Unusual sites of malignancy: case 3. Solitary splenic metastasis in lung cancer with spontaneous rupture.
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Biomedical subjects
Publications and source records attributed to H Dhingra.
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Castleman's disease is a clinicopathological entity in which growth of lymphoid tissue is unregulated. It may present as asymptomatic involvement of one lymph node group or as a multicentric disease with systemic symptoms. Unlike localized disease, for which surgical excision is curative regardless of the histological type, multicentric disease often necessitates aggressive systemic therapy and portends a poor outcome. Superior vena caval thrombosis is an uncommon manifestation associated with Castleman's disease.
Our previously reported randomized study of patients with untreated, potentially resectable clinical stage IIIA non-small-cell lung cancer found that patients treated with perioperative chemotherapy and surgery had a significant increase in median survival compared to patients treated with surgery alone. We have now re-analyzed the results of the study with a median time from random allocation to analysis for all patients of 82 months. The increase in survival conferred by perioperative chemotherapy was maintained during the period of extended observation.
BACKGROUND: Patients with resectable stage IIIA non-small-cell lung cancer have a low survival rate following standard surgical treatment. Nonrandomized trials in which induction chemotherapy or a combination of chemotherapy and radiation prior to surgery were used to treat patients with regionally advanced primary cancers have suggested that survival is improved when compared with treatment by surgery alone. PURPOSE: We performed a prospective, randomized study of patients with previously untreated, potentially resectable clinical stage IIIA non-small-cell lung cancer to compare the results of perioperative chemotherapy and surgery with those of surgery alone. METHODS: This trial was designed to test the null hypothesis that the proportion of patients surviving 3 years is 12% for either treatment group against the alternate hypothesis that the 3-year survival rate would be 12% in the surgery alone group and 32% in the perioperative chemotherapy group. The estimated required sample size was 65 patients in each group. The trial was terminated at an early time according to the method of O'Brien and Fleming following a single unplanned interim analysis. The decision to terminate the trial was based on ethical considerations, the magnitude of the treatment effect, and the high degree of statistical significance attained. In total, 60 patients were randomly assigned between 1987 and 1993 to receive either six cycles of perioperative chemotherapy (cyclophosphamide, etoposide, and cisplatin) and surgery (28 patients) or surgery alone (32 patients). For patients in the former group, tumor measurements were made before each course of chemotherapy and the clinical tumor response was evaluated after three cycles of chemotherapy; they then underwent surgical resection. Patients who had documented tumor regression after preoperative chemotherapy received three additional cycles of chemotherapy after surgery. RESULTS: After three cycles of preoperative chemotherapy, the rate of clinical major response was 35%. Patients treated with perioperative chemotherapy and surgery had an estimated median survival of 64 months compared with 11 months for patients who had surgery alone (P < .008 by log-rank test; P < .018 by Wilcoxon test). The estimated 2- and 3-year survival rates were 60% and 56% for the perioperative chemotherapy patients and 25% and 15% for those who had surgery alone, respectively. CONCLUSIONS: In this trial, the treatment strategy using perioperative chemotherapy and surgery was more effective than surgery alone. IMPLICATIONS: This clinical trial strengthens the validity of using perioperative chemotherapy in the management of patients with resectable stage IIIA non-small-cell lung cancer. Further investigation of the perioperative chemotherapy strategy in earlier stage lung cancer is warranted.
BACKGROUND: Taxol, a complex plant product (a diterpene) extracted from the bark of Taxus brevifolia, has demonstrated substantial anticancer activity in ovarian and breast cancers, malignant melanoma, and acute myelogenous leukemia. Due to allergic reactions in phase I and early phase II studies, use of a 24-hour infusion of taxol with prophylactic dexamethasone, diphenhydramine, and cimetidine has been recommended. PURPOSE: In this phase II study, we attempted to determine the efficacy and toxicity of taxol in patients with advanced (stage IIIB or IV) non-small-cell lung cancer who had never received chemotherapy. METHODS: Patients were not excluded because of prior surgery or because of radiotherapy administered more than 4 weeks before study entry. Taxol was administered in the hospital at a dose of 200 mg/m2 as an intravenous infusion over 24 hours and repeated every 3 weeks, provided that patients had recovered from any toxic effects. Dexamethasone, cimetidine, and diphenhydramine were given before chemotherapy to prevent hypersensitivity reactions. Therapy was continued for at least two courses unless there was rapid disease progression and for at least three courses if no change was observed and no grade 3 or 4 toxic effects occurred. Treatment was continued for six more courses after maximum response or for two more courses after complete remission but was discontinued if disease progressed. RESULTS: Of the 27 patients entered in the study, 25 were assessable for toxic effects and response. One patient had an allergic reaction that was not life threatening. The overall response rate was 24% (one complete response and five partial responses). An additional seven patients (28%) had minor response. Granulocytopenia was the dose-limiting toxic effect, and neutropenic fever occurred in eight of 118 courses. One additional patient developed neutropenic sepsis with hypotension but recovered with intensive treatment. CONCLUSIONS: Taxol appears to have activity against non-small-cell carcinoma of the lung. IMPLICATIONS: A phase II study combining taxol, etoposide, and cisplatin and using hematopoietic stimulating factors is now proposed. The optimal dose for combination chemotherapy has yet to be determined. An important consideration is potential cardiac effects of taxol with other drugs.
Cerebral malaria is an unusual and treatable cause of stupor and coma, and it can present suddenly in a healthy person. It is diagnosed by finding parasites on a blood smear and is treated either with chloroquine or with quinine, pyrimethamine, and sulfadiazine.