Biomedical subjects

Akihiko Osaki

Publications and source records attributed to Akihiko Osaki.

14 recordsLinked to original sources

PubMed2006

Maturation of dendritic cells and T-cell responses in sentinel lymph nodes from patients with breast carcinoma.

BACKGROUND: Methods for identifying sentinel lymph nodes (SNs) and their clinical significance have been established. Recent advances in molecular immunology have enabled the analysis of precise immune responses. The objective of the current study was to clarify the dendritic cell (DC) maturation, T-helper type 1 (Th-1) and Th-2 responses, and regulatory T-cell responses of SNs in patients with breast carcinoma. METHODS: SNs and non-SNs were identified by radioguided and blue dye-guided methods in 70 consecutive patients with clinically lymph node negative (N0) breast carcinoma. Lymphocytes were collected from SNs and non-SNs and were subjected to flow cytometric analysis (FCM) using antibodies of CD83-fluorescein isothiocyanate (FITC), CD80-phycoerythrin (PE), CD86-PE, CD40-PE, human leukemic D-related antigen (HLA-DR)-FITC, CD4-FITC, and CD25-PE. Total RNA was extracted from SNs and non-SNs, and the expression of CD83, interleukin 12p40 (IL-12p40), interferon gamma (IFN-gamma), IL-4, IL-10, and Foxp3 was evaluated by using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The immunologic status of SNs was analyzed further with regard to micrometastases, which were identified as negative microscopically but positive according to an RT-PCR analysis that was specific for mammaglobin. RESULTS: SNs were detectable in 70 of 71 consecutive patients (98.6%) with clinically N0 breast carcinoma. Fourteen of 70 patients (20.0%) had positive metastasis in SNs. When SNs were compared with non-SNs in 56 metastasis-negative patients, FCM revealed that HLA-DR-positive, CD80-positive, CD86-positive, and CD40-positive cell populations were decreased significantly in SNs. RT-PCR analysis demonstrated that, among 44 patients with metastasis-negative SNs, the expression levels of CD83 and IFN-gamma mRNA were significantly lower in SNs compared with non-SNs. Immunologic parameters also were compared between 44 metastasis-negative SNs and 14 metastasis-positive SNs. The metastasis-positive SNs demonstrated significantly higher expression of CD83, IL-12p40, IFN-gamma, IL-10, and Foxp3 mRNA than the metastasis-negative SNs. Correction of micrometastasis detected by mammaglobin enhanced these differences consistently. CONCLUSIONS: In patients with breast carcinoma, cellular immune responses, from DC maturation to Th-1 responses, appeared to be less active in SNs compared with non-SNs before metastasis developed. Once metastasis was established in SNs, DC maturation was triggered and was followed by the up-regulation of Th-1 responses, which may reflect antigen-specific immune responses in SNs. Unlike DC maturation and Th-1 responses after metastasis in SNs, up-regulation of Th-2 and regulatory T-cell responses developed in parallel.

Adult↗

PubMed2006

Potential role of HER-2; in primary breast tumor with bone metastasis.

HER-2 is an important prognostic factor in breast cancer, and its overexpression is observed in 20-60% of cases with micrometastases in the bone marrow. The aim of this study was to explore the potential functional role of HER-2 in primary breast tumors with bone metastases. Forty-eight primary breast tumors with simultaneous or non-simultaneous bone metastases were studied. The expression of hormone receptors, and metastasis and growth factor-related proteins were assessed by immunohistochemical staining. The correlation in statistical significance was assessed by the Chi-square test. Of the 48 breast tumors, 11 (22.9%) were HER-2-positive and 37 were HER-2-negative. There was no significant difference in HER-2 status and clinicopathologic factors between the two groups. Of the 11 HER-2-positive tumors, there were 2 and 3 cases that showed positive nuclear expression for estrogen and progesterone receptors, respectively. No extranuclear expression of HRs was detected in these tumors. For metastasis-related proteins such as c-Met, VEGF, and MTA-1, which are activated by HER-2, only some insignificant focal expression of these proteins was observed. An increased level of pAkt was observed in 9 (81.8%) of 11 tumors, and an increased expression of CXCR4 was observed in 6 (54.5%) of 11 tumors. The frequency of increased levels of pAkt and CXCR4 was not significant between HER-2-positive and -negative tumors. The increased levels of pAkt and CXCR4 are induced by factors that are both dependent and independent of HER-2, and the activation of HER-2/CXCR4/ Akt signaling pathway in primary breast tumors may contribute to the formation of bone metastases in breast cancer.

