Risk factors of local recurrence following implant-based breast reconstruction in breast cancer patients.

BACKGROUND: The number of patients desiring implant-based breast reconstruction has been increasing. While local recurrence is observed in patients with breast reconstruction, only a few reports have focused on the risk factors for local recurrence and the prognosis after developing local recurrence. METHODS: We analyzed 387 patients who underwent implant-based breast reconstruction during the period from 2004 to 2017 in Hiroshima City Hospital. We retrospectively examined the risk factors for local recurrence and the outcomes of patients developing such recurrence after implant-based breast reconstruction. RESULTS: The median follow-up time was 59 months. The local recurrence rate was 3.1% (n = 12). The most common reason for detecting local recurrence was a palpable mass. Four patients with local recurrence had recurrence involving the skin just above the primary lesion and needle biopsy tract. All patients with local recurrence received surgery and systemic therapy and most patients received radiation therapy, all have remained free of new recurrence to date. Multivariate analysis showed lymphatic vessel invasion (HR, 6.63; 95% CI, 1.40-31.36; p = 0.017) and positive or < 2 mm vertical margin (HR, 9.72; 95%CI, 1.23-77.13; p = 0.047) to be associated with significantly increased risk of local recurrence. CONCLUSIONS: The risk factors for local recurrence following implant-based breast reconstruction were lymphatic vessel invasion and positive or < 2 mm vertical margin. Removal of the skin just above the primary lesion and needle biopsy tract and adjuvant radiation therapy might improve local outcomes. Patients with local recurrence following implant-based breast reconstruction appear to have good outcomes with appropriate treatment.

Immune factors associated with the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer.

Immune activation plays an important role in achieving the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer. We evaluated how the immune response contributes to various therapeutic effects. This study was conducted on 43 patients with stages II-IV breast cancer who received preoperative chemotherapy followed by surgery. Peripheral natural killer (pNK) cell activity and the neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratio (PLR) were assessed before and after chemotherapy. Tumor-infiltrating lymphocytes (TILs) and levels of 14 tumor microenvironmental factors, analyzed by next-generation sequencing, were assessed in formalin-fixed, paraffin-embedded sections of preoperative biopsy samples and surgical specimens. Univariate analysis showed that grade 2 (G2) and better therapeutic effects were significantly associated with human epidermal growth factor receptor 2 (HER-2)-positive cancer, lower PLRs, and higher NK cell and interleukin-6 levels after chemotherapy. The disappearance of axillary lymph-node metastasis was significantly associated with HER-2-positive cancer; increased pNK cell activity and lower PLRs and vascular endothelial growth factor (VEGF) levels after chemotherapy; and increased cytotoxic T lymphocyte antigen 4 (CTLA-4) levels in regulatory T cells (Tregs) and ≥5% TILs before chemotherapy. Multivariate analysis showed that G2 and better therapeutic effects tended to be associated with higher NK cell levels after chemotherapy (odds ratio = 1.02; 95% confidence interval, 0.99-1.05; P = 0.07). The activation of local and systemic immune responses by downregulation of immunosuppressive factors, such as VEGF and CTLA-4 in Tregs, had variable pathological and therapeutic effects after preoperative chemotherapy in patients with breast cancer.

Relationships of physical and breast cancer phenotypes with three single-nucleotide polymorphisms (rs2046210, rs3757318, and rs3803662) associated with breast cancer risk in Japanese women.

