Systemic vasculitis in a patient with small-cell neuroendocrine bronchial cancer

A 75-yr-old male hospitalized for vascular purpura with joint pain had a medical history of polymyalgia rheumatica. A generalized oedematous syndrome occurred and the patient also presented with haemoptysis and complained of transient paraesthesia of the hands and feet. Renal biopsy showed lesions of focal segmental proliferative glomerulonephritis associated with a few cellular crescents. Lung biopsy showed small-cell neuroendocrine carcinoma. After the first course of chemotherapy signs of vasculitis disappeared. Small-cell neuroendocrine carcinomas, which represent 25% of all lung cancers, have numerous paraneoplastic (especially neurological) extrapulmonary manifestations. Disseminated vasculitis has never been described with this type of cancer, whereas nonsmall-cell carcinomas are associated essentially with cutaneous vasculitis or purpura rheumatica. In the case reported here, anticancer chemotherapy allowed vasculitic manifestations to be treated.     

Intermittent-low dose G-CSF treatment in a patient with chronic neutropenia

Tamoxifen induces apoptosis (programmed cell death) in human erythroleukemia K562 cells. Nitric oxide synthase activity and expression increased in apoptotic cells by 315% and 280%, respectively, compared to controls. The specific inhibitor of nitric oxide synthase, L-NAME, protected K562 cells from tamoxifen-induced apoptosis, whereas the nitric oxide donor, sodium nitroprusside (SNP), potentiated the apoptotic effect of the drug. In addition, 5-lipoxygenase was activated by tamoxifen and the specific enzyme inhibitor, MK886, protected K562 cells against the drug. Conversely, the 5-lipoxygenase product, 5-hydroperoxyeicosatetraenoic acid, enhanced the tamoxifen-induced apoptosis. Finally, tamoxifen altered also membrane properties of K562 cells.     

Local treatment with tumor necrosis factor alpha in a patient with lung cancer

Tumor Necrosis Factor alfa (TNFa) is a cytokine with cytolytic and cytotoxic properties. First clinical trials in which TNF was administered parenterally date back to early 70-ties. Soon it was noticed that when administered strictly to the tumor mass TNF exhibits high anti-tumor efficacy, exemplified by total or at least substantial regression of the tumor mass while producing minor and controllable symptoms. In this paper the case of local administration of the recombinant TNFa directly into the tumor mass constricting the bronchus was presented.     

Expression and interconversion of neuron-specific enolase in patient sera and extracts from small-cell lung cancer cells

The isoforms of gamma-enolase were characterized in serum from patients with small-cell lung cancer (SCLC) and in extracts from SCLC cell lines and malignant melanoma tumor tissue. Large variations in the expression of the 3 gamma-isoforms of enolase were observed. These forms probably represent the homodimeric gamma gamma-enolase, the heterodimeric alpha gamma-enolase and the monomeric forms of gamma-enolase. Only the dimeric forms are enzymatically active. The predominant gamma-enolase in the cell lines is the heterodimeric alpha gamma-enolase. The SCLC cell lines can be divided into two groups: one with negligible gamma gamma-enolase expression and considerable amounts of the nonneuronal alpha alpha-enolase and a second group with a large fraction of gamma gamma-enolase concomitant with a low expression of alpha-enolase. Similar patterns are observed in tissue extracts from malignant melanoma. When changing buffer conditions by increasing the ionic strength and decreasing the Mg2+ concentration, interconversions between the isozymes occur. In contrast to the predominant alpha gamma-enolase in extracts from cell lines, the multiple forms of gamma-enolase in serum might be caused by a subunit exchange facilitated by the low Mg2+ concentration in plasma. However, there seems to be a stable equilibrium between the isoforms in undiluted patient serum. The induction of subunit exchange by perturbation in ionic strength and/or Mg2+ concentration indicates a need for caution when choosing diluents for use in assays for neuron-specific enolase.     

Accelerated nodulosis in a patient with psoriasis and arthritis during treatment with methotrexate

A 66-year-old woman with longstanding psoriasis involving the skin presented with asymmetrical polyarthritis. Methotrexate (MTX) was given initially intramuscularly and orally. Intramuscular MTX was discontinued, and a few months after she had been taking only oral MTX she developed nodules, first in surgical incisions, and subsequently in her buttocks, thighs, legs, and arms. Reduction of the dose of oral MTX was followed by gradual diminution in size of the nodules and then total disappearance.     

Results of radiation therapy for limited small-cell lung cancer

Results of radiotherapy were reviewed in 68 patients with limited small-cell lung cancer from the aspect of local control. Thirty-one patients achieved CR (46%), while the other 31 remained at PR. The 1-, 2-, 3-, and 5-year cumulative survival rates were 57%, 28%, 21%, and 16%, respectively, for 15 months in MST. Thirty-six patients developed local recurrence (53%) and 46 had distant metastasis (68%). The thirty-one patients with CR had a 43% 2-year-survival rate and 23 months in MST. The remaining 37 patients (PR + NC) had respective figures of 13% and 13 months (p < 0.025). There was no statistically significant difference between radiation dose and local thoracic failure among the patients. Of the 31 patients with CR, 28 had achieved CR at 45Gy (17 received 55Gy or more, and 11 less than 55Gy). In the former, the local control rate, 2-year-survival and MST were 94%, 53% and 44 months, while in the latter these were 45%, 27% and 17 months, respectively. Thirty-five patients were irradiated by the shrinking field technique according to tumor reduction; however, this technique did not influence the treatment results. To obtain better results, it is first necessary to achieve CR at initial chemo-radiotherapy. As to irradiation, randomized trials between 50Gy and 60Gy would require patients with CR at 45Gy.     

A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications associated with total knee arthroplasty. The American College of Chest Physicians recommends twice-daily, fixed-dose low-molecular-weight heparin (LMWH) as routine prophylaxis in this patient population. This study represents a cost analysis of ardeparin and enoxaparin, the two LMWHs currently available for this indication in the United States. Costs for treating DVT, PE, and major bleeding episodes were derived from values reported in the literature. Both ardeparin and enoxaparin were found to produce significant cost savings when used routinely as DVT prophylaxis after knee replacement surgery compared with no prophylaxis. Based on the currently available data, enoxaparin 40 mg once daily appears to be the least costly LMWH for routine pharmacoprophylaxis of DVT in patients undergoing knee replacement surgery.     

Results of initial surgery and adjuvant chemotherapy in treating small-cell lung cancer

The changes in the intestinal mucosal permeability were observed by quantitatively assessing plasma to luminal clearance of 99mTc-labeled DTPA, and the influence of platelet activating factor (PAF) on it was investigated. The results showed that intestinal permeability was significantly elevated after severe burn and was positively correlated with increase in PAF in the intestinal tissue (r = 0.94, P < 0.01). PAF antagonist therapy could significantly attenuate postburn intestinal mucosal permeability. It is concluded that PAF is one of the important factors causing increased intestinal permeability after severe burn.     

Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide

BACKGROUND: For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. METHODS: We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. RESULTS: Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P=0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P<0.001). CONCLUSIONS: Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.