A novel test of the surgical margin in patients with lung cancer undergoing limited surgery: lavage cytologic technique.
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Adult↗
Biomedical subjects
K Takami
Publications and source records attributed to K Takami.
Ancient allelism at the cytosolic chaperonin-alpha-encoding gene of the zebrafish.
The T-complex protein 1, TCP1, gene codes for the CCT-alpha subunit of the group II chaperonins. The gene was first described in the house mouse, in which it is closely linked to the T locus at a distance of approximately 11 cM from the Mhc. In the zebrafish, Danio rerio, in which the T homolog is linked to the class I Mhc loci, the TCP1 locus segregates independently of both the T and the Mhc loci. Despite its conservation between species, the zebrafish TCP1 locus is highly polymorphic. In a sample of 15 individuals and the screening of a cDNA library, 12 different alleles were found, and some of the allelic pairs were found to differ by up to nine nucleotides in a 275-bp-long stretch of sequence. The substitutions occur in both translated and untranslated regions, but in the former they occur predominantly at synonymous codon sites. Phylogenetically, the alleles fall into two groups distinguished also by the presence or absence of a 10-bp insertion/deletion in the 3' untranslated region. The two groups may have diverged as long as 3.5 mya, and the polymorphic differences may have accumulated by genetic drift in geographically isolated populations.
Alleles↗
Increased expression of inflammatory mediators in small-airway epithelium from tobacco smokers.
To study the inflammatory responses of small-airway epithelium in smokers, we harvested enough living epithelial cells (1.97 x 10(6) +/- 0.74 x 10(6)) with a new ultrathin fiberscope from the very peripheral airways of 22 current smokers and 17 subjects who never smoked after informed consent was obtained. The cells were keratin positive and composed mainly of nonciliated cells. The expression levels of inflammatory markers [interleukin (IL)-8 and intercellular adhesion molecule (ICAM)-1] were evaluated with RT-PCR. The magnitude of the mRNA levels corrected by beta-actin transcripts of IL-8 and ICAM-1 was significantly higher in the smokers than in the nonsmokers (P < 0.001). Furthermore, among current smokers, IL-8 mRNA levels correlated positively with the extent of smoking history [in pack. years (packs/day x no. of years of smoking); r = 0.754, P < 0.001]. Spontaneously released IL-8 and soluble ICAM-1 levels (n = 12) from cultured epithelial cells were elevated in subjects with a smoking history than in those without it (IL-8, 1,580 +/- 29.6 vs. 354 +/- 39.4 pg. 10(6) cells(-1). 24 h(-1); P < 0.001; soluble ICAM-1, 356.0 +/- 45.9 vs. 112.9 +/- 12.9 pg. 10(6) cells(-1). 24 h(-1); P < 0.01 by Student's t-test ). In contrast, the epithelial cells from the main bronchi did not show such differences between smokers and nonsmokers. Our study highlighted a close link between smoking and the expression of inflammatory mediators such as IL-8 and ICAM-1 in small airways. Our results also suggested that this new ultrathin bronchofiberscope promised a good approach for the evaluation of cellular changes in the small airways.
Biopsy↗
[Diagnosis and treatment of small peripheral lung cancer].
Recently, routine clinical use of CT scan has enabled the detection of many small pulmonary nodules. Concurrently, high-resolution CT(HRCT) has made great advances in the diagnosis of small peripheral lung cancer. In the tumor of adenocarcinoma, non-invasive bronchioloalveolar carcinoma(BAC) component having a replacement growth pattern of alveolar lining cells shows ground-glass opacity(GGO) on HRCT. On the basis of analysis of small peripheral adenocarcinoma (= < 2 cm), patients with tumors showing > = 50% GGO had no metastatic tendency. Therefore, simple wedge resection may be acceptable as a radical operation. On the other hand, since patients with tumors < 50% GGO had slight metastatic tendency depending upon the tumor size, segmentectomy with mediastinal lymph node sampling should be considered only for tumors = < 15 mm.