Adult↗

PubMed2005

Elimination of late potentials by quinidine in a patient with Brugada syndrome.

The beneficial effects of quinidine on ST-segment elevation, inducible ventricular tachyarrhythmias, and episodes of ventricular tachyarrhythmia have been reported in Brugada syndrome. This is the first report describing quinidine-induced elimination of the late potential, which is considered one of the parameters for an arrhythmic event, in a patient with Brugada syndrome.

Anti-Arrhythmia Agents↗

PubMed2005

A Japanese phase I study of continuous oral capecitabine in patients with malignant solid tumors.

BACKGROUND: This study aimed to evaluate the tolerability and pharmacokinetics of capecitabine, given twice daily for 6 weeks without interruption, and to identify the maximum tolerated dose (MTD) and the suggested phase II schedule. METHODS: The initial dose of capecitabine was 251 mg/m2 twice daily, without interruption, and a dose escalation schedule was planned according to a modified Fibonacci scheme. Patients received oral capecitabine twice daily for at least 6 weeks unless grade 3 or 4 toxicity was observed. Blood and urine samples were collected for pharmocokinetic analysis on days 1 and 15. RESULTS: Sixteen patients with malignant solid tumors (seven breast, seven colorectal, and two gastric) were enrolled, all of whom were evaluable. Among 4 patients treated with capecitabine 1255 mg/m2 twice daily, one experienced grade 4 hemorrhagic gastric ulcer and one experienced grade 3 skin toxicity. Consequently, this dose was defined as the MTD, and gastrointestinal and cutaneous effects were identified as dose-limiting toxicities. There was no grade 3/4 diarrhea at any dose level. There was also no grade 4 hematologic toxicity at doses below the MTD, and there were no treatment-related deaths. Two patients with breast cancer had partial responses, at capecitabine doses of 502 mg/m2 and 1255 mg/m2, twice daily. Pharmacokinetic data show that high concentrations of doxifluridine (5'-DFUR) occur in tumor cells within 2 h after administration of capecitabine. CONCLUSION: The MTD of continuous oral capecitabine over 6 weeks was 1255 mg/m2 twice daily. Because of the higher occurrence of skin disorders reported in this study with a continuous treatment regimen, an intermittent treatment regimen of 828 mg/m2, administered twice daily for 3 weeks, followed by a 1-week rest period, was recommended for phase II studies. This regimen is being evaluated in phase II studies in Japanese patients with gastric, colorectal, and breast cancers.

Administration, Oral↗

PubMed2005

Current and future roles of neoadjuvant chemotherapy in operable breast cancer.

Neoadjuvant chemotherapy was initially used only as treatment for locally advanced breast cancer. However, because breast cancer is considered to be a systemic disease in which distant micrometastases are already present at the time of the initial diagnosis, primary systemic therapy may be beneficial in the eradication of these micrometastatic lesions. Despite the fact that no survival benefit of neoadjuvant chemotherapy over adjuvant chemotherapy has yet been demonstrated, the clinical indication for neoadjuvant chemotherapy is being extended not only to stage T3/4 tumors but also to some stage T1/2 operable breast cancers. The current clinical benefits of the use of neoadjuvant chemotherapy are that (1) the safety of neoadjuvant chemotherapy is comparable with that of adjuvant chemotherapy, (2) neoadjuvant chemotherapy increases the possibility of the use of breast-conserving surgery, and (3) pathologic complete response may be a predictive indicator of better survival. Importantly, the response to neoadjuvant chemotherapy in vivo could provide a useful prediction of prognosis and help define strategies for an individual patient's future treatment with alternative chemotherapy regimens or molecular-targeting agents. Furthermore, the discovery of predictive markers for tumor response to neoadjuvant chemotherapy through the analysis of complementary DNA microarrays and proteomics may also help facilitate individualized chemotherapy, particularly by improving survival in patients with breast cancer with a poor prognosis. Herein we review the current status and future role of neoadjuvant chemotherapy in operable breast cancer in terms of its survival benefit and the potential for the individualization of adjuvant therapy for these patients.

Antineoplastic Agents↗

PubMed2005

Rationale for sequential tamoxifen and anticancer drugs in adjuvant setting for patients with node- and receptor-positive breast cancer.

