PubMed Health⌕ Search

Biomedical subjects

Yukitoshi Satoh

Publications and source records attributed to Yukitoshi Satoh.

17 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

Successful treatment of chemo-refractory pulmonary metastases of renal pelvic cancer by second-line chemotherapy including gemcitabine followed by salvage surgery.

A 51-year-old woman developed multiple pulmonary metastases after receiving nephroureterectomy and two cycles of adjuvant chemotherapy for the treatment of renal pelvic transitional cell carcinoma. All metastases disappeared after four cycles of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by radiotherapy; however, 8 months later two pulmonary metastases recurred. The patient was entered into a phase I study of combination chemotherapy with gemcitabine, etoposide and cisplatin, designed for chemorefractory urothelial cancer. The lung masses showed significant reduction after two cycles of this chemotherapy; following salvage surgery, the patient has been well with no evidence of recurrence for more than 3 years.

Antineoplastic Combined Chemotherapy Protocols↗

Micropapillary clusters in early-stage lung adenocarcinomas: a distinct cytologic sign of significantly poor prognosis.

BACKGROUND: It is known that patients who have pulmonary adenocarcinomas with a pathologic micropapillary pattern (pMPP) featuring small papillary tufts that lack a central fibrovascular core have a poor prognosis. Although the pMPP initially was identified in surgical material, preoperative detection is desirable from the standpoint of making treatment decisions. Therefore, the authors focused on cytologic features resembling the pMPP in lung adenocarcinomas, with particular reference to the survival of patients with pathologic Stage I disease. METHODS: The authors reviewed clinical course data, preoperative cytologic specimens, and histologic materials from 110 patients with Stage I adenocarcinoma of the lung who presented between 1986 and 1995. Cytology of micropapillary clusters (MPCs) was characterized by round, 3-dimensional, cohesive clusters of neoplastic cells (consisting of > 3 cells and < 20 cells) with a pseudopapillary configuration. Total counts of cohesive clusters that consisted of more than three neoplastic cells on slides and frequencies of MPCs were investigated. RESULTS: All patients (54 females and 56 males) had a preoperative diagnosis of malignancy and underwent complete surgical resection. The patients with Stage I disease were subclassified into an MPC-positive group (n = 41) and an MPC-negative group (n = 69). The 5-year survival rate was 91.3% for patients in the MPC-negative group and 75.6% for patients in the MPC-positive group; this difference was statistically significant. CONCLUSIONS: MPC cytology is a distinct prognostic marker for early-stage lung adenocarcinoma with poor prognosis. The presence of this component, therefore, should alert the clinician to the need for close follow-up.

Adenocarcinoma↗

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↗

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↗

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↗

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↗

Cytology of pulmonary adenocarcinomas showing enteric differentiation.

OBJECTIVE: To evaluate cytologic differences between primary pulmonary adenocarcinomas showing enteric differentiation (PAED) primary pulmonary adenocarcinomas of ordinary structure (PAC) and pulmonary metastases from colorectal carcinomas (MCR). STUDY DESIGN: During an 18-year period (1986-2003), cytologic materials were obtained from 5 PAEDs confirmed by pathologic examination of surgically resected specimens at the Cancer Institute Hospital. Aspiration cytologic and/or imprint smears of routine samples stained by the Papanicolaou method from the PAED cases were reviewed in comparison with 10 cases each of PAC showing a tubular pattern and MCR. RESULTS: The aspiration biopsy cytology and imprints showed similar features. Abundant necrotic debris in the background was recognized in a majority of all cases independent of the group. None to slight overlapping of tumor cells and less frequent palisading or glandular arrangements were characteristic features of PAED, significantly differing from MCR. Moreover, differences in nuclear features were evident as follows: in the MCR group, nuclear chromatin was hyperchromatic and coarsely condensed, and there were prominent nucleoli, whereas a slightly hyperchromatic pattern with some small to enlarged nucleoli was typical of PAED and PAC cases. CONCLUSION: Although diagnosis of PAED by routine cytology is difficult due to the features of the lesion, differential diagnosis between PAED, PAC and MCR is a possible using conventional cytologic criteria.

Adenocarcinoma↗

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↗

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↗