Biomedical subjects

Yasuhiro Tamaki

Publications and source records attributed to Yasuhiro Tamaki.

At least 37 records · Page 2Linked to original sources

PubMed2005

Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer.

The control of gene transfection in the body is a core issue in gene therapy. Photochemical internalization is a technology that allows light-induced delivery of DNA, drugs or other biological factors directly inside cells. Usually it requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. Here we present a system for in vivo DNA delivery in which these two components are assembled into one structure. This is a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer phthalocyanine, which provides the photosensitizing action. The ternary complex showed more than 100-fold photochemical enhancement of transgene expression in vitro with reduced photocytotoxicity. In an animal experiment, subconjuctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site. This work demonstrates a new biomedical application for dendrimers, and the first success in the photochemical-internalization-mediated gene delivery in vivo.

Animals↗

PubMed2005

Suppression of laser-induced choroidal neovascularization by oral administration of SA3443 in mice.

The effect of a synthetic cyclic disulfide compound, SA3443, on neovascularization was investigated. In vitro, enzyme-linked immunosorbent assay and RT-PCR demonstrated that SA3443 suppressed the expression of the hypoxia-induced vascular endothelial growth factor (VEGF) at both protein and mRNA levels in ARPE-19 cells. In vivo, the administration of SA3443 to mice with laser-induced choroidal neovascularization (CNV) suppressed the leakage from the lesions and reduced their size. Furthermore, the expression level of VEGF protein was significantly reduced by the administration of SA3443. Taken together, our results demonstrate that SA3443 suppresses VEGF production and reduces vascular leakage and the growth of mouse experimental CNV.

Administration, Oral↗

PubMed2005

Properties of growth and molecular profiles of rat progenitor cells from ciliary epithelium.

Recent studies have demonstrated that multipotent retinal stem or progenitor cells can be isolated from the ciliary epithelium (CE) of the eye using a neurosphere culture. In this study, we investigated the properties of growth and differentiation, and molecular profiles of rat adult ciliary epithelium (CE)-derived retinal progenitors and forebrain (FB) derived neurospheres. Under clonogenic culture conditions, we found that the CE-derived neurospheres contained fewer undifferentiated cells compared with the FB-derived neurospheres, and that CE-derived neurospheres initially expressed the set of Notch pathway molecules genes including Notch 1 and Delta 1, HES-1 and HES-5, but partially lose their expression after passaging. Furthermore, we found that the CE-derived neurospheres did not express several markers for in vivo embryonic retinal progenitors. Additionally, when the eye was divided into four subregions along its dorsoventral and nasotemporal axes and progenitor cells were obtained from the subregions, the progenitor cells did not express the subregion specific transcription factors, suggesting that subregional specificity is not maintained in vitro. Together, our results demonstrate that CE-derived progenitor cells may have intrinsic limitations in the production of cell types.

Animals↗

PubMed2005

Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers.

PURPOSE: LATS1 and LATS2 are tumor suppressor genes implicated in the regulation of cell cycle. Methylation status of the promoter regions of these genes as well as its correlation with their mRNA levels were studied in human breast cancers. Correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics of breast tumors were also studied. EXPERIMENTAL DESIGN: Methylation status of promoter regions of LATS1 and LATS2 was studied by a methylation-specific PCR and mRNA expression levels of LATS1 and LATS2 were determined by a real-time PCR assay in 30 breast cancers. In addition, correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics was studied in 117 breast cancers. RESULTS: Methylation-specific PCR showed that of 30 tumors, LATS1 promoter region was hypermethylated in 17 tumors (56.7%) and LATS2 promoter region was hypermethylated in 15 (50.0%) tumors. LATS1 mRNA levels in breast tumors with hypermethylation (2.15 +/- 0.37, mean +/- SE) were significantly (P < 0.01) lower than those without hypermethylation (6.09 +/- 1.38), and LATS2 mRNA levels in breast tumors with hypermethylation (1.42 +/- 0.66) were also significantly (P < 0.01) lower than those without hypermethylation (3.10 +/- 1.00). The decreased expression of LATS1 or LATS2 mRNA was significantly associated with a large tumor size, high lymph node metastasis, and estrogen receptor and progesterone receptor negativity. Furthermore, the decreased expression of LATS1 mRNA, but not LATS2 mRNA, was significantly (P < 0.05) associated with a poor prognosis. CONCLUSIONS: Hypermethylation of the promoter regions of LATS1 and LATS2 likely plays an important role in the down-regulation of their mRNA levels in breast cancers, and breast cancers with a decreased expression of LATS1 or LATS2 mRNA levels have a biologically aggressive phenotype.

