A nomogram constructed using intraoperative ex vivo shear-wave elastography precisely predicts metastasis of sentinel lymph nodes in breast cancer

OBJECTIVE: To develop a nomogram and validate its use for the intraoperative evaluation of nodal metastasis using shear-wave elastography (SWE) elasticity values and nodal size METHODS: We constructed a nomogram to predict metastasis using ex vivo SWE values and ultrasound features of 228 axillary LNs from fifty-five patients. We validated its use in an independent cohort comprising 80 patients. In the validation cohort, a total of 217 sentinel LNs were included. RESULTS: We developed the nomogram using the nodal size and elasticity values of the development cohort to predict LN metastasis; the area under the curve (AUC) was 0.856 (95% confidence interval (CI), 0.783-0.929). In the validation cohort, 15 (7%) LNs were metastatic, and 202 (93%) were non-metastatic. The mean stiffness (23.54 and 10.41 kPa, p = 0.005) and elasticity ratio (3.24 and 1.49, p = 0.028) were significantly higher in the metastatic LNs than those in the non-metastatic LNs. However, the mean size of the metastatic LNs was not significantly larger than that of the non-metastatic LNs (8.70 mm vs 7.20 mm, respectively; p = 0.123). The AUC was 0.791 (95% CI, 0.668-0.915) in the validation cohort, and the calibration plots of the nomogram showed good agreement. CONCLUSIONS: We developed a well-validated nomogram to predict LN metastasis. This nomogram, mainly based on ex vivo SWE values, can help evaluate nodal metastasis during surgery. KEY POINTS: • A nomogram was developed based on axillary LN size and ex vivo SWE values such as mean stiffness and elasticity ratio to easily predict axillary LN metastasis during breast cancer surgery. • The constructed nomogram presented high predictive performance of sentinel LN metastasis with an independent cohort. • This nomogram can reduce unnecessary intraoperative frozen section which increases the surgical time and costs in breast cancer patients.ope

Chemosensitivity to doxorubicin of ER-positive/HER2-negative breast cancers with high 21-gene recurrence score: A study based on in vitro chemoresponse assay.

AIM: The 21-gene recurrence score (RS) predicts a clinical benefit of chemotherapy for individuals with ER-positive/HER2-negative breast cancer. Using in vitro chemoresponse assay, we compared the chemosensitivity according to RS in these patients. METHOD: Among the patients with Oncotype Dx assay, we identified 63 patients who had chemotherapy response assays to doxorubicin based on adenosine triphosphate. The degree of chemosensitivity to doxorubicin was translated into the cell death rate (CDR). The RS was also dichotomized with a cutoff of 26. RESULTS: Of 63 patients, 34 (54%), 17 (27%), and 12 patients (19%) had a low, intermediate, and high RS, respectively. The mean CDR differed significantly according to categorized RS, with 17.3±10.8 in the low RS group vs. 23.6±16.3 in the intermediate RS group vs. 28.8±12.6 in the high RS group (P = 0.024, One-way ANOVA test). The mean CDR was significantly higher in the higher RS (26≥) group compared with the lower RS (30) group compared with the low RS (<18) group (P = 0.012, the Student's t-test). Also, continuous RS and CDR correlated positively (Pearson's R = 0.337; P = 0.007). High RS demonstrated the odds ratio (OR = 26.33; 95% CI = 1.69-410.0) for predicting tumors with chemosensitivity on the multivariate analysis. CONCLUSIONS: The chemosensitivity measured by in vitro chemoresponse assay was different according to the RS. Our findings support that tumors with high RS has the chemosensitivity even though they are luminal/HER2-negative tumors.ope

Risk Factors for a False-Negative Result of Sentinel Node Biopsy in Patients with Clinically Node-Negative Breast Cancer

