Ok Hee Woo

Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer.

Background:The balance in the immune system between immune surveillance against non–self-antigens and tolerance of self-antigens is known to be associated with the prognosis of breast cancer patients. However, immunologic signals in tumor microenvironment according to biological characteristics of cancer cells have not been clearly elucidated. CD4+ T cells, CD8+ T cells, and forkhead box P3-positive (Foxp3+) regulatory T cells (Tregs) are the main keys for immune surveillance and tolerance, respectively. We evaluated the correlations between the immunologic balance and tumor characteristics and their impact on recurrence. Patients and Methods:CD8+ T cells and Foxp3+ Tregs were detected by immunohistochemistry using the paraffin-embedded tumor samples from the 72 patients with early stage (I to III) breast cancer. Clinicopathologic data including tumor size and grade, lymph node metastasis, stage, patient’s age, expression status of estrogen receptor (ER), progesterone receptor, p53, Ki-67, and human epidermal growth factor receptor-2/neu, and recurrence were reviewed. Results:The decreased number of CD8+ T cells was significantly associated with tumors with lymph node metastasis (P=0.027), higher stage (stage III, P=0.013), and immunopositivity of Ki-67 (P=0.026). In contrast, the increased number of Foxp3+ Tregs was significantly correlated with tumors with lymph node metastasis (P=0.027), immunopositivity for p53 (P=0.026), and positive for Ki-67 (P<0.001). There were significant correlations between the increased Foxp3+ Treg/CD4+ T-cell ratio and lymph node metastasis (P=0.011), the expression of ER (P=0.023), and immunopositivity of p53 (P=0.031) and Ki-67 (P= 0.003). Of note, lower Foxp3+ Treg/CD4+ T-cell ratio was significantly associated with triple-negative breast cancer (P=0.004). Disease-free survival of analyzed patients was significantly associated with the number of Foxp3+ Tregs (dichotomized by a cutoff point of 17, P= 0.014) only. Univariate analysis indicated that tumor grade (P=0.017), the expression of ER (P=0.032), and non–triple-negative breast cancer (P=0.022) were independent prognostic factors for disease-free survival. Conclusions:Our data showed that lymph node metastases, immunopositivity of p53 and Ki67, and non–triple-negative tumors were associated with high regulatory T-cell infiltration. The role of immunologic balance as a prognostic marker for recurrence must be evaluated more clearly in the future study.

Incidental extracardiac findings at cardiac CT angiography: comparison of prevalence and clinical significance between precontrast low-dose whole thoracic scan and postcontrast retrospective ECG-gated cardiac scan

Purpose To compare the prevalence and clinical significance of incidental extracardiac findings at cardiac CT angiography (CCTA) with precontrast low-dose whole thoracic scan (LDCT) and ECG-gated CCTA. Materials and Methods We reviewed 254 patients who underwent CCTA. All participants first underwent LDCT to determine a range for CCTA and to screen unrecognized extracardiac lesions. CCTA was reconstructed with a small field of view of the heart. Clinically significant extracardiac findings were defined as abnormalities requiring further diagnostic work up, therapeutic intervention, or follow-up. Results On LDCT, 285 extracardiac findings were detected in 62.6% patients; on CCTA, 18 findings in 7% patients. Among these, 66 findings in 20.4% patients were considered clinically significant on LDCT, and 4 findings in 1.6% patients on CCTA. Conclusion Clinically significant extracardiac findings are common in patients undergoing CCTA with a considerable number of extracardiac findings being detected only on LDCT. We advise performing whole thorax LDCT prior to CCTA.

Can MR Imaging Contribute in Characterizing Well-circumscribed Breast Carcinomas?

Most well-circumscribed breast masses are benign lesions such as cysts, fibroadenomas, and intramammary lymph nodes. Nevertheless, 10%-20% of breast malignancies are well-circumscribed masses, and these malignancies include papillary, mucinous, medullary, and metaplastic carcinomas, as well as malignant phyllodes tumors. Therefore, it is important to differentiate these well-circumscribed breast malignancies from benign breast lesions, but it is not easy to do so with conventional imaging modalities such as mammography and ultrasonography (US). As an emerging adjunctive imaging method, magnetic resonance (MR) imaging has substantial potential in characterizing well-circumscribed breast carcinomas. Analysis of the lesion signal intensity on nonenhanced T2-weighted MR images, determination of the enhancement pattern, and kinetic curve assessment can greatly help differentiate malignant from benign well-circumscribed breast lesions. Therefore, breast MR imaging can play a substantial role in distinguishing between well-circumscribed benign and malignant breast lesions, especially in cases that are difficult to diagnose by using conventional imaging. In this article, the MR imaging findings of the subtypes of well-circumscribed malignant breast lesions-intracystic papillary carcinoma, invasive papillary carcinoma, mucinous carcinoma, medullary carcinoma, metaplastic carcinoma, and malignant phyllodes tumor-are described and correlated with the histopathologic, mammographic, and US findings.

