Metástasis ováricas de carcinoma de células pequeñas de pulmón / Ovarian metastases of small cell carcinoma oat-cell type of lung

La incidencia de cáncer de pulmón sigue aumentando, sobre todo en las mujeres y, aunque las metástasis en ovario son raras, hay que tenerla en cuenta en el estudio de extensión y seguimiento del mismo, porque en la mayoría de los casos en el momento del diagnóstico se verifica diseminación a distancia. Presentamos el caso de una paciente de 29 años en la que se planteó duda diagnóstica inicialmente entre tumor ovárico maligno con metástasis pulmonares versus linfoma, llegándose al diagnóstico final de carcinoma de células pequeñas tipo oat-cell de pulmón con metástasis ováricas.

The incidence of lung cancer is increasing, especially in women, and although metastasis in the ovary is uncommon it should be taken into account in the extension study and monitoring of the same because distant spread is verified in most cases at the time of diagnosis. We report the case of a 29-year-old patient which diagnostic doubt arose initially from malignant ovarian tumor with lung metastases or lymphoma, and she came to the final diagnosis of small cell carcinoma oat-cell type of lung with ovarian metastases.

[Small cell neuroendocrine carcinoma of the urinary bladder: report on two cases and review of the literature]

Small cell [Neuroendocrine] carcinoma of the urinary bladder is a rare but highly aggressive malignancy. The neoplastic cells exhibit both neuroendocrine and epithelial differentiation. It is morphologically indistinguishable from the more common pulmonary small cell carcinoma. It can occur either in association with urothelial [transitional cell] carcinoma or in a pure form. Presenting signs and symptoms are non specific. Histologically, it can mimic poorly differentiated urothelial carcinoma and lymphoma. Muscle invasion is almost invariably present at diagnosis and mortality is mainly due to metastases rather than loco regional recurrence. The optimal therapeutic modality is still controversial. In this article, we report on two cases occurring in a pure form and we briefly review the published literature regarding the clinical presentation, morphology, differential diagnosis, prognosis and treatment

Una variedad genética de la UDP-glucuronosil transferasa asociada a toxicidad gastrointestinal por irinotecan / A prevalent genetic variety of UDP-glycuronosyl transferase predicts high risk of irinotecan toxicity

Los avances en genética y biología molecular han impulsado la aparición de nuevas áreas de estudio en la medicina, como la farmacogenómica, la cual intenta predecir la respuesta y toxicidad a drogas en función de la variabilidad genética de cada individuo, constituyendo los llamados síndromes fármacogenómicos. La oncología podría beneficiarse debido a la gran toxicidad de sus fármacos. Hay varios loci genéticos que se están analizando por su potencial valor predictivo y hasta ahora sólo tres de ellos demostraron cierto grado de utilidad clínica. En especial, el estudio del número de repeticiones del dinucleótido timina-adenina (TA) en el promotor de la enzima UDP-glucuronosil-transferasa (UGT) mostró ser capaz de predecir neutropenia severa en pacientes expuestos a dosis intermedias y altas de irinotecan. Comunicamos el caso de una paciente con cáncer de pulmón de células pequeñas que padeció toxicidad hematológica y gastrointestinal grave tras haber sido tratada con dosis relativamente bajas (65 mg/m2) de irinotecan, y en quien un análisis del ADN leucocitario mostró la presencia de homocigosis para siete repeticiones de TA. Este caso es un ejemplo de aplicabilidad clínica del test, se discute su utilidad como predictor de toxicidad y la conducta a tomar frente a pacientes con estas características.

The advances in genetics and molecular biology have raised new areas in medicine, such as pharmacogenomics, which tries to predict drug responses and toxicities based on the individual genetic variability, describing the so called: pharmacogenomic syndromes. Oncology would find this development extremely useful because of the severe toxicity of chemotherapy. There are a lot of genetic loci under investigation for their potential in predicting drug toxicity, but only three of them have showed clinical usefulness up to now. In particular, quantification of the number of thymine-adenine (TA) dinucleotics in the promoter region of the UDP-glucuronosyl-transferase 1A1 enzime (TA indel) proved to be capable of predicting severe neutropenia in patients exposed to intermediate or high doses of irinotecan. Herein we report a case of a patient with small cell lung cancer who suffered severe hematological and gastrointestinal toxicity after being treated with relatively low doses (65 mg/m2) of irinotecan and whose leucocyte DNA analysis showed the presence of seven TA repetitions in both alleles. This case is an example of the clinical applicability and the utility of the test as a toxicity predictor. We also discuss the clinical decisions that may be taken with these patients.