Adult↗

PubMed2005

Usefulness of three-dimensional multidetector-row CT images for preoperative evaluation of tumor extension in primary breast cancer patients.

PURPOSE: Usefulness of three dimensional (3D) multidetector-row CT (MDCT) images for preoperative evaluation of tumor extension was studied in primary breast cancer patients. METHODS: 3D-MDCT tumor images of 143 tumors in 143 patients with primary breast cancer were created with the volume rendering method. The transverse tumor size (TS) and vertical tumor size (VS) were then measured in an anterior-posterior view of the 3D-MDCT images. The pathological tumor size was determined according to a map of the tumor spread prepared by pathologists using multi-sliced (3-5 mm intervals) surgical specimens and compared with the tumor size on 3D-MDCT images. RESULTS: First, the optimal method for creating 3D-MDCT tumor images was determined for the first 40 patients (learning set), resulting in a fairly good correlation of tumor size on 3D-MDCT images with pathological tumor size (r = 0.983 for TS and r = 0.958 for VS). We then carried out a validation study on the next 103 patients (validation set). The 3D-MDCT tumor size's strong correlation with the pathological tumor size demonstrated a high rate of accuracy (r = 0.974 for TS and r = 0.977 for VS). Subset analyses according to histological type showed that correlation coefficients were r = 0.979 for TS and r = 0.981 for VS of invasive ductal carcinomas (n = 88), r = 0.948 for TS and r = 0.970 for VS of ductal carcinomas in situ (n = 10), and r = 0.984 for TS and r = 0.976 for VS of invasive lobular carcinomas (n = 5). CONCLUSION: 3D-MDCT images can assess breast cancer tumor extension highly accurately, and thus seems to be useful for planning the extent of resection in breast conserving surgery.

Adult↗

PubMed2005

Clonogenic analysis of ciliary epithelial derived retinal progenitor cells in rabbits.

In lower vertebrates, multipotential retinal stem cells reside in a far peripheral retinal zone known as the ciliary marginal zone while more fate-restricted progenitor cells are located immediately adjacent to this retinal margin. To determine whether mammalian ciliary epithelium contains heterogenous stem cell and progenitor cell populations similar to lower vertebrates, we investigated the heterogeneity of the retinal progenitor (or stem) cells isolated from adult rabbit eyes, which are large and suited for precise identification of the region. Under clonogenic culture conditions for a neurosphere assay, spheres were generated from approximately 0.1% of the ciliary epithelial cells and expressed retinal selective markers when plated under conditions producing differentiation. Subsequently, we found that 13.7% of the primary spheres gave rise to a secondary sphere and that 77% of the primary sphere colonies were unipotential progenitors that generated either neurons or glial cells exclusively, while 23% were at least bipotential that could give rise to both cell types using double-labelled immunocytochemistry. Taken together, our results demonstrate that the ciliary epithelium of adult rabbits contains both (at least) bipotential retinal progenitor (or stem) cells and unipotential fate-restricted progenitor cells, similar to lower vertebrates.

Animals↗

PubMed2005

Nanotechnology-based photodynamic therapy for neovascular disease using a supramolecular nanocarrier loaded with a dendritic photosensitizer.

Photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD) was evaluated using a supramolecular nanomedical device, that is, a novel dendritic photosensitizer (DP) encapsulated by a polymeric micelle formulation. The characteristic dendritic structure of the DP prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. With its highly selective accumulation on choroidal neovascularization (CNV) lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity.

Animals↗

PubMed2005

Possible involvement of aromatase overexpression induced by cyclo-oxygenase-2 in the pathogenesis of idiopathic gynecomastia.

