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Small molecule inhibitors targeting epidermal growth factor receptor (EGFR) are known to be active against non-small cell lung cancer (NSCLC) although the pharmacodynamics of these agents on malignant pleural effusion (MPE) remains unclear. Here we describe a case of lung adenocarcinoma with massive MPE treated successfully by gefitinib and chest drainage. Using sequential MPE samples before and during gefitinib therapy, the morphological changes and apoptosis of cancer cells were analyzed. Apoptosis of cancer cells was detected as early as 4 hours on, but not before, gefitinib therapy, suggesting that the pharmacodynamic assessment of such molecular targeting agents might be feasible for MPE.

Introduction The aim of this study was to determine and evaluate the recommended dose of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 and evaluate the efficacy and safety in patients with previously treated non-small cell lung cancer. Methods In phase I, patients with previously treated non-small cell lung cancer were treated with docetaxel (starting dose 40 mg/m 2 ) intravenously on day 1 and oral administration of S-1 at a fixed dose of 80 mg/m 2 on days 1 to14 every 3 weeks. The recommended dose was the dose level preceding the maximum tolerated dose; once determined, patients were enrolled in phase II. Results The recommended dose of docetaxel was 40 mg/m 2 in combination with S-1 80 mg/m 2 /d. Of 30 patients enrolled in phase II part, 29 patients were eligible and analyzed. No complete response and 7 (24.1%) partial responses were observed, for an overall response rate of 24.1% (95% confidence interval, 10.3-43.5%). Median overall survival was 11.8 months. The 1-year survival rate was 42%. The grade 3 to 4 hematologic toxicities were neutropenia (34.5%), leukopenia (20.6%), and anemia (10.3%). The grade 3 to 4 nonhematological toxicities included fever 2 (6.9%), diarrhea 1 (3.4%), stomatitis 1 (3.4%), cerebral infarction 1 (3.4%), and pneumonitis 1 (3.4%). There was one treatment-related death due to relapse of drug induced pneumonitis. Conclusions This combination chemotherapy is highly active and well tolerated in previously treated patients with non-small cell lung cancer. These results are encouraging and warrant additional investigation.

Background Fluoroscopy-guided bronchoscopy is a safe and routine method used to obtain a histologic or cytologic specimen of peripheral lung nodules, but it has low sensitivity in diagnosing malignant tumors. Although feedback from rapid cytology tests are expected to improve diagnostic rates, the value of the routine use of rapid cytology tests has not been established. Materials and Methods We prospectively studied 657 patients with suspected peripheral malignant lung lesions on chest computed tomography who underwent fluoroscopy-guided bronchoscopy between January 2002 and December 2004. Rapid on-site cytopathologic examinations (ROSE) were performed during bronchoscopic examinations. The additional approach to the lesions was performed immediately after conventional bronchoscopic examinations when ROSE was not considered diagnostic. Results There were 528 patients diagnosed as having malignant lesions. In 477 of these patients (90.3%), final malignant diagnosis was established by the initial bronchoscopy. Among these, 84 patients (15.9%) were diagnosed only with the additional feedback from ROSE. Of 240 peripheral lesions ≤2 cm, 174 were found to be malignant. Without ROSE, 110 (63.2%) of peripheral malignant lesions were diagnosed by bronchoscopy. The integration of ROSE enabled us to diagnose an additional 40 patients (23.0%) by bronchoscopy. ROSE improved diagnostic yield independent of the site and histology of the lesions and experience of the operators. Conclusion ROSE increased the diagnostic yield of bronchoscopy from 74.4% to 90.3% and therefore is an effective reinforcement in bronchoscopic diagnosis of peripheral pulmonary malignancies. The use of ROSE in routine bronchoscopy should be encouraged.

我が国の市町村で行われている肺癌検診は, 年間700万人以上が受診しているが, 肺癌発見数は3600人弱 (発見率51/10万人) で, 受診者の増加に伴っていない. 都道府県別にみると発見率は最大111.5, 最小18.5でその差は最大6.2倍とバラツキは大きかった. 市町村別に見ると, 精検受診率や精検完了率が30%を下回る市町村も認められ, 受診者数5000人以上の市町村の6.3%で過去2年間肺癌は1例も発見されていなかった. 肺癌検診は外的精度管理の枠組みがないまま, 急速に普及していった. 市町村事業と位置づけられてからは, 実施数や費用のみが問題とされており, 精度については検討されておらず, 受診者にも精度に関する情報は提供されていない. 今後は対象者や精度管理指標の基準値を盛り込んだ運用指針の見直しと, 第3者機関による検診成績の情報公開が必要である.

