Biomedical subjects

Sakae Okumura

Publications and source records attributed to Sakae Okumura.

14 recordsLinked to original sources

PubMed2007

Recurrence patterns in patients with early stage non-small cell lung cancers undergoing positive pleural lavage cytology.

BACKGROUND: Cytologic approaches such as pleural lavage cytology (PLC) are considered as possible aids to assessing prognosis of lung cancers. However, there is some controversy whether radical surgery is warranted based on the positive PLC findings with stage I non-small cell lung cancers (NSCLCs). METHODS: From January 1991 to December 2002, PLC was performed before any manipulation or resection of the lung for 853 consecutive patients who had no macroscopic pleural effusion, dissemination, or diffuse adhesions and who subsequently underwent curative resection for NSCLCs. Results of PLC with reference to clinicopathologic characteristics, adjuvant therapy, 5-year survival, and recurrence patterns were analyzed. RESULTS: PLC findings were positive in 41 patients (4.8%), rates being most frequent with adenosquamous carcinomas and adenocarcinomas. In the positive group, distant metastases (72%) and pleural recurrence (25%) (p = 0.0011) were often observed, and the survival rate was significantly poorer (p < 0.002), even for patients with stage I disease (p = 0.009). As adjuvant therapies in the positive group after resection, 6 patients received hypotonic cisplatin and 15 received a distilled water infusion into the pleural space. Although only 2 patients had pleural recurrence, these therapies did not improve long-term outcome. CONCLUSIONS: PLC is a distinct prognostic factor for early stage lung carcinomas. Thus, we suggest that cytologic examination of PLC should be routine, even for patients with stage I NSCLCs before beginning lung resection. Moreover, curative resection, followed by adjuvant systemic therapy, could be necessary for improvement of outcome.

Adolescent↗

PubMed2006

Postoperative ischemic change in bronchial stumps after primary lung cancer resection.

BACKGROUND: The bronchopleural fistula (BPF) is a major complication after lung surgery. We have reviewed our experience with ischemic changes in bronchial stumps, some of which resulted in BPFs (we term this postoperative ischemic bronchitis (POIB)) and studied predisposing factors. METHODS: A total of 1015 patients undergoing curative resection of lung cancers between 1991 and 2002 were reviewed. Details regarding bronchofiberscopic findings within the first 15 postoperative days were carefully reviewed with particular attention to factors possibly affecting the occurrence of POIB: the techniques for bronchial closure and mediastinal lymph node dissection (LND). Information about clinical profiles and histologic status was also analyzed. RESULTS: The incidence of POIB was 2.5% (29/1015), affecting 26 males and 3 females. The most common site was the right intermediate trunk stump (n=4; 7.1%), followed by the left upper (n=8; 3.4%), right lower (n=5; 3.4%), right middle (n=2; 3.3%), and left lower (n=4; 3.2%) lobar bronchial stumps. BPFs eventually resulted in 3 patients (10%) out of 29 with POIB and in 4 (0.4%) out of 986 without it (p<0.0001). Being male, a smoker, having diabetes mellitus, having postoperative respiratory complications and subcarinal LND proved to exert a significant impact with regard to POIB. CONCLUSIONS: Surgeons must bear in mind the possibility of POIB occurrence, especially in cases undergoing particular types of lobectomy (right middle and lower, left upper, right lower or right middle) accompanied by subcarinal LND and having postoperative respiratory complications. Moreover, in appropriate groups with tumors of the right upper lobe or left upper segment, limited mediastinal LND might allow avoidance of POIB.

Aged↗

PubMed2005

Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization.