Adenocarcinoma↗
[Use of percutaneous cardiopulmonary support (PCPS) for extended surgery in patients with T4 tumor].
Since 1991, we have performed operations for tumors invading the upper airway, left atrium or main pulmonary artery with percutaneous cardiopulmonary support (PCPS) stand by support available. Of 15 cases with PCPS stand by, 6 patients actually underwent operation using PCPS. There were three esophageal cancers invading the carina, two lung neoplasms with left atrial invasion and one neoplasm extending to the main pulmonary artery. One of three patients with esophageal cancer had massive bleeding in the trachea resulting in airway obstruction. For this patient, emergency PCPS was carried out followed by the total removal of the thoracic esophagus and combined resection of membranous portion of the carina. As a result, a substantial amount of time (6 hours) was required. The two patients with reconstruction of the carina due to esophageal cancer were also successfully treated by using PCPS. Two patients with malignant pulmonary neoplasms invading the left atrium underwent combined resection of the lung and left atrium using a combination of PCPS and ventricular fibrillation under normothermia. In conclusion, PCPS should be accepted as a standard technique for patients with advanced thoracic malignancies in whom cardiac arrest or ventilation support is thought to be necessary for the complete removal of the tumor.
Adult↗
[Prognostic assessment of resected lung cancer based on the new international staging system: analysis by histologic types].
The purpose of this study is to assess the validity of the new international staging system for lung cancer revised in 1997 and to clarify the prognostic value of histologic type. Of 1,042 patients with primary lung cancer who underwent resection from 1982 to 1995, 549 patients with adenocarcinoma (AD) and 363 with squamous cell carcinoma (SQ) were included in this study. Overall deaths including operative deaths were treated as the terminal event. For patients with AD, 5-year survival rates were 83% in T1N0M0, 70% in T2N0M0, 46% in T2N1M0, 45% in T3N0M0, 43% in T1N2M0, 32% in T1N1M0, 27% in T2N2M0, 25% in T3N1M0, and 10% in T3N2M0, respectively. For patients with SQ, 5-year survival rates were 80% in T1N0M0, 78% in T1N1M0, 67% in T1N2M0, 60% in T3N0M0, 56% in T2N0M0, 47% in T2N1M0, 36% in T3N1M0, 26% in T2N2M0, and 10% in T3N2M0, respectively. Survival of T1N2M0 was significantly better than that of T2N2M0 and similar to that of T3N0M0 and T2N1M0 both in AD and SQ. In AD survival was dominantly affected by N factor, while in SQ survival was strongly correlated with T factor. In conclusion, we propose that T1N1M0, T2N1M0, T3N0M0 and T1N2M0 should be classified as stage II and T3N2M0 be included into stage IIIB for AD. The TNM grouping for SQ is same as that for AD except setting T1N1M0 as stage IB and T2N0M0 as stage II.
Aged↗
Prevention of infection of influenza virus in DQ6 mice, a human model, by a peptide vaccine prepared according to the cassette theory.
We proposed a strategy (cassette theory) in which non-binding peptides for murine major histocompatibility complex (MHC) class II molecules are introduced into a MHC-binding component to render the resultant hybrid peptides bound to the MHC and thus immunogenic in animals carrying the relevant MHC. It was shown that 46F/HA127-133/54A(18mer) peptide which was prepared by introducing hemagglutinin (HA)127-133 of influenza virus into the H-2Ab binding component induced significant T cell responses and antibodies (Ab) specific for HA127-133 in H-2Ab mice. Further we found that the H-2Ab binding component had a supermotif for human class II molecules (i.e. HLA-DQ6). In the present study, a new peptide vaccine, H3-H3, was prepared by combining 46F/HA127-133/54A(18mer) as a carrier and HA127-133 attached to the C terminus of 46F/HA127-133/54A(18mer) as a hapten and the effect of vaccine was examined in DQ6 mice which carry HLA-DQ6 alone as MHC class II molecules and thus may be regarded as a model of the DQ6 positive individuals. Since 46F/HA127-133/ 54A(18mer) induced merely Ab against HA127-133, it was assumed that H3-H3 induced mainly HA127-133 specific Ab in DQ6 mice without undesirable Ab production against the carrier. Indeed, H3-H3 elicited T cell responses and induced HA127-133 specific Ab in DQ6 mice. Furthermore, administration of H3-H3 inhibited growth of influenza virus until 9 weeks after the last immunization in DQ6 mice.
