A multicenter phase II study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer: Kyushu thoracic oncology group trial

Purpose: This multicenter phase II study was conducted to investigate the efficacy and safety of carboplatin in combination with paclitaxel administered according to a biweekly schedule as a first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). Patients and methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. Paclitaxel (140 mg/m²) was administered intravenously on day 1, in combination with carboplatin at an area under the concentration time curve (AUC) of 3, every 2 weeks. Results: Seventy-four patients (45 men) with a median age of 62 years (range 40–74) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 35.1% [95% confidence interval (CI): 24.4–47.1%], with 26 partial responses. The median survival was 357 days, and the median time to progression was 218 days. Toxicity was generally mild; National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grades 3 and 4 neutropenia was observeded in 50.0% of the patients, and grades 3 and 4 nausea/vomiting in 4.1%. Conclusions: Biweekly carboplatin combined with paclitaxel demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of carboplatin combined with paclitaxel administered every 3 weeks but with a more favorable toxicity profile, and the present data indicate that the regimen is suitable for use on an outpatient basis.     

Phase I study of biweekly paclitaxel and carboplatin administration in patients with advanced non-small cell lung cancer

A phase I study of a biweekly outpatient regimen composed of carboplatin (CBDCA) and paclitaxel (TXL) was conducted for advanced non-small cell lung cancer. TXL was given in combination with a fixed dose of CBDCA (AUC 3) every 2 weeks. The starting dose of TXL was 100 mg/m2, and the dose was escalated in increments of 20 mg/m2. Three to six patients were allocated to each level. Toxicities were evaluated in the first 4 courses to determine the maximum tolerated dose (MTD). TXL 160 mg/m2 dosages proved to be MTD, and the dose limiting toxicity (DLT) was hematotoxicity (neutropenia). The patients, however, recovered from neutropenia using G-CSF immediately, when G-CSF was used. Gastrointestinal toxicity was well-tolerated. A response was found in 9 out of 20 patients who received 4 courses or more (45%). These results suggest that the recommended dose would be CBDCA (AUC 3) + TXL 140 mg/m2. The biweekly regimen has a high level clinical activity and excellent tolerability, and is suitable for outpatients. We started a phase II study because of these results.     

Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues

BACKGROUND: DNA double-strand breaks (DSB) are the major lethal lesions induced by ionizing radiation. The capability for DNA DSB repair is crucial for inherent radiosensitivity of tumor and normal cells. DNA-PKcs, Ku 70, Ku 85, Xrcc4, and Nbs1 play a critical role in DNA DSB repair. METHODS: We immunohistochemically investigated the expression of DNA-PKcs, Ku 70, Ku85, Xrcc4, and Nbs1 in 134 specimens from various normal and tumor tissues with different radiosensitivity. RESULTS AND CONCLUSION: Immunopositivity to Ku70, Ku85, DNA-PKcs, Xrcc4, and Nbs1 was found in all tumor tissues examined. The staining for Ku70, Ku85, and DNA-PKcs was nuclear; but, for Xrcc4 and Nbs1, it was nuclear and cytoplasmic. There were no apparent differences in the expression of these five proteins among cancerous tissues and the corresponding normal tissues. No apparent differences in nuclear staining intensity were detected in the expression of these five proteins among tumor tissues with different radiosensitivity, although non-Hodgkins' lymphoma (B or T cell) tended to show a lower expression than the others. The stromal cells generally expressed these five proteins at much lower frequency than either tumor or epithelial cells in both tumor and normal tissues.     

Usefulness of positron emission tomography-CT for diagnosis of primary bone marrow lymphoma in children

Primary bone marrow lymphoma (PBML) is hard to diagnose in children, due to the difficult identification of malignant cells in bone marrow. The first case, a 5-year-old boy, showed knee swelling with an intermittent fever. The second case, a 12-year-old girl, showed fever of unknown origin without lymphadenopathy or hepatosplenomegaly. In both cases, the diagnosis was not confirmed despite the repeated bone marrow aspirations. Finally, bone marrow aspiration and biopsy at the positive site by positron emission tomography (PET)-CT contributed to definitive diagnosis of PBML. The PET-CT is useful for the accurate diagnosis of PBML in children with non-specific symptoms.     

