Evaluating mmp-2 and tgfß-ri expression in circulating tumor cells of pancreatic cancer patients and their correlation with clinical evolution / Avaliação da expressão de mmp-2 e tgfß-ri em células tumorais circulantes de pacientes com câncer de pâncreas e sua correlação com evolução clínica

ABSTRACT Background: Metastasis is common in the diagnosis of pancreatic cancer, and the presence of epithelial-mesenchymal transition markers in circulating tumor cells may suggest worse prognosis. Aim: To correlate the number of circulating tumor cells (CTCs) in the peripheral blood of patients with a locally advanced or metastatic pancreatic tumor and the protein expression involved in epithelial-mesenchymal transition (EMT) in CTCs with clinical characteristics, progression-free survival (PFS) and overall survival (OS). Method: This was a prospective study conducted using peripheral blood samples collected at three different times. CTCs were quantified by the ISET test and analyzed by immunocytochemistry. Proteins involved in EMT (vimentin, TGFß-RI and MMP2) were analyzed in all CTCs. Results: Twenty-one patients were included. Median CTCs detected were 22, 20 and 8 CTCs/8 ml blood at baseline, first and second follow-up, respectively. No statistically significant correlation was found in correlating the number of CTCs and the evaluated clinical characteristics, PFS, or OS. There was no difference in PFS and OS among the EMT markers in the groups with and without markers. Conclusion: CTC analysis was not relevant in this sample for comparing clinical findings, PFS and OS in patients with pancreatic cancer. However, marker analysis in CTCs could be useful for the MMP-2 and/or TGFß-RI expression, as observed by the separate PFS curve.

RESUMO Racional: A metástase é comum no diagnóstico de câncer de pâncreas; presença de marcadores de transição epitélio-mesenquimal nas células tumorais circulantes (CTCs) podem sugerir pior prognóstico. Objetivo: Correlacionar o número de CTCs no sangue periférico de pacientes com tumor de pâncreas localmente avançado ou metastático e expressão de proteínas envolvidas na transição epitélio-mesenquimal (TEM) nas CTCs com características clínicas, sobrevida livre de progressão (SLP) e global (SG). Método: Estudo prospectivo realizado por meio de coletas de sangue periférico em três tempos distintos. As CTCs foram quantificadas pelo sistema ISET e analisadas por imunocitoquímica. Proteínas envolvidas na TEM (vimentina, TGFß-RI e MMP2) foram analisadas em todas as CTCs. Resultados: Foram incluídos 21 pacientes. A mediana de CTCs detectadas foi de 22, 20 e 8 CTCs/8 ml de sangue no baseline, primeiro e segundo seguimentos, respectivamente. Na correlação entre número de CTCs e as características clínicas levantadas, SLP, SG não houve correlação estatisticamente significante. Nos marcadores de TEM não houve diferença de SLP e SG entre os grupos que apresentaram e não apresentaram marcação. Conclusão: As CTCs não se mostraram relevantes na comparação dos achados clínicos, SLP e SG em pacientes com câncer de pâncreas. No entretanto, pode ser que para a análise de marcador seja útil, como observado pelas curvas separadas de expressão de MMP-2 e TGFß-RI nas CTCs.

Circulating tumor cells as a new and additional approach to follow-up patients with serous low-grade ovarian adenocarcinoma: a case report and review of the literature

Background: Current methods for follow-up of Ovarian Cancer (OC) are widespread, especially with CA125, which, however, is not a perfect biomarker and thus further investigation for new methods of evaluation are warranted. The feasibility of Circulating Tumor Cells (CTCs) in advanced OC was investigated in this case report. Case presentation: A 19-year-old woman with advanced low-grade serous papillary adenocarcinoma and relapsed disease did not have a CA125 correspondent with disease relapse. CTCs were evaluated, compared with CA125 and with image exams. Relapses were not correspondent to elevations of CA125. CTCs demonstrated usefulness, being proportional to major disease relapse, especially in the peritoneum. CTCs may be used as a complementary diagnosis tool when marginal/small increases in CA-125 levels are observed. Conclusions: In OC, CTCs can be an important tool to predict recurrence, response to treatment and improve the quality of decision-making, in order to offer the best treatment to a determined group of patients (AU)

Aortic dissection during antiangiogenic therapy with sunitinib. A case report / Dissecção de aorta em terapia anti-angiogênica com sunitinibe. Um relato de caso

