New strategies for the treatment of carcinoma of unknown primary / 中华肿瘤杂志

Carcinoma of unknown primary (CUP) is a kind of metastatic tumor whose primary origin cannot be identified after adequate examination and evaluation. The main treatment modality of CUP is empiric chemotherapy, and the median overall survival time is less than 1 year. Compared with immunohistochemistry, novel method based on gene expression profiling have improved the sensitivity and specificity of CUP detection, but its guiding value for treatment is still controversial. The approval of immune checkpoint inhibitors and pan-cancer antitumor agents has improved the prognosis of patients with CUP, and targeted therapy and immunotherapy based on specific molecular characteristics are the main directions of future research. Given the high heterogeneity and unique clinicopathological characteristics of CUP, "basket trial" is more suitable for clinical trial design in CUP.

Sintomas geniturinários em mulheres com câncer de mama em tratamento quimioterápico / Genitourinary symptoms in women with breast cancer during chemotherapy treatment

Introdução: O câncer de mama representa a neoplasia mais incidente em mulheres, com projeção para representar 29% de todos os tipos de câncer para o biênio 2018-2019 no Brasil. A quimioterapia é a modalidade terapêutica mais utilizada para o tratamento desta neoplasia, utilizando-se largamente a droga ciclofosfamida, a qual apresenta diversos eventos adversos, dentre eles a supressão gônodal que pode induzir ou intensificar os sintomas menopausais. Objetivo: Analisar a qualidade de vida e ocorrência de sintomas geniturinários durante o tratamento quimioterápico adjuvante com os esquemas FAC; AC-T, CMF ou TC para câncer de mama. Método: Estudo prospectivo que avaliou mulheres antes (T0) e 30 dias após a realização do tratamento quimioterápico(T1). Foram avaliadas quanto ao status menopausal, a força e resistência exercida pelos músculos do assoalho pélvico com o perineômetro, além, de responderem a um questionário sociodemográfico, escala de avaliação da menopausa e o ICIQ-SF. Os dados foram analisados por meio de testes com qui-qradrado, teste t, análise multifatorial para medias repetidas, LSD-Fisher e análise de componentes principais. Resultados: A média de idade foi de 46,3 anos (DP± 5,77), as caraterísticas de maior prevalecia foram a hipertensão arterial (35%), carcinoma ducal infiltrante (90,2%), e estadiamento clinico em IIA (40%). Anterior a quimioterapia 60% das mulheres apresentavam ciclos menstruais regulares, mas nenhuma manteve a regularidade após quimioterapia tornaram-se amenorreicas. A escala de avaliação da menopausa apresentou piora significativa dos sintomas menopausais quando comparados T0 e T1(p<0,05) e quanto ao ICIQ-SF todas as mulheres apresentaram aumento significativo das médias do score final (p<0,001), demonstrando piora dos sintomas urinários e qualidade de vida. Os valores de contração rápida e lenta verificados com o perineômetro em T0 apresentaram redução significativa em T1 (p<0,05) e observou-se aumento da incidência de incontinência urinária de esforço. A análise dos componentes principais sintetizou os resultados mostrando que as variáveis obtidas pela perineometria, Escala de avaliação de menopausa ICIQ-SF não diferiam entre grupos de quimioterapia, status menopausal e número de partos (p>0,05), porém ao longo das avaliações, entre T0 e T1, houve diferença estatística (p<005). Conclusão: A exposição ao tratamento quimioterápico contendo ciclofosfamida, independente de outros fatores aqui avaliados, promove alterações geniturinárias