Primary Large Cell Neuroendocrine Carcinoma of the Breast: Radiologic and Pathologic Findings

Some breast neoplasms are classified as primary neuroendocrine carcinomas because they are positive for neuroendocrine markers. Although neuroendocrine carcinomas can originate from various organs of the body, primary neuroendocrine carcinomas of the breast are extremely rare. The diagnosis of primary neuroendocrine carcinoma of the breast can only be made if nonmammary sites are confidently excluded or if an in situ component can be found. Here we report a primary large-cell neuroendocrine carcinoma (LCNL) involving the left breast. Breast ultrasonography revealed a lobulated, heterogeneous, low-echoic mass in the left breast, and the lesion ap-peared as a well-defined, highly-enhancing mass on a chest computed tomography scan. Ultrasound-guided core needle biopsy was performed on the mass, and primary LCNC was confirmed by histopathologic examination.

64-slice coronary computed tomography angiography using low tube voltage of 80 kV in subjects with normal body mass indices: comparative study using 120 kV

Background The radiation dose of coronary computed tomography (CT) angiography (CCTA) is generally higher than that of CT scans of other parts of the body, and there is concern that the high radiation dose may result in increased cancer risk. Although various techniques have recently been introduced to lower the radiation dose of CCTA, there has been no direct comparison between protocols with 80 and 120 kV. Purpose To assess the image quality and radiation dose of 80-kV electrocardiography (ECG)-gated CCTA in subjects with a normal body mass index (BMI), compared to 120-kV ECG-gated CCTA. Material and Methods This retrospective study was approved by our local ethics board, and the requirement of written informed consent was waived. We analyzed the CCTA images of 100 subjects with BMIs < 25 kg/m2. Fifty subjects underwent 120-kV CCTA, and the other 50 subjects underwent 80-kV CCTA. Two blinded observers independently evaluated the subjective image quality of the coronary arteries. The objective image quality (signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]) and radiation dose were also measured in each group. Results Although the objective image quality of the 80-kV protocol images was significantly poorer than that of 120-kV protocol images (mean SNR, 14.9-4.7 vs. 19.8-4.4, P < 0.0001; mean CNR, 15.2±4.8 vs. 21.6-4.7, P < 0.0001), there was no significant difference in the subjective image quality between the two groups (mean image score, 4.7-1.1 vs. 4.5-0.7 for radiologist 1, P = 0.273; 5.0±1.0 vs. 4.8±1.0 for radiologist 2, P = 0.197). The radiation dose was reduced by 70% with the 80-kV protocol and by 88% with the 80-kV and ECG-based tube current modulation than with the 120-kV protocol (3.42±1.16 and 2.9±0.8 vs. 11.49-3.62 mSv, P < 0.0001). Conclusion The low tube voltage CCTA protocol using 80 kV allows significant reduction of the radiation dose without impairing the subjective image quality in subjects with normal BMIs.

Non-Calcified Ductal Carcinoma in Situ: Ultrasound and Mammographic Findings Correlated with Histological Findings

Purpose To evaluate radiological findings of non-calcified ductal carcinoma in situ (DCIS) and to correlate those with histological features. Materials and Methods From July 2002 to March 2006, 22 patients with histologically-proven non-calcified DCIS were included. Mammography was obtained in 19 patients, ultrasound in 18 patients, and both examinations in 15 patients. Radiological findings were evaluated according to the Breast Imaging Reporting and Data System by American College of Radiology. Histological tumor subtype and Van Nuys classification of DCIS were assessed. Results Histological subtypes consisted of mixed type in 11 patients (50%), comedo in 4 (18%), cribriform in 4 (18%), papillary type in 2 (9%), and solid in one (5%). According to Van Nuys classification, group 3 DCIS was observed in 13 (59%) patients. In the 19 patients who underwent mammography, 13 patients presented with abnormal findings: focal asymmetry in 7 patients (37%), masses in 4 (21%), skin thickening in one (5%), and architectural distortion in one (5%). In the 18 patients who had received breast ultrasound, a mass was present in 15 (83%) patients and ductal changes in 3 patients (17%). Sixty percent of patients with masses on ultrasound had group 3 DCIS and 100% of patients with ductal change had group 1 DCIS (p = 0.017). Conclusion Diagnosis of non-calcified DCIS by mammography is not an easy task due to the lack of typical malignant calcifications or masses. High resolution ultrasound can be useful for detecting non-calcified DCIS, and ultrasound findings are correlated with histological features.

