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.

Carcinoma papilar de tiroides y pancreatitis autoinmune: a propósito de un caso / Thyroid Papillary Carcinoma and Autoimmune Pancreatitis: A case study

El objetivo de este caso es resaltar la utilidad del ultrasonido endoscópico en pacientes con trastornos gastrointestinales. Este caso es interesante en vista que involucra dos patologías que no tienen relación entre si y que se diagnosticaron por ultrasonido endoscópico en una misma paciente, hablamos de la pancreatitis inmunológica y del carcinoma papilar de tiroides. El carcinoma papilar de tiroides se presenta en el 80 % de los casos de pacientes con neoplasia endocrina afectando a mujeres blancas, con una sobrevida mayor al 90 % si se diagnostica en estadios tempranos. En los últimos años se han descrito, cada vez con mayor frecuencia, enfermedades inflamatorias pancreáticas provocadas por mecanismos inmunológicos, que responden a tratamiento con esteroides. La disponibilidad de herramientas diagnósticas basadas en la imagen, la histología y la serología establecidas en los últimos años sirvió para determinar con exactitud la etiología de estas enfermedades.Se presenta el caso de femenina de 48 años, diabética tipo II, en tratamiento regular, cuyo motivo de consulta fue dolor abdominal difuso, gases y distensión abdominal. Se le realizó ecoendoscopia superior que concluyó lesión neoproliferativa de la cola del páncreas y aumento de volumen del lóbulo tiroideo derecho. La punción aspiración por ecoendoscopia de lesión en cola de páncreas reportó células acinares dispersas y dispuestas en grupos entremezclados con exudado inflamatorio mixto a predominio de linfocitos típicos y reactivos, histiocitos, compatibles con pancreatitis autoinmune y la punción aspiración de tiroides reportó células foliculares dispuestas en placas y papilas con atipias nucleares, abundante citoplasma denso, agrandamiento nuclear con anisonucleosis moderada, aclaramiento cromatínico con micro nucléolos, numerosas hendiduras y pseudoinclusiones nucleares concluyendo carcinoma papilar. También se le realizó determinación de IgG4 que resultó positiva...

The objective of this work is the importance of using endoscopic ultrasound in patients with gastrointestinal disorders; this case is interesting given that it involves two unrelated pathologies, which were diagnosed by endoscopic ultrasound in a same patient. We talk about the immunological Pancreatitis and Papillary Carcinoma of Thyroid. The Papillary Carcinoma of Thyroid is the Endocrine Neoplasm that occurs in 80 % cases, affecting white women, with one survival rate greater than 90 %, if diagnosed in early stages. In recent years more and more frequently pancreatic inflammatory diseases caused by immunological mechanisms, which respond to treatment with steroids have been described. The availability of diagnostic tools based on the image, the histology and serology, established in recent years, served to determine accurately the etiology of these diseases. The case of female 48 years, diabetic type II, under regular treatment, whose reason for consultation was: the presence of diffuse abdominal pain, gas, as well as positive abdominal distension. The patient underwent upper digestive ecoendoscopy. It concludes: pancreas´s tail neoproliferative lesion, as well as, and increase in volume of the right thyroid lobe, etiology to be clarify. FNA of the lesion of the tail of the pancreas reported acinar, scattered cells, arranged in groups intermingled with mixed inflammatory exudate, with predominance of typical and reactive lymphocytes, histiocytes, consistent with Immunological Pancreatitis. FNA of thyroid reported groups of follicular cells arranged in plates and papillae with nuclear atypias, abundant dense cytoplasm, and nuclear enlargement with moderate anisonucleosis, chromatinic, with micronucleus, numerous cracks and nuclear pseudo inclusions, which concludes Thyroid Papillary Carcinoma. Also it was done Ig4, proving positive. The patient underwent surgery of the thyroid, currently responding well to medical treatment.

Carcinoma papilar seroso primario del peritoneo: reporte de un caso / Peritoneum primary papillary serous carcinoma: case report

Primary serous papillary carcinoma of the peritoneum is a rare neoplasm. It is characterized by peritoneal carcinomatosis, asertes and identical histology to ovarian serous papillary carcinoma, but wrth unaffected or only superficially affected ovaries. The main differential diagnoses are secondary peritoneal carcinomatosis, peritoneal tuberculosis, malignant peritoneal mesothelioma and peritoneal lymphomatosis. The computer tomography and CA 125 are the main diagnostic tools, but the histology is essential. In this report, we present a case of a 57 years old woman with this neoplasm, metastazised to colon, uterus and ovaries. She was treated with optimal cytoreduction and chemotherapy.