The pathogenesis of idiopathic gynecomastia, which shows no imbalance in serum estrogens and androgens levels unlike gynecomastia of other causes, is unknown. It seems to be of interest to study the in situ aromatase expression in idiopathic gynecomastia to investigate a possible involvement of intratumoral biosynthesis of estrogens in the pathogenesis of this disease. The expression level of aromatase mRNA was studied by a real-time polymerase chain reaction (PCR) assay in four idiopathic gynecomastia cases (two florid type and two fibrous type). In addition, the proportion of promoter usage (promoters I.3 I.4, l. 7, and PII) of the aromatase gene was determined by PCR-gel electrophoresis. Localization of aromatase and cyclo-oxygenase-2 (COX-2) expression was studied by immunohistochemistry. The aromatase mRNA level of the florid type gynecomastia (3.05 and 1.66) was higher than that in the fibrous type (0.76 and 0.04). The proportion of promoter Pll in the florid type (94.1% and 84.8%) was very high as compared with that of the fibrous type (0.7% and 0.5%). Immunohistochemical studies have revealed that aromatase and COX-2 were strongly expressed in the duct epithelial cells in the florid type, but they were weak or negative in the fibrous type. COX-2 is suggested to upregulate aromatase expression by enhancing the transcription via promoter Pll in idiopathic gynecomastia of the florid type but not of the fibrous type. Because idiopathic gynecomastia initially develops as the florid type and regresses as the fibrous type, a high estrogen milieu induced by increased aromatase expression is speculated to play some role in the pathogenesis of idiopathic gynecomastia.

Adolescent↗

PubMed2005

Time course of changes in optic nerve head circulation after acute reduction in intraocular pressure.

PURPOSE: To study the time course of changes in circulation in the optic nerve head (ONH) after acute reduction in intraocular pressure (IOP) and to evaluate the effects of a calcium antagonist, a nitric oxide synthetase (NOS) inhibitor, indomethacin, and sympathetic nerve amputation on the changes in ONH circulation after reduction of IOP. METHODS: In anesthetized albino rabbits, acute reduction of IOP (acute increase in ocular perfusion pressure [OPP]) was manometrically achieved and normalized blur (NB), a quantitative index of tissue blood velocity obtained with the laser speckle method, was serially monitored for 30 seconds and 60 minutes. The effects of systemic administration of 1 microg/kg per hour nilvadipine (a calcium antagonist), 300 microg/kg Nomega-nitro-l-arginine (l-NAME, a nonselective NOS inhibitor), and 5 mg/kg indomethacin or sympathetic nerve amputation on the changes in NB after reduction of IOP were studied. RESULTS: During changes in IOP from 10 to 40 mm Hg and then back to 10 mm Hg, NB exhibited no significant change. During changes in IOP from 10 to 60 mm Hg and then back to 10 mm Hg, NB initially decreased with an increase in IOP to 60 mm Hg and then increased to baseline level when IOP was returned to 10 mm Hg. In the nilvadipine-treated rabbits, during changes in IOP from 10 to 40 mm Hg and back to 10 mm Hg and during the changes from 10 to 60 mm Hg and back to 10 mm Hg, NB decreased with increase in IOP to 40 or 60 mm Hg and then increased to slightly above the baseline when IOP returned to 10 mm Hg. l-NAME, indomethacin, and sympathetic nerve amputation each had little effect on the time course of change in NB. CONCLUSIONS: ONH circulation was stably maintained after reduction of IOP from 40 to 10 mm Hg but not after that from 60 to 10 mm Hg. The changes in NB after reduction of IOP occurred quickly and were partially impaired with a calcium antagonist, but not with the NOS inhibitor, indomethacin, or sympathetic nerve amputation. These findings suggest the importance of vascular smooth muscle in maintaining stable ONH circulation against reduction of IOP in a fashion nearly independent of NO, endogenous prostaglandins, and the sympathetic nervous system.

Acute Disease↗

PubMed2005

Prediction of response to docetaxel by immunohistochemical analysis of CYP3A4 expression in human breast cancers.

BACKGROUND: Docetaxel (DOC) is inactivated by CYP3A4, high expression of which in tumor tissue might serve as a resistance mechanism. In the present study, the CYP3A4 protein level in breast cancers was determined by immunohistochemistry, and its relationship with the response to DOC treatment was studied. MATERIALS AND METHODS: Thirty-one patients with locally advanced (n = 21) or recurrent (n = 10) breast cancers underwent tumor biopsy, followed by DOC treatment (60 mg/m2 q3w). Expression of CYP3A4 was studied by immunohistochemistry. RESULTS: Patients with CYP3A4 negative tumors (n = 15) by immunohistochemistry showed a significantly (P < 0.01) higher response rate (67%) to DOC treatment than those with CYP3A4 positive tumors (n = 16, 19%). The positive predictive value, negative predictive value, and diagnostic accuracy of CYP3A4 expression by immunohistochemistry in the prediction of response to DOC were 67%, 81%, and 74%, respectively. CONCLUSION: Immunohistochemical analysis of CYP3A4 expression in tumor cells might be clinically useful in the prediction of tumor response to DOC.