Introduction: Breast cancer represents the most common cancer in women, projected to represent 29% of all cancers for the 2018-2019 biennium in Brazil. Chemotherapy is the most widely used therapeutic modality for the treatment of this neoplasm, largely using the drug cyclophosphamide, which has several adverse events, including gonodal suppression that can induce or intensify menopausal symptoms. Objective: To analyze the quality of life and occurrence of genitourinary symptoms during adjuvant chemotherapy treatment with FAC regimens AC-T, CMF or CT for breast cancer. Method: Prospective study that evaluated women before (T0) and 30 days after chemotherapy (T1). They were evaluated for menopausal status, strength and endurance exerted by the pelvic floor muscles with the perineometer, and answered a sociodemographic questionnaire, menopause assessment scale and the ICIQ-SF. Data were analyzed using chi-square tests, t-test, repeated-factor multifactorial analysis, LSD-Fisher and principal component analysis. Results: The mean age was 46.3 years (SD ± 5.77), the most prevalent characteristics were arterial hypertension (35%), infiltrating ducal carcinoma (90.2%), and clinical staging in IIA (40%). Prior to chemotherapy 60% of women had regular menstrual cycles, but none maintained regularity after chemotherapy became amenorrheic. The menopause assessment scale showed a significant worsening of the menopausal symptoms when compared to T0 and T1 (p<0.05). Regarding the ICIQ-SF, all women presented a significant increase in the final score means (p<0.001), showing a worsening of the urinary symptoms and quality of life. The fast and slow contraction values verified with the perineometer at T0 showed a significant reduction at T1 (p<0.05) and an increased incidence of stress urinary incontinence was observed. The principal component analysis summarized the results showing that the variables obtained by perineometry, ICIQ-SF Menopause Rating Scale did not differ between chemotherapy groups, menopausal status and number of deliveries (p>0.05), but throughout the evaluations, between T0 and T1, there was a statistical difference (p<005). Conclusion: Exposure to chemotherapeutic treatment containing cyclophosphamide, regardless of other factors evaluated here, promotes genitourinary changes

Effect of Arrabidaea chica extract against chemically induced breast cancer in animal model

Abstract Purpose: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. Methods: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. Results: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. Conclusion: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.

Chorioallantoic urothelial tumor avatar. A clinical tool for phenotype-based therapy

Abstract In the muscle invasive bladder cancer (MIBC) standard of care treatment only patients presenting a major pathological tumor response are more likely to show the established modest 5% absolute survival benefit at 5 years after cisplatin-based neoadjuvant chemotherapy (NAC). To overcome the drawbacks of a blind NAC (i.e. late cystectomy with unnecessary NAC adverse events) with potential to survival improvements, preclinical models of urothelial carcinoma have arisen in this generation as a way to pre-determine drug resistance even before therapy is targeted. The implantation of tumor specimens in the chorioallantoic membrane (MCA) of the chicken embryo results in a high-efficiency graft, thus allowing large-scale studies of patient-derived "tumor avatar". This article discusses a novel approach that exploits cancer multidrug resistance to provide personalized phenotype-based therapy utilizing the MIBC NAC dilemma.

Hormone receptor-negative as a predictive factor for pathologic complete response to neoadjuvant therapy in breast cancer / Receptor hormonal negativo como fator preditivo para resposta patológica completa ao tratamento neoadjuvante de câncer de mama

ABSTRACT Objective To define a predictive factor for pathologic complete response, compare the oncologic outcomes associated with the degree of pathologic response after neoadjuvant chemotherapy, and to analyze pathologic complete response as a prognostic factor for overall survival and progression-free survival. Methods A retrospective study of patients admitted to Hospital Estadual Mário Covas and Hospital Anchieta from 2008 to 2012, with locally advanced breast cancer. Hormone receptor status, HER2 status, histologic and nuclear grade, age upon diagnosis and histological type of the tumor were analyzed. Pathologic evaluation of the tumor was subdivided into pathologic complete response, defined by the absence of tumor; intermediate response, considered as a favorable stage; and poor response, considering low-responder patients. Data obtained were submitted to statistical analysis. Results The study included 243 patients. There was an association of pathologic complete response with HER-2 negative, histological grade 3, stage III, hormone receptor negative, positive lymph node, older age and more advanced tumors. However, after multivariate analysis the only predictor of pathologic complete response was the presence of negative hormone receptor. By analyzing the prognostic factors, hormone receptor negative was considered as an independent risk factor, and pathologic complete response was considered as an independent protective factor. Conclusion Hormone receptor negative is predictive of pathologic complete response and is an isolated risk factor for lower progression-free survival and overall survival. Pathologic complete response is a protective factor for these same survival analyses.

