Radiomics-based model for predicting pathological complete response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

AIM: To develop and validate a radiomics-based model for predicting response to neoadjuvant chemotherapy (NAC) using baseline computed tomography (CT) images in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: A radiomics signature for predicting pathological complete response (pCR) was developed using radiomics features selected by a random forest classifier on baseline CT images, and imaging predictors were identified in the training set (87 patients). By incorporating imaging predictors and radiomics signature, an imaging-based model was constructed using multivariate logistic regression analysis and validated in an independent validation set consisting of 48 patients with CT from outside institutions. The performance and clinical usefulness of the imaging-based model for predicting pCR were evaluated using area under the receiver operating characteristic curve (AUC) and decision curve analysis. Using a cut-off determined in the training set, the positive likelihood ratios of the imaging-based model were calculated and compared with imaging and histological predictors. RESULTS: The radiomics signature was developed based on six stable radiomics features. An imaging-based model incorporating radiomics signature, tumour shape, tumour size, and clinical stage showed good performance for predicting pCR in both the training (AUC, 0.85; 95% confidence interval [CI], 0.78-0.93) and validation (AUC, 0.75; 95% CI, 0.60-0.86) sets, providing a larger net benefit in decision curve analysis. The imaging-based model showed a higher positive likelihood ratio (1.91) for pCR than imaging and histological predictors (1.33-1.63). CONCLUSIONS: The radiomics-based model using baseline CT images may predict the response of patients with MIBC to NAC.

The robustness of T2 value as a trabecular structural index at multiple spatial resolutions of 7 Tesla MRI.

PURPOSE: To evaluate the robustness of MR transverse relaxation times of trabecular bone from spin-echo and gradient-echo acquisitions at multiple spatial resolutions of 7 T. METHODS: The effects of MRI resolutions to T2 and T2* of trabecular bone were numerically evaluated by Monte Carlo simulations. T2 , T2*, and trabecular structural indices from multislice multi-echo and UTE acquisitions were measured in defatted human distal femoral condyles on a 7 T scanner. Reference structural indices were extracted from high-resolution microcomputed tomography images. For bovine knee trabecular samples with intact bone marrow, T2 and T2* were measured by degrading spatial resolutions on a 7 T system. RESULTS: In the defatted trabecular experiment, both T2 and T2* values showed strong ( |r| > 0.80) correlations with trabecular spacing and number, at a high spatial resolution of 125 µm3 . The correlations for MR image-segmentation-derived structural indices were significantly degraded ( |r| < 0.50) at spatial resolutions of 250 and 500 µm3 . The correlations for T2* rapidly dropped ( |r| < 0.50) at a spatial resolution of 500 µm3 , whereas those for T2 remained consistently high ( |r| > 0.85). In the bovine trabecular experiments with intact marrow, low-resolution (approximately 1 mm3 , 2 minutes) T2 values did not shorten ( |r| > 0.95 with respect to approximately 0.4 mm3 , 11 minutes) and maintained consistent correlations ( |r| > 0.70) with respect to trabecular spacing (turbo spin echo, 22.5 minutes). CONCLUSION: T2 measurements of trabeculae at 7 T are robust with degrading spatial resolution and may be preferable in assessing trabecular spacing index with reduced scan time, when high-resolution 3D micro-MRI is difficult to obtain.

CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.

Clinical relevance of lymph node ratio in breast cancer patients with one to three positive lymph nodes.

BACKGROUND: To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT). METHODS: Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR). RESULTS: Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17-0.89; P=0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT. CONCLUSION: This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.

Effects of single-dose dexmedetomidine on the quality of recovery after modified radical mastectomy: a randomised controlled trial.

BACKGROUND: Dexmedetomidine is a highly selective α2 agonist with analgesic, anxiolytic, and anti-inflammatory properties. We investigated the effect of a single dose of dexmedetomidine on patient-perceived quality of recovery and clinical recovery variables after modified radical mastectomy under general anesthesia in this randomized, double-blind, placebo-controlled study. METHODS: After Institutional Review Board approval, ninety two female patients were randomly allocated to receive intravenously either saline (Group C, N.=46) or 0.5 µg/kg of dexmedetomidine (Group D, N.=46) five min before the end of surgery. The quality of recovery was assessed using a 40-item quality-of-recovery scoring system (QoR-40) preoperatively and 24 h after surgery. Pain intensity, rescue analgesics, and postoperative nausea and vomiting (PONV) were assessed at postanesthesia care unit (PACU), 1-6 h, and 6-24 h after surgery. RESULTS: Postoperative global QoR-40 scores were higher in Group D compared with Group C (181 [175-187] vs. 174 [154.5-181.5], P=0.004); postoperative QoR-40 scores were improved in the dimensions of emotional state, physical comfort, and psychological support. Total amount of tramadol during 24 h after surgery was significantly lower in Group D than in Group C (54 vs. 76 mg, P=0.006). The incidence of PONV was lower in Group D than in Group C in PACU (21% vs. 43%, P=0.026) and 6-24 h period after surgery (10% vs. 41%, P=0.012). Heart rate and mean blood pressure were significantly lower in Group D as compared with Group C at 5 min after administration of dexmedetomidine, 1 min after extubation, and 20 min after arrival in PACU. CONCLUSION: The use of a single dose dexmedetomidine improved the quality of recovery and reduced analgesic requirements and the incidence of PONV in the early postoperative period after modified radical mastectomy.