BACKGROUND: Recent genome-wide association studies have shown that many single-nucleotide polymorphisms (SNPs) are associated with breast cancer risk. However, it is often unclear how these SNPs are related to breast cancer. Analysis of associations between SNPs and phenotypes may be important for determining mechanisms of action, including carcinogenesis. METHODS: In previous case-control studies, we found three SNPs (rs2046210, rs3757318, and rs3573318) associated with breast cancer risk in Japanese women. Among these SNPs, two (rs2046210 and rs3757318) are located at 6q25.1, in proximity to the estrogen receptor 1 gene (ESR1). Using data from these studies, we examined associations between factors related to breast cancer risk, such as height, weight, and breast density, and the three SNPs in cases and controls. We also investigated whether the SNPs correlated with breast cancer features, such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type-2 (HER2) status, and clinical stage. RESULTS: There was a significant difference in mean height between risk and non-risk allele carriers for rs2046210 (156.0 ± 5.8 vs. 154.3 ± 5.5 cm, p = 0.002), and rs3757318 (155.8 ± 5.7 vs. 154.7 ± 5.6 cm, p = 0.035) in cases, but no significant associations between height and these SNPs in controls. There was also a significant difference in breast density between risk and non-risk allele carriers for rs2046210 (p = 0.040) and rs3757318 (p = 0.044) in cases. rs2046210 and rs3757318 risk allele carriers tended to have higher breast density in all subjects and in controls. In cases, rs3757318 risk allele carriers were also significantly more likely to be ER-negative compared to non-risk allele carriers (ER-positive rate: 77% vs. 84%, p = 0.036). CONCLUSIONS: SNPs rs2046210 and rs3757318, which are associated with breast cancer risk in Japanese women, were significantly associated with height and high breast density, and this association was particularly strong in those with breast cancer. These findings suggest that SNPs in the ESR1 gene region affect phenotypes such as height and breast density.

Nab-Paclitaxel Followed by 5-Fluorouracil, Epirubicin and Cyclophosphamide in Neoadjuvant Chemotherapy for Resectable Breast Cancer: A Phase II Trial.

BACKGROUND: The aim of this phase II study was to evaluate combined nab-paclitaxel (nab-PTX) with sequential anthracycline-based therapy as a neoadjuvant chemotherapy. METHODS: We enrolled 41 patients with advanced breast cancer (stage IIA - IIIC). All patients were to receive three-weekly nab-PTX (260 mg/m2) for four cycles followed by three-weekly 5-fluorouracil, epirubicin and cyclophosphamide (FEC) for four cycles. Trastuzumab administration was permitted in human epidermal growth factor receptor 2 (HER2)-positive patients. RESULTS: The overall pathological complete response (pCR) rate was 24% (10 of 41). In patients with luminal A, luminal B (HER2-), luminal B (HER2+), triple-negative and HER2, the pCR rates were 0% (0/2), 7% (1/14), 42% (3/7), 25% (4/16) and 100% (2/2), respectively. The most significant toxicities of nab-PTX were grade 2/3 peripheral sensory neuropathy (24%) and grade 3/4 neutropenia (26%). Febrile neutropenia was not observed in any patient. The most significant toxicities of FEC were grade 3/4 neutropenia (24%) and grade 3 febrile neutropenia (9%). One patient died of sepsis secondary to pneumonia during FEC treatment. CONCLUSIONS: Neoadjuvant chemotherapy using nab-PTX with trastuzumab every 3 weeks followed by FEC was suitably tolerated and associated with a high pCR rate of 55% for patients with HER2-positive breast cancer.

Influence of breast density on breast cancer risk: a case control study in Japanese women.

BACKGROUND: Mammography is the standard examination for breast cancer screening of woman aged ≥ 40 years. High breast density on mammography indicates that mammary gland parenchyma occupy a high percentage of the breast. The objective of this study was to investigate factors associated with breast density and the risk of high breast density for breast cancer. METHODS: A multicenter case-control study was performed in 530 patients and 1043 controls. Breast density was classified as C1-C4 using the Breast Imaging Reporting and Data System (BI-RADS). Clinical factors were obtained from questionnaires or medical records, and the influence of each factor (breast density, menopausal status, body mass index (BMI), parity, presence or absence of breastfeeding history, age at menarche, age at first birth, and familial history of breast cancer) on breast cancer risk in all patients was calculated as an age-adjusted odds ratio (OR). Multivariate logistic regression analyses were then performed in all patients and in pre- and postmenopausal and BMI-stratified groups using factors with a significant age-adjusted OR as adjustment factors. RESULTS: Age-adjusted ORs for breast cancer were significant for breast density, BMI, parity, and breast feeding, but not for age at menarche, age at first birth, or family history of breast cancer. In multivariate analysis, there was a significant correlation between breast density and breast cancer in postmenopausal women (OR for C1 vs. C2 1.90 [95% CI 1.34-2.70]; C1 vs. C4 2.85 [95% CI 1.10-7.16]). This correlation was also significant in patients in the third BMI quartile (22.3-24.5 kg/m2) (OR for C1 vs. C4 8.76 [95% CI 2.38-42.47]); and fourth BMI quartile (>24.5 kg/m2) (OR for C1 vs. C2 1.92 [95% CI 1.17-3.15]; C1 vs. C4 11.89 [95% CI 1.56-245.17]). CONCLUSION: Breast density on mammography is a risk factor for breast cancer after adjustment for other risk factors. This risk is particularly high in postmenopausal women and those with a high BMI.