RESUMO Objetivo Definir um fator preditivo para resposta patológica completa, comparar os resultados oncológicos associados com o grau de resposta patológica, após quimioterapia neoadjuvante, e analisar a resposta patológica completa como fator prognóstico para sobrevivência global e livre de progressão de doença. Métodos Estudo retrospectivo de pacientes admitidas no Hospital Estadual Mário Covas e Hospital Anchieta, no período de 2008 a 2012, com câncer de mama localmente avançado. Foram utilizados status dos receptores hormonais, proteína HER2, grau histológico e nuclear, idade do paciente ao diagnóstico e tipo histológico do tumor. A avaliação patológica do tumor foi subdividida em resposta patológica completa, definida com ausência de tumor; resposta intermediária, considerada como um estádio favorável; e resposta ruim, considerando os pacientes pouco respondedores. As informações obtidas foram submetidas à análise estatística. Resultados Foram incluídas 243 pacientes. Verificou-se associação de resposta patológica completa entre HER-2 negativo, grau histológico 3, estadiamento III, receptor hormonal negativo, linfonodo positivo, maior idade e tumores mais avançados. Porém, após análise multivariada, o único fator preditivo de resposta patológica completa foi presença de receptor hormonal negativo. Ao analisar fatores prognósticos, receptor hormonal negativo permaneceu como variável independente de risco, e resposta patológica completa, como variável independente de proteção. Conclusão O receptor hormonal negativo é fator preditivo isolado de resposta patológica completa e fator de risco para menor sobrevida livre de doença e sobrevida global. Já a resposta patológica completa é fator protetor para estas mesmas análises de sobrevivência.

Rare complications of multikinase inhibitor treatment

ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.

Características humorales de los tumores de cabeza y cuello en pacientes tratados con nimotuzumab / Humoral characteristics of head and neck tumors in patients treated with nimotuzumab

Se efectuó un estudio observacional, descriptivo y retrospectivo de 36 pacientes incluidos en el ensayo clínico (fase IV) Seguridad y efectividad del nimotuzumab en tumores de cabeza y cuello, desarrollado en el Hospital Oncológico Conrado Benítez de Santiago de Cuba, desde enero de 2013 hasta diciembre de 2016, con vistas a identificar las características humorales de dichos tumores en los afectados. Se utilizó la prueba t de Student con una significación estadística de p <0,05. Predominaron el sexo masculino en mayores de 60 años de edad, los efectos adversos clínicos y el tumor de faringe; el estadio clínico III y el carcinoma epidermoide bien diferenciado fueron los más frecuentes. No existieron diferencias estadísticamente significativas entre los parámetros de laboratorio antes del tratamiento combinado con nimotuzumab y durante este. Dicho medicamento constituyó una alternativa terapéutica segura, ventajosa y factible como parte del plan terapéutico convencional en las condiciones asistenciales

An observational, descriptive and retrospective study of 36 patients included in the (phase IV) clinical trial Security and effectiveness of nimotuzumab in head and neck tumors was carried out. It was developed at Conrado Benítez Oncological Hospital in Santiago de Cuba, from January, 2013 to December, 2016, aimed at identifying the humoral characteristics of these tumors in the affected patients. The Student t test was used with a statistical significance of p <0.05. There was a prevalence of the male sex in older than 60 years, the clinical adverse effects and the pharynx tumor; the clinical stage III and the well differentiated epidermoid carcinoma were the most frequent findings. There were no statistically significant differences among the laboratory parameters before and during the combined treatment with nimotuzumab. This medication constituted a sure, advantageous and feasible therapeutic alternative as part of the conventional therapeutic plan in assistance conditions

Huge recurrent gastric neuroendocrine tumor: a second-line chemotherapeutic dilemma

Chemotherapy is considered "state of the art" for the treatment of poorly differentiated neuroendocrine neoplasms. Unfortunately, there is no standard effective post-first-line treatment for relapsing high-grade gastroenteropancreatic neuroendocrine neoplasms. We report the case of a patient with a gastric neuroendocrine carcinoma stage IV, with massive gastrointestinal bleeding at diagnosis. After the first line of platin-based chemotherapy a major tumoral response was documented, but the patient relapsed after 4 months. A second line of chemotherapy treatment was given, with the FOLFOX regimen, and the patient has been free of progression for almost 2 years. There is no second-line standard treatment accepted for this type of carcinoma, but 5-fluorouracil combined with oxaliplatin showed interesting antitumor activity.