目的. 大阪肺癌集検研究班が担当してきた肺癌集検での喀痰細胞診の成績を検討した.対象と方法.大阪府下8市町の一般住民を対象として, 1981年より胸部X線間接撮影と喀痰細胞診による肺癌検診を行ってきた.喀痰細胞診は40歳以上で喫煙指数400以上の者, および血痰の自覚症状を有する者 (高危険群) を対象とした.成績.1981年から2000年の20年間の受診者総数は297,628人で, この中から235人の肺癌を発見した.喀痰細胞診を行った高危険群からは, 130人の肺癌が発見され扁平上皮癌は64人であった.そのうち36人が肺門部扁平上皮癌で喀痰による発見は34人であった.喀痰細胞診で発見された扁平上皮癌は10万対110と20年間で変わらないが, 肺門部扁平上皮癌が1996年以降では約1/2に低下した.結論喀痰細胞診は, 肺門部早期扁平上皮癌の発見に不可欠な検査で, 肺癌発見率を上昇させるためには高危険群特に50歳以上の男性の多い集団を対象とした検診を行うべきである.さらに十分な精度管理のもとに喀痰細胞診の精度を高めることが必要である.

Background . Pure ground-glass opacity (PGGO) is a new entity that has been clearly defined on high-resolution computed tomography (CT) during the last half decade. It is important to investigate the natural history of PGGO through long-term observation for the management of this new entity. Methods . We investigated 19 patients with PGGO(s) defined on high-resolution computed tomography and retained as PGGO for more than 2 years. The PGGOs of 11 patients were detected at annual mass screening by low-radiation–dose CT (low-dose CT), 7 at follow-up CT after cancer resection, and 1 incidentally on CT. After long-term observation, 10 of 19 patients underwent operation and 9 are currently being followed-up with CT. Their growth characteristics and histologic findings are reported. Results . The median follow-up period was 32 months, ranging from 24 to 124 months. The sizes of PGGOs at the time of discovery were 4 to 18 mm in largest diameter (average 8.6 mm). During follow-up, the size of PGGO showed no change in 8 patients, increased slightly (up to 5 mm) in 6 patients, and increased by more than 5 mm in 5 patients. Ten patients had limited resection (segmentectomy or wide wedge resection) with negative surgical margin by intraoperative lavage cytology of the resection margin of the lung. Of them, 5 patients had adenocarcinoma, 3 pulmonary lymphoproliferative disorder, and 1 each atypical adenomatous hyperplasia and focal fibrosis. There was no clear tendency between the degree of size change and histology. In all but 1 of 9 patients with follow-up only, the PGGOs showed either no change or only a slight increase within 5 mm in largest diameter. Conclusions . These data suggest that some PGGOs will never progress to clinical disease and would be included in the category of overdiagnosis bias. However, a prior history of lung cancer should significantly raise the index of suspicion, as 4 of 5 proven cancer cases in this small series fell into that category. Because of the difficulties of preoperative and intraoperative histodiagnosis of PGGO, minimally invasive surgery may be appropriate from the viewpoints of both diagnosis and curability.

The histologic types of lung cancer cases diagnosed in 1979-1980 (n=799) and 1987 (n=587) were independently reviewed by two pathologists in order to investigate the reproducibility of the diagnosis of the histologic type when the WHO classification (1981) was used. The specimens from 354 surgical cases and biopsy or cytology specimens from 1032 non-surgical cases were reviewed. The inter-observer agreement was 87.9% (kappa=0.79) for surgical cases and 81.4% (kappa=0.72) for non-surgical cases. When compared to the original diagnosis, the agreement was 86.8% (kappa=0.78) for surgical and 86.4% (kappa=0.79) for non-surgical cases in 1979-1980 and the agreement was 92.8% (kappa=0.87) for surgical and 89.1% (kappa=0.83) for non-surgical cases in 1987. By histologic type, no difference in the agreement was observed except for large cell carcinoma. The distribution of histologic types after the review differed only slightly (less than 6%) from the original distribution. This suggests that in Osaka, Japan, the diagnosis based on the WHO classification (1981) had only a limited influence on the distribution of histologic types, and is not a major reason for the changing trends in lung cancer incidence by histologic type.

