THW for adjuvant RAI therapy of cN1b patients at intermediate risk and with apparently complete tumor resection.

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.

Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma

ABSTRACT Objective The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. Subjects and methods Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. Results The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). Conclusions The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction / Efeito do Nebivolol sobre Parâmetros do MIBG e Exercício na Insuficiência Cardíaca com Fração de Ejeção Normal

Abstract Background: More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. Objectives: To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. Methods: Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO2). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. Results: After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO2 and 123I-MIBG scintigraphic parameters. Conclusion: Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.

Resumo Fundamento: Mais de 50% dos pacientes com insuficiência cardíaca têm fração de ejeção preservada (ICFEN). A cintilografia marcada com iodo 123 com metaiodobenzilguanidina (123I-MIBG) e o teste cardiopulmonar do exercício (TCPE) são marcadores de prognóstico da ICFEN. O nebivolol é um betabloqueador com propriedade vasodilatadora. Objetivos: Avaliar o impacto da terapia com nebivolol sobre as variáveis da cintilografia com 123I-MIBG e do TCPE em pacientes com ICFEN. Métodos: Vinte e cinco pacientes realizaram cintilografia com 123I-MIBG para avaliar a taxa de washout e a relação coração/mediastino precoce e tardia. Durante o TCPE, foi analisado o comportamento da pressão arterial sistólica (PAS), frequência cardíaca (FC) durante o esforço e a recuperação (FCR) e o consumo de oxigênio (VO2). Após avaliação inicial, separamos nossa amostra em grupos controle versus intervenção, iniciamos o nebivolol e repetimos os exames após 3 meses. Resultados: Após o tratamento, o grupo intervenção apresentou melhora na PAS (149 mmHg [143,5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0,016]), FC em repouso (78 bpm [65,5-84 bpm] versus 64,5 bpm [57,5-75,5 bpm, p = 0,028]), PAS no pico do esforço (235 mmHg [216,5-249 mmHg] versus 198 mmHg [191-220,5 mmHg], p = 0,001), FC no pico do esforço (124,5 bpm [115-142 bpm] versus 115 bpm [103,7-124 bpm], p = 0,043) e FCR no 1º minuto (6,5 bpm [4,75-12,75 bpm] versus 14,5 bpm [6,7-22 bpm], p = 0,025) e no 2º minuto (15,5 bpm [13-21,75 bpm] versus 23,5 bpm [16-31,7 bpm], p = 0,005), porém não apresentou mudança no VO2 de pico e nos parâmetros da cintilografia com 123I-MIBG. Conclusão: Apesar de um melhor controle da PAS e na FC em repouso e durante o esforço e uma melhora na FCR, o nebivolol não ocasionou efeito positivo sobre o VO2 de pico e nos parâmetros da cintilografia com 123I-MIBG. A ausência de efeito sobre a atividade adrenérgica pode ser a causa da falta de efeito sobre a capacidade funcional.

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.

Low-dose-rate brachytherapy for patients with transurethral resection before implantation in prostate cancer. Long-term results

ABSTRACT We analyzed the long-term oncologic outcome for patients with prostate cancer and transurethral resection who were treated using low-dose-rate (LDR) prostate brachytherapy. Methods and Materials: From January 2001 to December 2005, 57 consecutive patients were treated with clinically localized prostate cancer. No patients received external beam radiation. All of them underwent LDR prostate brachytherapy. Biochemical failure was defined according to the "Phoenix consensus". Patients were stratified as low and intermediate risk based on The Memorial Sloan Kettering group definition. Results: The median follow-up time for these 57 patients was 104 months. The overall survival according to Kaplan-Meier estimates was 88% (±6%) at 5 years and 77% (±6%) at 12 years. The 5 and 10 years for failure in tumour-free survival (TFS) was 96% and respectively (±2%), whereas for biochemical control was 94% and respectively (±3%) at 5 and 10 years, 98% (±1%) of patients being free of local recurrence. A patient reported incontinence after treatment (1.7%). The chronic genitourinary complains grade I were 7% and grade II, 10%. At six months 94% of patients reported no change in bowel function.Conclusions: The excellent long-term results and low morbidity presented, as well as the many advantages of prostate brachytherapy over other treatments, demonstrates that brachytherapy is an effective treatment for patients with transurethral resection and clinical organ-confined prostate cancer

