Effect of ozone oil for prevention and treatment of sorafenib-induced hand-foot skin reactions: a randomized controlled trial / 南方医科大学学报

OBJECTIVE@#To compare the effects of medical ozone oil and urea ointment for prevention and treatment of hand-foot skin reaction (HFSR) caused by sorafenib in patients with hepatocellular carcinoma (HCC).@*METHODS@#A total of 99 patients diagnosed with advanced HCC according to National Comprehensive Cancer Network (NCCN) who were scheduled to receive sorafenib treatment for the first time were enrolled in this study between April, 2018 and January, 2020. The patients were randomized into medical ozone oil group (@*RESULTS@#Eight patients were excluded for poor compliance or protocol violations, leaving a total of 91 patients for analysis, including 44 in medical ozone oil group and 47 in urea ointment group. Sixteen (36.4%) of patients in ozone oil group developed HFSR, a rate significantly lower than that in urea ointment group (57.4%; @*CONCLUSIONS@#Medical ozone oil can significantly reduce the incidence and severity of HFSR to improve the quality of life of HCC patients receiving sorafenib treatment.

Combination of TACE and Sorafenib Improves Outcomes in BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre Experience

ABSTRACT Background & Aim. Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. Material and methods. We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. Results. Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. Conclusion. TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.

Partial response to sorafenib treatment associated with transient grade 3 thrombocytopenia in a patient with locally advanced thyroid cancer

Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative 131I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A 18FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors.

O que ocorre com o balanço hídrico durante e após a reversão do choque séptico? / What happens to the fluid balance during and after recovering from septic shock?

Objetivo: Avaliar o balanço hídrico acumulado durante o período do choque e determinar o que ocorre com ele nos 7 dias que se seguem à reversão do choque. Métodos: Estudo prospectivo e observacional, realizado em pacientes com choque séptico. Foram incluídos pacientes com pressão arterial média ≥ 65mmHg e lactato < 2,0mEq/L desmamados há menos de 12 horas do uso de vasopressores, sendo esse dia considerado o Dia 1. O balanço hídrico diário foi registrado por 7 dias após recuperação do choque. Os pacientes foram divididos em dois grupos, segundo a mediana da coorte para o balanço hídrico acumulado durante o período do choque: Grupo 1 ≤ 4,4L (n = 20) e Grupo 2 > 4,4L (n = 20). Resultados: Inscrevemos, neste estudo, um total de 40 pacientes. No Dia 1 do estudo, o balanço hídrico acumulado era de 1,1 [0,6 - 3,4] L no Grupo 1 e 9,0 [6,7 - 13,8] L no Grupo 2. No Dia 7 do estudo, o balanço hídrico acumulado era de 8,0 [4,5 - 12,4] L no Grupo 1 e 14,7 [12,7 - 20,6] L no Grupo 2 (p < 0,001 para ambos). A seguir, após a recuperação do choque, o balanço hídrico continuou a aumentar em ambos os grupos. Em comparação ao Grupo 1, o Grupo 2 teve um tempo mais longo de permanência na unidade de terapia intensiva e no hospital. Conclusão: São frequentemente observados balanços hídricos positivos em pacientes com choque séptico, o que pode estar relacionado a desfechos piores. Durante o período do choque, mesmo que o balanço hídrico fosse previamente positivo, este se torna ainda mais positivo. Após a recuperação do choque, o balanço hídrico continua a aumentar. Esse grupo com um balanço hídrico mais positivo permaneceu por mais tempo na unidade de terapia intensiva e no hospital. .

Objective: We aimed to evaluate the cumulative fluid balance during the period of shock and determine what happens to fluid balance in the 7 days following recovery from shock. Methods: A prospective and observational study in septic shock patients. Patients with a mean arterial pressure ≥ 65mmHg and lactate < 2.0mEq/L were included < 12 hours after weaning from vasopressor, and this day was considered day 1. The daily fluid balance was registered during and for seven days after recovery from shock. Patients were divided into two groups according to the full cohort’s median cumulative fluid balance during the period of shock: Group 1 ≤ 4.4L (n = 20) and Group 2 > 4.4L (n = 20). Results: We enrolled 40 patients in the study. On study day 1, the cumulative fluid balance was 1.1 [0.6 - 3.4] L in Group 1 and 9.0 [6.7 - 13.8] L in Group 2. On study day 7, the cumulative fluid balance was 8.0 [4.5 - 12.4] L in Group 1 and 14.7 [12.7 - 20.6] L in Group 2 (p < 0.001 for both). Afterwards, recovery of shock fluid balance continued to increase in both groups. Group 2 had a more prolonged length of stay in the intensive care unit and hospital compared to Group 1. Conclusion: In conclusion, positive fluid balances are frequently seen in patients with septic shock and may be related to worse outcomes. During the shock period, even though the fluid balance was previously positive, it becomes more positive. After recovery from shock, the fluid balance continues to increase. The group with a more positive fluid balance group spent more time in the intensive care unit and hospital. .