Sixty-three patients with extensive-stage small-cell lung cancer were randomized to receive either cyclophosphamide, vincristine, doxorubicin and etoposide (CODE) alone or CODE plus recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF administration in support of CODE chemotherapy resulted in increased mean total received dose intensity for all drugs (P = 0.03) with a significant improvement in survival (P = 0.004).

肺腺癌の化学療法に対する効果と細胞形態像を検討した.対象とした原発性肺腺癌26例の化学療法2コース終了後の治療効果はPR9例, NC11例, PD6例であった.細胞形態学的検討には, 擦過あるいは穿刺吸引細胞診のパパニコロウ染色標本を用いて, 癌細胞の核の大きさと形態, クロマチンの染色性, 核小体の形状を観察した.PRが得られた症例に多く出現した腺癌細胞は, 細胞や核が大型で, 大小不同が強く, 核は類円形で微細クロマチンが増量していた.NC症例に多く出現した腺癌細胞は, 細胞および核が小型で, 核形は不整形, クロマチンが不均等疎に分布した.PD症例には粗顆粒状クロマチンを有する腺癌細胞の出現率が高かった.肺腺癌では細胞形態学的検討により, 抗癌化学療法の効果がある程度予想され得ると考えられた.

Data on 16 potential risk factors for myelosuppression were assessed in 134 patients who received either vindesine and cisplatin (VP) or mitomycin C, vindesine and cisplatin (MVP) for inoperable stage III or IV non-small cell lung cancer in a randomized trial. Determinant factors for myelosuppression were evaluated by using univariate analysis and the logistic regression model. Recursive partitioning and amalgamation (RPA) was also used to define patient subgroups frequently suffering from severe bone marrow toxicity. Overall, 33 (25%) of 134 patients experienced at least one episode of grade 4 leukopenia. In univariate analysis, age, body surface area, serum creatinine, and pretreatment hemoglobin concentration were associated with severe leukopenia. A multivariate analysis using the logistic regression method showed that only raised creatinine level was an independent predictor for grade 4 leukopenia (P = 0.049). The RPA model generated three distinct subgroups based on age, body surface area and regimen. The three subgroups were distinguished by the frequency of severe (grade 4) leukopenia (50%, 25%, and 2.4%, respectively) (P0.001). Grade 4 leukopenia occurred more frequently in patients in class 3 (ageor = 65 years and treatment with MVP). The RPA model was useful in identifying the risk factors for myelosuppression induced by cisplatin-based chemotherapy, and in defining patient subgroups with elevated risk of toxicity.

We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of 'receiver operator characteristics' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.

Despite recent advances in control of acute emesis following cisplatin-based chemotherapy regimens, delayed emesis remains a significant cause of treatment-related morbidity and factors associated with delayed emesis have not yet been evaluated. A prospective randomised trial was conducted to compare the efficacy and toxicity of granisetron, dexamethasone plus prochlorperazine with granisetron alone in controlling cisplatin-induced delayed emesis and to identify the important factors that influence its occurrence and severity. Seventy cisplatin-naive patients with inoperable solid tumors participated in the trial. Patients who received 80 mg m-2 or 100 mg m-2 of cisplatin were randomly assigned to receive either granisetron 40 micrograms kg-1 intravenously (i.v.) on day 1, dexamethasone 20 mg i.v. on days 2 and 3 and prochlorperazine 5 mg orally thrice daily on days 1-5 or granisetron 40 micrograms kg-1 i.v. on day 1 alone. There was no difference in their acute antiemetic efficacy. A combination regimen was more effective than granisetron alone in preventing delayed symptoms, with superior rates of complete plus major responses of 77% vs 51% (P = 0.0460). Treatment arm was the only determinant factor for the occurrence of delayed emesis (P = 0.0101).