El carcinoma papilar seroso primario del peritoneo es una neoplasia rara. Se caracteriza por carcinomatosis peritoneal, ascitis y una histología idéntica al carcinoma seroso papilar de ovario, pero sin comprometerlo o afectándolo sólo superficialmente. Se debe plantear como principales diagnósticos diferenciales la carcinomatosis peritoneal secundaria, la tuberculosis peritoneal, el mesotelioma peritoneal maligno y la linfomatosis peritoneal. La tomografía computada y el CA 125 representan las principales herramientas diagnósticas, sin embargo, la histología resulta imprescindible. En el presente artículo, presentamos un caso de una mujer de 57 años con esta neoplasia en que se demostró además compromiso de colon, útero y anexos. Se manejó con citoreducción óptima y quimioterapia posterior.

Postoperative chemoradiation in patients with localized gastric adenocarcinoma: Single center experience.

Background : 5-Flourouracil (FU)-based chemotherapy (CT) and concurrent 45 Gy radiotherapy (RT) is one of the standard postoperative approaches currently used in gastric carcinoma. The high toxicity rates of this treatment leads to interruption of treatment in the majority of patients. In our study, we investigated the rates of toxicity and treatment discontinuation observed during postoperative FU-based chemoradiotherapy (CRT); retrospectively evaluated the effect of CRT and the other prognostic factors on local and distant control and survival. Patients and Methods: A total of 160 patients consisting of 97 total and 63 subtotal gastrectomy receiving postoperative CRT, have been studied retrospectively. Results : Patients who had to discontinue the treatment for a median of 6 (range, 3-13) days experienced toxicity during treatment at a rate of 43%. During the 21 (range, 4-68) months of follow-up local recurrences were observed in 8 (5%) patients and distant recurrences were observed in 41 (25.6%) patients. While the 1-3 year overall survival (OS) rates were 75% and 42%, 13-year disease-free survival (DFS) rates were 63% and 42%, respectively. In the univariate analysis for OS and DFS demonstrated statistical significance for below those 60 years of age, D1-D2 dissection type, negative surgical margin, early treatment beginning, the absence of invasion, and early stage disease. D1D2 dissection type, early treatment begining, age below 60 years and early stage disease significantly improve OS and DFS in multivarite analysis. Conclusions: Survival is worse in patients older than 60 years, had late treatment begining, advanced stage and D0 dissection.

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.

Uso do TSH humano recombinante no câncer diferenciado de tireóide / Recombinant human TSH use in differentiated thyroid cancer

O seguimento imediato após tireoidectomia total (TT), em pacientes com câncer diferenciado de tireóide (CDT), tradicionalmente é feito com a ablação de remanescentes tireoidianos (RT) com 131I, na vigência de hipotireoidismo. O seguimento tardio do CDT inclui o uso de doses supressivas de T4, dosagem seriada da tireoglobulina (Tg), pesquisa de corpo inteiro (PCI) com 131I e ultra-sonografia (US) cervical. Nos últimos anos, tem-se mostrado que a ablação de RT com a ajuda do TSH recombinante humano (rhTSH) tem a mesma eficácia que a ablação de RT observada com a elevação endógena do TSH, mas sem os sintomas e piora de qualidade de vida descritos no hipotireoidismo. A dosagem da Tg estimulada com TSH endógeno ou exógeno, 9 a 12 meses após o tratamento inicial do CDT, associado à US cervical, pode identificar pacientes de baixo risco potencialmente curados de sua doença e nos quais a supressão do TSH não necessita ser tão intensa, evitando as complicações cardíacas e ósseas da tireotoxicose exógena prolongada. Finalmente, apesar de não existirem estudos randomizados que avaliem o papel do rhTSH no tratamento do CDT metastático, os resultados do tratamento combinado do rhTSH e 131I mostram um benefício clínico na maioria dos pacientes tratados.

Traditionally, the immediate treatment of patients with differentiated thyroid carcinoma (DTC) after total thyroidectomy (TT) is thyroid remnant ablation (TRA) with 131I, during hypothyroidism. Late follow-up of DCT includes suppressive doses of T4, serial measurements of thyroglobulin (Tg), whole body scan (WBS) with 131I and cervical ultrasound (US). In the last years, TRA with the aid of recombinant human TSH (rhTSH) has shown not only to avoid symptoms of hypothyroidism and a lower quality of life, but also to have the same efficacy as TRA during endogenous TSH elevation. Stimulated Tg with endogenous or exogenous TSH, 9 to 12 months after the initial treatment of DTC, associated with cervical US, is able to identify low-risk patients virtually cured of their disease, in whom TSH suppression does not need to be so strict, avoiding the heart and bone complications of prolonged exogenous thyrotoxicosis. Finally, in spite of the absence of randomized studies designed to evaluate the role of rhTSH in metastatic DTC disease, results of the combined treatment of rhTSH and 131I show a clinical benefit in the majority of treated patients.