Utility of the Absolute Lymphocyte Count and Neutrophil/Lymphocyte Ratio for Predicting Survival in Patients with Metastatic Breast Cancer on Eribulin: A Real-World Observational Study.

INTRODUCTION: Previous studies have suggested that the efficacy of eribulin is influenced by the activity of antitumor immunity of patients. Absolute lymphocyte count (ALC) and the neutrophil/lymphocyte ratio (NLR) are easily available parameters associated with the immunological status of patients. OBJECTIVE: Here we tried to classify patients' immunological status by using the scatter plot of ALC and NLR, and investigated its utility for predicting survival among patients with metastatic breast cancer receiving eribulin. METHODS: The medical records of 125 patients who received eribulin for metastatic breast cancer at our hospital between July 2011 and April 2019 were retrospectively reviewed. Uni- and multivariate analyses were performed to determine the association between baseline ALC/NLR and progression-free survival (PFS)/overall survival (OS). The cutoff values for ALC and NLR were determined using scatter plot analysis. RESULTS: The entire cohort was classified into immunologically favorable (ALC ≥1,500/µL, 30 patients), intermediate (ALC <1,500/µL, NLR <5.0, 76 patients), and unfavorable (NLR ≥5.0, 19 patients) groups. Univariate analysis showed significant differences in PFS and OS between the groups, whereas multivariate analysis revealed that ALC ≥1,500/µL and NLR ≥5.0 were independent predictors of PFS, with adjusted hazard ratios (95% CI) of 0.57 (0.33-0.99) and 1.78 (1.00-3.15), respectively. NLR ≥5.0 was also associated with worse OS (adjusted hazard ratio: 0.55; 95% CI 0.35-0.88; p = 0.013). CONCLUSIONS: Among patients with metastatic breast cancer receiving eribulin, survival outcomes were well stratified according to baseline peripheral blood ALC and NLR. Accordingly, high ALC and NLR can be used as predictive markers for longer disease control and worse survival, respectively.

N-acetyltransferase 2 polymorphism and breast cancer risk with smoking: a case control study in Japanese women.

BACKGROUND: Recent studies have suggested that the association between smoking and breast cancer risk might be modified by polymorphisms in the N-acetyltransferase 2 gene (NAT2). Most of these studies were conducted in Western countries, with few reports from East Asia. METHODS: We conducted a case-control study of 511 breast cancer cases and 527 unmatched healthy controls from December 2010 to November 2011 in Japan. Unconditional logistic regression was used to analyze the association of smoking with breast cancer risk stratified by NAT2 phenotype. RESULTS: In this population, 11 % of the cases and 10 % of the controls were classified as a slow acetylator phenotype. Compared to never smokers, current smokers had an increased breast cancer risk in multivariate analysis [odds ratio (OR) = 2.27, 95 % confidence interval (95 %CI) = 1.38-3.82]. Subgroup analyses of menopausal status indicated the same tendency. Subgroup analyses of NAT2 phenotype, the ORs in both of rapid and slow acetylator phenotype subgroups were comparable, and no interactions were observed between smoking status and NAT2 phenotype (p = 0.97). A dose-dependent effect of smoking on breast cancer risk was seen for the rapid acetylator phenotype, but not for the slow acetylator phenotype. CONCLUSION: Given the high frequency of the rapid acetylator phenotype, these results show that smoking is a risk factor for breast cancer among most Japanese women. It may be of little significance to identify the NAT2 phenotype in the Japanese population.

Impact of modifiable lifestyle factors on outcomes after breast cancer diagnosis: the Setouchi Breast Cancer Cohort Study.