Current clinical and histopathological criteria used to define lung squamous cell carcinomas (SCCs) are insufficient to predict clinical outcome. To make a clinically useful classification by gene expression profiling, we used a 40 386 element cDNA microarray to analyse 48 SCC, nine adenocarcinoma, and 30 normal lung samples. Initial analysis by hierarchical clustering (HC) allowed division of SCCs into two distinct subclasses. An additional independent round of HC induced a similar partition and consensus clustering with the non-negative matrix factorization approach indicated the robustness of this classification. Kaplan-Meier analysis with the log-rank test pointed to a nonsignificant difference in survival (P = 0.071), but the likelihood of survival to 6 years was significantly different between the two groups (40.5 vs 81.8%, P = 0.014, Z-test). Biological process categories characteristic for each subclass were identified statistically and upregulation of cell-proliferation-related genes was evident in the subclass with poor prognosis. In the subclass with better survival, genes involved in differentiated intracellular functions, such as the MAPKKK cascade, ceramide metabolism, or regulation of transcription, were upregulated. This work represents an important step toward the identification of clinically useful classification for lung SCC.

Biomarkers, Tumor↗

PubMed2005

Classification of parietal pleural invasion at adhesion sites with surgical specimens of lung cancer and implications for prognosis.

Parietal pleural invasion of non-small cell lung cancer (NSCLC) is a factor for poor prognosis, and a tumor of any size that invades the parietal pleura is classified as T3. However, with microscopic invasion beyond elastic fibers of the visceral pleura but no penetration to the parietal pleura at tight adhesion sites (we term this p1-3), classification as to the T factor is unclear. Among 1,179 consecutive patients with NSCLCs who underwent curative surgery between 1980 and 2002, 20 were in this category. Here, a comparison was made with subgroups of p stages IB, II, and IIIA with regard to histology, pleural invasion, and survival rates. To maximize the power of assessing prognostic potential, we set the significance level at 0.10, one-sided. The p1-3 condition sites of the 20 cases were the parietal pleura for 17 cases and the pericardium, diaphragm, and chest wall for one each of the remainder. The 5-year survival rate for these p1-3 patients was 71.6%. Significant differences were observed between p1-3 and IIIA groups. Although the 5-year survival rates did not significantly differ between p1-3 and T3N0 or unequivocal T3 subgroups, the prognosis of p1-3 patients was rather better than that of T3 and identical to T2. It was demonstrated that p1-3 status is not a factor warranting T3 classification for NSCLCs. Considering the prognosis, pathologic p1-3 tumors should be managed as a T2 disease for the present.

Aged↗

PubMed2005

Phase I study of combination chemotherapy with gemcitabine and irinotecan for non-small cell lung cancer.

UNLABELLED: A phase I study combining a fixed dose of gemcitabine with differing doses of CPT-11 every two weeks for previously treated non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A total of 21 patients with previously treated non-small cell lung cancer were treated every two weeks with CPT-11 followed by gemcitabine. The gemcitabine dose was fixed at 1000 mg/m2. The starting dose of CPT-11 (50 mg/m2) was then escalated different patients in 25 mg/m2 increments until 150 mg/m2 (level 5), the recommended dose as a single agent in Japan. RESULTS: Dose-limiting toxicity was only observed at level 5, in three of nine patients receiving the highest dose of CPT-11. One patient had grade 3 diarrhea, and two could not continue chemotherapy with grade 1 diarrhea or grade 1 neutropenia on day 15. Hematologic toxicity with this combination regimen, however, was generally mild. No grade 4 neutropenia, and only one case of grade 3 leukopenia was noted at level 5. Compliance with the combination regimen was good and there was no cumulative toxicity with the subsequent courses. Twenty-five courses of therapy were given at level 5 and the percentage of actual delivered doses/planned doses was 82%. CONCLUSIONS: The combination chemotherapy has only very mild toxicity and dose which can be recommended with this regimen are 1000 mg/m2 for gemcitabine and 150 mg/m2 for CPT-11 every two weeks.

Adult↗

PubMed2005

Antipyrine test predicts pharmacodynamics in docetaxel and cisplatin combination chemotherapy.