Response to sorafenib treatment in advanced metastatic thyroid cancer / Resposta ao tratamento com sorafenibe em pacientes com carcinoma metastático de tireoide

Objective: To investigate the efficacy of sorafenib in progressive radioiodine resistant metastatic thyroid carcinoma.Subjects and methods: Off-label observational study. Sorafenib 400 mg twice daily was evaluated. Therapy duration was 12 ± 3 months (range 6-16 months).Results: Eight patients were included (seven papillary, one insular variant). The eight patients meeting study criteria received sorafenib 400 mg orally twice a day until disease progression or unacceptable toxicity developed. One patient showed a partial response with tumor regression of -35%, six months after the beginning of the treatment; five patients exhibited stable disease and two patients had progressive disease and died. Thyroglobulin decreased within 4 weeks in all patients by 50% ± 23%.Adverse events: one patient had heart failure, and recovered after sorafenib withdrawal. However, she died five months later of sudden death.Conclusion: These data suggest a possible role for sorafenib in the treatment of progressive metastatic DTC. Adverse event are usually manageable, but severe ones may appear and these patients should be strictly controlled.

Objetivo: Investigar a eficácia do sorafenibe no carcinoma de tireoide metastático progressivo e refratário à iodoterapia.Sujeitos e métodos: Estudo observacional do efeito do sorafenibe off-label administrado 400 mg duas vezes ao dia. A duração da terapia foi de 12 ± 3 meses (variação de 6-16 meses).Resultados: Oito pacientes foram incluídos (sete com variante papilífera e um com variante insular). Os oito pacientes que preencheram os critérios do estudo receberam o sorafenibe 400 mg por via oral duas vezes por dia até progressão da doença ou toxicidade inaceitável. Um paciente apresentou uma resposta parcial com regressão tumoral da lesão alvo de 35% seis meses após o início do tratamento; cinco pacientes apresentaram doença estável e dois pacientes progrediram e morreram. A tireoglobulina diminuiu 50% ± 23% em 4 semanas em todos os pacientes.Eventos adversos: um paciente teve insuficiência cardíaca e morreu por morte súbita cinco meses após a retirada do sorafenibe.Conclusão: Esses dados sugerem um possível papel para sorafenibe para o tratamento do CDT metastático progressivo.

Eficácia das terapias não convencionais (Pentoxifilina e Nicotinamida/Alopurinol) comparadas a metilprednisolona intravenosa no tratamento da oftalmopatia de Graves / Effectiveness of unconventional therapies ( Pentoxifylline and Nicotinamide / Allopurinol ) compared to intravenous methylprednisolone in the treatment of Graves' ophthalmopathy

A oftalmopatia de Graves (OG) se constitui em uma das manifestações clínicas mais marcantes da Doença de Graves. Mais freqüente em mulheres, pode atingir qualquer faixa etária e produzir alterações negativas na qualidade de vida dos pacientes acometidos. Trata-se de doença auto-imune cuja fisiopatologia centra-se em atividade inflamatória desencadeada por diversos antígenos presentes nos tecidos extra-ocular, com infiltrado linfocitário importante, adipogênese e produção de glicosaminoglicanos levando ao aspecto típico de inflamação e proptose. Os casos mais leves podem ser tratados com medidas locais, enquanto que casos mais graves, frequentemente, recebem terapia com glicocorticoides, particularmente pulsoterapia com metilprednisolona. O objetivo deste estudo foi comparar o uso de dois esquemas terapêuticos (associação de nicotinamida/alopurinol ou pentoxifilina por via oral) com a terapia padrão (corticóide em pulsoterapia). Foram recrutados pacientes portadores de OG classificados como moderada ou moderadamente grave e em atividade (definidos pelo NO SPECS e CAS) , distribuídos em três grupos de tratamento, a saber : G1- Pentoxifilina , G2- Nicotinamida/Alopurinol e G3- Metiprednisolona em pulsoterapia, distribuídos por conveniência. Para investigar a resposta ao tratamento clínico instituído, foram usados o CAS, a medida da proptose ocular por meio de exoftalmômetro, a dosagem de interleucinas séricas(TNF-α e IL-6), registros fotográficos dos olhos dos pacientes avaliados e a TC de órbitas...

