Kenji Nishii

Complementary roles of pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in diagnosis and prognosis of small-cell lung cancer (SCLC)

In this study, we evaluated the clinical usefulness of ProGRP and NSE for diagnosis and prognosis of small-cell lung cancer (SCLC). Serum levels of ProGRP and NSE were determined in 108 healthy subjects, 103 patients with benign pulmonary diseases, 142 with non-small cell lung cancer (NSCLC), and 114 with SCLC. Sensitivity of ProGRP in diagnosis of SCLC was significantly higher than that of NSE (64.9 vs. 43.0%, P < 0.001). The difference was substantial in patients with limited disease (56.5 vs. 20.3%, P < 0.001). However, 11 of 40 SCLC patients with normal levels of serum ProGRP (27.5%) showed elevated levels of serum NSE. In the SCLC patients receiving chemotherapy, the CR rate in patients with elevated NSE levels was significantly lower than in patients with normal levels of NSE (18.5 vs. 61.7%, P < 0.001). Elevation of both ProGRP and NSE was a poor prognostic factor, and patients with elevated levels of either ProGRP or NSE showed shorter survival than those without. From multivariate analysis, NSE was found to have a greater effect on survival of SCLC patients than ProGRP. These findings indicate that ProGRP is more sensitive than NSE for diagnosis of SCLC, while NSE is superior to ProGRP as a prognostic factor. In conclusion, both ProGRP and NSE are useful tumor markers and they have a complementary role for each other in diagnosis and prognosis of SCLC.

A case-control study of lung cancer screening in Okayama Prefecture, Japan

The effectiveness of lung cancer screening in reducing mortality still remains uncertain. In order to evaluate the efficacy of lung cancer screening, a case-control study was conducted in Okayama Prefecture, Japan. The study area consisted of 34 municipalities where a population-based lung cancer screening had been conducted. Chest X-ray examinations for all participants and sputum cytology for high-risk participants were offered annually. The cases analyzed in this study consisted of 412 individuals aged between 40 and 79 who died of lung cancer. A total of 3490 controls, two to ten for each case matched by gender, year of birth, and living district were randomly collected. Screening histories of cases were compared with those of and matched controls for the identical calendar period prio to diagnosis of the case. Smoking adjusted odds ratio (OR) of death from lung cancer for screened individuals versus unscreened, within 12 months before diagnosis, was calculated as 0.59 (95% confidence interval: 0.46-0.74; P=0.0001). The OR for women (0.39, 95% confidence interval: 0.24-0.64) was lower than that for men (0.67, 95% confidence interval: 0.51-0.87), although both were statistically significant. These results suggest that lung cancer screening contributes to reducing lung cancer mortality by 41%.

Evaluation of various cytological examinations by bronchoscopy in the diagnosis of peripheral lung cancer

To improve the efficacy of fibreoptic bronchoscopy in the diagnosis of peripheral lung cancer, we evaluated the effectiveness of various techniques for obtaining samples for cytological examination. Between January 1984 and December 2000, flexible fibreoptic bronchoscopy under fluoroscopic guidance was performed in 1372 patients with lung cancer having no visible endoscopic findings. Histological examination of specimens obtained by forceps biopsy and cytological examinations on imprints of biopsy specimens, brushing, selective bronchial lavage, curettage, transbronchial needle aspiration, rinse fluids of the forceps, brush, curette, and aspiration needle, and all fluids aspirated during the bronchoscopic examinations were evaluated for diagnostic power. Using these techniques, the overall diagnostic rate with bronchoscopy was 93.4%. The sensitivity of the histological examination was 76.9%; additional imprint cytology increased the sensitivity to 84.8% (P<0.0001), while additional cytology on the rinse fluid of the forceps increased the sensitivity to 83.7% (P<0.0001). The addition of both imprint cytology and cytology on the rinse fluid of the forceps increased the diagnostic rate to 86.2% (P<0.0001). Our results indicate that cytological examinations of the imprints of biopsy samples and the rinse fluids of the forceps and the brush improve the efficacy of fibreoptic bronchoscopy in the diagnosis of peripheral lung cancer.