The primary purpose of this large cohort study is to investigate the effects on breast cancer outcomes of modifiable lifestyle factors after breast cancer diagnosis. These factors include physical activity, smoking, alcohol consumption, obesity and weight gain after diagnosis, alternative medicine and dietary factors. Women diagnosed with Stage 0 to III breast cancer are eligible for participation to this study. Lifestyle, use of alternative medicine, psychosocial factors, reproductive factors and health-related quality of life will be assessed using a questionnaire at the time of breast cancer diagnosis (baseline), and 1, 2, 3 and 5 years after diagnosis. Clinical information and breast cancer outcomes will be obtained from a breast cancer database. The primary endpoint will be disease-free survival. Secondary endpoints are overall survival, health-related quality of life, breast cancer-related symptoms and adverse events. Patient recruitment commenced in February 2013. Enrollment of 2000 breast cancer patients is planned during the 5-year recruitment period. The concept of the study is described in this article.

Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case-control study in Japanese women.

BACKGROUND: Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk. METHODS: A case-control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses. RESULTS: High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR=1.37 [95% CI: 1.11-1.70]), rs3757318 (OR=1.33[1.05-1.69]), and rs3803662 (OR=1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers. CONCLUSION: In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers.

Association between mammographic breast density and lifestyle in Japanese women.

A high mammographic breast density is considered to be a risk factor for breast cancer. However, only a small number of studies on the association between breast density and lifestyle have been performed. A cross-sectional study was performed using a survey with 29 questions on life history and lifestyle. The breast density on mammography was classified into 4 categories following the BI-RADS criteria. The subjects were 522 women with no medical history of breast cancer. The mean age was 53.3 years old. On multivariate analysis, only BMI was a significant factor determining breast density in premenopausal women (parameter estimate, -0.403; p value, 0.0005), and the density decreased as BMI rose. In postmenopausal women, BMI (parameter estimate, -0.196; p value, 0.0143) and number of deliveries (parameter estimate, -0.388; p value, 0.0186) were significant factors determining breast density;breast density decreased as BMI and number of deliveries increased. Only BMI and number of deliveries were identified as factors significantly influencing breast density. BMI was inversely correlated with breast density before and after menopause, whereas the influence of number of deliveries on breast density was significant only in postmenopausal women in their 50 and 60s.

The anti-proliferative effect of heat shock protein 90 inhibitor, 17-DMAG, on non-small-cell lung cancers being resistant to EGFR tyrosine kinase inhibitor.

Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, is frequently observed after initiation of TKIs therapy. Non-small-cell lung cancers (NSCLC) with activating EGFR mutations were reported to be sensitive to heat shock protein 90 (Hsp90) inhibitors regardless of the secondary TKI-resistant T790M mutation. We established EGFR-TKI resistant clones for PC-9 cell lines, harboring EGFR exon 19 deletions, with or without the secondary T790M mutation. We examined the anti-proliferative effect of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an orally active Hsp90 inhibitor, on the growth of NSCLC cell lines in vitro and in vivo. In MTS assay, the IC(50) values of 17-DMAG for 13 EGFR-mutant cell lines including eight EGFR-TKI resistant cell lines ranged from 0.04 to 0.16 µM while those for seven EGFR-wild type cell lines ranged from 1.6 to 27.4 µM. Western blot analysis revealed that phospho-EGFR, phospho-Akt, phospho-MAPK, cdk4, and cyclin D1 were more readily depleted by 17-DMAG treatment in EGFR-mutant cell lines than in EGFR-wild type cell lines. Cleaved PARP expression confirmed apoptosis in response to 17-DMAG treatment in EGFR-mutant cell lines but not in EGFR-wild type cell lines. In mice xenograft models, 17-DMAG significantly reduced the growth of EGFR-mutant lines irrespective of T790M mutation. These results suggested that 17-DMAG is a potential novel therapeutic agent for NSCLC patients with EGFR mutations with or without EGFR-TKI resistance.

Impact of contrast-induced nephropathy and cardiovascular events by serum cystatin C in renal insufficiency patients undergoing cardiac catheterization.

We assessed the usefulness of serum cystatin C for predicting contrast-induced nephropathy (CIN) in patients (n = 100) undergoing coronary catheterization. After a 12-month follow-up, the incidence of CIN was 8.3% (n = 5) in patients with mild renal insufficiency (estimated glomerular filtration rate [eGFR] 60-89 mL/min per 1.73 m²), 34.4% (n = 10) in those with moderate renal insufficiency (eGFR 30-59 mL/min per 1.73 m²), and 100% (n = 3) in those with severe renal insufficiency (eGFR 15-29 mL/min per 1.73 m²). The sensitivity was 81.8% and specificity was 90.9% at the cutoff level of serum cystatin C >1.18 mg/L. Serum cystatin C levels were significantly (P < .001) higher in the patients with moderate renal insufficiency in the CIN group than those in the non-CIN group. Multivariate logistic regression analysis demonstrated that baseline serum cystatin C independently predicted short-term mortality (odds ratio [OR], 0.311; 95% confidence interval [CI] 0.058-0.538; P = .026). Baseline serum cystatin C significantly predicted the occurrence of CIN in the patients with moderate renal insufficiency.