Infantile inflammatory pseudotumor of the facial nerve as a complication of epidermal nevus syndrome with cholesteatoma

The first reported case of facial paralysis due to an inflammatory pseudotumor (IPT) of the facial nerve as a complication of epidermal nevus syndrome (ENS) is herein presented. A 10-month-old female patient was diagnosed with ENS at 3 months of age. She was referred to us because of moderate left facial paralysis. Epidermal nevi of her left auricle extended deep into the external ear canal. Otoscopy revealed polypous nevi and cholesteatoma debris filling the left ear. Computed tomography showed a soft mass filling the ear canal, including the middle ear, and an enormously enlarged facial nerve. Surgical exploration revealed numerous polypous nevi, external ear cholesteatoma, and tumorous swelling of the facial nerve. The middle ear ossicles were completely lost. The facial paralysis was improved after decompression surgery, but recurred 5 months later. A second operation was conducted 10 months after the first. During this operation, facial nerve decompression was completed from the geniculate ganglion to near the stylomastoid foramen. Histological diagnosis of the facial nerve tumor was IPT probably caused by chronic external ear inflammation induced by epidermal nevi. The facial paralysis gradually improved to House–Blackmann grade III 5 years after the second operation.     

A new subpopulation of intestinal intraepithelial lymphocytes expressing high level of T cell receptor gamma delta.

The murine intestinal epithelium contains T cell receptor (TcR) gamma delta-bearing T cells in high frequency. In the present report, we showed that TcR gamma delta-bearing intestinal intraepithelial lymphocytes (IEL) from C3H/He (H-2k) mice can be divided into two subpopulations based on TcR expression level; a subpopulation with a remarkably high level of TcR expression and a subpopulation with a moderate level of TcR expression, designated as TcR gamma delta hi IEL and TcR gamma delta mod IEL, respectively. In flow cytometric analysis, the TcR gamma delta hi IEL expressed a high level of TcR (mean fluorescence channel 518) when compared with the TcR level of TcR gamma delta+ T cells in other lymphoid organs (mean fluorescence channel 88). The TcR gamma delta hi IEL were detected in IEL from mice of H-2k and H-2k/b haplotypes but not in H-2b and H-2d haplotypes. V delta 4, which was reported to be frequently expressed in IEL of H-2k mice, was preferentially expressed by TcR gamma delta hi IEL. These results suggested that the existence of the TcR gamma delta hi population is related to the high frequency of V delta 4 in H-2k mice.     

Treatment with linezolid in a neonate with meningitis caused by methicillin-resistant Staphylococcus epidermidis

Recent findings have focused on the possible role of linezolid (LZD) as a suitable candidate for the treatment of central nervous system infections. LZD treatment for meningitis has been sporadically reported in adults, but there are no reports in neonates or infants. We report a case of meningitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) in a neonatal girl. The patient had intraventricular hemorrhage on postnatal day 1 and was treated with ventricular drainage. Twenty-two days after drainage, the patient developed a fever and seizure. Although ampicillin and ceftriaxone were given empirically for meningitis, an increased cell count and protein were observed in cerebrospinal fluid (CSF). Vancomycin (VCM) was administered intravenously because MRSE was detected from CSF 2 days after the administration of ampicillin and ceftriaxone. However, intravenous administration of VCM did not show any effect. Subsequent treatment of LZD successfully reduced the cell count and protein in CSF. Conclusion: LZD may be a treatment option for neonates and infants for drain-associated meningitis caused by MRSE.     

Prevalence of previously undiagnosed airflow limitation in patients who underwent preoperative pulmonary function test

Although being a rapidly expanding socioeconomical burden worldwide, chronic obstructive pulmonary disease (COPD) is often overlooked because of its insidious progression. Since spirometry is the primary tool for the diagnosis of COPD, physicians should be aware of the disease in any situation where interpreting spirometry. This study was to estimate the prevalence of undiagnosed COPD among patients who underwent spirometry as a preoperative evaluation for elective surgeries. Patients aged 40 years or older who completed routine spirometry as a preoperative evaluation for elective surgeries between January to December, 2000. Medical records were reviewed for medical history, clinical findings, smoking status, and discharge diagnoses for patients who demonstrated airflow limitation (AL), defined as FEV(1)/FVC<70% on spirometry. Of the 1031 patients who qualified for the study, 263 (26%) presented AL. Sixty-nine of these patients with AL (26%) had underlying conditions that could account for AL, such as asthma and previously diagnosed COPD. The remaining 194 patients with AL (74%) were suspected to have undiagnosed COPD, 90% of which was mild in severity. Only 30 (15%) of these patients appeared to be diagnosed have received a diagnosed as COPD by physician on this occasion. This study testifies that COPD is often unnoticed, and demonstrates that every spirometry, such as in preoperative evaluation, gives a clue to identify affected individuals, for which awareness of the disease is essential.