Oridonin induces growth inhibition and apoptosis in human gastric carcinoma cells by enhancement of p53 expression and function

The tumor suppressive role of oridonin, an active compound extracted from Rabdosia rubescens, has been proven in several gastric cancer (GC) cell lines. The present study aimed to evaluate the effect of oridonin on another GC cell line, SNU-216, and explore the potential mechanisms. The viable cell numbers, cell migration, survival fraction, and cell viability were, respectively, evaluated by trypan blue exclusion assay, wound healing assay, clonogenic assay, and CCK-8 assay. Cell apoptosis was determined by flow cytometry assay and western blot. The expression of p53 was inhibited by transient transfection, and the efficiency was verified by western blot. qRT-PCR was performed to measure the mRNA expression of p53. Western blot was used to evaluate the protein expression of apoptosis, DNA damage and p53 function related factors. We found that oridonin significantly inhibited cell proliferation, migration, and survivability, and enhanced cell apoptosis in SNU-216 cells. However, it had no influence on HEK293 cell viability. Oridonin also remarkably enhanced the anti-tumor effect of cisplatin on SNU-216 cells, as it significantly increased apoptotic cells and decreased cell viability. Moreover, the mRNA and protein expression of p53 was significantly up-regulated in oridonin-treated cells, while Mdm2 expression was down-regulated. Furthermore, oridonin enhanced p53 function and induced DNA damage. Knockdown of p53 or employing the caspase inhibitor, Boc-D-FMK, reversed the effect of oridonin on cell viability and apoptosis-related protein expression. The present study demonstrated that oridonin exhibited an anti-tumor effect on GC SNU-216 cells through regulating p53 expression and function.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Sarcoma fusocelular de laringe / Fusocellular sarcoma of the larynx

El cáncer representa un problema de salud a nivel mundial dentro de las enfermedades crónicas no trasmisibles y es una de las primeras causas de muerte en la sociedad actual. El cáncer de laringe forma parte de los tumores malignos de cabeza y cuello, siendo el tipo histológico más frecuente el carcinoma epidermoide, tiene como ubicación más frecuente la glotis y aparece raramente en menores de 40 años. Por otra parte los sarcomas que se originan en la cabeza y el cuello son neoplasias malignas muy poco frecuentes, correspondiendo al 1 por ciento de las neoplasias malignas de esta región y al menos del 10 por ciento de todos los sarcomas del organismo. Se realiza la presentación de un caso de un paciente de 21 años con el diagnóstico histológico de sarcoma fusocelular subglótico, lo cual resulta interesante tomando en cuenta que la edad del paciente, así como el tipo histológico y la ubicación del tumor, no son frecuentes en nuestras consultas(AU)

Cancer represents a global health problem within non-communicable chronic diseases and is one of the leading causes of death in today's society. Laryngeal cancer forms part of malignant tumors of the head and neck, the most common histological type being epidermoid carcinoma, which is more frequently located in the glottis and rarely appears under 40 years. On the other hand sarcomas originating in the head and neck are very rare malignancies, corresponding to 1 percent of the malignancies of this region and at least 10 percent of all the sarcomas of the organism. The presentation of a case of a 21-year-old patient with the histological diagnosis of subglottic fusocellular sarcoma is presented, which is interesting considering that the patient's age, as well as the histological type and the location of the tumor, are not a case frequent in our consultations(AU)

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.