Two phase I trials of irinotecan (CPT-11) in combination with cisplatin were conducted. In both cases, the dose-limiting toxicities were leukopenia and/or diarrhea. During these trials the pharmacokinetics of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were investigated to evaluate the relationship between pharmacokinetic parameters and diarrhea, since this is an unpredictable and severe toxicity of combination chemotherapy using CPT-11 and cisplatin. Twenty-three previously untreated patients with advanced lung cancer were evaluated in the pharmacokinetic study. Ten patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 60 mg/m2. The other 13 patients received CPT-11 at 80 or 90 mg/m2 plus cisplatin at 80 mg/m2 with the granulocyte colony-stimulating factor support (2 micrograms/kg x 16 days). CPT-11 was given as a 90-min intravenous infusion on days 1, 8, and 15. Cisplatin was given on day 1. The pharmacokinetics of CPT-11 and SN-38 were analyzed on day 8 during the first course of treatment. The maximum tolerated dose of CPT-11 was 90 mg/m2 in both phase I trials. The severity of diarrhea was best correlated with the peak plasma concentration of SN-38 among the pharmacokinetic parameters tested. In addition, patients with a plasma SN-38 level > 12.4 ng/ml at 1.75 h after the start of CPT-11 infusion had a higher incidence of Eastern Cooperative Oncology Group grade 3-4 diarrhea than those with a lower SN-38 level (P = 0.0003). Stepwise logistic regression analysis identified the SN-38 concentration as a significant contributor to the development of diarrhea (P = 0.0021). We conclude that there is a clear relationship between the SN-38 concentration and diarrhea during chemotherapy with CPT-11 plus cisplatin.

大阪肺癌集検研究班では, 1981年より胸部X線撮影と喀痰細胞診による肺癌検診を実施しているが, 1990年までの10年間に, 喀痰細胞診でDあるいはEと判定された症例の, 精検および追跡調査の結果について報告する. 喀痰を提出した高危険群所属者は, 男女合計16,992人で, 有効喀痰は16,795人が提出した. 要精検者は402例, 原発性肺癌患者は28例であり, したがって陽性反応適中率は6.97%となった. 要精検者のうち判定D群は53例で, 発見された肺癌患者は14例, 陽性反応適中率は26.42%であった. 一方, 判定E群は14例で, 発見された肺癌患者は9例, 陽性反応適中率は64.29%であった. 臨床病期1期肺癌の比率は, 判定D群14例中12例85.7%と, 判定E群6例中2例33.3%よりかなり高かった. また, 判定D群14例中10例は喀痰細胞診単独発見例であり, すべて臨床病期1期であった. 肺癌または喉頭癌以外の判定D群37例, 判定E群3例を追跡し, 5年以上追跡しえた判定D群の16例, 判定E群の2例からは肺癌を発見しえず, Eと判定した2例はfalse positiveと考えられた

Soluble cytokeratin fragment 19 levels were measured with an enzyme immunoassay method developed by Boehringer Mannheim (Enzymun-Test CYFRA 21-1) in the serum of 185 patients with lung cancer [149 with non-small-cell lung cancer (NSCLC) and 36 with small-cell lung cancer (SCLC)] and 97 patients with benign lung diseases in order to determine its clinical usefulness in the diagnosis of lung cancer and follow-up of treatment. We used the cut-off value of 3.5 ng ml-1, established by the Japan CYFRA research group. This cut-off value is based on calculations using the receiver operating characteristic approach instead of using the 95% specificity approach recommended by other authors. The resulting sensitivity and specificity for the group of all lung cancer patients were 65.4% and 84.5% respectively. The sensitivity was highest (76.1%) for squamous cell carcinoma and lowest (44.4%) for SCLC. For NSCLC patients, when CYFRA 21-1 levels were analysed by node (N) factor, patients who presented with mediastinal lymph node metastasis (N2 or N3) demonstrated higher serum CYFRA 21-1 levels (5.6; interquartile range 3.2-11.5 ng ml-1) than patients without mediastinal node metastasis (N0 or N1, 3.9; interquartile range 2.2-10.0 ng ml-1; Mann-Whitney U-test, P = 0.0373). We compared the discriminatory power of CYFRA 21-1 with that of other tumour markers including carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). The area under the curve (AUC) of each ROC curve was calculated using the CLABROC program for statistical analysis. CYFRA 21-1 appeared to have the most discriminatory power of the markers tested in the diagnosis of lung cancer. In serial measurements of 14 patients receiving chemotherapy or radiotherapy, a high degree of correlation was noted between serum levels of CYFRA 21-1 and extent of clinical response (Wilcoxon, P = 0.0093).