Cystatin C: a better marker to detect coronary artery sclerosis.

BACKGROUND: Nowadays, early detection and treatment can often keep chronic kidney disease patients from getting worse and prevent the occurrence of cardiovascular disease. Cystatin C (Cys-C) is a new marker for renal dysfunction. This study investigated whether Cys-C played an important role for screening coronary artery disease. METHODS: The consecutive 88 outpatients (51 males and 37 females), who were suspected of having effort angina pectoris or asymptomatic ischemic heart disease, were enrolled. Serum Cys-C, which was obtained within 3 months before coronary angiography, was assessed with the presence or absence of coronary arteriosclerosis, the number of culprit arteries, and blood biochemical parameters. RESULTS: Mean serum Cys-C was 0.82+/-0.29 mg/l. Significant differences in the estimated creatinine clearance (p=0.036), hemoglobin A1c (p=0.01), left ventricular ejection fraction (p=0.01), creatinine (p=0.007), Cys-C (p=0.006), and high-density lipoprotein (HDL) cholesterol (p=0.001) were observed between the patients with or without coronary arteriosclerosis. Serum Cys-C was significantly greater in the multi-vessel disease (MVD) group than the 0 vessel disease (0VD) group (p<0.001). HDL cholesterol was significantly lower in the MVD group than the 0VD and single-vessel disease groups (p=0.002 and p=0.005, respectively). CONCLUSION: The results of this study suggest Cys-C might be one of the risk factors for coronary arteriosclerosis in the patients with suspected ischemic heart disease without any history of coronary artery disease. Cys-C was a useful marker to detect coronary artery disease and the level of Cys-C could reflect the severity of coronary arteriosclerosis.

Clinicopathological relevance of UbcH10 in breast cancer.

Abrogated mitotic progression is a common hallmark of cancer. UbcH10, one of the components of the ubiquitin/proteasome pathway, plays a pivotal role in the regulation of mitotic progression. Abnormal UbcH10 activity is reported in certain types of human cancers; its overexpression is occasionally encountered in cancerous tissue compared with adjacent normal tissue. Current studies have suggested the critical role of UbcH10 in the spindle assembly checkpoint and the subsequent accurate separation of sister chromatids, which is orchestrated by a series of molecular interactions governed by the complex and diverse cell cycle machinery. To validate the potential role of UbcH10 in cell proliferation in cancer, we have analyzed the clinicopathological relevance of UbcH10 in progression of breast cancer using a combinatorial approach of human tumor arrays and biochemical analyses. Our results show that the percentage of tested samples which stained positive for UbcH10 in breast cancer tissues is significantly higher compared to the adjacent nonmalignant tissue. Furthermore, results from the clinicopathological analysis have revealed that elevated expression of UbcH10 is associated with higher histological grade tumors. In addition, depletion of UbcH10 by RNA interference in breast cancer cells resulted in decreased cellular proliferation, while overexpression of UbcH10 significantly enhanced cellular growth in breast cancer. Our results suggest a pathological correlation between UbcH10 and cell proliferation in breast cancer. Thus, aberrant UbcH10 activity may induce the dysfunction of proper cell cycle progression and result in the aggressive behavior of tumor cells in patients with breast cancer.

[Chemotherapy after second-line chemotherapy for patients with advanced or metastatic breast cancer].