Purpose: Although sentinel lymph node biopsy (SLNB) can accurately represent the axillary lymph node (ALN) status, the false-negative rate (FNR) of SLNB is the main concern in the patients who receive SLNB alone instead of ALN dissection (ALND). Materials and Methods: We analyzed 1,886 patientswho underwent ALND after negative results of SLNB,retrospectively. A logistic regression analysis was used to identify risk factors associated with a falsenegative (FN) result. Cox regression model was used to estimate the hazard ratio of factors affecting disease-free survival (DFS). Results: Tumor located in the upper outer portion of the breast, lymphovascular invasion, suspicious node in imaging assessment and less than three sentinel lymph nodes (SLNs) were significant independent risk factors for FN in SLNB conferring an adjusted odds ratio of 2.10 (95% confidence interval [CI], 1.30 to 3.39), 2.69 (95% CI, 1.47 to 4.91), 2.59 (95% CI, 1.62 to 4.14), and 2.39 (95% CI, 1.45 to 3.95), respectively. The prognostic factors affecting DFS were tumor size larger than 2 cm (hazard ratio [HR], 1.86; 95% CI, 1.17 to 2.96) and FN of SLNB (HR, 2.51; 95% CI, 1.42 to 4.42) in SLN-negative group (FN and true-negative), but in ALN-positive group (FN and true-positive), FN of SLNB (HR, 0.64; 95% CI, 0.33 to 1.25) did not affect DFS. Conclusion: In patients with risk factors for a FN such as suspicious node in imaging assessment, upper outer breast cancer, less than three harvested nodes, we need attention to find another metastatic focus in non-SLNs during the operation. It may contribute to provide an exact prognosis and optimizing adjuvant treatments.ope

Measuring Tumor Extent Based on Subtypes Using Magnetic Resonance Imaging: Radiologic-Pathologic Discordance and High Positive Margin Rates in Breast Cancer

Purpose: We evaluated the clinical value of breast magnetic resonance imaging (MRI) in patients who underwent breast-conserving surgery (BCS). The degree of correlation between pathology size and MRI or ultrasonography (US) size was compared based on breast cancer subtypes. In addition, we investigated the positive margin rates. Methods: Patients with invasive breast cancer who underwent preoperative breast MRI and US between 2011 and 2016 were included in the study. Lin's concordance correlation coefficient was used to measure the correlation between MRI or US andpathologic tumor extent. Tumor extent was defined as pathologic tumor size, including in situ carcinoma. Margin positivity was assessed based on frozen-section examination. Results: A total of 516 patients with a single tumor who underwent BCS were included in the study. The correlation between pathologic size and MRI was significantly higher than that of US (r = 0.6975 vs. 0.6211, p = 0.001). The superiority of MRI over US in measuring the pathologic extent was only observed in triple-negative breast cancer (TNBC; r = 0.8089 vs. 0.6014, p < 0.001). The agreement between MRI or US and tumor extent was low for the human epidermal growth factor receptor 2 (HER2)-positive subtype (MRI: 0.5243, US: 0.4898). Moreover, the positive margin rate was higher in the HER2-positive subtype than in the others (luminal/HER2-negative: 11.6%, HER2-positive: 23.2%, TNBC: 17.8%, p = 0.019). The post hoc analysis showed that the HER2-positive subtype was more likely to show positive margins than the luminal/HER2-negative subtype (p = 0.007). Conclusion: Breast MRI was superior to US in the preoperative assessment of the pathologic extent of tumor size; this was most evident in TNBC. For HER2-positive tumors, imaging-pathologic discordance resulted in higher positive margin rates than that with other subtypes.ope

Comparisons of tumor-infiltrating lymphocyte levels and the 21-gene recurrence score in ER-positive/HER2-negative breast cancer

BACKGROUND: Recent studies have shown that tumors with extensive tumor-infiltrating lymphocytes (TILs) have a higher probability of pathologic complete response, even in luminal/human epidermal growth factor 2 (HER2)-negative breast cancer. We compared TIL levels and the 21-gene recurrence score (RS) in estrogen receptor (ER)-positive/HER2-negative breast cancer. METHODS: We evaluated the percentage of stromal TILs in 198 ER-positive/HER2-negative patients in whom RS was obtained by examining slides of surgical specimens by standardized methodology proposed by the international TIL Working Group. TIL levels were categorized as high (>/= 60%), intermediate (11-59%), or low (/= 26) but it was not significant (p = 0.155). Furthermore, multivariate analysis revealed that high RS was not an independent factor associated with high TIL levels. Chemo-endocrine therapy was more frequently performed among patients with high TILs and less frequently among those with low or intermediate TILs (p < 0.001). CONCLUSIONS: Despite of a weak correlation between continuous TIL levels and RS, we found that tumors with high TIL levels tended to have a higher RS in ER-positive/HER2-negative breast cancer. Further study is warranted considering the clinical outcomes.ope

Ex Vivo Shear-Wave Elastography of Axillary Lymph Nodes to Predict Nodal Metastasis in Patients with Primary Breast Cancer