Ciclooxygenase inhibitor and metronomic chemotherapy association for the treatment of metastatic anal sac carcinoma in dog: case report / Inibidor de ciclo-oxigenase associado à quimioterapia metronômica no tratamento de carcinoma de saco anal metastático canino: relato de caso

Metronomic chemotherapy consists of an anticancer modality treatment. It is applicable in patients at an advanced stage, with the objective of increasing overall survival. The aim of this study was to report an anal sac apocrine carcinoma case in a dog with lymph node metastasis treated with metronomic chemotherapy sequential to surgery and conventional chemotherapy using gemcitabine and carboplatin. Metronomic chemotherapy was associated with cyclooxygenase-2 (COX-2) inhibitors, due to strong tumor COX-2 immunohistochemistry expression. Metronomic chemotherapy was initiated with cyclophosphamide, but it was replaced by lomustine, also in metronomic dosage, due to adverse effects. Treatment showed effectiveness, since the patient's overall survival exceeded 1095 days (36 months), considerably higher than the mean overall survival expected for this pathology.(AU)

Quimioterapia metronômica consiste em uma modalidade de tratamento anticancerígeno, aplicável a pacientes em estadiamento avançado, com o objetivo de aumentar a sobrevida global. O objetivo deste trabalho foi relatar um caso de carcinoma apócrino do saco anal, em uma cadela, com metástase em linfonodo tratado com quimioterapia metronômica sequencial à cirurgia e quimioterapia convencional utilizando-se gencitabina e carboplatina. O tratamento metronômico foi associado ao uso de inibidores de ciclo-oxigenase-2 (COX-2), baseando-se na constatação de sua expressão tumoral. A terapia metronômica iniciou-se com ciclofosfamida, mas houve necessidade de substituição pela lomustina, também em dose metronômica, devido à ocorrência de efeitos adversos. O tratamento mostrou ser eficaz, pois a sobrevida do paciente ultrapassa 1095 dias (36 meses) desde a cirurgia, sendo consideravelmente maior que a média relatada para essa patologia.(AU)

Electrochemotherapy as palliative treatment in patients with thyroid papillary carcinoma / Eletroquimioterapia como tratamento paliativo em pacientes com carcinoma papilar da tireoide

ABSTRACT INTRODUCTION: Local progression of papillary thyroid carcinoma (PTC) after failure of standard therapies may cause pain, ulceration, and bleeding. As patients are fully aware of the tumor growth, they might suffer high grade anxiety. Electrochemotherapy (ECT) is a new local palliative treatment for skin metastases of malignant melanoma or other tumors, including squamous head e neck cancer patients. OBJECTIVE: To evaluate the impact of ECT in patients with local progression of PTC. METHODS: Four patients with local progression of PTC were treated with ECT based on Bleomycin, and evaluated according to tumor response, local pain and side effects. RESULTS: In all cases, some grade of tumor response was observed, lasting 6, 7, 12 and 8 months, respectively. Also, reduction of local pain and anxiety was registered in all patients. Tumor infiltrated skin necrosis was the only collateral effect of the treatment. ECT induced a tumor response in all PTC patients with improvement of symptoms. CONCLUSIONS: ECT may be an option for local palliative treatment in PTC patients with local tumor progression.

Resumo Introdução: A progressão local do carcinoma papilífero de tireoide (CPT) após a falha da terapia de rotina pode causar dor, ulceração e sangramento. Considerando que os pacientes estão perfeitamente cientes do crescimento tumoral, podem apresentar um alto grau de ansiedade. A eletroquimioterapia (EQT) é um novo tratamento paliativo para metástases de pele de melanoma maligno ou de outros tumores, inclusive em pacientes com carcinoma escamoso de cabeça e pescoço. Objetivo: Avaliar o impacto da EQT em pacientes com progressão local de CPT. Método: Quatro pacientes com progressão local de CPT foram tratados com EQT com base em bleomicina, e avaliados em relação ao grau de resposta tumoral, dor local, efeitos colaterais. Resultados: Em todos os casos, foi observado algum grau de resposta tumoral, que perdurou por 6, 7, 12 e 8 meses, respectivamente. Da mesma forma, foi registrada diminuição da dor local e da ansiedade em todos os pacientes. Necrose cutânea na infiltração tumoral foi o único efeito colateral do tratamento. EQT induziu resposta tumoral em todos os pacientes com CPT, com melhora dos sintomas. Conclusões: EQT pode ser uma opção para o tratamento paliativo tópico em pacientes com CPT com progressão tumoral local.