Adult↗

PubMed2005

Three-dimensional ultrasound imaging of breast cancer by a real-time intraoperative navigation system.

BACKGROUND: In order to achieve a good cosmetic result without increasing the risk of ipsilateral breast cancer recurrence after breast conserving surgery, it is very important to minimize the resection volume of the breast without compromising the negativity of the surgical margin. For this purpose, it is necessary to obtain precise information on tumor extension. We therefore developed a three-dimensional (3-D) ultrasound navigation system for breast cancer surgery, which can be performed in the operating room just before surgery. METHODS: We obtained 3-D breast tumor images by the 3-D ultrasound navigation system in 40 patients with primary breast cancer (stage 0-II) who underwent mastectomy or breast conserving surgery. The tumor size was measured in a coronal view of the 3-D tumor image and compared with the tumor size obtained from a pathological map of the tumor extension. RESULTS: We obtained 3-D tumor images in 38 patients (success rate=95%). The tumor size in the images showed a very strong correlation with the pathological tumor size (r=0.898). The difference in tumor size between the 3-D images and pathology was less than 1 cm in 29 tumors (76.3%) and less than 2 cm in 36 (94.7%). On the other hand, the difference in tumor size between palpation and pathology was less than 1 cm in 19 out of 38 tumors (50.0%) and less than 2 cm in 29 tumors (76.3%). The absolute difference between the 3-D images and pathology was significantly less than that between palpation and pathology (p=0.0197). CONCLUSIONS: Our 3-D ultrasound navigation system is useful in visualizing breast tumor extension and is more accurate than palpation. The system is expected to be helpful in deciding on the appropriate surgical margin in breast cancer surgery, resulting in a better cosmetic outcome without increasing the risk of surgical margin positivity.

Adult↗

PubMed2005

[The feasibility of FEC (75) as adjuvant chemotherapy for Japanese breast cancer patients].

Recently, high-dose FEC (fluorouracil, epirubicin, and cyclophosphamide) has been increasingly used in adjuvant chemotherapy for breast cancer in Japan. However, the safety and tolerability of high-dose FEC are not well evaluated in Japanese breast cancer patients. We studied the feasibility of FEC (75) (fluorouracil: 500 mg/m(2), epirubicin: 75 mg/m(2), and cyclophosphamide:500 mg/m(2), q 3 w, 6 cycles) as adjuvant chemotherapy for 59 primary breast cancer patients. Out of these patients, 56 (94.9%) finished 6 cycles-FEC. The mean epirubicin dose received was 431.7 mg/m(2) (95.9% of the intended dose of 450 mg/m(2)). Forty-five (76.2%) of 59 patients experienced neutropenia of grade 3 or 4, while the rates of febrile neutropenia (grade 3) and infection (grade 2) were 3.4% and 10.2%, respectively. Anemia (88.2%), fatigue (42.4%), nausea (40.6%), liver dysfunction (40.7%), and vomiting (18.7%) occurred, however most of them were mild and categorized into grade 1 or 2. No patients developed any cardiac failure symptoms. This study shows FEC (75) is well tolerable as adjuvant chemotherapy for Japanese breast cancer patients.

Adult↗

PubMed2004

Down-regulation of intratumoral aromatase messenger RNA levels by docetaxel in human breast cancers.