Tratamento do câncer de pequenas células de pulmão: doenca limitada: resultados de uma única instituicão / Treatment of limited stage small-cell lung cancer: results from a single center

OBJETIVO: Relatar os resultados de tratamento de pacientes com câncer de pulmão de pequenas células com doenca limitada (CPPC-DL), num período de dez anos, numa única instituicão, para controle de qualidade e comparacão com dados de literatura. MATERIAIS E MÉTODOS: Entre janeiro de 1992 e dezembro de 2002, 101 pacientes portadores de CPPC-DL completaram tratamento em nossa instituicão. Seus resultados foram revistos e incluíram quimioterapia, radioterapia, a seqüência dos dois tratamentos e o uso de irradiacão profilática cerebral (PCI). A radiacão foi administrada com dose mediana de 45 Gy em 1,8 a 2 Gy por fracão. A dose mediana de PCI foi de 25 Gy em dez fracões. RESULTADOS: O seguimento mediano foi de 50,6 meses e a idade mediana dos pacientes foi de 63 anos. Houve 85 mortes confirmadas, 5 pacientes foram perdidos de seguimento e 11 estavam vivos. O tempo de sobrevida mediano foi de 11 meses, a sobrevida global em dois e cinco anos foi de 25,5 por cento e 10 por cento, respectivamente. Não houve diferenca significante na sobrevida global em dois ou cinco anos segundo a idade e sexo dos pacientes. Também não houve diferenca significante na sobrevida global entre os pacientes que realizaram PCI ou não, ou foram tratados em dois períodos diferentes (1997-2002 vs. 1992-1996). CONCLUSAO: Os resultados de tratamento dos pacientes portadores de CPPC-DL na nossa instituicão refletem as constantes mudancas no manuseio do CPPC. Nossa sobrevida global em dois anos de 25,5 por cento é semelhante a outros resultados uni-institucionais publicados, mas menor que os resultados de 47 por cento a 54 por cento recentemente publicados por grupos cooperativos.

Small cell lung cancer: an update on therapeutic aspects.

Small cell lung cancer comprises approximately 20% of all lung cancers and continues to be a difficult management issue. More than two-thirds of cases present with extensive disease, which has spread beyond the himithorax and regional ipsilateral nodes. While response rates to chemotherapy are relatively high, durable responses are rare, and long-term survival rates are anecdotal. Although many attempts have been made to develop new therapies, a combination of etoposide with either cisplatin or carboplatin remains the most widely used first-line therapy for extensive disease. For those with limited disease, chemotherapy with concomitant radiotherapy (given with the first or second cycles of chemotherapy) is considered the standard of care. Over the last decade, several new drugs and targeted agents have been identified with the aim to improve outcome of this malignancy. In this review we highlight recent developments in the management of this tumour.

Evaluation of curative and palliative radiotherapy efficacy in extensive stage small cell lung cancer

To evaluate the efficacy of curative and palliative radiotherapy in the treatment of extensive stage small cell lung cancer [E-SCLC], and compare therapy effect on survival with or without metastatic disease. From January 1998 through December 2004, 128 patients with E-SCLC were treated with radiotherapy and concomitants combined chemotherapy. Radical radiotherapy, consisting of approximately 60 Gy given in up to 30 fractions was performed in 53 [41.4%] of these patients. Others [58.6%] were treated with palliative dose radiotherapy. In all patients, chemotherapy was planned with cisplatin [80 mg/m2] intravenously [i.v.] on day 1, and etoposide [120 mg/m2] i.v. on days 1, 2 and 3, every 3 weeks for 3-6 cycles. Conventional follow-up of patients was conducted at Izmir Oncology Center, Izmir, Turkey. All results were evaluated statistically. One hundred and twenty-four patients [96.9%] were males. The mean age was 58.49 [ +/- 9.01], ranging from 37-78 years. Metastases were initially determined in 64 patients [50%]. The median follow up of patients was 287.41 days and median survival was 354.87 days. One year survival rate was 35.8%, and 2-year survival rates was 16.9% in the radical radiotherapy group, while these rates were 26.6% and 8% in the others. According to the statistical findings; the gains in duration of median survival with the curative thoracic irradiation are 151.97 days in all 128 patients. This study shows that curative radiotherapy at the primary tumor provides an additional survival benefit in patients with metastatic disease compared with palliative radiotherapy. This finding raises the question of whether treatment with radical thoracic radiotherapy with concomitant chemotherapy, consisting of first-line drugs, might be more beneficial and cost-effective as well as a less toxic treatment of E-SCLC