CONTEXT: Sunitinib is an antiangiogenic drug that has been approved for treating metastatic renal cancer. Its action as a tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFRs) and other angiogenesis receptors may lead to adverse effects such as hypertension and heart failure. However, reports in the literature on an association between sunitinib therapy and acute aortic dissection are rare. CASE REPORT: We report the case of a 68-year-old man with metastatic renal carcinoma who developed acute aortic dissection during sunitinib therapy. He had no history of hypertension or any other risk factor for aortic dissection. After aortic dissection had been diagnosed, sunitinib was withdrawn and an aortic endoprosthesis was placed. Afterwards, the patient was treated clinically with antihypertensive drugs and new therapy for renal cancer consisting of temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway. CONCLUSION: Hypertension is a common event when antiangiogenic drugs are used in oncology. However, knowledge of other severe cardiovascular events that may occur in these patients, such as acute aortic dissection, is important. Adequate control over arterial pressure and frequent monitoring of patients during the first days of antiangiogenic therapy is essential for early diagnosis of possible adverse events. .

CONTEXTO: Sunitinibe é uma droga antiangiogênica aprovada para tratamento de câncer renal metastático. Sua ação como inibidor de tirosina quinase de receptores de fatores de crescimento do endotélio vascular (VEGFR) e de outros receptores de angiogênese pode levar a eventos adversos como hipertensão e insuficiência cardíaca. No entanto, é escassa na literatura a associação da terapia com sunitinibe e dissecção aguda de aorta. RELATO DE CASO: Relatamos o caso de um paciente do sexo masculino de 68 anos com câncer renal metastático que desenvolveu dissecção aguda de aorta durante tratamento com sunitinibe. O paciente não tinha histórico prévio de hipertensão nem outro fator de risco para dissecção de aorta. Após diagnóstico da dissecção de aorta, a droga foi suspensa e o paciente foi submetido à colocação de endoprótese na aorta, evoluindo posteriormente com controle clínico da pressão arterial e nova terapia para câncer renal com tensirolimo, um inibidor da via proteína alvo da rapamicina em mamíferos (mTOR). CONCLUSÕES: A hipertensão é um evento comum com uso de drogas antiangiogênicas na oncologia. No entanto, é importante o conhecimento de outros eventos cardiovasculares graves, como dissecção aguda de aorta, que podem ocorrer nesses pacientes. Controle adequado da pressão arterial e monitorização frequente dos pacientes nos primeiros dias de terapia antiangiogênica são essenciais para diagnóstico precoce de possíveis eventos graves. .

Circulating tumor cells: basic concepts and some clinical applications

The spread of cancer requires the presence of circulating tumor cells (CTCs), which are rare cells surrounded by billions of normal hematopoietic cells in the bloodstream. It is believed thatCTCs tend to metastasize to certain organs, thus, their presence may determine invasive tumor behavior. Generally, these cells are undetectable by conventional histopathological analysisand imaging exams with high resolution. Therefore, more sensitive immunohistochemical and molecular assays have been developed that have allowed the specific detection of metastatic tumor cells in regional lymph nodes, peripheral blood and bone marrow. This article reviews theliterature regarding CTCs and tumors of the breast, colorectal, pancreas and lung as it pertains to forms of detection and clinicopathological correlations, in addition to future outlooks

Synchronous thyroid and colon metastases from epidermoid carcinoma of the lung: case report / Metástases sincrônicas de carcinoma epidermoide de pulmão em tireoide e cólon: relato de caso

CONTEXT: Non-small cell lung cancer (NSCLC) progresses to distant metastases in most cases. The most frequent sites for distant metastases are the bones, central nervous system, adrenal glands and liver. Dissemination to the skin, myocardium, thyroid gland and intestine may occur, but is rare. CASE REPORT: We describe a case of squamous cell carcinoma in the lungs, with metastases in the colon and thyroid, in a 66-year-old female patient. The lesion was unresectable and chemotherapy was started. The patient evolved with intestinal subocclusion, and colonoscopy showed the presence of a polyp. Biopsy and immunohistochemical analysis on the polyp showed that it was compatible with squamous cell carcinoma of pulmonary origin. At a follow-up consultation, the patient presented a thyroid nodule. A aspiration biopsy and cellblock immunohistochemistry confirmed the squamous cell carcinoma of pulmonary origin. After third-line chemotherapy, the patient progressed with acute obstructive abdomen due to a retroperitoneal mass. She underwent exploratory laparotomy and died due to surgical complications. Metastases to the thyroid and colon are rarely reported in cases of epidermoid carcinoma of the lungs. Gastrointestinal involvement in pulmonary metastases may affect the stomach, small intestine and colon, and cases of bleeding and perforation have already been reported. Although richly vascularized, the thyroid is an infrequent site for metastases. Such sites reflect poor prognoses for the clinical evolution. We did not find any previous reports in the literature, on lung cancer with metastases concomitantly in the colon and thyroid, in a single patient.