Amino Acid Sequence↗
Mediastinal lymph node involvement as the initial manifestation of occult thyroid cancer in the surgical treatment of lung cancer: report of a case.
A 63-year-old man was referred to our institute for the treatment of squamous cell carcinoma of the upper lobe of his right lung. A right upper lobectomy of the lung was performed with a mediastinal lymph node dissection. The postoperative pathological examination of the dissected specimens revealed one of the superior mediastinal lymph nodes to be morbid with micrometastasis of occult thyroid cancer, while no node involvement was seen due to lung cancer. A right lobectomy of the thyroid gland with a modified radical neck dissection was done 4 years later after the confirmation of the absence of any recurrent sign of lung cancer. In the resected specimen, papillary thyroid microcarcinoma was observed with several intraglandular metastases and right regional lymph node involvement. Eight months later, a new primary lung cancer developed in the left lung, and a left upper lobectomy of the lung with a mediastinal lymph node dissection was performed. At that time, the absence of mediastinal lymph node metastasis from lung cancer or thyroid cancer was confirmed. Mediastinal lymph node involvement as the initial manifestation of occult thyroid cancer in surgical treatment for lung cancer is rare, but it is important to be aware of the possibility of incidentally detecting occult thyroid cancer in surgical dissections in this area for lung cancer. The appropriate surgical treatment should be determined while carefully considering the prognosis of the lung cancer as well as that of any coexisting malignancy.
Carcinoma, Papillary↗
Surgical treatment for metastatic lung tumors with incidentally coexisting lung cancer.
We report four surgically resected cases of a metastatic lung tumors with incidentally coexisting lung cancer. Two patients (Cases 1 and 2) were admitted for surgical treatment for pulmonary metastases from colon cancer, and the other two (Cases 3 and 4) were for pulmonary metastases from renal cell carcinoma. In only one patient (Case 3), one lesion among the multiple shadows on the preoperative computed tomography examination was rather strongly suspected to be primary lung cancer. In three patients (Cases 1, 2 and 3), one of the resected lesions in each individual case was diagnosed as lung adenocarcinoma by an intraoperative examination using frozen sections, and was later histologically confirmed. In Case 4, one of the resected lesions was postoperatively determined to be lung adenocarcinoma. All coexisting lung cancers, treated with partial resection of the lung, were well-differentiated small-sized adenocarcinoma (T1N0), while the other lesions resected in each case were metastases from the individual cancer. Problems in preoperative diagnosis and surgical treatment for metastatic lung tumors with incidentally coexisting lung cancer are discussed.
Adenocarcinoma↗
Survival and postoperative complications after extended surgery for non-small-cell lung cancer. A retrospective study.