The efficacy of lung cancer screening conducted in 1990s: four case/control studies in Japan

The efficacy of lung cancer screening is still controversial. In order to evaluate efficacy of mass screening for lung cancer in 1990s, the Japanese Ministry of Health and Welfare planned to conduct four independent case-control studies in four different regions; Miyagi, Gunma, Niigata, and Okayama Prefecture. The study design of all the four studies was a matched case-control study in which the decedents from lung cancer were defined as cases. In Gunma Prefecture, a screening examination is annual miniature chest X-ray only, whereas sputum cytology is added for high-risk screenees in others. Matching conditions were gender, year of birth, smoking histories (except Okayama), and municipality. Smoking adjusted odds ratio (OR) of dying from lung cancer for those screened within 12 months before case diagnosis compared with those not screened ranged 0.40-0.68. Three of four studies revealed statistically significant reduction of the risk for lung cancer death. OR of pooled analysis, where all sets were combined and analyzed, was 0.56 (95% confidence interval: 0.48-0.65). Recent mass screening program for lung cancer in Japan could reduce the risk for lung cancer death. However, the possibility exists that some confounding factors affected the results. In order to elucidate whether the results can be applied to Western countries, further studies will be required.

Whole blood interferon-gamma assay for baseline tuberculosis screening among Japanese healthcare students.

Background The whole blood interferon-gamma assay (QuantiFERON-TB-2G; QFT) has not been fully evaluated as a baseline tuberculosis screening test in Japanese healthcare students commencing clinical contact. The aim of this study was to compare the results from the QFT with those from the tuberculin skin test (TST) in a population deemed to be at a low risk for infection with Mycobacterium tuberculosis. Methodology/Principal Findings Healthcare students recruited at Okayama University received both the TST and the QFT to assess the level of agreement between these two tests. The interleukin-10 levels before and after exposure to M tuberculosis-specific antigens (early-secreted antigenic target 6-kDa protein [ESAT-6] and culture filtrate protein 10 [CFP-10]) were also measured. Of the 536 healthcare students, most of whom had been vaccinated with bacillus-Calmette-Guérin (BCG), 207 (56%) were enrolled in this study. The agreement between the QFT and the TST results was poor, with positive result rates of 1.4% vs. 27.5%, respectively. A multivariate analysis also revealed that the induration diameter of the TST was not affected by the interferon-gamma concentration after exposure to either of the antigens but was influenced by the number of BCG needle scars (p = 0.046). The whole blood interleukin-10 assay revealed that after antigen exposure, the median increases in interleukin-10 concentration was higher in the subgroup with the small increase in interferon-gamma concentration than in the subgroup with the large increase in interferon-gamma concentration (0.3 vs. 0 pg/mL; p = 0.004). Conclusions/Significance As a baseline screening test for low-risk Japanese healthcare students at their course entry, QFT yielded quite discordant results, compared with the TST, probably because of the low specificity of the TST results in the BCG-vaccinated population. We also found, for the first time, that the change in the interleukin-10 level after exposure to specific antigens was inversely associated with that in the interferon-gamma level in a low-risk population.

Serum Soluble Interleukin-2 Receptor in Patients with Lung Cancer.

未治療の肺癌患者54症例を対象に血清可溶性インターロイキン2受容体 (sIL-2R) を測定し, その臨床的意義について検討した.肺癌患者の血清sIL-2Rの測定値は751±432U/mlであり, 37例 (69%) が530U/ml (健常人の平均値+2S.D.) 以上であった. 血清sIL-2Rは病期III/IV期では病期I/II期に比して有意に高値であった. 小細胞癌では同じ病期の非小細胞癌に比較して血清sIL-2Rは低値であった. 血清sIL-2Rと血清アルブミンおよび血清choline esteraseとの問には有意な負の相関関係, 血清sIL-2Rと血清CRPとの問には有意な正の相関関係が認められた. 非小細胞癌においては血清sIL-2R高値 (600U/ml以上) のものは予後不良の傾向が認められた.以上より, 血清sIL-2Rは肺癌患者, 特に非小細胞肺癌患者の腫瘍量の有用な指標であり, 予後因子となりうる可能性が示唆された.

Two cases of small cell carcinoma of the lung associated with carcinomatous leptomeningitis.

肺小細胞癌69例の治療経過中に2例の癌性髄膜症を経験した.症例1は, 化学療法により完全寛解を得た後, 癌性髄膜症で再発し, 発症後7週間で死亡した.剖検時, 腫瘍細胞は髄膜のみに認められ, 癌性髄膜症の発症がなければさらに長期の生存が可能と思われた.症例2は, 化学療法による部分寛解中に癌性髄膜症を発症し, 脳脊髄への放射線照射と抗癌剤髄腔内投与が著効を示し, 発症後9ヶ月間の長期にわたり癌性髄膜症を管理し得た.