To clarify the role of cytochrome P450 in docetaxel and cisplatin combination chemotherapy, cytochrome P450 activity was measured by simple antipyrine test, and its correlation with the drugs' pharmacodynamics was assessed. Twenty-five patients with advanced non-small cell lung cancer received an antipyrine test and were treated with docetaxel and cisplatin. Plasma antipyrine concentration (C) was measured 4 and 24h after oral administration of 500 mg antipyrine. Antipyrine disappearance rate (ADR) was calculated by: [(C(4h)-C(24h))/C(4h)]x100. ADR correlated significantly with neutropenia nadir. ADR and alpha(1)-acid glycoprotein were selected for independent predictors of neutropenia by multiple regression analysis. In addition, 25 patients were separated into "low ADR" (<40%) and "high ADR" groups (>40%). Grade 3--4 neutropenia was observed in 7/9 "low ADR" patients (77%), whereas grade 3--4 neutropenia was observed in 5/16 "high ADR" patients (31%). We concluded that antipyrine test and cytochrome P450 play an important role in predicting toxicities of docetaxel and cisplatin combination chemotherapy.

Adenocarcinoma↗

PubMed2005

Pulmonary adenocarcinomas with enteric differentiation: histologic and immunohistochemical characteristics compared with metastatic colorectal cancers and usual pulmonary adenocarcinomas.

Primary pulmonary adenocarcinomas with enteric differentiation (PAED) are mainly composed of tall-columnar cells that show similarity to intestinal epithelia and colorectal carcinomas. In this study, we analyzed the immunostaining profiles of 7 PAEDs in comparison with 14 metastatic colorectal carcinomas (MCRs) and 30 usual pulmonary adenocarcinomas (PACs), using antibodies against CDX-2, cytokeratin 7 (CK7), cytokeratin 20 (CK20), TTF-1, surfactant apoprotein-A (SP-A), Napsin A, and MUC2. The positive rates for CDX-2, CK7, CK20, TTF-1, SP-A, Napsin A, and MUC2 were 71%, 100%, 43%, 43%, 14%, 0%, and 43%, respectively, in the PAEDs; 100%, 0%, 86%, 0%, 0%, 0%, and 57% in the MCRs; 3%, 100%, 0%, 93%, 73%, 90%, and 0% in PACs. As expected, immunoreactivity of CDX-2, CK20, and MUC2 was detected in PAEDs. The observed decrease or loss of immunoreactivity for TTF-1, SP-A, and Napsin A indicates that these lesions demonstrate a shift away from their pulmonary phenotype, although CK7 expression was retained. The results indicate that CK7 and CK20 may be useful markers for distinction of PAEDs from MCRs.

Adenocarcinoma↗

PubMed2004

Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles.

BACKGROUND: Classification of high-grade neuroendocrine tumours (HGNT) of the lung currently recognises large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC) as distinct groups. However, a similarity in histology for these two carcinomas and uncertain clinical course have led to suggestions that a single HGNT classification would be more appropriate. Gene expression profiling, which can reproduce histopathological classification, and often defines new subclasses with prognostic significance, can be used to resolve HGNT classification. METHODS: We used cDNA microarrays with 40?386 elements to analyse the gene expression profiles of 38 surgically resected samples of lung neuroendocrine tumours and 11 SCLC cell lines. Samples of large-cell carcinoma, adenocarcinoma, and normal lung were also included to give a total of 105 samples analysed. The data were subjected to filtering to yield informative genes before unsupervised hierarchical clustering that identified relatedness of tumour samples. FINDINGS: Distinct groups for carcinoids, large-cell carcinoma, adenocarcinoma, and normal lung were readily identified. However, we were unable to distinguish LCNEC from SCLC by gene expression profiling. Three independent rounds of unsupervised hierarchical clustering consistently divided SCLC samples into two main groups with LCNEC samples largely integrated with these groups. Furthermore, patients in one of the groups identified by clustering had a significantly better clinical outcome than the other (83% vs 12% survived for 5 years; p=0.0094. None of the highly proliferative SCLC cell lines subsequently analysed clustered with this good-prognosis group. INTERPRETATION: Our findings show that HGNT of the lung can be classified into two groups independent of SCLC and LCNEC. To this end, we have identified many genes, some of which encode well-characterised markers of cancer that distinguish the HGNT groups. These results have implications for the diagnosis, classification, and treatment of lung neuroendocrine tumours, and provide important insights into their underlying biology.