大阪肺癌集検研究班が, 1981-1990年の10年間に行った肺癌検診において, 高危険群所属者22,753人 (受診者の24.5%) に喀痰容器が配布されたが, 回収率は87.3%, 有効検体率は98.7%であった. 精検は76人 (0.4%) で, 精検受診率は98.7%, 精検完了率は96.0%であった.高危険群所属者で, 喀痰細胞診により発見された肺癌は29人 (中心型扁平上皮癌は21人) で, このうち喀痰細胞診のみによる発見は15人 (中心型扁平上皮癌は13人) であった. 中心型扁平上皮癌の, 経年受診7人中6人, その他の受診14人中9人が臨床病期1期であった.喀痰細胞診により発見された肺癌の切除率は48.3%, 絶対的治癒切除率は27.6%であった. 1981-1983年, 1984-1986年, 1987-1990年の3時期にわけて男性中心型扁平上皮癌の標準化発見比を算出した結果, それぞれ1.595, 1.189および0.680となった.

Background and Methods. Thirty-nine roentgenologically occult lung cancers in 29 patients were treated using photodynamic therapy (PDT) and/or thoracic radiotherapy (TRT) from January 1986 to March 1992. With the exception of one mixed-tumor case, all were squamous cell carcinomas. Results. Initial PDT achieved complete responses in 25 of 39 (64%) of the cancers. Of the remaining 14 cancers that showed less than complete response (CR), 10 of the 14 (71.4%) showed a CR when subsequently treated with TRT, yielding an overall CR rate of 89.7% for cancers treated. Although nine patients experienced recurrences, six of these had CR when treated with PDT and/or TRT. To date, 22 patients are alive. Causes of death in the patients enrolled in this study are as follows: pyothorax (2); heart failure due to pulmonary hypertension (1); chronic respiratory insufficiency (1); subsequent primary brain cancer (1); and subsequent primary lung cancer (1). Only one died of primary lung cancer. Conclusions. These findings suggest that PDT and/or TRT may be used as an alternative to surgery in the treatment of selected patients with roentgenologically occult lung cancer.

BACKGROUND In the classification recently proposed by the Pathology Committee of International Association for the Study of Lung Cancer, small cell lung carcinoma (SCLC) was divided into three subtypes: pure SCLC, mixed small cell/large cell carcinoma (mixed SC/LC), and combined SCLC. METHODS To examine the clinical utility of this classification, histologic specimens, cytologic specimens obtained by brushing or fine-needle aspiration, and sputum cytologic specimens from 430 patients with SCLC were reviewed. RESULTS When the subtype of SCLC was determined from the biopsy specimen, cytologic specimen obtained by brushing or fine-needle aspiration, and sputum cytologic specimen, the frequency of mixed SC/LC was 25 of 299 (8.4%), 75 of 400 (18.8%), and 8 of 232 (3.4%), respectively. Whatever the diagnostic method, patients with mixed SC/LC showed a poorer response to treatment and worse prognosis than those with pure SCLC: a median survival of 144 days versus 285 days when classified with the use of biopsy specimens; 160 days versus 275 days with cytologic specimens obtained by brushing or fine-needle aspiration; and 47 days versus 259 days with sputum cytologic specimens, respectively. CONCLUSIONS These findings showed that mixed SC/LC should be separated from pure SCLC as a distinctive group and that cytologic studies of specimens obtained by brushing or fine-needle aspiration were sensitive and useful procedures for this purpose.