Rol de la cirugía citoreductora y quimioterapia hipertérmica en el tratamiento de la carcinomatosis peritoneal / Cytoreductive surgery and hyperthermic chemotherapy role in peritoneal carcinomatosis treatment

El objetivo de este artículo es ofrecer una revisión sobre algunas estrategias terapéuticas actuales para pacientes con carcinomatosis peritoneal (CP), la que históricamente ha sido considerada como una condición terminal, sólo susceptibles de tratamientos y cuidados paliativos; y ocasionalmente de qui-mioterapia sistémica aislada con mala respuesta y supervivencias promedio inferiores a los 6 meses. La combinación de cirugía de citoreductora (CCR), que implica peritonectomía y resecciones multiviscerales con hipertermia y quimioterapia intraperitoneal intraoperatoria (HIPEC), es un concepto relativamente nuevo en el tratamiento de la enfermedad microscópica residual intraperitoneal. La indicación de este método se ha ido extendiendo de forma progresiva, para pacientes con CP muy bien seleccionados; y tiene base en varios estudios de fase III, cuya conclusión es que se puede obtener suficiente citoreducción. Sin embargo, hasta el momento existe cierto consenso basado en la evidencia, en que estaría indicada en pacientes portadores de pseudomixoma peritoneal, mesotelioma peritoneal y cáncer colorrectal; y en CP de otro origen, dependiendo de cada caso en particular.

The aim of this article is to provide a review of some current therapeutic strategies for patients with peritoneal carcinomatosis (PC), which historically has been considered a terminal condition, only amenable to palliative care, and occasionally systemic chemotherapy alone with poor response and lower average survival. The combination of cytoreductive surgery (CRS), which involves peritonectomy and multivisceral resections and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a relatively new intraperitoneal treatment of microscopic residual disease concept. The indication of this method has been extended progressively to highly selected patients with PC and it is based in several phase III studies, which concluded that it is possible to obtain sufficient cytoreduction. However, until now there is some consensus based on evidence, in which HIPEC would be indicated in patients with peritoneal PC originated in pseudomyxoma, peritoneal mesothelioma and colorectal cancer; and CP from another source, depending on each particularcase.

CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.

Exercise is associated with better quality of life in patients on TSH-suppressive therapy with levothyroxine for differentiated thyroid carcinoma / O exercício está associado com melhor qualidade de vida em pacientes em terapia de supressão de TSH com levotiroxina para o carcinoma diferenciado de tireoide

Objective : To evaluate if a supervised exercise training program improves the quality of life (QoL) of differentiated thyroid carcinoma (DTC) patients on TSH-suppressive therapy with levothyroxine (L-T4).Subjects and methods : Initially, a cross-sectional study was performed to compare the QoL and the health-related quality of life (HRQoL) between subclinical hyperthyroidism (SCH) patients (n = 33) and euthyroid subjects (EU; n = 49). In the prospective phase of the study, SCH patients were randomized in a non-blinded fashion to either participate (SCH-Tr = trained patients; n = 16) or not (SCH-Sed = untrained patients; n = 17) in a supervised exercise training program. The exercise program consisted of 60 minutes of aerobic and stretching exercises, twice a week, during twelve weeks. The QoL was assessed by the application of the WHOQOL-Bref, and the SF-36 was used to assess the HRQoL.Results : SCH patients had statistically lower scores than EU on the “physical” domain of WHOQOL-Bref, besides “physical function”, “role-physical”, “bodily pain”, “general health”, “vitality”, “role-emotional”, and “mental-health” domains of SF-36. After three months, SCH-Tr patients showed improvement in the “physical” and “psychological” domains of WHOQOL-Bref (p < 0.05), and in the “physical function”, “role-physical”, “bodily pain”, “vitality” and “mental health” domains of SF-36.Conclusion : Patients on TSH-suppressive therapy with L-T4 for DTC had impaired QoL and HRQoL compared to EU, but it was improved after 3-months of an exercise training program. Exercise seems to play an important role in the follow-up of DTC patients, since it seems to minimize the adverse effects of the treatment on QoL and HRQoL. Arq Bras Endocrinol Metab. 2014;58(3):274-81.