Progressive encephalomyelitis with rigidity: a paraneoplastic presentation of oat cell carcinoma of the lung. Case report

A encefalomielite progressiva com rigidez e mioclonia (PEWR) é doença neurológica rara, caracterizada por rigidez muscular, espasmos dolorosos, mioclonia e evidência de envolvimento de tronco cerebral e medula espinhal. Um paciente branco de 73 anos foi admitido com história de 10 dias de espasmos musculares dolorosos e rigidez muscular contínua no membro inferior esquerdo. Apresentava espasmos involuntários em membros inferiores e evoluiu com encefalopatia associada a sinais de nervos cranianos e sintomatologia de trato longo de medula espinhal. A tomografia computadorizada de crânio e a ressonância magnética de coluna foram normais. O LCR evidenciou pleocitose linfocítica, sem outras alterações. A EMG mostrou atividade muscular involuntária, de duração de 2-6 segundos, intervalo de 30-50 ms e uma freqüência de 2/segundo no membro inferior esquerdo. Foram detectados anticorpos anti-GAD no sangue. Na evolução, foram observados sinais radiográficos de neoplasia pulmonar, sendo posteriormente diagnosticado carcinoma de pequenas células de pulmão. O paciente faleceu duas semanas após o diagnóstico de câncer.

Carcinoma de pequenas células em esôfago: relato de caso e revisão / Small cell carcinoma of the esophagus: a case report and literature review

O caso de um paciente do sexo masculino, com 54 anos, portador de carcinoma de pequenas células primitivas em terço inferior de esôfago. As manifestações iniciais da doença se caracterizaram por emagracimento acentuado e dores epigástricas com 3 meses de evolução. Ao exame físico observamos sinais evidentes de doença consuntiva. O estadiamento oncológico revelou acometimento secundário de linfonodos para-aórticos, mesentéricos e do tronco celíaco (doença extensa), além de possível invasão de aorta descendente. O tratamento baseou-se na quimioterapia com cisdiaminodicloroplatinum e etoposide, obtendo-se remissão clínica completa com três ciclos. Como consolidação do resultado, o paciente recebeu radioterapia externa dirigida ao local do tumor primário, porém a resposta obtida não se manteve, havendo progressão local e sistêmica após 40 dias do término da radioterapia. O óbito se deu em função de infecção respiratória e múltiplas metástases 9 meses do diagnóstico ...

Four cases of therapy-related leukemia

Combination chemotherapy and radiation therapy have contributed to the successful treatment of various cancer patients. But the development of second malignancies is an inevitable complication of long-term cytotoxic treatment. The most serious and frequent of such complications is acute myelogenous leukemia (AML). Therapy-related leukemia is generally fatal. Since the number of patients exposed to chemotherapy is increasing each year, the clinical significance of this entity cannot be underestimated. There have been many investigations of therapy-related leukemia, but in Korea published reports are rare. We describe four such cases, involving one older female with lung cancer and three children with acute lymphoblastic leukemia (ALL) and malignant lymphoma. Alkylating agents were used for chemotherapy, and in one case, topoisomerase II inhibitor. Irrespective of the causative agents, the latency periods were relatively short, and despite induction chemotherapy in two, all survived for only a few months. During the follow-up of patients treated for primary malignancies, the possibility of therapy-related leukemia should always be borne in mind.

Carcinoma de pequenas células do esôfago / Small cell carcinoma of the esophagus

Small cell carcinoma of the esophagus is a rare tumor, described to the first time by Mckeown in 1952. Clinically it is very similar to small cell carcinoma of the lung, with quick evolution and early dissemination. It is more frequent in men between 60 and 70 years of age. The patients usually have dysphagia and weight loss. Most of the tumours arise in the middle and distal third of the esophagus. Chronic alcohol and tobacco use are usually present. The manegement of primary small cell cancer of the esophagus remains controversial with groups reporting treatment based on operation alone, local radiotherapy, chemotherapy alone, or operation with adjuvant therapy. Overall survivel remains poor at a mean of 5.1 months, with the best rate of survivel in patients undergoing operation with adjuvant chemotherapy. The authors relate two cases of a small cell carcinoma of the esophagus. Both of these patients was female and white, with 51 and 64 years old. The first mainestation was dysphagia and weight loss. Histologic study from endoscopic biopsies reveled the diagnosis. The treatment was, in the both cases surgery, however in one case, chemotherapy and mediastinal irradiation was associated to the ressection. The authors comment the more important aspects about this pathology, and the treatment and survival of the patients

Preliminary study of efficacy of intravenous cisplatin plus oral etoposide in small cell lung cancer.