CONTEXTO: O câncer de pulmão de células não pequenas evolui, na maioria dos casos, com metástases a distância. Ossos, sistema nervoso central, glândula adrenal e fígado são os sítios mais frequentes de metástases. Disseminação para pele, miocárdio, tireoide e intestino pode ocorrer, entretanto é rara. RELATO DE CASO: Descrevemos um caso de carcinoma espinocelular (CEC) de pulmão com metástase em cólon e tireoide, em mulher de 66 anos. A lesão era irressecável, e foi iniciada quimioterapia. A paciente evoluiu com suboclusão intestinal e a colonoscopia evidenciou pólipo colônico cuja biópsia e imunoistoquímica (IHQ) foram compatíveis com CEC de origem pulmonar. Em consulta de acompanhamento, detectou-se nódulo tireoidiano cuja punção aspirativa e IHQ de cellblock confirmaram CEC de origem pulmonar. Após quimioterapia de terceira linha, a paciente evoluiu com abdome agudo obstrutivo por massa retroperitoneal, sendo submetida a laparotomia exploradora, vindo a falecer por complicações da cirurgia. Metástases para tireoide e cólon são raramente reportadas em carcinomas epidermoides de pulmão. O envolvimento gastrointestinal por metástases de pulmão pode acometer estômago, intestino delgado e cólon, e casos de sangramento e perfuração já foram reportados. Embora ricamente vascularizada, a tireoide é sítio infrequente de metástases. Os sítios refletem prognósticos reservados na evolução clínica. Não encontramos, na literatura, relato prévio de câncer de pulmão com metástases em cólon e tireoide concomitantes em um único paciente.

Paliative chemotherapy based in etoposide Leucovorin and 5 Fluorouracil (ELF) using leucovorin in low dose in the treatment of patients with advanced gastric cancer

A great percentage of diagnosed gastric cancer cases are encountered in advanced stages with distant metastases. In these cases, the standard treatment is palliative chemotherapy. In the ELF chemotherapy regime, the dose of leucovorin (Lv) varies from 300 to 500mg/m2. However, there are no studies that demonstrate therapeutic equivalence between high and low doses of Lv. OBJECTIVE: Retrospectively analyze the response rates and toxicity profile of the ELF scheme with low doses of Lv offered to patients with metastatic gastric cancer. MATTERS AND METHODS: Evaluated were patients treated with etoposide (120mg/m2/day), Lv (20mg/m2/day) and 5-fluorouracil (500mg/m2/day), D1 and D3 cycles repeated every three weeks. RESULTS: Sixty-eight patients were treated, 69% men, with median age of 60.24 years. Occurred six complete responses (8.8%), five partial responses (7.4%) and 38.2% of the patients presented stable disease. The median overall survival was 9.15 months (IC95%, 6.06-12.95), while patients with overall response was 16.05 months (IC95%, 10.48-21.63) and in those that presented stable disease or progression was 9.01 months (IC95%, 4.71-13.31; p=0.669). Grade III and IV low frequency toxicity was observed. CONCLUSIONS: In the present sample, the ELF regime with low-dose leucovorin presented an excellent toxicity profile. In spite of the low response rate, the respondent patients presented an equivalent overall survival to the other regimens of the literature.

Dermatomyositis related to a male germ cell carcinoma: a case report

Dermatomyositis is an autoimmune disorder that affects mainly muscles and skin. In some cases it may be associated to neoplasms occurring before the diagnosis of cancer. Its relation to germ cell tumor is not well documented, so we describe a case of a patient with history of muscle weakness and cutaneous rash that preceded cancer for 6 months. Dermatomyositis must remind of a possible occult neoplasm and its remission may follow the treatment of the tumor.