Microbiologic Profile of Nipple Swab Culture and its Association With Postoperative Complications in Prosthetic Breast Reconstruction.

BACKGROUND: In breast surgeries, a lactiferous duct leading to lactic glands of breast parenchyma allows direct contamination by normal bacterial flora of the nipple-areola complex. Complete blockage of nipple flora from the intraoperative field is almost impossible. OBJECTIVES: We aimed to analyze the microbiological profile of nipple flora of breast cancer patients who underwent an implant-based immediate breast reconstruction after a total mastectomy, and to evaluate the association of nipple bacterial flora with postoperative complications. METHODS: A retrospective chart review was performed of patients who underwent an implant-based immediate breast reconstruction after a total mastectomy. A nipple swab culture was performed preoperatively. Patient demographics, surgical characteristics, and complications were compared between positive and negative nipple swab culture groups. Microbiological profile data including antibacterial resistance were collected. RESULTS: Among 128 breasts, 60 cases (46.9%) had positive preoperative nipple swab culture results. Staphylococcus epidermidis accounted for 41.4% of microorganisms isolated. A multivariate logistic regression analysis of postoperative complications revealed that the presence of nipple bacterial flora was a risk factor for capsular contracture. Seven cases of postoperative infection were analyzed. In 2 cases (40% of pathogen-proven infection), the causative pathogen matched the patient's nipple bacterial flora, which was methicillin-resistant S. epidermidis in both cases. CONCLUSIONS: Nipple bacterial flora was associated with an increased risk of capsular contracture. Preoperative analysis of nipple bacterial flora can be an informative source for treating clinically diagnosed postoperative infections. More studies are needed to determine the effectiveness of active antibiotic decolonization of the nipple.

Value of Breast MRI and Nomogram After Negative Axillary Ultrasound for Predicting Axillary Lymph Node Metastasis in Patients With Clinically T1-2 N0 Breast Cancer.

BACKGROUND: There are increasing concerns about that sentinel lymph node biopsy (SLNB) could be omitted in patients with clinically T1-2 N0 breast cancers who has negative axillary ultrasound (AUS). This study aims to assess the false negative result (FNR) of AUS, the rate of high nodal burden (HNB) in clinically T1-2 N0 breast cancer patients, and the diagnostic performance of breast magnetic resonance imaging (MRI) and nomogram. METHODS: We identified 948 consecutive patients with clinically T1-2 N0 cancers who had negative AUS, subsequent MRI, and breast conserving therapy between 2013 and 2020 from two tertiary medical centers. Patients from two centers were assigned to development and validation sets, respectively. Among 948 patients, 402 (mean age ± standard deviation, 57.61 ± 11.58) were within development cohort and 546 (54.43 ± 10.02) within validation cohort. Using logistic regression analyses, clinical-imaging factors associated with lymph node (LN) metastasis were analyzed in the development set from which nomogram was created. The performance of MRI and nomogram was assessed. HNB was defined as ≥ 3 positive LNs. RESULTS: The FNR of AUS was 20.1% (81 of 402) and 19.2% (105 of 546) and the rates of HNB were 1.2% (5/402) and 2.2% (12/546), respectively. Clinical and imaging features associated with LN metastasis were progesterone receptor positivity, outer tumor location on mammography, breast imaging reporting and data system category 5 assessment of cancer on ultrasound, and positive axilla on MRI. In validation cohorts, the positive predictive value (PPV) and negative predictive value (NPV) of MRI and clinical-imaging nomogram was 58.5% and 86.5%, and 56.0% and 82.0%, respectively. CONCLUSION: The FNR of AUS was approximately 20% but the rate of HNB was low. The diagnostic performance of MRI was not satisfactory with low PPV but MRI had merit in reaffirming negative AUS with high NPV. Patients who had low probability scores from our clinical-imaging nomogram might be possible candidates for the omission of SLNB.

Machine learning with multiparametric breast MRI for prediction of Ki-67 and histologic grade in early-stage luminal breast cancer.