The synergism of combined high-dose etoposide with standard dose cisplatin (HD-EP) was evaluated in 20 patients who had relapsed after treatment of small cell lung cancer. Each patient was given etoposide at 500 mg/m2/day on days 1 to 3 and cisplatin at 80 mg/m2 (two patients given 120 mg/m2) on day 1; autologous bone marrow was not transplanted. Five patients were given recombinant human granulocyte colony-stimulating factor (rhG-CSF, 50 micrograms/m2) in an attempt to reduce HD-EP induced neutropenia. The overall response was 50% (9 of 18); one complete response (6%), eight partial responses (44%), seven no change (39%), and two progressions of disease (11%). Of the 18 evaluable patients, 12 had been treated with regimens of conventional doses of etoposide with conventional doses of cisplatin or carboplatin, and of these, five (42%) achieved a partial response. The median duration of response was 8.4 weeks (range, 5.3 to 17.7) and the median survival time was 20.3 weeks (range, 1.6 to 91). All of the patients developed severe myelosuppression; rhG-CSF did not shorten the period of the leukopenia. Mucositis and liver dysfunction were the major nonhematologic manifestations of toxicity. Two treatment-related deaths resulted from sepsis. These results suggest that the activities of high doses etoposide with standard doses of cisplatin are synergistic against small cell lung cancer.

From January 1978 to March 1984, a series of 159 patients with newly diagnosed small cell lung cancer (SCLC) was treated with combination chemotherapy with or without chest radiation at the Osaka Prefectural Habikino Hospital. By March 31, 1989, ten patients (6.3%) had survived for 5 years or more after the initial chemotherapy, including nine of 95 patients (9.5%) with limited disease and one of 64 patients (1.6%) with extensive disease. All these 5-year disease-free survivors, except for one patient whose response could not be assessed by chest radiograph because of radiation fibrosis, had a complete response. Nine of the 71 patients (12.7%) treated with combination regimens containing doxorubicin survived 5 years or more, and only one of the 88 (1.1%) treated with regimens without doxorubicin had long-term survival (P less than 0.01). The sex, performance status (PS), and chest radiation after systemic chemotherapy did not correlate statistically with long-term survival (P greater than 0.05). Three of the ten patients died free of SCLC. Two of the ten patients (20%) developed second malignancies and died. The remaining patient died of pneumonia. The Cox regression analysis identified the PS and doxorubicin-containing regimens as important factors indicating improved survival. Combination regimens containing doxorubicin have, therefore, been found to be very effective in improving survival and achieving long-term survival.

The mechanism by which soluble proteins, such as carboxypeptidase Y, reach the vacuole inSaccharomyces cerevisiaeis very similar to the mechanism of lysosomal protein sorting in mammalian cells. Vps10p is a receptor for transport of soluble vacuolar proteins inS. cerevisiae.vps10+, a gene encoding a homologue ofS. cerevisiae PEP1/VPS10, has been identified and deleted from the fission yeastSchizosaccharomyces pombe. Deletion of thevps10+gene resulted in missorting and secretion ofSch. pombevacuolar carboxypeptidase Cpy1p, indicating that it is required for targeting Cpy1p to the vacuole.Sch. pombeVps10p (SpVps10p) is a type I transmembrane protein and its C-terminal cytoplasmic tail domain is essential for Cpy1p transport to the vacuole. Cells expressing green fluorescent protein-tagged SpVps10p produced a punctate pattern of fluorescence, indicating that SpVps10p was largely localized in the Golgi compartment. In addition,Sch. pombe vps26+,vps29+andvps35+, encoding homologues of theS. cerevisiaeretromer componentsVPS26,VPS29andVPS35, were identified and deleted. Fluorescence microscopy demonstrated that SpVps10p mislocalized to the vacuolar membrane in these mutants. These results indicate that thevps26+,vps29+andvps35+gene products are required for retrograde transport of SpVps10p from the prevacuolar compartment back to the Golgi inSch. pombecells.

Photodynamic therapy (PDT) utilizing Photofrin is proving to be effective for the treatment of early stage lung cancers. The effect of PDT utilizing YAG-OPO laser as new light source was evaluated in 26 patients (29 lesions) with early stage lung cancers. YAG-OPO laser is solid state tunable laser which is easy to change wavelength between 620 and 670 nm exciting various kinds of photosensitizers. Moreover, YAG-OPO laser is more reliable, smaller and has less consumables than argon-dye laser or excimer-dye laser. As the result of PDT with YAG-OPO laser, complete remission (CR) was obtained in 82.6% of the 29 lesions, partial remission (PR) in 13.8% and no change (NC) was obtained in 3.4%. We conclude that PDT utilizing YAG-OPO laser is efficacious in the treatment of early stage lung cancers and can achieve complete remission.

