Cisplatin plus Docetaxel Chemotherapy for Thoracic Lymph Node Metastasis from Cancer of Unknown Primary - Experience of Three Cases.

The optimal chemotherapeutic regimen for cancer of unknown primary (CUP) remains uncertain. We encountered 3 cases with CUP who presented with thoracic lymph node metastasis. Detailed physical examination and diagnostic tests, including laboratory investigations, bronchoscopy, upper and lower gastrointestinal studies, computed tomography of the head, neck, abdomen and pelvis and (18)F-fluorodeoxyglucose positron emission tomography, failed to identify the primary site in these cases. The patients were treated with the cisplatin plus docetaxel chemotherapy regimen. Concomitant thoracic radiotherapy was conducted in one patient and surgical resection in another. All patients showed good response to the chemotherapy and achieved long-term disease-free survival.

The association of transforming growth factor beta 1 gene polymorphisms with the emphysema phenotype of COPD in Japanese.

OBJECTIVE: The transforming growth factor beta-1 gene (TGFB1) is one of the most promising candidate genes for chronic obstructive pulmonary disease (COPD). Several case-control studies have been performed and generated inconsistent results. The possible reasons for these discrepancies include the diversity of ethnic populations and the heterogeneity of COPD, including emphysema and airway disease. We designed this study to investigate the association of single nucleotide polymorphisms (SNPs) of TGFB1 with the emphysema phenotype in the Japanese population. METHODS: Eight SNPs in TGFB1 (rs2241712, rs1982072, and rs1800469 in the promoter region; rs1982073 in exon 1; rs2241716 and rs4803455 in intron 2; rs6957 and rs2241718 in the 3' region) were genotyped by allelic discrimination assays in 70 COPD patients with emphysema phenotype and 99 healthy smokers. The emphysema phenotype was identified by high-resolution computed tomography imaging using Goddard's method. RESULTS: The frequency of one significant haplotype structured by the eight SNPs was significantly higher in the emphysema group (10%) than in the healthy smokers (4%, p=0.02). In the emphysema group, the predicted value of forced expiratory volume in 1 second after bronchodilator administration was significantly associated with the minor alleles of the two SNPs (rs1800469 and rs1982073, p=0.007 and 0.032, respectively), however, the low attenuation area and carbon monoxide diffusing capacity were not associated with the SNPs. In addition, the rs1800469T and rs1982073C alleles were significantly more prevalent in patients with severe and very severe airflow limitation than in those with mild and moderate airflow limitation (p=0.007 and 0.041, respectively). CONCLUSIONS: One significant haplotype of TGFB1 is associated with the emphysema phenotype in the Japanese population. Two TGFB1 SNPs (rs1800469 and rs1982073) are associated with the severity of COPD in patients with emphysema phenotype.

Selective IgM deficiency accompanied with IgG4 deficiency, dermal complications and a bronchial polyp.

BACKGROUND: IgM deficiency is a rare primary immunodeficiency. As few studies of selective IgM deficiency have been reported among the various other types of primary immunodeficiencies, the detailed pathogenesis of this disorder remains to be elucidated. CASE SUMMARY: We clinically analyzed a 37-year-old woman who presented with IgM and IgG4 deficiency and ectopic bronchial pneumonia, and investigated immunological functions. Occlusive pneumonia was repeatedly observed in the right S6 area, and bronchoscopy revealed a polyp in the right B6 orifice, which was later identified as a fibroepithelial polyp after transbronchial endoscopic polypectomy. Two months later, pneumonia involving the right inferior lobe developed. Systemic erythema and pigmentation with bleb formation were also observed on the skin, and were thought to be drug-induced exanthema following a biopsy. Serum levels of IgM and IgG4 were extremely low at 3.0mg/dl and less than 2.0mg/dl, respectively. Circulating CD20 positive B cells were mildly reduced and memory B cells were markedly decreased. The majority of B cells expressed IgM on their surface. There were no abnormalities in cell counts of neutrophils, T cells, NK cells and monocytes. Chemotaxins, bactericidal activity and phagocytosis of neutrophils were normal. DISCUSSION: There have been no case reports of selective IgM deficiency with concurrent IgG4 deficiency, various dermal symptoms and a bronchial polyp, as demonstrated in our patient.

Utility of single-slice high-resolution CT in upper lung field combined with low-dose spiral CT for lung-cancer screening in the detection of emphysema.

OBJECT: The present study was undertaken to evaluate the utility of low-dose spiral CT scanning, combined with single-slice high-resolution CT (HRCT), in the detection of pulmonary emphysema on CT (CTPE) together with screening for lung cancer. SUBJECTS AND METHODS: For 657 individuals who visited for screening of lung cancer, single-slice HRCT of the upper lung field was added on conventional low-dose spiral CT scanning in order to detect low attenuation area (LAA) visually. The individuals were classified into four groups according to the visual extent of LAA in bilateral upper lung fields: no LAA, subtle PE (0%25%), and compared spirometry among the four groups. RESULTS: LAA was detected in 23.3% of all subjects (subtle PE in 12.2%, mild PE in 9.9% and moderate to severe PE in 1.2%) by adding one HRCT slice whereas only in 6.4 % LAA was detected by conventional low-dose helical CT scanning at 10 mm slice alone. The airway obstruction (FEV1/FVC<70%) was observed only in 1.07%. The severity of emphysema was associated with older age, prevalence of having smoking history and Brinkman index. As the severity of emphysema, the FEV1/FVC, MMEF, and V25/HT showed lower values. CONCLUSIONS: It is suggested that single-slice HRCT of the upper lung field combined with conventional low-dose spiral CT scanning for screening of lung cancer may also be useful for the detection of LAA, which may promote smoking cessation.