PURPOSE: We evaluated chemotherapy after second-line chemotherapy for patients with advanced or metastatic breast cancer. PATIENTS & METHODS: Retrospectively, we evaluated 27 patients who received chemotherapy after second line chemotherapy. RESULTS: Eighteen patients received anthracycline(A)and/or taxane(T)containing chemotherapy regimens, 16 patients received chemotherapy regimens containing anticancer drugs except A and T, and 13 patients received oral fluoropyrimidines. Of all 48 chemotherapy regimens, 15(31.4%)regimens demonstrated response to chemotherapy. The clinical response rate was statistically equal among each chemotherapy regimen, and whenever patients received chemotherapy in any line. In univariate analysis, hormone receptor status, ECOG performance status(PS), and response to the first- or second-line chemotherapy were significantly associated with clinical response to chemotherapy after second-line chemotherapy. In multivariate analysis, only hormone receptor was significant. For overall survival according to response to first- or second-line chemotherapy, the difference was not significant. Meanwhile, overall survival according to response to chemotherapy after second-line chemotherapy was significant. CONCLUSIONS: Chemotherapy after second-line chemotherapy demonstrated a response similar to any regimen or any line. Patients having negative hormone receptor should receive chemotherapy after second-line chemotherapy.

Evaluation of breast lymphatic pathways with indocyanine green fluorescence imaging in patients with breast cancer.

BACKGROUND: In patients with early breast cancer, sentinel lymph node biopsy (SLNB) has been emerging as a new standard of care. The use of SLNB with a blue dye is convenient and safe, but it requires a high level of technical skill. Recently, an instrument that can provide fluorescence imaging of lymphatic flow has been introduced. In the present study, we analyzed breast lymphatic pathways and discussed its potential as a modality to complement the use of SLNB with a blue dye. METHODS: Thirty-seven consecutive patients with breast cancer were examined. To obtain fluorescence imaging, an invisible near-infrared fluorescence imaging system was used. After indocyanine green was subdermally injected in the subareolar site and at two sites around the tumor, the subcutaneous lymphatic drainage pathway (LDP) was observed. RESULTS: In 27 (72.9%) of the patients, the number of LDP from the periareolar area was one or two. In 21(63.6%) of 33 patients with subdermal injection around the tumor, no LDP was observed from the peritumoral area. Lymphatic connection between the peritumoral area and the periareolar area was observed very frequently (91.7%). In 26 (70.3%) of the patients, multiple routes joined together and only one route was ultimately directed to the axilla. Significant correlation was seen between body mass index (BMI) and the transit time to the axilla after injection (p = 0.0038). Additionally, a significant correlation was seen between the number of LPD from the periareolar area and the distance between detected SLNs and the fluorescence line-disappearing point (p = 0.034). CONCLUSIONS: This instrument can provide some important information, and can be an available and reliable navigator for SLNB with a blue dye.

The significance of 123I-BMIPP delayed scintigraphic imaging in cardiac patients.

BACKGROUND: Earlier studies have not fully investigated the significance of radionuclide planar imaging in cardiac patients using the fatty acid analogue 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP). OBJECTIVES: This study was to clarify the effectiveness of 123I-BMIPP in assessing the heart-to-mediastinum ratio (H/M) and myocardial washout rate (WR) in patients with heart disease. METHODS: Myocardial 123I-BMIPP imaging was performed in 33 patients (20 with chronic heart failure [CHF] and 13 with stable angina pectoris [AP]) and 11 control subjects. Myocardial 123I-BMIPP planner images were obtained 30 min (early image) and 4 h (delayed image) after tracer injection. The left ventricular ejection fraction (LVEF) was measured by quantitative gated single photon emission computed tomography. The concentration of plasma brain natriuretic peptide (BNP) was measured before the scintigraphic study. RESULTS: (1) Delayed H/M was much lower in CHF than in AP (1.93 +/- 0.37 vs. 2.21 +/- 0.38, p < 0.05) and controls (vs. 2.47 +/- 0.38, p < 0.001). (2) The WR in CHF and AP were higher than the WR in controls (39.8 +/- 12.7% and 38.7 +/- 11.1 vs. 27.9 +/- 10.2%, p < 0.01 and p < 0.05, respectively). (3) In all subjects, LVEF was correlated with delayed H/M (r = 0.39, p < 0.01). And, the BNP was correlated with both the WR (r = 0.36, p < 0.05) and delayed H/M (r = - 0.29, p = 0.05). CONCLUSION: These data strongly suggest that the delayed H/M and myocardial WR of 123I-BMIPP enhances the assessment of the myocardial fatty acid metabolism disorders in patients with heart disease in both masked and unmasked conditions.

Tumor inhibitory effect of gefitinib (ZD1839, Iressa) and taxane combination therapy in EGFR-overexpressing breast cancer cell lines (MCF7/ADR, MDA-MB-231).