Objetivo : Avaliar se um programa de exercícios supervisionado melhora a qualidade de vida (QV) de pacientes com carcinoma diferenciado de tireoide (CDT) em tratamento de supressão de TSH com levotirotoxina (L-T4).Sujeitos e métodos : Inicialmente, foi feito um estudo cruzado para se comparar a QV e a qualidade de vida relacionada à saúde (QVRS) em pacientes com hipertireoidismo subclínico (HSC, n = 33) e indivíduos eutiroides (EU; n = 49). Na fase prospectiva do estudo, os pacientes com HSC foram randomizados de forma não cega para participar (HSC-Tr = pacientes treinados; n = 16) ou não (HSC-Sed = pacientes não treinados; n = 17) de um programa de exercícios supervisionado. O programa de exercícios consistiu de 60 minutos de atividade aeróbica e alongamento, duas vezes por semana, por 12 semanas. A qualidade de vida foi avaliada pelos questionários WHOQOL-Bref, e a QVRS pelo SF-36.Resultados : Os pacientes com HSC apresentaram escores estatisticamente mais baixos do que os EU no domínio “físico” do WHOQOL-Bref, além dos domínios “função física”, “papel físico”, “dor corporal”, “saúde geral”, “vitalidade”, “papel emocional” e “saúde mental” do SF-36. Após três meses, os pacientes HSC-Tr mostraram melhora nos domínios “físico” e “psicológico” do WHOQOL-Bref (p < 0,05) e nos domínios “função física”, “papel físico”, “dor corporal”, “vitalidade” e “saúde mental” do SF-36.Conclusão : Os pacientes em terapia de supressão de TSH com L-T4 para CDT apresentaram QV e QVRS afetados negativamente quando comparados com sujeitos EU, mas essas avaliações melhoraram após ...

Iodoterapia de baixas doses (30mCi e 50mCi) em regime ambulatorial, para casos de carcinoma diferenciado da tireoide, classificados como de baixo risco ou de risco intermediário / Low dose iodine therapy (30mCi and 50mCi) in the outpatient setting, for cases of differentiated thyroid carcinoma classified as low risk or intermediate risk

A radioiodoterapia tem duas finalidades: -radioablação: utilizada após a tireoidectomia total, com o objetivo de destruir tecido tireoidiano remanescente, em geral tecido normal, e facilitar o acompanhamento com a dosagem de tireoglobulina sérica. Em geral são utilizadas atividades de 1.100 a 3.700 MBq (30 a 100 mCi); e -terapêutica: além de buscar destruir tecido remanescente, elimina micrometástases locoregionais e metástases à distância. Em geral são utilizadas atividades acima de 3.700 MBq (100 mCi). O objetivo principal da Radioiodoterapia (RIT) é a redução do risco de desfechos desfavoráveis relacionados ao tumor e não apenas facilitar o seguimento. Esta recomendação se justifica também no objetivo de se evitar complicações precoces e tardias relacionadas à exposição ao radioiodo. A atividade a ser administrada de radioiodo em pacientes com Carcinoma Diferenciado da Tireoide (CDT) varia de acordo com o objetivo do tratamento. É importante salientar que a terapia deve ser a mais eficaz possível com o menor risco de exposição à radiação necessária. Nos pacientes de baixo risco que sejam considerados como tendo benefício clínico com a RIT, o objetivo do tratamento é promover a ablação de tecido remanescente. Esta ablação pode ser definida como a ausência de captação de radioiodo em leito tireoidiano em estudo cintilográfico, ou a ausência de níveis séricos detectáveis de tireoglobulina estimulada. As doses baixas são de administração ambulatorial e que essa inclusão não trará impacto financeiro para o SUS, vez que, hoje, os doentes de baixo risco ou de risco intermediário e sem suspeita de doença residual microscópica, indicações para doses baixas, são tratados com doses de 100 mCi, que exigem internação em quartos especificamente destinados para esse tratamento e limitam o acesso a ele. Os membros da CONITEC presentes na 18ª reunião do plenário realizada nos dias 31/7 e 1/8/2013 recomendaram a ampliação de uso da iodoterapia de baixas doses (30mci e 50mci), em regime ambulatorial, para casos de carcinoma diferenciado da tireoide classificados como de baixo risco ou de risco intermediário.