Purpose: There is still a clinical need to easily evaluate the metastatic status of lymph nodes during breast cancer surgery. We hypothesized that ex vivo shear-wave elastography (SWE) would predict precisely the presence of metastasis in the excised lymph nodes. Methods: A total of 63 patients who underwent breast cancer surgery were prospectively enrolled in this study from May 2014 to April 2015. The excised axillary lymph nodes were examined using ex vivo SWE. Metastatic status was confirmed based on the final histopathological diagnosis of the permanent section. Lymph node characteristics and elasticity values measured by ex vivo SWE were assessed for possible association with nodal metastasis. Results: A total of 274 lymph nodes, harvested from 63 patients, were examined using ex vivo SWE. The data obtained from 228 of these nodes from 55 patients were included in the analysis. Results showed that 187 lymph nodes (82.0%) were nonmetastatic and 41 lymph nodes (18.0%) were metastatic. There was significant difference between metastatic and nonmetastatic nodes with respect to the mean (45.4 kPa and 17.7 kPa, p<0.001) and maximum (55.3 kPa and 23.2 kPa, p<0.001) stiffness. The elasticity ratio was higher in the metastatic nodes (4.36 and 1.57, p<0.001). Metastatic nodes were significantly larger than nonmetastatic nodes (mean size, 10.5 mm and 7.5 mm, p<0.001). The size of metastatic nodes and nodal stiffness were correlated (correlation coefficient of mean stiffness, r=0.553). The area under curve of mean stiffness, maximum stiffness, and elasticity ratio were 0.794, 0.802, and 0.831, respectively. Conclusion: Ex vivo SWE may be a feasible method to predict axillary lymph node metastasis intraoperatively in patients undergoing breast cancer surgery.ope

Comparison of standardized uptake value of 18F-FDG-PET-CT with 21-gene recurrence score in estrogen receptor-positive, HER2-negative breast cancer

BACKGROUND: We investigated the relationship between 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) standardized uptake value (SUV) and 21-gene recurrence score (RS) in estrogen receptor (ER)-positive/HER2-negative breast cancer. MATERIALS AND METHODS: One hundred sixty-seven patients were identified among those who underwent preoperative 18F-FDG-PET-CT and had RS. Maximum SUV was obtained from 18F-FDG-PET-CT; the cut-off point was 4. RESULTS: The continuous RS and SUV correlated positively (Pearson's R = 0.555; P < 0.001). An inverse correlation was found between progesterone receptor (PR) expression by reverse transcriptase-polymerase chain reaction, and SUV (Pearson's R = -0.408; P < 0.001). Good agreement between dichotomized RS (<26 vs. ≥26) and SUV (<4 vs. ≥4) was observed in 137 of 167 patients (82.0%; 95% confidence interval [CI], 76.2-87.9). Among patients with low SUV, 114 of 115 (99.1% [95% CI, 97.4-100.0]) had tumors with lower RS (<26). Although 23 of 52 women (44.2% [95% CI, 30.7-57.7]) with high SUV had higher RS (≥26), all 13 women with high RS (≥31) had high-SUV tumors. Most cases with disagreements between SUV and RS (n = 30) were classified as high SUV/lower RS (n = 29). The discordant group had higher grade or elevated Ki67 expression (≥20%) compared with the low SUV/lower RS group (n = 109), but higher PR expression compared with the high SUV/higher RS group (n = 23). Multiple logistic regression analysis showed that high SUV were associated with higher RS (≥26). CONCLUSIONS: SUV, as a biologic parameter represented using a continuous variable, was found to associate with RS in ER-positive, HER2-negative breast cancer. Further studies may reveal the biology underlying the discordance between the markers.ope