Since the survival benefit of tamoxifen (TAM) combined with anticancer drugs in treating node- and receptor-positive breast cancer is small, appropriate treatment schedules and the rationale for the combination remains unclear. We examined the effect of estradiol (E2) on sensitivity to anticancer drugs to clarify the survival benefit of tamoxifen combined with anticancer drugs. We used the MTT assay to assess the effect of E2 on sensitivity to anticancer drugs in the E2 receptor-positive and -negative breast cancer cell lines, MCF-7 and MDA-MB-231, respectively. We assessed the expression of apoptosis-related proteins by Western blotting, and evaluated apoptosis using the TUNEL method. Serum levels of E2 were measured using an enzyme-labeled radioimmunoassay in patients with premenopausal breast cancer before and during treatment with tamoxifen. Estrogen administration decreased sensitivity in MCF-7 cells to the anticancer drugs, adriamycin (ADM), mitomycin C (MMC), and paclitaxel (TXL), evaluated as increases in the IC50 values for ADM (4.1-fold), MMC (1.9-fold) and TXL (13.0-fold), compared with those of each drug alone. Estradiol in MDA-MB-231 cells similarly increased the IC50 values for ADM (9.5-fold), MMC (15.6-fold), and TXL (2.4-fold). The decreased sensitivity to these anticancer drugs was associated with the attenuation of apoptosis. Estrogen dose-dependently increased the expression of Bcl-2 protein in MCF-7, but not in MDA-MB-231 cells, and suppressed the expression of Bax and cytochrome c induced by anticancer drugs in association with decreased apoptosis compared with the effect of each drug alone. Phosphorylation of the Bcl-2 protein induced by TXL was decreased in the presence of E2 in MCF-7 cells. Serum levels of E2 were increased in 5 patients without amenorrhea and in 1 patient with amenorrhea after treatment with TAM alone in adjuvant therapy, compared with levels before treatment. Estradiol decreased sensitivity to ADM, MMC, and TXL in MCF-7 and MDA-MB-231 breast cancer cells, and this was associated in part with an increase in the amount of Bcl-2 protein, and decreases in levels of Bax and cytochrome c leading to apoptosis. These results suggest that therapy with TAM and anticancer drugs should be sequentially scheduled with anticancer drugs followed by TAM in an adjuvant setting to treat patients with breast cancer for a potentially improved survival benefit.

Adult↗

PubMed2005

Intractable gastrointestinal bleeding from angiodysplasia in a patient of Bernard-Soulier syndrome--report of a case--.

We herein report a case of gastrointestinal bleeding induced by angiodysplasia of the cecum in a case of Bernard-Soulier syndrome with recurrent breast cancer. In spite of endoscopic hemostatic therapy and interventional embolization, she had repeated massive bleeding from the cecal lesion. In addition, she had chronic hepatitis C and progressive liver tumors metastasized from breast cancer, and she finally died of hepatic failure. There are four case reports in the literature describing Bernard-Soulier syndrome with gastrointestinal bleeding angiodysplasia. The reported cases benefited from hormonal, endoscopical hemostasis and surgical therapy. In our case, because of her terminal metastatic breast cancer, only conservative treatments were administered after the third bleed. Both the endoscopic hemostatic method and interventional embolization showed only a temporary effect. Surgical treatment should be considered if the general condition can tolerate a surgical procedure.

Angiodysplasia↗

PubMed2004

Neoadjuvant chemotherapy for local advanced breast cancer with stage IIIB.

In this study, we have done a retrospective evaluation of the clinical benefits of neoadjuvant chemotherapy in 25 patients with stage IIIB, locally advanced breast cancer in terms of response rate and survival benefit. Most of these patients were treated with an anthracycline-based regimen such as CAF and EC, and some were also treated sequentially with docetaxel. An overall objective response was observed in 15 patients (60%), composed of 1 patient (4%) with a complete response (CR) and 14 (56%) with a partial response (PR). No progressive disease was observed. Following neoadjuvant chemotherapy, locoregional treatment (mastectomy without partial resection) was carried out in 24 patients, 1 of whom also received radiotherapy. The rate of local recurrence in neoadjuvant chemotherapy with anthracycline-based regimens was lower than those of adjuvant chemotherapy with anthracycline-based and non-anthracycline-based regimens (10.0% versus 33.3% and 28.5%, respectively). By contrast, the rate of distant metastasis with neoadjuvant chemotherapy was higher than that seen with anthracycline-based adjuvant chemotherapy regimens (35.0% versus 11.1%, respectively), while the rate of distant metastasis in non-anthracycline-based regimens was even higher at 66.6%. The 5-year survival in the responders treated with neoadjuvant chemotherapy was better than in the non-responders (90.9% versus 50.0%; NS, P=0.28, log-rank test). The survival at 5 years in the patients treated with neoadjuvant chemotherapy was inferior to that with adjuvant anthracycline-based chemotherapy regimens (69.7% versus 77.8%), although the survival in neoadjuvant chemotherapy was better than those of non-anthracycline-based adjuvant regimen (69.7% versus 66.7%). However, at 10 years the overall survival with anthracycline-based neoadjuvant chemotherapy regimens was superior to that seen with either anthracycline or non-anthracycline-based adjuvant chemotherapy regimens. These results suggest that primary (neoadjuvant) systemic therapy with anthracycline-based regimens for locally advanced, stage IIIB, breast cancer may have a potential survival benefit when given in combination with adjuvant chemotherapy, as it will provide the best means of decreasing both local recurrence and distant metastasis.