Graves ’ophthalmopathy (GO) constitutes one of the most striking manifestations of Graves’ disease. More common in women, ocurr at any age group and produce negative changes in the quality of life of affected patients. It is an autoimmune disease whose physiopathology focuses on various inflammatory activity triggered by antigens present in extraocular tissues with significant lymphocyte infiltration, production of glycosaminoglycansadipogenesis leading to the typical appearance of inflammation and proptosis. The mild cases can be treated with local measures, while more serious cases often receive glucocorticoid therapy, particularly methylprednisolone pulse therapy. The aim of this study was to compare the use of two regimens (combination of nicotinamide / allopurinol or pentoxifylline orally) with standard therapy (intravenous steroid pulse therapy). We recruited patients with OG classified as moderate or moderately severe and active (defined by NO SPECS and CAS), divided into three treatment groups, namely: Pentoxifylline-G1, G2-Nicotinamide /Allopurinol-and G3 Metiprednisolona in pulse, distributed for convenience. To investigate the response to clinical treatment, the CAS were used to measure the ocular proptosis through exophtalmomether, the dosage of serum interleukins (TNF-α and IL-6), photographic records of the eyes of patients evaluated CT orbits...

Targeted molecular therapies in thyroid carcinoma: [review] / Terapias moleculares direcionadas em câncer de tireoide: [revisão]

Thyroid cancer incidence has significantly increased in the last three decades and many patients seek medical attention for its treatment every year. Among follicular cell-derived tumors, the majority are differentiated thyroid carcinomas (DTC), whose prognosis is very good with only 15 percent of the cases presenting disease persistence or recurrence after initial treatment. Medullary thyroid carcinoma has a worse prognosis, especially in patients with diffused cancers at the time of initial surgery. Traditional treatment options for persistent or recurrent disease include additional surgery, radioiodine treatment and TSH-suppression in DTC patients; external beam radiotherapy, and cytotoxic chemotherapy, often have low efficacy and many patients with advanced disease ultimately die. In the last two decades many of the molecular events involved in cancer formation have been uncovered. This knowledge has prompted the development of novel therapeutic strategies mainly based on the inhibition of key molecular mediators of the tumorigenic process. In particular the class of small-molecule tyrosine kinase inhibitors was enriched by many compounds that have reached clinical trials and in some cases have had approval for clinical use in specific cancers. Many of these compounds entered clinical trials also for locally advanced or metastatic thyroid carcinomas showing very promising results.

O câncer de tireoide tem aumentado significativamente nas últimas três décadas e muitos pacientes têm buscado cuidados médicos para o tratamento a cada ano. Entre os tumores derivados de células foliculares, a maioria é carcinoma diferenciado de tireoide (CDT), cujo prognóstico é muito bom, em que somente em 15 por cento dos casos a doença é persistente ou recorrente após o tratamento inicial. O carcinoma medular de tireoide tem um prognóstico pior, especialmente em pacientes com câncer difuso no momento da cirurgia inicial. As opções no tratamento tradicional para a doença persistente ou recorrente incluem cirurgia adicional, radioiodoterapia e supressão de TSH em pacientes CDT; a radioterapia externa e a quimioterapia citotóxica apresentam com frequência uma baixa eficácia e muitos pacientes com doença avançada não sobrevivem. Nas últimas duas décadas, muitos dos eventos envolvidos na formação do câncer tornaram-se conhecidos. Esse conhecimento possibilitou o desenvolvimento de novas estratégias terapêuticas, baseadas principalmente na inibição de mediador molecularchave no processo tumorigênico. Em particular, a classe das pequenas moléculas inibidoras de tirosina-quinase foi enriquecida por muitos compostos investigados em estudos clínicos e alguns casos foram aprovados para uso clínico em tipos específicos de câncer. Muitos desses compostos foram aplicados em estudos clínicos de câncer de tireoide com extensa invasão local ou metástase, mostrando resultados muito promissores.

Terapéutica de pénfigo-no esteroidea / Non-steroid therapy in pemphigus

Se hace una revisión de los recursos terapéuticos no esteroideos, empleados en el tratamiento de las diferentes formas clínicas de pénfigo. Se enumeran los factores que condicionan la elección de dicha terapéutica; forma clínica, edad, embarazo, concomitancia con otras enfermedades, interacción con otros fármacos y efectos adversos. El esteroide continúa siendo la droga de primera elección, debiendo estar asociado con otras medicaciones adyuvantes, habitualmente desde su inicio, a fin de promover un descenso más rápido del mismo, con menor incidencia de complicaciones. En los pénfigos graves se preferirá su asociacián con inmunosupresores, en primer lugar con la azatioprina o bien con ciclofosfamida. La dapsona, como las tetraciclinas, será alternativa para algunas formas más leves de pénfigo, mientras que los pulsos de ciclofosfamida, así como la plasmaféresis, deberán reservarse para aquellos casos graves que no hayan respondido a las terapéuticas convencionales

Penfigoide ampollar / Bullous pemphigoid

Se realizó una revisión del tema "Penfigoide ampollar", analizando ubicación nosológica, epidemiología, clínica, variantes, laboratorio, inmunohistopatología, diagnóstico diferencial, pronóstico y tratamiento