Some kinds of breast cancer cell lines, similar to several types of solid tumors, express epidermal growth factor receptor (EGFR). However, gefitinib, an EGFR tyrosine kinase inhibitor, is not effective for all these cell lines. Similarly, taxane is effective for many of the cell lines, although some, such as the multidrug-resistant MCF7/ADR cell line, show taxane-resistance. Here, we examined the growth inhibitory effect of combination treatment with gefitinib and taxane on the breast cancer cell lines MDA-MB-231 (EGFR-positive) and MCF7/ADR (EGFR- and HER2-positive). To estimate the combined effect, a Combination Index was calculated for each cell line. The combination of gefitinib and taxane showed a strong synergistic effect on MCF7/ADR cells, but an invitro additive-antagonistic effect on MDA-MB-231 cells. Similarly, the combination treatment showed a significantly increased tumor inhibitory effect on MCF7/ADR xenografts, but not on MDA-MB-231 xenografts. Regarding the mechanism of the synergistic effect, Western blotting analysis revealed that taxane activated the EGFR-Akt pathway in MCF7/ADR cells but not in MDA-MB-231. To determine the optimal sequential administration of gefitinib and taxane for MCF7/ADR cells, we used flow cytometry to analyze the cell cycle and apoptosis; finding that taxane treatment followed by gefitinib produced a higher rate of G2 arrest and apoptosis than gefitinib treatment followed by taxane. These results suggest gefitinib overcomes the drug-resistance of these cells, thereby increasing the effects of taxane on MCF7/ADR cells. Further, activation of the EGFR-Akt pathway by taxane is related to this synergistic effect.

Biocompatibility of polyvinylalcohol gel as a vitreous substitute.

Polyvinylalcohol (PVA) hydrogel cross-linked by gamma irradiation was assessed as a possible vitreous substitute. From a series of experiments, rise of intraocular pressure and inflammatory changes in the vitreous cavity after operation were observed in some cases. Crab-eating macaques were used for this experiment. PVA gels were injected into vitreous cavity after vitrectomy and followed clinically by opthalmoscopy, tonometry, fundus photography, electroretinogram (ERG), chemotaxis, and flare cell meter. Histopathologic examination by light and electron microscopy was performed after 3 months. As a result, there were no significant changes in ophthalmoscopic findings. No abnormal rising of intraocular pressure (IOP) was recognized. ERG did not show meaningful amplitude weakness. From the photon counting of flare cell meter, significant break of blood-aqueous barrier and blood-retinal barrier was not observed. Histopathologic examination revealed that all layers of the retina were intact and no loss of tissue was evident. However, in PVA gel-injected eyes, some vacuolations of the inner retina were found in some specimens. To conclude, PVA gel was well tolerated in these experiments. The gel with a network similar to the vitreous body showed the best biocompatibility, though it is necessary to investigate the biocompatibility for the long-term. PVA gel is a good candidate for a vitreous substitute.

Use of multifocal visual evoked potential tests in the objective evaluation of the visual field in pediatric epilepsy surgery.

OBJECT: To evaluate objectively the visual fields of patients with pediatric epilepsy who are uncooperative with perimetry and in whom postoperative visual field deficits are expected, the authors investigated the usefulness of the multifocal visual evoked potential (VEP) method. METHODS: Normal waves in multifocal VEP were determined in 21 healthy children (21 eyes) 6 to 15 years of age (mean 11.4 years). Responses from eight sites in each child were divided into four quadrants (superior and inferior temporal and superior and inferior nasal). In each quadrant, two response waves were grouped and averaged. The peak latency and amplitude at approximately 100 msec were used for assessment. In three cases involving patients with epilepsy, multifocal VEP measurements were also recorded and compared with the peak latency and amplitude in the healthy children. In these children, no significant differences were observed in the peak latency of amplitude among four quadrants using one-way analysis of variance. In each patient, multifocal VEP tests showed abnormal waves in the quadrant corresponding to the lesion demonstrated in neuroradiological images. This result was useful in the treatment of choice and the postoperative evaluation. CONCLUSIONS: Multifocal VEP tests can be useful in evaluating the visual field of children objectively. They can also be valuable in assessing preoperative visual field defects and revealing changes in the visual field after treatment.