Low iodine diet does not improve the efficacy of radioiodine for the treatment of Graves’ disease

Objective Consuming a low-iodine diet (LID) is a widely accepted practice before administering radioiodine (131I) to evaluate and to treat thyroid disease. Although this procedure is well established for the management of patients with differentiated thyroid cancer, its use in patients with benign disease is unclear. So, we aimed to evaluate the influence of a LID on the outcome in patients with Graves’ disease (GD) treated with131I. Subjects and methods We evaluated 67 patients with GD who were divided into 2 groups: one group (n = 31) consumed a LID for 1-2 weeks, and the second group (n = 36) was instructed to maintain a regular diet (RD). Results The LID group experienced a 23% decrease in urinary iodine after 1 week on the diet and a significant 42% decrease after 2 weeks on the diet. The majority (53%) of the patients in the LID group had urinary iodine levels that were consistent with deficient iodine intake. However, there was no difference in the rate of hyperthyroidism’s cure between the LID and the RD groups 6 months after 131I therapy. Furthermore, the therapeutic efficacy did not differ in patients with varying degrees of sufficient iodine intake (corresponding urinary iodine levels: < 10 μg/dL is deficient; 10-29.9 μg/dL is sufficient; and > 30 μg/dL is excessive). Conclusion In the present study, we demonstrated that although a LID decreased urinary iodine levels, those levels corresponding with sufficient or a mild excess in iodine intake did not compromise the therapeutic efficacy of131I for the treatment of GD.

Brachytherapy and radical prostatectomy in patients with early prostate cancer / Braquiterapia e prostatectomia radical em portadores de câncer localizado de próstata

Summary Objective: this study analyzes the survival of prostate cancer patients cared for at a hospital in Minas Gerais, Brazil according to one of the following treatments: iodine-125 seed implantation or radical prostatectomy. From January 2002 to December 2005, 129 patients underwent either brachytherapy (64 patients) or surgery (65 patients). Methods: all had prostate-specific antigen, Gleason scores and clinical stage recorded prior to treatment. Biochemical relapse was defined as prostate-specific antigen (PSA)>0.4ng/mL for radical prostatectomy, and any elevation equal or higher than 2ng/mL over the PSA nadir for implanted patients. To analyze the effect of treatment on biochemical recurrence-free survival (BRFS), Kaplan-Meier curves and Cox regression were generated. Mean follow-up time was 56.1 months for patients with the implant, and 26.6 months for those operated on. BRFS in 5 years was 69% (95% CI: 58.18-77.45) for the whole cohort. Discussion: when stratified according to treatment, survival of patients who had undergone brachytherapy (79.70%) was higher to those operated on (44.30%; pvalue= 0.0056). Upon multivariate analysis, independent predictors were iPSA (HR: 2.91, 95% CI: 1,32-6,42), Gleason score (HR: 2.18, 95% CI: 1,00-4,81) and treatment modality (HR: 2.61, 95% CI: 1.18-5,75). Risk of biochemical failure was higher with surgery than brachytherapy, which may be related to the failure criteria adopted, which is different for each therapy, as well as the high rate of histological progression between preoperative prostate biopsy and surgical specimen. Conclusion: it was found that brachytherapy is a good therapeutic option for low risk prostate cancer.