조기대장암에서 림프절 전이의 예측인자로서의 현미부수체 불안정성의 역할

Dept. of Medicine/석사Background: Surgical resection is the main treatment for early colorectal cancer because of the chance of regional lymph node metastasis. The risk of lymph node metastasis depends on pathological staging. However, even with risk factors of lymph node metastasis, more than 70% of patients who undergo surgical resection for early colorectal cancer appear not to have regional lymph node metastasis. Colorectal cancers with high-frequency microsatellite instability (MSI-H) are reported to have decreased likelihood of metastasis to either regional lymph nodes or distant organs. The aim of this study is to evaluate microsatellite instability as a predictive factor for regional lymph node metastasis.Patients and Methods: One hundred forty-seven patients with early colorectal cancer who underwent surgical resection from Jan 2011 to May 2011 were enrolled. Genomic DNA was extracted from normal and tumor tissue and amplified by polymerase chain reaction. Five microsatellite markers were used (BAT-25, BAT-26, D2S123, D5S346, and D17S250). Tumors that showed instability at 40% or more were classified as MSI-H, whereas other tumors were classified as low frequency MSI (MSI-L) or no instability (MSS). Results: Among 147 T1 colorectal cancer patients, 24 patients had lymph node metastasis. Histology, lymphovascular involvement, and depth of invasion were statistically significant factors of lymph node metastasis. MSI-high, MSI-low, and MSS colorectal cancers accounted for 7%, 5%, and 88%, respectively, of the 147 T1 colorectal cancer cases. Microsatellite status was not statistically significant in lymph node metastasis. Ten patients with MSI-H had no lymph node metastasis. There was no difference in disease-free survival or overall survival between patients with MSI-H and patients with MSI-L/MSS.Conclusions: In T1 colorectal cancer, histologic grade, presence of lymphvascular invasion, and depth of tumor invasion are the factors associated with lymph node metastasis. Although further investigation is needed, microsatellite instability may be a molecular marker of early colorectal cancer that can help predict regional lymph node metastasis.restrictio

Discharge Behaviour of an Automotive Battery

본 연구에서는 자동차에 탑재되는 배터리와 전기를 소모하는 부속장비와의 관계를 고찰하기 위하여 시뮬레이션 소프트웨어에 채용?? 특정 배터리에 대한 수식적 모델을 제시하고자 자동차 배터리의 방전 특성에 대한 실험을 수행하였다. 배터리의 service history (최근의 충.방전과 정지 시간)는 용량에 영향을 미치므로, 본 연구에서는 일정한 온도와 방전율로 제한된 조건인 한국산업표준규격에 따라 자동차용 배터리에 적용되는 중부하실험 및 경부하실험과 보유용량실험을 수행하였다. 배터리 방전시 전압의 변화를 시간과 cycle에 대한 다항식으로 변환하여 시뮬레이션 소프트웨어의 입력변수로 활용하였다.The experiments were conducted to get discharge behavior of an automotive battery. Capacity of battery is affected by the service history, and the life test should be conducted under specific condition of temperature and discharge rate. Life test of heavy load, light load, and reserve capacity were performed under the guidance of Korean industrial standard battery test. The voltage variation of the battery during life test was transformed to polynomial equation to be used as an input variable of simulation software.The experiments were conducted to get discharge behavior of an automotive battery. Capacity of battery is affected by the service history, and the life test should be conducted under specific condition of temperature and discharge rate. Life test of heavy load, light load, and reserve capacity were performed under the guidance of Korean industrial standard battery test. The voltage variation of the battery during life test was transformed to polynomial equation to be used as an input variable of simulation software

The Prognostic Impact of Early Change in 18F-FDG PET SUV After Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer

SUV, which is an indicator of the degree of glucose uptake in (18)F-FDG PET, can be applied as a prognostic factor in various malignant tumors. We investigated the prognostic impact of early changes in (18)F-FDG PET uptake in patients with locally advanced breast cancer who received neoadjuvant chemotherapy. METHODS: We retrospectively identified 87 patients who were treated with neoadjuvant chemotherapy followed by surgery for locally advanced breast cancer. All patients underwent (18)F-FDG PET at baseline and after 3 cycles of neoadjuvant chemotherapy, and the SUVmax of the primary tumor was assessed in each scan. Pathologic slides were retrospectively reviewed, and the residual cancer burden (RCB) index was calculated to estimate pathologic response. RCB-0 indicates no residual disease; patients with residual disease were categorized as RCB-1 (minimal residual disease), RCB-2 (moderate residual disease), or RCB-3 (extensive residual disease). RESULTS: There was a negative correlation between reduction in SUVmax and RCB index (r = -0.408; P 66.4%), metabolic responders had significantly better recurrence-free and overall survival than metabolic nonresponders among poor-pathologic-response patients. In contrast, among metabolic responders, there was no survival difference according to pathologic response. CONCLUSION: The early change in (18)F-FDG PET SUVmax after third-cycle neoadjuvant chemotherapy is an independent and good prognostic marker beyond pathologic response in patients with locally advanced breast cancer. We suggest that in these patients, the use of ΔSUVmax should be considered not only for the assessment of tumor response but for the prediction of posttreatment outcome.restrictio