False negative results in axillary lymph nodes by ultrasonography and ultrasonography-guided fine-needle aspiration in patients with invasive ductal carcinoma.

PURPOSE: For preoperative evaluation of ALN status using various methods, axillary US and subsequent US-FNA targeting the LNs suspicious for metastasis are the most widely used methods. The purpose of our study was to assess the rate of false-negative results at preoperative ultrasonography (US) and ultrasonography guided fine needle aspiration (US-FNA) of axillary lymph nodes (ALNs) in breast cancer patients and the number of false-negative lymph nodes, and to evaluate factors related to ALN false negative results in US and/or US-FNA in patients diagnosed with invasive ductal carcinoma. MATERIALS AND METHODS: Among 317 patients who underwent surgery for invasive ductal carcinoma during 2009 in Severance hospital, 237 patients had no reported ALN metastasis on preoperative US-FNA and US. We retrospectively reviewed the subsequent surgical pathology and clinicopathologic findings and assessed the rate of false-negative results from US and US-FNA of ALN and the number of false-negative lymph node. We performed univariate analysis and multivariate logistic regression analysis to evaluate the relationships between variable clinicopathologic factors (T-stage, position of ALN, hormone receptors, histologic grade, lymphovascular invasion (LVI) and performance of FNA) and cytologic results (false-negative result; FNALN and true negative result; TNALN) from US and/or US-FNA of ALN. RESULTS: The rate of false-negative results was 42.4 % (59/139) in both US and US-FNA of ALN but among them, 57.6 % (34/59) showed only one metastatic ALN. Breast cancer with FNALN on US and US-FNA was significantly related to positive estrogen receptor (p = 0.003), positive progesterone receptor (p = 0.001), and the presence of LVI (p = 0.004) in univariate analysis. In multivariate analysis, high T stages (≥ T2, odds ratio (OR) 4.007, p = 0.004) and LVI (OR 7.951, p = 0.001) showed significant correlation with FNALN on US and US-FNA. CONCLUSION: More than half of patients with FNALN showed only one metastatic ALN. LVI and high T-stages were the most important factors attributed to FNALN on US and US-FNA in patients with invasive ductal carcinoma.

Elevated levels of preoperative CA 15-3 and CEA serum levels have independently poor prognostic significance in breast cancer.

BACKGROUND: To evaluate the prognostic value of preoperative tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA), in breast cancers. PATIENTS AND METHODS: Preoperative CA 15-3 and CEA levels of 1681 patients were measured. The association of both tumor markers levels with clinicopathological parameters and outcomes was investigated by univariate and multivariate analyses. RESULTS: Among 1681 patients, elevated preoperative CA15-3 and CEA levels were identified in 176 and 131 patients, respectively. Higher preoperative CA 15-3 and CEA levels were significantly associated with a larger tumor size, axillary node metastases, and advanced stage. Patients with elevated CA 15-3 and CEA levels showed worse survival, even in stage-matched analysis. Patients with normal levels of both CA15-3 and CEA showed better survival than those with one or both markers levels elevated. In multivariate analysis, elevated preoperative CA 15-3 and CEA levels were independent prognostic factors. The statistical significance of elevated preoperative tumor markers levels on survival was solidified with longer follow-up and larger study population. CONCLUSIONS: Elevated preoperative CA 15-3 and CEA levels are associated with tumor burden and showed independent prognostic significance. Therefore, new treatment strategies are necessary for patients with elevated preoperative CA 15-3 and CEA levels in clinical practice.

The diagnosis of non-malignant papillary lesions of the breast: comparison of ultrasound-guided automated gun biopsy and vacuum-assisted removal.