Resumo Introdução: este estudo avaliou a sobrevida de portadores de câncer localizado de próstata assistidos em um hospital de Minas Gerais, segundo duas modalidades terapêuticas: implante de sementes iodo-125 e prostatectomia radical. A população estudada foi de 129 pacientes tratados no período de janeiro de 2002 a dezembro de 2005 – 64 submetidos à braquiterapia e 65 à cirurgia. Métodos: todos obtiveram registro do antígeno prostático específico, escores de Gleason e estadiamento clínico anterior ao tratamento. A recidiva bioquímica foi definida como PSA > 0,4 ng/mL para prostatectomia radical, e qualquer elevação de 2 ng/mL ou mais a partir do PSA nadir para os pacientes implantados. Para análise do efeito do tratamento na sobrevida livre de recidiva bioquímica (SLRb), foram geradas curvas de Kaplan-Meier e foi efetuada regressão de Cox. O tempo mediano de seguimento foi de 56,1 meses para os implantados e de 26,6 meses para os operados. Discussão: a SLRb em 5 anos para toda coorte foi de 69% (IC95%:58,18-77,45), sendo superior para aqueles submetidos à braquiterapia (79,70%) em relação aos operados (44,30%; p-valor 0,0056). Na análise multivariada, os fatores preditores independentes foram iPSA (HR:2,91; IC95%:1,32-6,42), escore de Gleason (HR:2,18; IC95%:1,00- 4,81) e modalidade de tratamento (HR:2,61; IC95%:1,18- 5,75). O risco de falha bioquímica foi maior com a cirurgia, comparado à braquiterapia, o que pode estar relacionado ao elevado índice de progressão histológica entre biópsia prostática pré-operatória e peça cirúrgica, e pelo critério de falha adotado, distinto para cada terapêutica. Conclusão: foi possível constatar que a braquiterapia é uma boa opção terapêutica para o câncer de próstata de baixo risco.

Persistent and recurrent disease in patients with papillary thyroid carcinoma with clinically apparent (cN1), but not extensive, lymph node involvement and without other factors for poor prognosis

Objective Lymph node metastases (LNM) are frequent in patients with papillary thyroid cancer (PTC). The risk of persistent disease (PD) and tumor recurrence (TR) is increased when factors for poor prognosis other than LNM exist, when LNM are numerous, large, detected by preoperative ultrasonography (US), or exhibit extranodal extension. This study evaluated the risk of PD and TR in patients with LNM not exhibiting these characteristics.Subjects and methods Eighty-six patients with 5 or fewer LNM detected during intraoperative inspection, but not by preoperative US, who had no other factors for poor prognosis [tumors > 4 cm, extensive extrathyroid invasion, vascular invasion, aggressive histological subtype, distant metastases, incomplete tumor resection], were studied. All patients underwent total thyroidectomy followed by radioiodine ablation. PD was defined as metastases on initial post-therapy whole-body scans (RxWBS) or detected by imaging methods up to 12 months after ablation. TR was defined as structural disease diagnosed more than one year after ablation in patients without PD.Results PD was diagnosed in 3/86 patients (3.5%). TR was observed in 2/83 patients (2.5%) after 62 months of follow-up. There was no case of death due to the disease. A correlation was observed between pre-ablation Tg and PD or TR [1/48 (2%) with Tg ≤ 2 ng/mL versus 2/22 (9%) with Tg > 2 ≤ 10 ng/mL versus 2/7 (28.5%) with Tg ≥ 10 ng/ml)]. It is noteworthy that 38 patients had up to 3 positive LN and pre-ablation Tg ≤ 2 ng/ml, and none of them had PD or TR.Conclusions The frequency of PD and TR was low in patients with PTC with 5 or fewer LNM and without other factors for poor prognosis. Low postoperative stimulated Tg was predictive of the absence of PD and TR in these patients.

Liposomal topical capsaicin in post-herpetic neuralgia: a safety pilot study / Capsaicina lipossomal tópica na neuralgia pós-herpética: um estudo piloto de segurança

Topical treatments have gained popularity for general use as an adjunct to systemic drugs in neuropathic pain, but their use produces variable clinical results and local adverse events. Objective To evaluate the safety and analgesic effect of a formulation of liposomal capsaicin (LC) (0.025%) in patients with post herpetic neuralgia (PHN). Method Patients who remained symptomatic after first-and second-line treatment were randomized to receive LC for six weeks in a placebo-controlled, crossover design study. Clinical assessment was performed at baseline, in the second, fourth and sixth week of treatment. Results Thirteen patients completed both treatment periods. Visual Analog Scale (VAS) was significantly decreased after the end of the study (p = 0.008), however the effect of treatment was not significant (p = 0.076). There was no difference on global impression of change and other pain characteristics. LC was safe and well tolerated. However, at the concentration used, its analgesic effects were marginal and not significant. .