Adult↗

PubMed2002

Utility of technetium-99m methoxyisobutyl isonitrile uptake analysis for prediction of the response to chemotherapy in advanced and relapsed breast cancer.

BACKGROUND: Technetium-99m methoxyisobutyl isonitrile (Tc-SESTAMIBI) is a substrate of P-glycoprotein and multidrug-resistance associated protein in drug-resistant cells. To assess the clinical effectiveness of Tc-SESTAMIBI for predicting the chemotherapy response to treatment with anthracyclines and vinca alkaloids, we retrospectively evaluated the relationship between the accumulation of Tc-SESTAMIBI and the tumor response. METHODS: Thirteen patients, including 12 advanced cases and 1 relapsed case, were investigated, all of whom had been treated with anthracyclines or a vinca alkaloid regimen. The accumulation of Tc-SESTAMIBI was compared at 10 min and 2 h after Tc-SESTAMIBI administration. The relationship between the accumulation of Tc-SESTAMIBI and the tumor response following treatment with anthracyclines and vinca alkaloids was assessed. RESULTS: Eight of 13 patients responded to treatment with anthracyclines and vinca alkaloids, whereas 5 patients did not respond to treatment. At 10 min, 6 (75.0% ) of the 8 responding patients had a high accumulation of Tc-SESTAMIBI, whereas 4 (80.0% ) of the 5 non-responding patients had a low accumulation of Tc-SESTAMIBI. The overall predictive value was 76.9%. The relationship was not statistically significant (Fisher's test). The difference in the decrease of accumulation of Tc-SESTAMIBI between 10 min and 2 h was not associated with tumor response to treatment in 6 of the responding patients with high accumulation. Two false negative cases and one false positive case were observed, suggesting the presence of another factor contributing to drug sensitivity in tumor response, such as apoptosis-related genes. CONCLUSIONS: Assessment of the initial accumulation of Tc-SESTAMIBI can be a predictive marker of tumor response to treatment with anthracyclines and vinca alkaloids in patients with advanced and relapsed breast cancer. Further studies are required to explore other factors involved in the tumor response to treatment with anthracyclines and vinca alkaloids.

Adult↗

PubMedDate not supplied

The role of HER-2 oncoprotein in drug-sensitivity in breast cancer (review).

Overexpression of human epidermal growth factor receptor-2 (HER-2) oncoprotein is an important prognostic factor associated with a poor prognosis in breast cancer. Although treatment with trastuzumab, an anti-HER-2 antibody, increases drug-sensitivity in vitro and in vivo, the role of HER-2 oncoprotein in drug-sensitivity is still uncertain. The present work discusses the clinical significance of the HER-2 oncoprotein in drug-sensitivity in breast cancer based on previous clinical and basic results and reviews the current concept of HER-2 oncoprotein in drug-sensitivity. Introduction of HER-2 oncoprotein in vitro induces resistance to several anticancer drugs, including taxanes, cisplatin (CDDP) and 5-fluorouracil (5-FU) in breast cancer cells. The acquisition of drug-resistance by introduction of the HER-2 gene, however, depends on the cell type, because transfection of the HER-2 gene per se does not necessarily induce resistance to the same drugs in all types of breast cancer cells. In clinical studies, patients with HER-2 overexpression responded better to an anthracycline-based regimen than patients with low HER-2 expression, and their overall survival was also superior. In contrast, a correlation between the response to a cyclophosphamide + methotrexate + 5-FU regimen and overexpression of HER-2 is not certain. Taxanes responsiveness in patients with HER-2 oncoprotein overexpression was superior in patients with low HER-2 expression. Treatment with trastuzumab increased drug-sensitivity to anthracyclines, CDDP, and taxanes, but not to 5-FU, in breast cancer cells. Although the mechanism(s) by which trastuzumab enhances drug-sensitivity is not fully understood, modulation of the signal transduction pathways leading to apoptosis, such as down-regulation of the anti-apoptotic protein, Bcl-2, might be an important target to increase drug-sensitivity in breast cancer. HER-2 overexpression can be a good indicator for the selection of aniticancer drugs, especially for anthracycline containing regimens. To modulate HER-2-targeting therapy, the mechanism(s) by which trastuzumab enhances drug-sensitivity requires elucidation at the molecular level, including determination of other factors that influence drug-sensitivity, leading to a more promising treatment for individual patients receiving combination therapy with trastuzumab and anticancer drugs for breast cancer.

