Prognostic factors in advanced non-small cell lung cancer: elevated serum levels of neuron specific enolase indicate poor prognosis

BACKGROUND: Non-small cell lung cancer (NSCLC) is resistant to chemotherapy and prognosis of advanced NSCLC patients is considered to be dependent on various prognostic factors. METHODS: We analyzed prognostic factors in patients with advanced NSCLC who had been enrolled in clinical trials conducted by the Okayama Lung Cancer Study Group between 1978 and 1992 using two kinds of multivariate analysis, Cox's multivariate analysis and recursive partitioning and amalgamation (RPA) analysis. RESULTS: The first analysis was performed on 261 patients using 28 variables. Performance status (PS), clinical stage, liver metastasis or serum albumin level was an independent prognostic factor by Cox's analysis. In the second analysis performed on 128 patients having data on neuron specific enolase (NSE), NSE was the most important prognostic factor. Using the RPA method, three subgroups with significantly different survival potentials were defined. Among them, patients with normal serum NSE levels and good PS were found to obtain a markedly favorable prognosis [median survival time (MST) 22.1 months, 3-year survival rate 42.9%], whereas the survival of patients with elevated serum NSE levels and bone metastasis was extremely short (MST 4.7 months, 3-year survival rate 0%). CONCLUSIONS: These results indicate that analysis of prognostic factors including serum levels of NSE is useful for predicting the survival of patients with advanced NSCLC.     

Progress in chemotherapy for colorectal cancer

Among colorectal cancer patients with recurrent or metastatic sites, survival was significantly prolonged for a group undergoing LV/5-FU therapy based on biochemical modulation compared with a group receiving no chemotherapy (best supportive care). LV/5-FU combination therapy is recognized as the standard therapy for colorectal cancer, but recently LV/5-FU plus oxaliplatin and LV/5-FU plus CPT-11 have appeared to be more effective than LV/5-FU in some randomized studies. Capecitabine, UFT/LV and S-1 are new oral drugs that are at least comparable to LV/5-FU in antitumor activity, but superior in tolerability, which benefits the patients' quality of life, especially elderly patients with colorectal cancer. Clinical combination studies using CDDP or CPT-11 with these oral drugs are now being performed. Much is expected of these drugs.     

Significance of reduction surgery for giant hepatocellular carcinoma with diffuse lung metastases and multiple intrahepatic metastases

Continuous systemic infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (500 mg/body/day) was performed for advanced hepatocellular carcinoma (HCC) after hepatectomy with diffuse lung metastases and multiple intrahepatic metastases. This infusion chemotherapy, cisplatin was continued for five days, and discontinued for two days, whereas 5-fluorouracil was administered every day and repeated four weeks as one course basally. Remnant metastases had almost disappeared after systemic chemotherapy for 10 weeks. In our experience, the response rate in 13 patients who underwent reduction surgery for multiple HCC was 84.6%. Continuous infusion of low-dose CDDP/5-FU may be effective in patients having absolute non-curative resection.     

Expandable metallic stent for the treatment of left-sided colonic obstruction with malignant disease

Recently, it was reported that an EMS (expandable metallic stent) was useful for treatment of colorectal obstruction. In our department, EMSs were used for seven patients with left-sided colonic obstruction with unresectable malignant disease. After these treatments with EMS, their symptoms were improved and they were able to intake food. Stomal formation was avoided except in one patient with severe soiling. In conclusion, EMS is thought to be useful for the improvement of quality of life in the patients with unresectable malignant colonic obstruction.     

A dominant positive and negative selectable gene for use in mammalian cells.

We have constructed three different fusion genes containing the herpes simplex virus thymidine kinase (HSV tk) and the bacterial neomycin phosphotransferase (neo) genes. All three fusion genes utilize the HSV tk promoter but differ at the junction of their components. We have determined if the fusion genes are bifunctional by introducing them into mammalian cells and testing for function of the individual components. One of the fusion genes, TNFUS 69, produced a bicistronic message and a fusion protein that has TK and NEO protein functions. This and other fusion genes of a similar nature could serve as dominant positive and negative selectable markers in mammalian cells.     

An elder case of neurosarcoidosis associated with brain infarction]

A 75-year-old woman with sarcoidosis developed sudden weakness of the left upper and lower limbs. Neurological examination revealed left-sided hemiplegia, hyperreflexia with pathological reflexes and hypesthesia. She was disoriented and euphoric. Diffusion-weighted brain MRI showed high intensity lesions in the right parietooccipital lobes. Electroencephalogram showed diffuse slowing of the background activity. Serum lysozyme increased to 18.4 mg/ml, CSF protein to 51 mg/dl. After admission, she presented psychotic manifestation followed by a progressive disturbance of consciousness. Epithelioid granulomas without caseous necrosis were present in the biopsied lymph node and specimens from the occipital cortex, indicating neurosarcoidosis. Necrosis was also present in the sampled brain tissue. The psychotic symptoms and consciousness disturbance rapidly ameliorated after the treatment with oral prednisolone, 40 mg/day. Neurosarcoidosis should be considered even in an elder case of sarcoidosis complicated with a stroke.