Os tratamentos tópicos ganharam popularidade para uso geral como um adjuvante de medicamentos sistêmicos na dor neuropática, mas seu uso produz resultados clínicos variáveis e eventos adversos locais. Objetivo Avaliar o efeito de segurança e analgesia de uma formulação de capsaicina lipossomal (LC) (0,025%) em pacientes com neuralgia pós-herpética. Método Os pacientes que permaneceram sintomáticos após tratamento de primeira e de segunda linha foram randomizados para receber LC durante seis semanas em um estudo cruzado controlado por placebo. A avaliação clínica foi realizada no início do estudo, na segunda, quarta e sexta semana de tratamento. Resultados Treze pacientes completaram dois períodos de tratamento. Escala Visual Analógica diminuiu significativamente após o final do estudo (p = 0,008), no entanto, o efeito do tratamento não era significativo (p = 0,076). Não houve diferença na impressão global de mudança e de outras características da dor. LC foi segura e bem tolerada. No entanto, para a concentração utilizada, os seus efeitos analgésicos foram marginais e não significativos. .

Efectos de la dosis ablativa de iodo 131 sobre las glándulas salivales en pacientes con carcinoma diferenciado de tiroides / Effects of myeloablative doses of iodine 131 on the salivary glands in patients with differentiated thyroid carcinoma

INTRODUCCIÓN: El tratamiento ablativo con radioyodo (131I) para el Cáncer Diferenciado de Tiroides produce un conocido efecto sobre las glándulas salivales, que puede expresarse como sialoadenitis. La xeroftalmía y la obstrucción nasolacrimal también han sido reportadas como complicaciones del uso de la terapia ablativa. La sialoadenitis puede ocurrir en el período inmediato post-tratamiento, dentro de las primeras 48 horas, o de manera tardía, luego de 3 a 6 meses de haberse administrado la terapia. Algunas revisiones en la bibliografía han reportado una incidencia de sialoadenitis aguda luego de la administración del 131I que va desde el 24 al 67% y de sialoadenitis crónica del 11 al 43%, mostrando evidencia del daño de las glándulas salivales por centellografía entre un 10% al 60% de los pacientes con sintomatología aguda o crónica. OBJETIVOS: PRIMARIOS: Evaluar la prevalencia de afectación a nivel de las glándulas salivales en pacientes con Carcinoma Diferenciado de Tiroides tratados con dosis ablativas de 131I. Determinar si la/las dosis acumulativas de 131I pueden ser responsables de la lesión. Estudiar la sialoquímica de los pacientes tratados con 131I y describir la presencia de autoinmunidad y su relación con el grado de lesión en las glándulas salivales. SECUNDARIOS: Establecer si es necesario efectuar sialoquímica en todos los pacientes que recibirán 131I. Conocer si existen pacientes con alteraciones en las glándulas salivales previas al tratamiento de la dosis de 131I. Desarrollar mecanismos preventivos al eventual daño radioisotópico.

Abstract: Background: Ablative therapy with radioiodine (131I) for differentiated thyroid cancer produces a well-known effect on the salivary glands that maybe expressedas sialadenitis. Xerophtalmiaand nasolacrimal obstruction have also been reported as complications of ablative therapy. Sialadenitis can occur immediately after therapy, within the first 48 hours or as late event, 3-6 months after end of therapy. Literature revision shows an incidence of acute sialadenitis of 24-67% and chronic sialadenitis of 11-43% after 131I administration, demonstrating scintigraphic evidence of the damage of the salivary glands in 10-60% of the patients with acute or chronic presentations. OBJECTIVES: MAIN OBJECTIVE: To evaluate the prevalence of lesions of the salivary glands in patients with differentiated thyroid cancer treated with ablative doses of 131I. To determine if the cumulative dose of 131I can be responsible for such lesions.To analyze the sialochemistry findings in patients treated with 131I and to describe the presence and correlation of autoimmunity with the degree of damage of the salivary glands. SECONDARY OBJECTIVES: To establish if it would be dvisable to perform sialochemisty tests in all the patients that need ablative doses of 131I. To recognize if the patients present any lesions ofthe salivary glands before receiving 131I. To develop measures to prevent eventual radio isotopic damage.

External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

Purpose To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, there was no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine-125 provide similar bDFS, DMFS, and OS. .