Antineoplastic Agents↗

PubMedDate not supplied

Feasibility and therapeutic efficacy of weekly 1-h low-dose paclitaxel infusion for relapsed breast cancer.

The therapeutic efficacy of weekly paclitaxel infusion for relapsed breast cancer patients is not known. We assessed safety, feasibility, and therapeutic efficacy in a pilot study of weekly 1-h low-dose paclitaxel infusion for relapsed breast cancer in an outpatient clinic. Eighteen patients with relapsed breast cancer who had received prior chemotherapy regimens, including anthracyclines, mitomycin, and 5-fluorouracil beyond a second line of treatment were enrolled into the study. The dose of paclitaxel was between 40 mg/m(2) and 80 mg/m(2) per week in a 1-h infusion, and a treatment cycle was 4 weeks until there was no evidence of progressive disease. When a dose of 80 mg/m(2) was administered, the treatment cycle was weekly infusion three times with a 1-week interval per 4-week cycle. The mean treatment period was 5.5 months and the maximal length of administration was 8 months. The overall response rate was 44.4%, including 2 cases of complete response and 6 cases of partial response. Tumor response was observed in 3 of 7 cases of lung metastases (42.8%), 6 of 12 cases of soft tissue metastases (50.0%), and 1 of 3 cases of liver metastases (33.3%), whereas 8 cases with bone metastases did not respond. The mean time to response was 1.8 months and the mean response duration was 4.3 months. The dose between 31.5 mg/m(2)/wk and 79.7 mg/m(2)/wk was not associated with tumor response. Toxicities associated with weekly 1-h low-dose paclitaxel infusion were tolerable, and most were less than grade 2, including alopecia (100%), neutropenia (88.8%), flushing (66.6%), face edema (61.1%), numbness (55.5%), and myalgia (38.8%). There was 1 case of grade 3 neutropenia. Weekly 1-h low-dose paclitaxel might be a therapeutically effective, safe infusion and feasible as a salvage chemotherapy for relapsed breast cancer patients following failure of prior chemotherapy.

Adult↗

PubMedDate not supplied

Expression and distribution of human telomerase catalytic component, hTERT, in human breast tissues.

BACKGROUND: Activation of telomerase is essential in a variety of malignant tumors. However, the regulation of its activation and the expression of human telomerase reverse transcriptase (hTERT) are not fully understood in breast tissues. MATERIALS AND METHODS: In order to clarify this point, the telomerase activity was examined by telomeric repeat amplification protocol (TRAP) assay and quantified by hybridization protection assay (HPA) and, moreover, the expressions of hTERT mRNA and protein were examined by RT-PCR and immunohistochemistry, respectively. RESULTS: Telomerase activity and the expression of hTERT mRNA were detected in 41(75%) and 37(67%) cases among 55 breast carcinomas, respectively. However, the telomerase ZV activity was detected in only 14(40%) among 35 benign breast tumors. Strong correlation was observed between telomerase activity and hTERT mRNA expression, as described previously. Moreover, the strong expression of hTERT protein in the nucleus of the cell was detected in 30 (57%) cases among 53 breast carcinomas and weak expression of the protein was also detected in 11 (35%) cases among 31 benign breast tumors by immunohistochemistry. There were 12 breast carcinomas which had no telomerase activity. Three of them had hTERT mRNA and protein and in 3 other cases, only hTERT protein was detected. Five cases had the expression of mRNA but not the protein and it was only one case which had no activity and expression of hTERT mRNA and protein. However, in benign tumors, 14 (87.5%) cases among 16 TRAP-negative tumors had no mRNA and protein expression. CONCLUSION: These results indicate that complicated regulation might be involved in the regulation of telomerase activity and also the activation of the gene may be important in the carcinogenesis of human breast carcinomas.