OBJECTIVE: We evaluated survival after extended surgery in patients with non-small-cell lung cancer and the effects of induction therapy on results and complications. SUBJECTS AND METHODS: Between April 1987 and March 1998, 127 patients with pathological T3 (pT3) or T4 (pT4) non-small-cell lung cancer underwent extended surgery combined with resection of neighboring organs. Of these, 35 received induction therapy. In the remaining 92, surgery preceded other therapy. Long-term results and postoperative respiratory complications were analyzed and compared between the patients with and without induction therapy. RESULTS: Overall 5-year survival after extended surgery was 37%. Five-year survival rates in the pT3 was 41% and that in the pT4 group 28% (p = 0.030). Five-year survival rate in the pN0-1 was 46% and that in the pN2-3 group 26% (p = 0.003). No significant difference was observed in survival curves between patients with and without induction therapy. Induction therapy responders showed better survival than nonresponders. To prevent postoperative fatal complications due to bronchopleural fistula, we prophylactically covered the bronchial stump using autologous tissue in 31 induction therapy patients, and no mortality due to complications was seen in this group. CONCLUSION: Long-term survival after extended surgery was observed in pT3 and pT4 patients, especially among those with a pN0-1 status. Induction therapy responders may be considered good candidates for extended surgery because of the favorable prognosis in contrast to that for nonresponders.
Carcinoma, Non-Small-Cell Lung↗
Combined resection of the aorta for an esophageal carcinoma invading the aorta through a right transthoracic approach.
The prognosis of esophageal carcinoma invading the thoracic aorta has been extremely poor, as it has been either not resected or only palliatively resected. In recent years a remarkable improvement in survival has been achieved in advanced esophageal carcinoma through an aggressive dissection of the upper mediastinal lymph nodes. This implied that resection only of the aorta without lymph node dissection in these patients was not adequate for curability. Although a resection of the aorta would seem to be performed more easily through a left thoracotomy than through a right thoracotomy, the upper mediastinal lymph node dissection was unsatisfactory through a left thoracotomy. Therefore, we performed combined resection of the aorta using a temporary aorta-aorta bypass together with upper mediastinal lymph node dissection through a right thoracotomy for four patients with the esophageal carcinoma invading the thoracic aorta. This operative procedure was performed safely, and had the advantage that full observation on the extent of the carcinoma was attained together with subsequent radical lymph node dissection in the same field through only the right thoracic approach. This operation may provide a possibility for cure to patients with an esophageal carcinoma invading the aorta, who would otherwise receive only palliative treatment.
Aged↗
Prognostic value of bronchiolo-alveolar carcinoma component of small lung adenocarcinoma.
BACKGROUND: Bronchiolo-alveolar carcinoma (BAC) is often observed in lung adenocarcinoma, but its clinicopathological and prognostic significance, especially in small peripheral lung adenocarcinoma, remains undetermined. METHODS: We assessed 206 consecutive cases of surgically resected small peripheral lung adenocarcinoma (less than 2 cm in diameter) recorded between 1973 and 1997. According to the component area of well differentiated BAC within maximally cut surface specimens of tumor tissue, we semiquantitatively classified the tumors into four types: those in which the BAC component comprised 0% (type I), 1% to 49% (type II), 50% to 99% (type III), and 100% (type IV) of the tumor tissue. RESULTS: Forty tumors were classified as type I, 75 as type II, 74 as type III, and 17 as type IV. The tumors with less BAC, especially type I and II, showed a significantly more aggressive nodal involvement and tumor stage, and consequently a worse prognosis, while type IV tumors had no nodal involvement and the most favorable prognosis. The patients with type III showed clinicopathological characteristics somewhere between those of type II and type IV patients. Among stage I patients, however, those with type II had the worst prognosis, while those with type I showed as good a prognosis as the other two groups. CONCLUSIONS: This novel classification based on the degree of BAC involvement in small peripheral lung adenocarcinoma may reflect clinicopathological and prognostic characteristics. This classification may prove practical for planning therapeutic strategies, in particular surgical treatment.
Adenocarcinoma↗
Differential effects of troglitazone and D-chiroinositol on glucosamine-induced insulin resistance in vivo in rats.