Biomarkers, Tumor↗

PubMed2004

[The result of VIP chemotherapy as an induction therapy in 6 patients with non-seminomatous extragonadal germ cell tumor].

We treated 6 patients with non-seminomatous extragonadal germ cell tumor (NSEGCT) by VP-16 + ifosfamide + cisplatin (VIP) chemotherapy as an induction therapy to investigate the effectiveness and safety. Primary lesions were located at the mediastinum in 4 patients and the retroperitoneum in 2 patients. As a rule, all patients were treated with VIP chemotherapy of 4 courses with or without second-line treatment such as chemotherapy, residual tumor resection and/or radiation. Following the induction therapy (VIP), 4 of 6 patients (67%) achieved complete or partial responses. After salvage therapy, 4 patients (67%) achieved complete responses and two other patients also achieved partial responses. However, only 2 of the 5 patients who had been follow-up for more than 2 years have remained disease free. The effects of VIP chemotherapy on non-seminomatous extragonadal germ cell tumor appeared to be similar to those of the conventional chemotherapies though the number of patients was small in the current study. It appears to be necessary to design more effective regimen.

Adult↗

PubMed2003

Early-stage lung adenocarcinomas with a micropapillary pattern, a distinct pathologic marker for a significantly poor prognosis.

Adenocarcinomas with a micropapillary pattern (MPP), featuring small papillary tufts lacking a central fibrovascular core, are thought to have a poor prognosis. To examine whether the MPP is a predictor of prognosis, clinicopathologic characteristics of adenocarcinomas were analyzed with particular reference to survival of early-stage patients. The subjects were 344 consecutive patients (female/male ratio 163:181) for whom complete surgical resection was undertaken at the Cancer Institute Hospital, Japan, during 1986-1995. Histologically, they were divided into two groups: MPP-positive (n = 139; 40%) and MPP-negative (n = 205; 60%). The following items were significantly more frequent in the MPP-positive group: metastasis to lymph nodes (p <0.001), pleural invasion (p = 0.02), intrapulmonary metastasis (p <0.001), and nonsmoking status (p = 0.002). In stage I patients (i.e., without lymph node metastasis, n = 154), 5-year survival of the MPP-positive group (n = 45) was 79%, significantly lower than the MPP-negative group (n = 109) of 93% (p = 0.004). In many cases of the c-stage I MPP-positive group, upstaging was necessary on the basis of pathologic findings for metastases, and the survival was between stage I and stage II. Our study clearly indicated that the MPP is a distinct prognostic marker for lung adenocarcinoma, particularly regarding apparent stage I diseases.

Adenocarcinoma, Papillary↗

PubMed2002

Loss of heterozygosity and the smoking index increase with decrease in differentiation of lung adenocarcinomas: etiologic implications.

To better understand causative relations of smoking to lung adenocarcinomas, the frequency of loss of heterozygosity (LOH) of all autosomal chromosomes was compared among the three grades of histological differentiation with 119 pulmonary adenocarcinomas (AC) and 41 squamous cell carcinomas (SCC), using Southern blotting. The fractional allelic loss (FAL) values, defined as (number of chromosome arms with LOH)/(number of informative arms), and smoking index (a product of number of cigarettes per day and duration in years) for all ACs were 0.19 and 520 whereas those for SCCs were 0.34 and 1,160, respectively. Those for well- (n=33), moderately (n=63) and poorly (n=23) differentiated ACs were 0.100, 0.197, 0.295 and 310, 480, 1,010, respectively. These results showed that less differentiated ACs are more similar to SCC in terms of LOH frequency and smoking.

Adenocarcinoma↗

PubMed2002

Pulmonary metastases from a low-grade endometrial stromal sarcoma confirmed by chromosome aberration and fluorescence in-situ hybridization approaches: a case of recurrence 13 years after hysterectomy.