Seguimento de pacientes de alto risco com carcinoma diferenciado de tireóide sem doença persistente após a terapia inicial / Follow-up of high-risk patients with differentiated thyroid cancer without persistent disease after initial therapy / Follow-up of high-risk patients with differentiated thyroid cancer without persistent disease after initial therapy

Este estudo avaliou o seguimento de pacientes com câncer de tireóide de alto risco, após a terapia inicial. Foram selecionados 125 pacientes de alto risco (tumor >4 cm e/ou invasão extra-tireoidiana e/ou metástases linfonodais e idade >45 anos), com ressecção tumoral completa. Todos foram tratados com tireoidectomia total e ablação com 131I [3,7­5,5 GBq (100­150 mCi)] e foram excluídos 18 casos (14,8 por cento) com metástases na PCI pós-dose (t-PCI). O valor preditivo negativo da Tg estimulada <1 ng/ml combinada ao US cervical na primeira avaliação (6­12 meses após a terapia ablativa) foi de 96,2 por cento para ausência de recidivas em até 5 anos. Este valor aumentou para 98,7 por cento quando acrescentamos a PCI com 185 MBq (5 mCi) 131I (d-PCI). O valor preditivo positivo (VPP) da Tg estimulada >1 ng/ml foi de 52 por cento para presença de metástases detectadas até 5 anos depois, mas considerando apenas pacientes que apresentaram d-PCI e US negativos inicialmente, o VPP foi 19 por cento (9 por cento se Tg 1­10 ng/ml vs. 40 por cento se Tg >10 ng/ml). Tg reduziu espontaneamente nos pacientes com Tg estimulada >1 ng/ml na primeira avaliação, US e d-PCI negativos e sem recidiva no seguimento, sendo indetectável em metade destes ao final de 5 anos. No primeiro ano após a terapia ablativa, 20 pacientes tiveram captação em leito tireoidiano na d-PCI com Tg estimulada e US negativos e não foram tratados com 131I; estes evoluíram sem recidiva e 60 por cento apresentavam uma d-PCI sem nenhuma captação após 5 anos. Em pacientes sem doença aparente (no US e d-PCI) e Tg estimulada <1 ng/ml, a recidiva em 5 anos foi de apenas 1,3 por cento. Um algoritmo para o seguimento de pacientes de alto risco após a terapia inicial é apresentado por este estudo.

This study evaluated the follow-up of high-risk patients with thyroid cancer after initial therapy. A total of 125 high-risk patients (tumor >4 cm and/or extrathyroid invasion and/or lymph node metastases, and age >45 years), with complete resection of the tumor, were selected. All patients underwent total thyroidectomy and ablation with 131I [3.7­5.5 GBq (100-150 mCi)]. Eighteen patients (14.8 percent) presenting metastases on post-dose whole-body scan (RxWBS) were excluded. The negative predictive value of stimulated Tg <1 ng/ml in combination with neck US during first assessment (6­12 mo. after ablative therapy) was 96.2 percent for the absence of recurrence up to 5 years. This value increased to 98.7 percent when adding WBS performed with 185 MBq (5 mCi) 131I (DxWBS). The positive predictive value (PPV) of stimulated Tg >1 ng/ml was 52 percent for the detection of the presence of metastases up to 5 years; however, considering only patients with initially negative DxWBS and US, the PPV was 19 percent (9 percent if Tg of 1­10 ng/ml vs. 40 percent if Tg >10 ng/ml). Tg levels decreased spontaneously in patients with stimulated Tg >1 ng/ml during first assessment, negative US and DxWBS, and no recurrence during follow-up, with Tg being undetectable in half these patients at the end of 5 years. Twenty patients presented uptake in the thyroid bed upon DxWBS during the first year after ablative therapy, with stimulated Tg and US being negative, and were not treated with 131I; these patients did not relapse and no uptake on DxWBS was observed in 60 percent after 5 years. Recurrence after 5 years was only 1.3 percent in patients without apparent disease (negative US and DxWBS) and stimulated Tg <1 ng/ml. An algorithm for the follow-up of high-risk patients after initial therapy is presented in this study.