Troglitazone and D-chiroinositol have been shown to exert antidiabetic effects by either potentiating or mimicking insulin action. We studied whether pretreatment with these compounds can prevent the deleterious effects of glucosamine on insulin action that may play an important role in hyperglycemia-induced insulin resistance. Normal Wistar rats were pretreated with troglitazone (100 mg/kg/d), D-chiroinositol (100 mg/kg/d), or placebo (saline) for 7 days. Glucosamine (50 micromol/kg/min) was then infused for 210 minutes, and a euglycemic glucose clamp was performed during the last 120 minutes. Pretreatment with troglitazone or D-chiroinositol had no effect on fasting plasma glucose or insulin or basal hepatic glucose output (HGO). Under the euglycemic-hyperinsulinemic (956+/-93 pmol/L) clamp condition, HGO in glucosamine-infused placebo-treated rats was not suppressed, but instead was increased over the basal level, indicative of hepatic insulin resistance. In contrast, HGO failed to increase during glucosamine infusion in rats pretreated with troglitazone but was not normally suppressed. This may indicate a partial improvement in the hepatic insulin resistance. D-Chiroinositol pretreatment had no effect on the glucosamine-induced increase in HGO. The glucose disposal rate (GDR) was 25% lower in rats infused with glucosamine versus saline-infused rats (25.5+/-2.5 v 34.1+/-2.0 mg/kg/min), indicative of peripheral insulin resistance. Pretreatment with D-chiroinositol (34.5+/-2.3 mg/kg/min) prevented the glucosamine-induced decrease in the GDR, indicating an improvement in peripheral insulin resistance. Troglitazone (25.2+/-3.3 mg/kg/min) was without effect. In conclusion, (1) in normal control rats, glucosamine infusion induced hepatic and peripheral insulin resistance; (2) D-chiroinositol, but not troglitazone, pretreatment prevented glucosamine-induced peripheral insulin resistance; and (3) troglitazone, but not D-chiroinositol, partially blocked the glucosamine-induced hepatic insulin resistance. D-Chiroinositol may provide a novel pharmacological approach to hexosamine-induced peripheral insulin resistance.
Animals↗
Successful removal of a primitive neuroectodermal tumor in the lung with gross extension into the left atrium.
We report here the successful multi-model treatment of a 31-year-old female demonstrating a primitive neuroectodermal tumor originating in the lower lobe of the right lung with gross extension into the left atrium via the inferior pulmonary vein. The tumor was markedly reduced by combination chemotherapy consisting of vincristine, doxorubicin, cyclophosphamide, and ifosfamide. The residual tumor was completely removed through a combined left atrial resection and right middle and lower lobectomy, using a percutaneous cardiopulmonary support system.
Adult↗
[Indications for intentionally limited resection for non-small-cell lung cancer].
Radiographically, there have been new advances in spiral computed tomography (CT) scanning are currently being studied as a screening tools. As a result, many cases of small-sized lung cancer have been discovered. Some are noninvasive or minimally invasive bronchioloalveolar carcinoma, which is characterized by a the unique sign of ground-glass opacity (GGO) on high-resolution CT (HRCT) scanning. In such cases, lymph node metastases are extremely rare. However, there is currently no definitive surgical modality for such lesions. To clarify the indications of limited resection (segmentectomy or wedge resection), preoperative tumor diameter, location, and, GGO area on HRCT were estimated in patients with clinical T1N0 disease. In patients whose tumor included > or = 50% GGO area and was 15 mm or less in diameter, or patients with pure GGO regardless of tumor size, wedge resection without lymph node dissection should be considered as an acceptable treatment. Video-assisted thoracic surgery is a useful approach for selected patients. On the other hand, in patients with tumors < 50% GGO area in the range of 10-15 mm in diameter, segmentectomy with systematic lymph node dissection or diligent lymph node sampling should be considered.
Carcinoma, Non-Small-Cell Lung↗
Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney.