AIM: To compare the histological upgrade rate of ultrasound (US)-guided vacuum-assisted removal (VAR) and US-14 G-automated core needle biopsy (ACNB) in the diagnosis of papillary breast lesions. MATERIALS AND METHODS: Two hundred and seventy-one biopsies of 230 papillary lesions were examined, which underwent subsequent surgical excision or long-term follow-up after US-ACNB (n = 206) or US-VAR (n = 65). The false-negative and atypical papilloma underestimation rate were compared between the ACNB and VAR groups. Patient and lesion characteristics were collected. The histological upgrade rates of the diagnosis were estimated and compared. RESULTS: Out of 271 papillary lesions, 195 (80.0%) were benign, 21 (7.7%) were atypical, and 55 (20.3%) were malignant. There were no false negatives or underestimated atypical papillomas in the VAR group. However, in the ACNB group, the false-negative rate was 7.6% (12 of 157 benign papillomas, 95% CI; 4.4-12.9%, p = 0.039) and the atypical papilloma underestimation rate was 33% (five of 15 atypical papillomas, 95% CI; 15.2-58.3%, p = 0.135). The histological upgrade rates of the diagnosis for papillary breast lesions were 0% for the VAR (0 of 66) group and 10.2% for the ACNB (21 of 206) group before adjusting for the population (p = 0.003). CONCLUSIONS: ACNB was associated with significantly higher false-negative and histological upgrade rates of diagnosis for papillary breast lesions than VAR.

Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers.

BACKGROUND: The objective of the study was to evaluate the implications of androgen receptor (AR) in breast cancers. PATIENTS AND METHODS: We investigated immunohistochemical AR expression from the tissue microarrays of 931 patients between 1999 and 2005, and analyzed demographics and outcomes using uni-/multivariate analyses. Tumors with ≥10% nuclear-stained cells were considered positive for AR. RESULTS: AR was expressed in 58.1% of patients. AR was significantly related to older age at diagnosis, smaller size, well-differentiated tumors, higher positivity of hormone receptors, non-triple-negative breast cancers (non-TNBCs), and lower proliferative index. In estrogen receptor (ER)-negative tumors, AR was distinctively associated with human epidermal growth factor receptor type 2 (HER2) overexpression. With a mean follow-up of 72.7 months, AR was positively related to survival in ER-positive but not in ER-negative tumors. In Cox's models, AR was an independent prognostic factor for disease-free survival in ER-positive cancers. Interestingly, molecular apocrine tumors (ER negative and AR positive) with HER2 positive status showed trends of poorer outcome, but AR had no impact on survival in patients with TNBC. CONCLUSIONS: AR is significantly associated with favorable features in breast cancers and related to better outcomes in ER-positive not in ER-negative tumors. These results suggest that AR could be an additional marker for endocrine responsiveness in ER-positive cancers and a candidate for therapeutic targeting of ER-negative tumors.

Expression of androgen receptors in primary breast cancer.

BACKGROUND: To investigate the clinicopathological significance of androgen receptor (AR) expression in primary breast cancers. PATIENTS AND METHODS: We evaluated AR using immunohistochemistry from 413 whole sections from January 2008 to March 2009 and analyzed the relationship between AR and clinicopathological parameters. Tumors with >/=10% nuclear-stained cells were considered to be positive for AR. The differences among variables were calculated by chi-square test. RESULTS: The expression rate of AR was 72.9% higher than those of estrogen receptors (ER) and progesterone receptors. AR expression was significant in patients with no elevated preoperative serum cancer antigen 15-3 levels, smaller tumor size, lower histologic grade and hormone receptor-positive and non-triple-negative breast cancer. However, AR expression was observed in 35% of triple-negative cancers. Metaplastic, medullary and mucinous types of carcinomas showed less AR expression. In the ER-negative subgroup, AR was significantly correlated with human epidermal growth factor receptor type 2 (HER-2) overexpression. CONCLUSIONS: AR is expressed in a significant number of breast cancers and is associated with lower tumor burden and favorable differentiation. There are many issues to be further investigated such as whether AR is an independent prognostic factor, whether it is a therapeutic target for the triple-negative breast cancers and whether it is associated with HER-2 signaling in ER-negative tumors.

Co-expression of nerve growth factor and p75NGFR in the inferior alveolar nerve after mandibular distraction osteogenesis.