Pulmonary metastasis from low-grade endometrial stromal sarcomas (ESSs) occasionally are found after long, disease-free periods, mostly as incidental histological or radiological discoveries. We describe a case of low-grade ESS presenting as nodular pulmonary metastases finally diagnosed by estrogen-receptor staining, cytogenetic and fluorescence in situ hybridization (FISH) analyses, and perusal of the histology of hysterectomy material. An abnormal nodule in the lung field was discovered by means of chest X-ray of a 47-year-old woman. She had been disease free for 13 years after hysterectomy for an alleged leiomyoma. A computed tomographic scan revealed nodules, with fluctuation in size over the 2-year period, in both lungs. Finally the lesion in the left lung was resected, and pulmonary endometriosis was suspected because of the lack of stromal cell nuclear atypia and positive immunohistochemical reactions for estrogen and progesterone receptors. However, a characteristic karyotype was identified cytogenetically: 46, XX, t(7;17)(p15;q11), the translocation of which, specific to ESS, was confirmed by FISH analysis. A final diagnosis of pulmonary metastases from an ESS could be made by reviewing the histology of the previous uterine tumor. In this case, metastatic lesions from an ESS showed a decrease as well as an increase in size, despite the malignant potential. Immunostaining for estrogen and progesterone receptors and cytogenetic and FISH analyses, together with clinical information on the past gynecological history, are valuable diagnostic keys.

Chromosomes, Human, Pair 17↗

PubMedDate not supplied

Sarcomatoid adenocarcinoma of the lung: clinicopathological, immunohistochemical and molecular analyses.

BACKGROUND: Biphasic lung cancers with admixtures of adenocarcinoma and sarcomatoid components but lacking true mesenchymal differentiation (sarcomatoid adenocarcinomas) are rare, and extensive studies of their clinicopathological characteristics and histogenesis have not been performed. MATERIALS AND METHODS: Six surgically resected sarcomatoid adenocarcinomas were compared clinicopathologically with 317 standard adenocarcinomas, and studied immunohistochemically and by loss of heterozygosity (LOH) analysis focusing on each component. RESULTS: In comparison with standard adenocarcinomas, the sarcomatoid adenocarcinomas occurred in older patients, were more likely to be associated with smoking and were more acinar than papillary, with a worse five-year prognosis. Immunohistochemically, sarcomatoid components were positive for epithelial markers in three cases. In one case the carcinoma showed retention of heterozygosity and the sarcomatoid components allelic loss, while all other cases showed retention or LOH in both components. CONCLUSION: The sarcomatoid adenocarcinoma exhibits different clinicopathological characteristics from standard adenocarcinomas. The present immunohistochemical and LOH analyses provided support for the idea that both components are derived from one precursor cell, and that progression may be by way of adenocarcinoma to sarcomatoid differentiation.

Adenocarcinoma↗

PubMedDate not supplied

Gefitinib efficacy associated with multiple expression of HER family in non-small cell lung cancer.

UNLABELLED: The aim of this study was to compare the relationship between HER family expression and clinical response to gefitinib. PATIENTS AND METHODS: Tissues from thirty-one non-small cell lung cancer (NSCLC) patients treated with a monotherapy of gefitinib were analyzed. Expressions of HER family in 31 tumors were examined by immunohistochemistry. RESULTS: The total expressions were 21 for EGFR (68%), 24 for HER2 (77%), 17 for HER3 (55%) and 4 for HER4 (13%). Fourteen out of 31 (45%) demonstrated triple expression of EGFR and HER2, as well as HER3 or HER4. A significantly better response rate (RR) and time to progression (TTP) were observed for the group with the triple expression than for the other groups (RR 50 vs. 11%; p < 0.05, median TTP 4.29 vs. 1.2 months; p < 0.05). CONCLUSION: Mutliple expression of the HER family might be related with the clinical response to gefitinib and EGFR mutation status.

Aged↗