The functional characteristics of rat organic anion transporter OAT1 were investigated using Xenopus laevis oocytes. Uptake of p-aminohippurate (PAH) by the oocytes expressing OAT1 was markedly inhibited by glutarate, alpha-ketoglutarate and probenecid, moderately inhibited by folate and methotrexate, but not inhibited by taurocholate or tetraethylammonium. Methotrexate and folate were transported by OAT1, but probenecid, a typical inhibitor of organic anion transporter, was not transported. Inhibition of PAH uptake by aliphatic dicarboxylates with various alkyl chain lengths was maximal at 5 (glutarate) and 6 (adipate) carbon atoms. OAT1-mediated PAH uptake was markedly inhibited by phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-dibutyrate and mezerein, but not by 4alpha-phorbol 12,13-didecanoate. The inhibitory effect of PMA was attenuated in the presence of staurosporine, suggesting that OAT1 is regulated by protein kinase C. These results suggest that the substrate recognition of OAT1 is comparable to that of renal basolateral organic anion transporter, and the transport activity is regulated by protein kinase C.
Animals↗
Fibroblast growth factor receptor-1 expression in the cortex and hippocampus in Alzheimer's disease.
Localization of fibroblast growth receptor (FGFR)-1 immunoreactivity was investigated immunochemically in postmortem brain tissue of Alzheimer's disease (AD) and age-matched control cases using a rabbit polyclonal antibody and a mouse monoclonal antibody specific for FGFR-1. In control cases, FGFR-1 immunoreactivity was identified in astrocytes in white matter and in hippocampal pyramidal neurons. In AD cases, the immunoreactivity in reactive astrocytes surrounding senile plaques was increased. The pattern of FGFR-1 immunoreactivity was confirmed in selected cases by in situ hybridization for FGFR-1 mRNA. Immunoreactivity using a monoclonal antibody demonstrated a similar distribution pattern. The localization of FGFR-1 is consistent with previous reports on the involvement of FGF-1 and FGF-2 in AD.
Aged↗
KAI1/CD82 expression in nonsmall cell lung carcinoma is a novel, favorable prognostic factor: an immunohistochemical analysis.
BACKGROUND: The KAI1/CD82 gene, the product of which is a member of the transmembrane-4 superfamily, is a suppressor of metastasis; as a result, it is inversely associated with tumor progression and is a favorable prognostic factor in some tumors. This study was performed to determine the prognostic value of KAI1/CD82 protein levels in nonsmall cell lung carcinoma (NSCLC). In addition, levels of KAIl/CD82 expression in metastatic lesions were determined and compared with those in primary NSCLC lesions. METHODS: KAI1/CD82 expression in 200 NSCLC patients who underwent potentially curative surgery was immunohistochemically detected with C33, an anti-KAI1/CD82 monoclonal antibody. According to the degree of KAI1/CD82 positive cancer cells within the tumor tissue, each sample was classified as KAI1/CD82 positive, KAI1/CD82 reduced, or KAI1/CD82 negative. RESULTS: Sixty-five samples (32.5%) were KAI1/CD82 positive, 31 (15.5%) were reduced, and 104 (52%) were negative. There was no significant association between KAI1/CD82 expression and clinicopathologic factors, but patients who were positive for KAI1/CD82 expression had significantly favorable prognoses for overall survival (P = 0.0026) and disease free survival (DFS; P = 0.0007) compared with the other groups. In particular, among patients with adenocarcinoma, similar results were even more significant. In multivariate analysis, immunohistochemical KAI1/CD82 expression in patients with NSCLC was an independent prognostic factor for overall survival and DFS; in those with adenocarcinoma, it was an even more valuable factor. In some patients with NSCLC, especially those with adenocarcinoma, KAI1/CD82 expression levels in metastatic lesions were diminished compared with levels of expression in the primary lung lesions. CONCLUSIONS: The immunohistochemically determined level of KAI1/CD82 expression in NSCLC cells within tumor tissue appears to be a favorable prognostic factor for overall survival as well as DFS. The results of this study suggest that decreased KAI1/CD82 expression may be associated with tumor progression and enhanced metastatic potential in some patients with this disease.
Adult↗