The relationship between preeclampsia, pregnancy-induced hypertension and maternal risk of breast cancer: A meta-analysis

Abstract Background. It has long been recognized that some human breast cancers are hormone dependent. Preeclampsia is a syndrome of pregnancy defined by the onset of hypertension and proteinuria and characterized by dysfunction of the maternal endothelium. Many hormonal changes occur with preeclampsia, and we hypothesize that these changes may influence the risk of maternal breast cancer. We also analyzed the relation between pregnancy-induced hypertension (PIH) and maternal risk of breast cancer. Methods. Among 13 relevant publications about preeclampsia and six relevant publications about PIH, some studies find preeclampsia associated with a lower risk of breast cancer, but others did not. Therefore, these results are inconclusive. We conducted meta-analysis to evaluate more precisely the relationship between preeclampsia, PIH and maternal risk of breast cancer. Results. The pooled estimate of the hazard ratio (HR) associated with preeclampsia was 0.86 (95% CI 0.73–1.01), and that associated with PIH was 0.83 (0.66–1.06), both based on the random effects model. Conclusion. Some suggestive but not entirely consistent nor conclusive evidence was found on the association between the history of preeclampsia or PIH with the subsequent risk of breast cancer.

Bevacizumab for salvage treatment of metastatic breast cancer: a systemic review and meta-analysis of randomized controlled trials

SummaryAlthough various new agents have been developed for the treatment of patients with metastatic breast cancer (MBC), overall survival rates have changed little in the last half century. We conducted meta-analysis to verify the clinical efficacy of bevacizumab for the salvage treatment of MBC. Event-based hazard ratios (HR) with 95% confidence intervals (95% CIs) were derived, and a test of heterogeneity was applied. Four studies, with a total of 2,860 patients, met the inclusion criteria for analysis. The pooled results of clinical efficacies were: HR for progression free survival 0.69 (95% CI, 0.58–0.81, z = 4.54, P <0.001); HR for overall survival 0.92 (95% CI, 0.82–1.03, z =1.44, P = 0.15); and HR for the clinical objective response rate 1.53 (95% CI, 1.37–1.71, z = 7.37, P < 0.001). In terms of overall survival, subgroup analysis demonstrated statistically significant improvement for the bevacizumab combination in the initial therapy subgroup (HR, 0.878; 95% CI, 0.771–0.999, z = 1.98, P = 0.048). Hypertension and proteinura were more common in the bevacizumab combination arm; however, these toxicities were managed with therapy. In conclusion, meta-analysis suggested benefits of a carefully managed bevacizumab-containing salvage regimen for patients with histologically or cytologically confirmed Her-2 negative MBC who have not received previous cytotoxic therapy. This treatment could improve both progression free survival and overall survival rates.

Dedifferentiated liposarcoma of retroperitoneum: spectrum of imaging findings in 15 patients

BACKGROUND Dedifferentiated liposarcoma is a high-grade nonlipogenic sarcoma that arises in the background of a preexisting well-differentiated liposarcoma. The purpose of this work is to evaluate the spectrum of radiologic appearance of retroperitoneal dedifferentiated liposarcoma with clinicopathologic features. METHODS Radiologic images and clinical histories of 15 patients with histologically verified retroperitoneal dedifferentiated liposarcoma were retrospectively studied. Patients included 11 men and 4 women, with mean age of 55.8 years (range, 36-74 years), and they underwent computed tomography (CT) (n=15) and magnetic resonance imaging (MRI) (n=5). RESULTS The mean size of the tumor was 22.6 cm with a range of 9.5-38 cm. Both CT and MRI showed well-circumscribed, large round, or lobulated retroperitoneal mass. The appearance of the tumor was classified as follows: Category I, nonfatty component within predominant fatty mass (n=5); Category II, focal fatty component within large nonfatty mass (n=6); Category III, well-defined fatty mass and well-defined nonfatty mass (n=1); Category IV, two masses with predominantly nonfatty component (n=3). CONCLUSION Retroperitoneal dedifferentiated liposarcomas present various spectra of imaging findings. While Categories I and III may suggest dedifferentiated liposarcoma, Categories II and IV may appear as other types of liposarcoma or other malignant retroperitoneal tumor.

Computer-aided detection (CAD) system for breast MRI in assessment of local tumor extent, nodal status, and multifocality of invasive breast cancers: preliminary study

BackgroundWe aimed to investigate the efficacy of computer-aided detection (CAD) for MRI in the assessment of tumor extent, lymph node status, and multifocality in invasive breast cancers in comparison with other breast imaging modalities.MethodsTwo radiologists measured the maximum tumor size, as well as, analyzed lymph node status and multifocality in 86 patients with invasive breast cancers using mammography, ultrasound, CT, MRI with and without CAD, and 18-fludeoxyglucose positron emission tomography (FDG-PET). The assessed data were compared with pathology.ResultsFor tumor extent, there were no significant differences between pathological size and measured size using mammography, ultrasound, CT, or MRI with and without CAD (P > 0.05). For evaluation of lymph node status, ultrasound had the best kappa coefficients (0.522) for agreement between imaging and pathology, and diagnostic performance with 92.1% specificity and 90.0% positive predictive value. For multifocality, MRI with CAD had the highest area under the receiver operating characteristic curve (AUC = 0.888).ConclusionsCAD for MRI is feasible to assess tumor extent and multifocality in invasive breast cancer patients. However, CAD is not effective in evaluation of nodal status.