During mandibular distraction osteogenesis (DO), the inferior alveolar nerve (IAN) is damaged during distractor activation, but spontaneously recovers during consolidation. Although many neurotrophic factors are known to play critical roles, there have been few studies on the mechanism of peripheral nerve recovery after DO. The aim of this study was to observe the expression pattern of p75NGFR (low-affinity receptor of NGF) and to detect autocrine growth activity in IANs following mandibular DO. Unilateral mandibular distractions (0.5mm each, twice per day for 10 days) were conducted on eight mongrel dogs. Two each were killed at 7, 14, 28 and 56 days after completing distraction. The distracted IAN and contralateral control nerve were harvested. Immunohistochemical staining was performed to determine p75NGFR expression, and double immunofluorescent staining to detect NGF and p75NGFR co-expression. Levels of p75NGFR expression were found to be significantly elevated at 7 and 14 days in Schwann cells located in the outer layer of axon, but were almost undetectable at 28 and 56 days. In double immunofluorescent images, the co-expression of NGF and p75NGFR was also detected at 7 and 14 days. p75NGFR plays an important role in remyelination due to its abundant expression in Schwann cells of damaged nerves, and NGF is an autocrine growth factor present in distracted IANs during the early consolidation period after mandibular DO.

Preoperative CA 15-3 and CEA serum levels as predictor for breast cancer outcomes.

BACKGROUND: To investigate the association between tumor markers [cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] and clinicopathological parameters and patient outcomes in breast cancer. MATERIALS AND METHODS: A total of 740 patients with stages I-III breast cancer had preoperative CA 15-3 and CEA concentrations measured. Univariate and multivariate analyses were used to investigate associations between marker concentration and clinicopathological parameters and patient outcomes. RESULTS: Among 740 patients, elevated preoperative levels of CA 15-3 and CEA were identified in 92 (12.4%) and 79 (10.7%) patients, respectively. Tumor size (>5 cm), node metastases (> or =4), and advanced stage (> or =III) were associated with higher preoperative levels. Elevated CA 15-3 and CEA levels were associated with poor disease-free survival (DFS, P = 0.0014, P = 0.0001, respectively) and overall survival (OS, P = 0.018, P = 0.015) even in stage-matched analysis. Patients with normal levels of both CA 15-3 and CEA showed better DFS and OS than those with elevated group. In multivariate analysis, age (<35 years), tumor size (>2 cm), node metastases, estrogen receptor expression, and elevated CA 15-3 and CEA preoperative values were independent prognostic factors for DFS. CONCLUSION: High preoperative CA 15-3 and CEA levels may reflect tumor burden and are associated with advanced disease and poor outcome. Measuring preoperative levels of CA 15-3 and CEA can be helpful for predicting outcomes.

Expression of vascular endothelial growth factor and its receptors after mandibular distraction osteogenesis.

During distraction osteogenesis, angiogenic activity is essential for new bone formation. This study examined the expression of vascular endothelial growth factor (VEGF) and two of its receptors, Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2), in cellular components after mandibular distraction osteogenesis. Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in six mongrel dogs. Two animals each were killed on days 7, 14 and 28 after completion of distraction. The distracted mandibular segments and contralateral undistracted control segments were harvested and processed for immunohistochemical examination. Seven days after distraction, there was a significant increase in the expression levels of VEGF and its receptors in the osteoblasts, osteocytes and immature fibroblast-like cells compared to control specimens. These levels were maintained for 14 days after distraction in the osteoblasts and fibroblast-like cells. Twenty-eight days after distraction, VEGF and VEGFR-1 were expressed only moderately/weakly in the osteoblasts, and no VEGFR-2 expression was detected in the cellular component of the distracted bone. Throughout the observation period, VEGFR-1 expression was stronger than that of VEGFR-2. The expression patterns of VEGF and its receptors suggest that it plays an important role in osteogenesis, and that osteoblasts and immature fibroblast-like cells of the distracted bone may have an autocrine growth effect during distraction osteogenesis.

Health-related quality of life in disease-free survivors of breast cancer with the general population.

BACKGROUND: Although most of the literature about health-related quality of life (HRQoL) focuses on breast cancer patients, few studies compared the HRQoL in disease-free breast cancer survivors with that of the general population. MATERIALS AND METHODS: We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Breast Cancer Module, McGill Quality of Life Questionnaire, Beck Depression Inventory, and Brief Fatigue Inventory to 1933 disease-free survivors for over 1 year after being diagnosed with stage 0 to III breast cancer. We performed multivariate-adjusted analyses in all HRQoL comparisons. RESULTS: The scores for some health-related quality of life [corrected] HRQoL scales were comparable for both disease-free breast cancer survivors and the general female population, but [corrected] there was a [corrected] clinically significant difference between the two groups [corrected] in cognitive and social functioning, fatigue, insomnia, financial difficulties, body image, future perspective, breast symptoms, and arm symptoms. [corrected] CONCLUSIONS: Disease-free survivors of breast cancer had good HRQoL, which was less affected by the type of treatment than it was by demographic characteristics, time since surgery, comorbidity, fatigue, and depression.