Recurrencia del cáncer vesical superficial con el uso de BCG / Recurrence in superficial bladder cancer with the use of BCG

La recurrencia del cáncer vesical superficial puede llegar a un 10-80 por ciento, la cual puede ser disminuida significativa con el uso de quimioterápicos o BCG post cirugía. El objetivo de este trabajo es analizar los resultados con el uso de BCG intravesical post cirugía, de acuerdo a nuestro protocolo de tratamiento. Se revisan retrospectivamente, las fichas clínicas de 108 pacientes, con diagnóstico de cáncer vesical, tratados en el Hospital Dr. Sótero del Río y en Clínica Integramédica. Sesenta y nueve pacientes con tumor vesical superficial (Tis, Ta, T1), (55 H y 14 M) fueron sometidos a resección transuretral. Un 55,1 por ciento (n=39) recibió BCG adyuvante y un 44,9 por ciento (n=31) fueron observados. El esquema de tratamiento fue de 25-27 mg de BCG/semana por 3 veces (esquema 1: n=4), 25-27 mg/semana por 6 veces (esquema 2: n=11) y 25-27 mg/semana por 6 veces más refuerzos (esquema 3: n=20). El control consistió en cistoscopia, con o sin citología urinaria, más estudio por imágenes del tórax y la vía urinaria superior. El seguimiento promedio fue de 36,2 meses, con una mediana de 16 meses (rango: 1-250 meses), en el 83,3 por ciento de los pacientes. La recurrencia global de los pacientes tratados y no tratados con BCG fue de 28,9 por ciento y 41,9 por ciento, respectivamente. En estadío 0is, 0a y I, la recurrencia con y sin BCG fue de un 25 por ciento y 100 por ciento, 25 por ciento y 37,5 por ciento, y de 35,7 por ciento y 38,5 por ciento, respectivamente. La recidiva de los tumores superficiales varió según el esquema de BCG empleado, siendo de un 50 por ciento con el esquema 1, 36,4 por ciento con el esquema 2 y 15,0 por ciento con el 3. En un subgrupo de 42 pacientes con tumores vesicales superficiales, todos seguidos por más de 12 meses, la recurrencia en los estadíos 0is y 0a y I, con y sin BCG, fue de 33,3 por ciento y 100 por ciento; 23,5 por ciento y 80 por ciento; y de 55,6 por ciento y 66,7 por ciento, respectivamente. En este subgrupo, la recidiva también resultó claramente dependiente del esquema de BCG utilizado, siendo de un 50 por ciento para el esquema 1, 44,4 por ciento para el esquema 2 y 20 por ciento para el 3. Estos resultados confirman la utilidad de un esquema de BCG con dosis de 25 o 27 mg por instilación. Para establecer fracaso o éxito en el tratamiento con BCG, el seguimiento debiera ser al menos de 12 meses, ya que una observación menor puede dar índices de recurrencia falsamente bajos...

Carcinoma papilar del páncreas / Papillary carcinoma of the pancreas

Se presentan historias clínicas, estudios complementarios y tratamientos efectuados en un caso de tumor de cabeza de páncreas de bajo grado de malignidad, muy raro y muy poco conocido, como así también, su favorable evolución hasta la fecha (32 meses), del que fuera portadora una mujer de 48 años que concurriera al Hospital "J. R. Vidal" de Corrientes en 1993. Se trata de un carcinoma papilar del páncreas, también conocido como "Tumor Quístico y Papilar" o "Neoplasia Sólida y Papilar" o "Neoplasia Sólida y Papilar Epitelial", el que fuera tratado con cirugía conservadora y quimioterapia postoperatoria, circunstancia poco frecuente (30 por ciento de la literatura consultada) y con una evolución favorable, evaluada clínica y tomográficamente. Hacemos notar la frecuencia baja del tumor y la terapéutica instituída, también poco frecuente, su nula morbilidad y la posibilidad de curación a los cinco años

Cisplatin-based chemotherapy in advanced ovarian cancer: initial experience in an Indian set-up.

Forty patients of advanced ovarian carcinoma were treated with monthly cycles of cyclophosphamide, adriamycin and cisplatin. Debulking surgery was done in 29 cases. Clinical complete response was seen in 70 percent and an overall response in 85 percent of cases. The median follow-up was 30 months. The actuarial overall survival was 45 percent and the disease free survival was 35 percent at 3 years. The present protocol appears to have an important influence on initial control of disease but relapses continue to occur following the treatment. Cytoreductive surgery before or after three cycles of chemotherapy has a favourable influence on disease free survival (DFS). Prolonged follow up will be necessary to determine the overall influence on long term survival.