A dose-escalation study of daily etoposide and carboplatin was carried out on 23 patients with advanced lung cancer using a starting dose of 40 mg/m 2 /day etoposide given orally for 21 days and 250 mg/m 2 carboplatin given intravenously (IV) on day 1. A total of 41 courses were given. Myelosuppression was the major dose-limiting toxicity. The maximum tolerated dose was reached at the fourth level with 40 mg/m 2 /day etoposide for 21 days and 400 mg/m 2 carboplatin on day 1, once every 4 weeks. Non-hematological toxicities were generally mild or reversible. The recommended doses of this combination chemotherapy are 40 mg/m 2 /day etoposide for 21 days and 350 mg/m 2 carboplatin on day 1. The response rate for non-small cell lung cancer and small cell lung cancer was 16.7% and 60% (95% confidence intervals of 3.6% to 41.4%, and 14.7% to 94.7%), respectively. A phase II study is necessary to define the efficacy and safety of this combination chemotherapy.

Sensitivity and specificity were evaluated for lung cancer screening conducted at 8 municipalities in Osaka Prefecture during 1981-1985. As a screening policy, all attendants were examined by miniature chest X-ray, and the high-risk group, defined as those who smoked cigarettes or had bloody sputum, were also examined by 3-day pooled sputum cytology. A total of 33,599 screening tests for 19,028 people who were 40 years old or more at the time of screening were conducted, resulting in 33,490 miniature chest X-ray examinations for 18,992 people and 11,420 sputum cytologies for 7,070 people. As a result, 43 lung cancer cases were detected. All test-negatives were followed by means of record linkage with the files of the Osaka Cancer Registry up to the end of 1986. There were 24 cases who were diagnosed as having lung cancer without having given a positive screening result in 1981-1986. Assuming the preclinical detectable phase of lung cancer to be one year uniformly, the sensitivity and specificity for the lung cancer screening were estimated to be 71.6% and 95.3%, respectively. The feasibility of increasing the sensitivity is discussed.

胸部X線上, 肺野末梢の腫瘤状陰影を呈する279例に経皮肺穿刺生検を299回施行した.悪性腫瘍182例中165例 (90.7%) に陽性所見を得た.得られた穿刺細胞像は, 原発性肺癌では, 喀痰細胞診や経気管支的擦過細胞診などの剥離細胞像と異なる所見もあり, 詳細に検討した.組織診との一致率は81.1%であった.転移性肺腫瘍では, 穿刺細胞診より大腸癌や腎癌の一部で原発巣推定可能な所見を得た.また, 陰性例19例 (延べ21回) についての検討を行い, その原因としては, 壊死物質しか得られなかったこと, 腫瘤の位置による手技的困難なことが考えられた.合併症については, 気胸21例 (7.0%), 血痰10例 (3.3%), 胸壁播種2例 (1.0%) であった.

A 59-year-old man was hospitalized complaining of pain in chest and shoulder with some weightloss of two months' duration. Physical examination revealed dullness to percussion and decreased breath sounds in right lower lung field. Chest roentgenograms showed the multiple nodular densitres in the right hemithorax and irregularly thickened pleura extended over the right hemidiaphragm. Laminograms demonstrated these tumor masses were in periphery with extrapulmonary nature or entrapped in the interlobar fissure. The aspiration biopsy of mass was read as adenocarcinoma and showed the negative alcian Blue-PAS reaction. The patient became progressively weaker and died 4 months after admission. At antopsy, entire right pleural space was involved with yellow-white, fleshy tumor tissue, most severely involved in the diaphragmatic and costal surface of the lower lobe. On cut-section, there was a large semispherical tumor mass on the diaphragmatic surface and spread of the tumor involved the costal, diaphragmatic and interlobar pleura. The diaphragm had been penetrated, and tumor was present over the peritoneum and especially over the omentum. Microscopic examination showed the characteristic apperance of mesothelioma as described elsewhere. There were areas shown glandnlar, tubular or tubulopapillary pattern with well-defined epithelial cells that graded gradually fibrosarcomatous areas.