[Functional variability of the autocorrelation structure of the EEG].

On an example of records EEG of 39 healthy subjects, the quantitative analysis of variability of the autocorrelation structure of one-second EEG segments was carried out on the basis of comparison of structural functions constructed for these segments. It was shown that more than 30% of cases, statistically significant sifferences were observed between the structural functions of successive one-second EEG segments shifted by 1-3 s, as compared to surrogate EEGs formed with the tangled random sequence of count points. On the basis of the obtained data, the index of nonstationarity of the EEG autocorrelation structure was proposed. This index can be used for the objective quantitative evaluation of the functional states of the human brain.

Expression of nerve growth factor and vascular endothelial growth factor in the inferior alveolar nerve after distraction osteogenesis.

The objective of this study was to evaluate changes occurring in the inferior alveolar nerve (IAN) subsequent to mandibular distraction osteogenesis, with regard to the expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). Unilateral mandibular distractions (0.5mm each, twice per day for 10 days) were conducted on 8 mongrel dogs. Two animals were killed at 7, 14, 28 and 56 days after completion of distraction. The distracted IAN and contralateral control nerve were then harvested and analysed histologically and immunohistochemically. Signs of acute nerve injury, including demyelination, were observed in the distracted IAN on the 7th and 14th day after distraction. At 56 days, the histological features of the distracted IAN were similar to those of the control nerve. The levels of NGF and VEGF expression were significantly elevated on the 7th and 14th day after distraction. NGF was expressed in most of the distracted nerve tissues, but VEGF was primarily detected in Schwann cells and the neurovasorum. VEGF expression had returned to normal but NGF expression was still profoundly elevated 28 days after distraction. NGF expression returned to normal levels at 56 days after distraction. NGF and VEGF appeared to have been elicited from the Schwann cells and damaged nervous tissues, and they may play important roles in the initial healing of damaged nerves. VEGF expression returned to normal more quickly than did NGF expression. This may indicate that hypoxic conditions within the distracted nerve had recovered to normal during the early stages of consolidation. Micro-vessels in the distracted nerve may have recovered more rapidly than did the nerve tissue itself.

Intraoperative examination of sentinel lymph nodes by immunohistochemical staining in patients with breast cancer.

AIM: To performed a prospective investigation of the relative merits of rapid cytokeratin immunohistochemical (CK-IHC) staining of the SLN removed during the operation of breast cancer patients. STUDY DESIGN: Between December 2002 and March 2004, 62 patients with T1 and T2 breast cancer were enrolled after undergoing successful sentinel lymph node biopsy. Eighty-nine sentinel lymph nodes (mean number, 1.44) were biopsied and first examined by hematoxylin-eosin (H&E) stained frozen section. All the tumour free sentinel lymph nodes by H&E stained frozen section were immunostained for cytokeratin using a rapid immunohistochemical assay (Cytokeratin (PAN), 1:50, Novocastra Lab., Newcastle, UK) during the operations. RESULTS: Rapid IHC staining revealed seven positive sentinel lymph nodes that were negative for metastasis by H&E staining. This study showed a sensitivity of 92.86%, a specificity of 100%, an accuracy of 98.9%, and a negative predictive value of 98.7%. CONCLUSIONS: The intraoperative examination of sentinel lymph nodes is an accurate and effective way of predicting the axillary lymph node status of patients with breast cancers.

Development of rat prostatitis model by oral administration of isoflavone and its characteristics.

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.

Ductal eccrine carcinoma presenting as a Paget's disease-like lesion of the breast.

Some types of skin appendage tumors, particularly ductal eccrine carcinomas (DEC), imitate breast carcinomas histologically, thus causing great diagnostic challenges. We describe a case of DEC presenting as an eczematous, crusted skin lesion on the right nipple-areolar complex in a 67-year-old woman. A skin biopsy done under the clinical impression of Paget's disease of the nipple was initially misinterpreted as infiltrating ductal carcinoma, and a subsequent modified radical mastectomy revealed DEC exclusively confined to the nipple with perinodal tumor metastasis in one of the axillary lymph nodes. This case highlights the diagnostic difficulty caused by the histologic homology between breast carcinomas and skin appendage tumors with ductal differentiation.