PURPOSE: The reason why chemotherapy induces resistance to subsequent hormonal therapy remains to be clarified in postmenopausal breast cancers. We hypothesized that chemotherapy might down-regulate the intratumoral biosynthesis of estrogens. Thus, we have studied the influence of chemotherapy (docetaxel) on intratumoral aromatase mRNA expression because aromatase is a key enzyme for intratumoral biosynthesis of estrogens. EXPERIMENTAL DESIGN: The mRNA levels of aromatase and its inducers [tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and cyclooxygenase 2 (COX-2)] were determined by a real-time polymerase chain reaction assay in breast cancer tissues obtained before and after neoadjuvant chemotherapy with docetaxel (four cycles of 60 mg/m2 every 3 weeks) in 16 postmenopausal patients with estrogen receptor (ER)- and/or progesterone receptor (PR)-positive breast cancers. ER and PR levels in tumor tissues were also determined by enzyme immunoassay before and after chemotherapy. RESULTS: The intratumoral aromatase mRNA levels decreased significantly (P < 0.05) after chemotherapy from 0.84 +/- 0.28 (mean +/- SE) to 0.47 +/- 0.28. The intratumoral TNF-alpha mRNA levels also decreased significantly (P < 0.05) after chemotherapy from 2.40 +/- 0.52 to 0.95 +/- 0.25. On the contrary, the intratumoral IL-6 and COX-2 mRNA levels showed a marginally significant increase (P = 0.07) and a significant increase (P < 0.05), respectively, after chemotherapy. PR levels showed a marginally significant decrease (P = 0.08) after chemotherapy, whereas ER levels were almost constant before and after chemotherapy. CONCLUSIONS: Antitumor activity of docetaxel is mediated, at least in part, through a down-regulation of aromatase expression in tumor tissues, resulting in the suppression of intratumoral estradiol synthesis. Aromatase expression seems to be regulated mostly by TNF-alpha, but not IL-6 and COX-2.

Aged↗

PubMed2004

COX-2-selective inhibitor, etodolac, suppresses choroidal neovascularization in a mice model.

Cyclooxygenases (COXs) are involved in choroidal neovascularization (CNV). However, the relative contribution of COX-1 and -2 to CNV has not been determined. In this study, the expression of COX-2 was investigated in CNVs in a murine laser-induced model. Subsequently, we found that experimental CNV expressed COX-2, most remarkably around the highly vascularized lesions. To examine the effect of COX-2 inhibition on CNV, etodolac, a non-steroidal anti-inflammatory drug with a high COX-2 selectivity, was tested on murine CNV model. The results demonstrated that the intensity of fluorescein leakage from the photocoagulated lesions decreased significantly compared to the control eyes following etodolac administration. The area of CNV lesions, as examined using histological sections and choroidal flatmounts at day 7, demonstrated that the average size of the CNV lesions was significantly reduced in the etodolac-treated eyes compared to the control eyes. Together, our results demonstrated that selective COX-2 inhibition suppresses CNV.

Angiography↗

PubMed2004

Prognostic significance of intra-tumoral estradiol level in breast cancer patients.

Although the intra-tumoral estradiol (E2) level is thought to be more closely related to the E2-inducible events such as progesterone receptor (PR) induction and tumor growth than the serum E2 level, prognostic significance of the intra-tumoral E2 level in breast cancer patients has yet to be studied. E2 level in tumor tissues obtained from 90 primary breast cancer patients were measured by the high-pressure liquid chromatography-radioimmunoassay method. Relationship between the intra-tumoral E2 level and the various clinicopathological factors including the prognosis was investigated. E2-high tumors (n=45) were significantly more likely to be estrogen receptor (ER)-positive tumors and PR-positive tumors than E2-low tumors (n=45). A significant correlation was observed between the intra-tumoral E2 level and PR level by a simple curve fit test (r=0.39, P<0.01) in the ER-positive tumors. Univariate analysis showed that lymph node status, intra-tumoral E2 level, ER, and PR were significant prognostic factors, and multivariate analysis showed that only lymph node status and PR status were significant independent prognostic factors. PR is induced by E2 through ER in human breast cancers. PR, which warrants both the presence of functional ER and the enough level of intra-tumoral E2, can serve as a better prognostic factor than intra-tumoral E2 level or ER in primary breast cancer patients probably because PR is a better marker of estrogen-dependency of tumor growth than intra-tumoral E2 level or ER.

Adult↗

PubMed2004

Contribution of bone-marrow-derived cells to choroidal neovascularization.

We investigated the involvement of bone-marrow derived cells to experimental choroidal neovascularization (CNV) in mice, whose bone marrow was reconstituted by either unfractionated bone-marrow cells or Lin-c(-)Kit(+)Sca-1+ enriched presumable hematopoietic stem cells from the green fluorescent protein (GFP) transgeneic mice. Immunohistochemical analysis demonstrated the presence of GFP-positive cells in the CNV lesion after unfractionated bone-marrow transplantation, as well as Lin-c(-)Kit(+)Sca-1+ cell transplantation. Some of the GFP-expressing cells also expressed CD-31 and PanEC antigen, markers of vascular endothelial cells. Our results suggest that bone-marrow derived cells may contribute endothelial cells in CNV.