Breast Neoplasms↗

PubMedDate not supplied

Factors that influence the incidence of microscopic carcinoma in frozen and preserved specimens from patients with breast carcinoma after breast-conserving surgery.

Because a positive margin is an important risk factor for decreased survival of patients with breast cancer after breast-conserving surgery (BCS), we examined the rate of positive surgical margins after BCS, determined from intraoperative frozen and preserved sections, and we assessed factors that influence the incidence of positive margins in surgical specimens. The cases of 172 patients who underwent BCS between June 1989 and March 2001 were studied. The pathologic features and positive margins were evaluated by microscopic examination of frozen and preserved sections. The grade of each positive margin was arbitrarily classified into one of four groups: i) cancer involved; ii) closed margin (<2 mm); iii) partially closed margin (>3 mm and <5 mm) and iv) free margin (>5 mm). Biomarkers were estimated by immunohistochemistry and DNA ploidy, and the relationship of clinical parameters was statistically analyzed using the chi(2) test. In 59 of 172 cases (34.3%), the surgical margin was positive: horizontal in 47 cases (27.3%) and vertical in 12 cases (6.9%). The free margin was significantly correlated with positive status of estrogen and progesterone receptors and middle age (35-50 years) in the patients, while clinicopathologic factors were not correlated with positive margins in surgical specimens. Although 17 cases of cancer were found in 9 frozen specimens and 8 preserved sections, the mammographic findings showed spiculated masses in 7 of the 9 frozen specimens (77.7%) and 4 of the 8 preserved sections (50%), and microcalcification in 2 frozen specimens (22.2%) and 4 preserved sections (50%). The overexpression (2+ or 3+) of the HER-2 protein was found in 8 of the 9 frozen specimens (87.5%) and in 7 of the 8 preserved sections (88.8%). In the 11 cases with spiculated masses, extensive intraductal components (EICs) of various grades were found; the presence of EICs in a spiculated lesion was observed in 5 of the 7 frozen specimens and in all 4 of the preserved sections. The local extension of breast carcinoma cells in BCS is associated in part with the findings of spiculation and microcalcification, which are associated with EICs. The overexpression of HER-2 protein appears to play a role in EICs in positive margins, and needs to be considered for avoiding positive margins in BCS on patients with breast carcinoma.

Adult↗

PubMedDate not supplied

Experimental study on fluorescent microspheres as a tracer for sentinel node detection.

BACKGROUND: Common tracers for sentinel node navigation surgery are blue dye and technetium-99m-labelled colloids. However, in most esophageal or lung cancer patients, it is impossible to detect the sentinel node among mediastinal nodes by blue dye because of the anthracotic pigmentation of mediastinal nodes. The use of technetium-99m-labelled colloids requires a special facility, while a large hot-spot at the injection site prevents detection of the sentinel node around the primary lesion. To overcome these problems, we investigated the use of fluorescent microspheres (0.1-20 microm in diameter) as tracers in animals and detected fluorescence-positive nodes by a simple ultraviolet light irradiation method. MATERIALS AND METHODS: Two milliliters of fluorescent microspheres 0.1-20 microm in diameter diluted to 2.5% weight per volume was injected via the tail vein of 30 rats; systemic side-effects were examined. One milliliter of 1.0 microm-diameter microspheres dilution was injected on the backs of 30 rats; local side-effects were examined. A microsphere dilution (0.2 ml, 1.0 microm-diameter microspheres) was injected into the footpad of 18 rats; the lymphatic pathway and drainage were examined. Five milliliters of 1.0 microm-diameter fluorescent microspheres was injected endoscopically into the submucosa of the esophagus, stomach and small and large bowels of 6 domestic pigs, and 5 ml was injected into the subadventitia of the esophagus or subserosa of the stomach, and small and large bowels. Fluorescence-positive lymph ducts or nodes were carefully observed under ultraviolet light irradiation. RESULTS: No systemic side-effects were observed in rats. Only mild edema and a mild inflammatory reaction were observed on the backs of rats. Fluorescent microspheres 0.1, 0.5 and 1.0 microm in diameter were detected in lymph ducts or nodes of pigs within 1 hour after injection. CONCLUSION: Sentinel node navigation surgery with the use of fluorescent microspheres might be feasible and advantageous for patients with esophageal or lung cancer, especially in the mediastinum.

Animals↗