Second-line chemotherapy of platinum compound plus CPT-11 following ADOC chemotherapy in advanced thymic carcinoma: analysis of seven cases.

BACKGROUND: Optimal chemotherapeutic regimen in thymic carcinoma remains uncertain and the efficacy of second line chemotherapy has not been established either. PATIENTS AND METHODS: We retrospectively evaluated the efficacy of an irinotecan plus cisplatin or carboplatin (IP) regimen as a salvage treatment for patients with unresectable thymic carcinoma that progressed after cisplatin, doxorubicin, vincristine and cyclophosphamide (ADOC) chemotherapy. Seven patients with histologically confirmed thymic carcinoma that was resistant to or who had relapsed after initial chemotherapy with ADOC were treated with IP. The treatment consisted of irinotecan (CPT-11, 60 mg/m2, days 1, 8 and 15) and cisplatin (80 mg/m2, day 1) or carboplatin (AUC 4) intravenously every 4 weeks, for at least 2 cycles. RESULT: Two patients achieved partial responses. Although another two patients showed a significant reduction of the primary thoracic lesion, the appearance of a new lesion was found in one and a metastatic lesion was unchanged in the other. Neutropenia over grade 3 was observed in all patients but none of the patients developed serious infections. There were no severe non-hematological toxicities, including diarrhea. CONCLUSION: We conclude that salvage chemotherapy may be useful in certain patients with thymic carcinoma and irinotecan may be a novel and alternative agent for relapsed thymic carcinoma.

Usefulness of bronchoscopic microsampling to detect the pathogenic bacteria of respiratory infection.

BACKGROUND: Bronchoscopic microsampling (BMS) is a method in which a device consisting of a wire with a polyester probe at the tip is used to collect bronchial epithelial lining fluid with bronchoscopy. In this study, we bacteriologically investigated sample collection using BMS to incorporate BMS into diagnosis of respiratory infection. METHODS: Strains of Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Mycobacterium avium complex (MAC), were used for experiments. In the standard sampling procedure using BMS, the probe coming out of the sheath was immersed in approximately 6 x 10(6) cfu/mL bacterial suspension for 30 s and cut into a tube containing 1 mL of normal saline solution. The tube was stirred for 1 min using a vortex. The sampling rate was calculated by the following equation: (actual amount of bacteria collected by BMS [colony forming units per milliliter])/(bacterial amount in suspension for sampling [colony forming units per milliliter]) x 100 (percentage). RESULTS: The sampling rate of S pneumoniae, H influenzae, and MAC showed no significant difference among three bacteria, but the sampling rate of P aeruginosa was higher. The shortened time of sampling, stirring, and the reduced bacterial amount in the suspension (1/100) did not significantly affect the rates of standard procedure. In contrast, in comparison with a protected specimen brush (PSB), the recoveries of S pneumoniae, H influenzae, and MAC using PSB were significantly lower than those by BMS, but the recovery of P aeruginosa was not significantly different. CONCLUSION: This in vitro study might suggested the usefulness of BMS as a new diagnostic technique capable of quantitative and stable sampling.

Salvage chemotherapy with carboplatin and paclitaxel for cisplatin-resistant thymic carcinoma--three cases.

The optimal chemotherapeutic regimen for thymic carcinoma remains uncertain and the utility of salvage therapy has also not been reported. Three cases of unresectable and locally advanced thymic carcinoma, resistant to prior chemotherapy with cisplatin are reported. These patients were treated with carboplatin and paclitaxel chemotherapy, as salvage chemotherapy. Although concomitant thoracic radiotherapy was performed in one patient, two showed a partial response and the other showed a minor response after carboplatin and paclitaxel chemotherapy. Thymic carcinoma is sensitive to platinum-based chemotherapy and paclitaxel appears to have significant activity against thymic carcinoma.

Phase I trial of bi-weekly paclitaxel and gemcitabine as second-line therapy for patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.

A phase I study was conducted to evaluate the maximum tolerated dose, feasibility, and efficacy of bi-weekly-administered paclitaxel and gemcitabine in patients with non-small-cell lung cancer (NSCLC) who had previously been treated with platinum-based chemotherapy. In a dose-escalation study, 18 patients, under 75 yr old, with unresectable NSCLC that had relapsed or was resistant after platinum-containing chemotherapy with performance status of 0-2 were enrolled. Patients were treated with paclitaxel and gemcitabine bi-weekly. The dose escalation levels of paclitaxel (mg/m2) at a fixed dose of gemcitabine 1000 mg/m2 were 110 (level 1), 130 (level 2), 150 (level 3), and 170 (level 4), respectively. All patients were eligible for evaluation of toxicities. At level 4, one patient developed an infection with grade 3 neutropenia and two other patients developed severe neurotoxicity (over grade 3). Thus, the recommended dose for phase II was paclitaxel 150 mg/m2 and gemcitabine 1000 mg/m2 due to dose-limiting toxicities including neutropenia and peripheral neurotoxicity. Partial response was seen in 4 cases of the 18 assessable patients, with an overall response of 22%. Bi-weekly paclitaxel and gemcitabine is feasible and appears to be an efficacious combination chemotherapy as second-line chemotherapy in refractory and recurrent patients with NSCLC who had been previously exposed to platinum-containing chemotherapy.