Animals↗

PubMed2004

Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women.

Since it is well established that inactivation of p53 is involved in pathogenesis of breast cancer, it seems to be reasonable to assume that p53 genetic polymorphism at codon 72 (p53Arg72Pro) which affects the function of p53 might have an influence on breast cancer risk. Thus, in the present study, we have studied the association of p53Arg72Pro polymorphism with breast cancer risk. A case-control study was conducted with 191 breast cancer patients and 218 healthy female controls. p53Arg72Pro polymorphism was examined in their association with breast cancer risk after adjustment for the epidemiological risk factors. Relationship between p53Arg72Pro polymorphism and clinicopathological characteristics of breast cancers was also studied. In addition, frequency of somatic p53 mutation was compared according to the genotype of p53Arg72Pro polymorphism. p5372Pro/Pro homozygotes showed a significant increase in the risk of estrogen receptor (ER) positive breast cancer (adjusted odds ratio (OR) = 2.04, P = 0.04) as compared with p5372Arg/Arg homozygotes, whereas such an association was not found between p5372Pro/Pro homozygotes and ER negative breast cancer risk. Subset analysis according to menopausal status showed that p5372Pro/Pro homozygotes were significantly associated with ER positive breast cancer risk in postmenopausal women (adjusted OR = 3.42, P = 0.01) but not in premenopausal women. Frequency of ER positive tumors was significantly (p < 0.01) higher in breast cancer patients with p5372Pro/Pro genotype (82.8%) than those with p5372Arg/Arg genotype (54.5%). Mutational analysis of p53 in tumors showed that p5372Pro/Pro homozygotes had a lower frequency of p53 mutation (3.5%) than p5372Arg/Arg homozygotes (10.5%). It is suggested that p53Arg72Pro polymorphism is associated with ER positive breast cancer risk, especially, in postmenopausal women. The higher frequency of p53 somatic mutation in p5372Arg/Arg homozygotes than p5372Pro/Pro homozygotes is consistent with the thesis that the function of p5372Pro/Pro is impaired so that a further alteration of p53 gene is less required in p5372Pro/Pro homozygotes than p5372Arg/Arg homozygotes.

Adult↗

PubMed2004

Sentinel lymph node biopsy using periareolar injection of radiocolloid for patients with neoadjuvant chemotherapy-treated breast carcinoma.

BACKGROUND: The feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) for patients with breast carcinoma have been investigated primarily for the situation in which the radiocolloid imaging agent is injected peritumorally. No such study has involved periareolar injection of radiocolloid, although the usefulness of this injection technique has been demonstrated in patients with early-stage breast carcinoma who have not been treated with NAC. The objective of the current study was to determine the feasibility and accuracy of SLN biopsy using periareolar injection of radiocolloid for patients with breast carcinoma who were treated with NAC. METHODS: Forty-seven patients with AJCC Stage II or III breast carcinoma who were treated with NAC were enrolled in the study. All patients underwent SLN biopsy, which involved a combination of periareolar injection of radiocolloid (technetium 99m tin colloid) and peritumoral injection of isosulfan blue dye, followed by backup axillary lymph node dissection. SLN metastases were examined by hematoxylin and eosin staining and immunohistochemical analysis using an anticytokeratin antibody. RESULTS: An SLN was identified successfully in 44 patients (94%). Twenty-nine patients (66%) had positive SLNs. Fifteen patients had negative SLNs, and 4 patients had positive non-SLNs. Thus, the false-negative rate was 12.1% (4 of 33 patients). The false-negative rate tended to be higher, although not statistically significantly so, among patients who had clinically positive axillary lymph nodes before and/or after NAC (15.8%; 3 of 19 patients) compared with patients who had clinically negative axillary lymph nodes both before and after NAC (7.1%; 1 of 14 patients). CONCLUSIONS: SLN biopsy using periareolar injection of radiocolloid is feasible after NAC. In patients with clinically negative axillary lymph nodes both before and after NAC, SLN biopsy was capable of predicting axillary lymph node status with an accuracy comparable to the accuracy associated with SLN biopsy for patients with early-stage carcinoma who have not been treated with NAC.

Adult↗