Twenty-three patients with small cell lung cancer were treated with combination chemotherapy consisting of Cisplatin at 100 mg/m2 given by 2 hours intravenous infusion on day 1 and oral etoposide 25 mg/caplet given twice a day for 21 days repeated every 28 days for 6 cycles. Of 23 cases, four cases were not evaluable due to early death (three of them died from febrile neutropenia). Median age of the patients was 59 years (range = 45-76 years). Five cases were female and eighteen cases were male. Median Karnofsky performance status was 70 per cent (range = 50-90%). Five cases were extensive disease and eighteen cases were limited disease. Of 5 extensive disease cases, 1 complete response (20%) and 3 partial responses (60%) were achieved. Of 14 limited disease patients, 1 complete response (7.1%) and 11 partial responses (78.6%) were achieved. Hematologic toxicities were severe causing three patients to die because of febrile neutropenia, nine cases (10.7%) had grade 3 and 4 neutropenia. Grade 3 and 4 anemia and thrombocytopenia were seen in 28.6 per cent and 8.3 per cent respectively. Median survival time of all cases was 7 months. Thus, the combination of intravenous cisplatin and prolonged administration of oral etoposide could be administered to small cell lung cancer patients with high response rate, however, because of its severe toxicities, special caution should be considered and the optimal duration of oral etoposide should be evaluated.

Etoposide (VP-16) containing combination chemotherapy for treatment of patients with small cell lung cancer.

A combination chemotherapy consisting of VP-16, vincristine, cyclophosphamide and CCNU was used to treat 24 patients of small cell lung cancer (extensive stage disease - 15 and limited stage - 9). In addition, radiotherapy of 1000 to 4000 cGys was given to primary disease in chest in 16 patients. The overall response rate was 95.8% with complete response (CR) in 9 (37.5%) and partial (PR) in 14 (58.3%) cases. The overall median survival was 24 weeks. In patients with CR, it was 39 weeks and in those with PR this was 22.5 weeks. The lone non-responder survived for only 8 weeks. The drugs were well tolerated.

Quimio-radioterapia em carcinoma tipo "oat cell" do esôfago / Chemoradiotherapy in oat cell carcinoma of esophagus

É relatado um caso de um paciente com carcinoma indiferenciado de pequenas células originário no esôfago que foi tratado com quimio-radioterapia. Durante a quimioterapia de induçäo com Ciclofosfamida, Epirrubicina e Etoposide houve desaparecimento completo da neoplasia. A radioterapia foi utilizada para consolidaçäo da resposta. Dois anos e meio após diagnóstico o paciente foi a óbito após desenvolvimento de múltiplas metástases.

Phase II study of cyclophosphamide, doxorubicin, and vincristine (CAV) and etoposide plus cisplatin (EP) alternating chemotherapy combined with radiotherapy in small cell lung cancer

The development of drug resistance is the major limiting factor influencing the survival of patients with small cell lung cancer (SCLC). We have thus examined the activity of cyclophosphamide, doxorubicin and vincristine (CAV) alternating with etoposide and cisplatin (EP) in 35 patients with SCLC. The treatment courses were alternated every 3 or 4 weeks. After induction chemotherapy, patients with limited disease (LD) received thoracic radiotherapy (5000 cGy), prophylactic cranial irradiation (3000 cGy) and maintenance chemotherapy and patients with extensive disease (ED) received maintenance chemotherapy only. In this group of 35 patients, 13 had limited disease (LD) and 22 had extensive disease (ED). After completion of the therapy, 100% of the patients with LD achieved complete plus partial remission (CR + PR) and 68% of the patients with ED achieved CR + PR. The median survival time was 66 weeks (15.3 months) in patients with LD and 44 weeks (10.2 months) in patients with ED. The over all survival for patients with LD was superior to that for patients with ED (p less than 0.05). Also, median response duration for patients with LD (35 wks) was longer than that for patients with ED (17 weeks) (p less than 0.05). The primary site was the most vulnerable site to relapse (18 patients). Toxicity was mild to moderate and acceptable, and there were no treatment-related deaths. These results suggest that the alternation of CAV and EP is effective treatment strategy in the management of SCLC. A randomized controlled study will be required to discriminate the actual effect of this alternating regimen.