OBJECTIVES: To investigate whether machine learning-based prediction models using 3-T multiparametric MRI (mpMRI) can predict Ki-67 and histologic grade in stage I-II luminal cancer. METHODS: Between 2013 and 2019, consecutive women with luminal cancers who underwent preoperative MRI with diffusion-weighted imaging (DWI) and surgery were included. For prediction models, morphology, kinetic features using computer-aided diagnosis (CAD), and apparent diffusion coefficient (ADC) at DWI were evaluated by two radiologists. Logistic regression analysis was used to identify mpMRI features for predicting Ki-67 and grade. Diagnostic performance was assessed using eight machine learning algorithms incorporating mpMRI features and compared using the DeLong method. RESULTS: Of 300 women, 203 (67.7%) had low Ki-67 and 97 (32.3%) had high Ki-67; 242 (80.7%) had low grade and 58 (19.3%) had high grade. In multivariate analysis, independent predictors for higher Ki-67 were washout component > 13.5% (odds ratio [OR] = 4.16; p < 0.001) and intratumoral high SI on T2-weighted image (OR = 1.89; p = 0.022). Those for higher grade were washout component > 15.5% (OR = 7.22; p < 0.001), rim enhancement (OR = 2.59; p = 0.022), and ADC value < 0.945 × 10-3 mm2/s (OR = 2.47; p = 0.015). Among eight models using these predictors, six models showed the equivalent performance for Ki-67 (area under the receiver operating characteristic curve [AUC]: 0.70) and Naive Bayes classifier showed the highest performance for grade (AUC: 0.79). CONCLUSIONS: A prediction model incorporating mpMRI features shows good diagnostic performance for predicting Ki-67 and histologic grade in patients with luminal breast cancers. KEY POINTS: • Among multiparametric MRI features, kinetic feature of washout component >13.5% and intratumoral high signal intensity on T2-weighted image were associated with higher Ki-67. • Washout component >15.5%, rim enhancement, and mean apparent diffusion coefficient value < 0.945 × 10-3 mm2/s were associated with higher histologic grade. • Machine learning-based prediction models incorporating multiparametric MRI features showed good diagnostic performance for Ki-67 and histologic grade in luminal breast cancers.

A Comparison of Aesthetic Outcomes of Umbilicoplasty in Breast Reconstruction with Abdominal Flap: Inverted-U Versus Vertical Oval Incision.

BACKGROUND: The umbilicus is a key aesthetic unit of the abdominal wall. It contributes to the natural curvature of the abdomen and is now considered as one of the most important factors in the overall results and patient satisfaction. In this study, we present an inverted-U incisional technique for umbilicoplasty. This study aims to describe the senior author's approach to umbilicoplasty and compare the aesthetic outcomes of the inverted-U method with those of the vertical oval incisional technique. METHODS: In this retrospective cohort study, we analyzed a total of 109 patients including 51 who underwent umbilicoplasty with the inverted-U incisional technique and 58 who had surgery with the vertical oval incisional method. With the description of our operative technique, the aesthetic outcomes of both techniques were compared by two independent surgeons using a 5-point Likert scale in terms of shape, size, depth, natural appearance and periumbilical scarring. Also, the total scores of the five items were calculated to give a final score for each patient (range, from 5 to 25 points). RESULTS: On all measured parameters, the inverted-U incisional technique produced favorable outcomes compared with the vertical oval incisional technique. Also, the inverted-U incisional technique was given significantly higher total scores than was the vertical oval incisional technique (inverted-U 14.73 ± 2.47 vs. vertical oval 11.26 ± 3.02, p = 0.002). CONCLUSIONS: In this study, an inverted-U incisional technique produced significantly favorable outcomes in terms of shape, size, depth, natural appearance and overall score compared to a vertical oval incision (p < 0.05). We believe that this technique enables surgeons to achieve a better shape, natural retrusive appearance and superior hood. LEVEL OF EVIDENCE III: In this study, an inverted-U incisional technique produced significantly favorable outcomes in terms of shape, size, depth, natural appearance and overall score compared to a vertical oval incision (p < 0.05). We believe that this technique enables surgeons to achieve a better shape, natural retrusive appearance and superior hood.

Characteristics and prognosis of 17 special histologic subtypes of invasive breast cancers according to World Health Organization classification: comparative analysis to invasive carcinoma of no special type.

BACKGROUND: Breast cancer is a heterogeneous disease with various histopathologic subtypes. Except for invasive carcinoma of no special type (NST), other subtypes are rare with limited data. The purpose of this study was to analyze the characteristics and prognosis of special histopathologic subtypes of breast cancer compared to NST. METHODS: A total of 136,140 patients were analyzed using the Korean Breast Cancer Society Registry database between January 1996 and March 2019. The clinicopathologic features and survival outcomes of special type breast carcinoma were compared with those of NST. RESULTS: The prevalence of special subtypes other than NST was 13.7% (n = 18,633). Compared to NST, patients with lobular, medullary, metaplastic, and micropapillary carcinoma had larger tumors (p < 0.001). Patients with mucinous, tubular, medullary, metaplastic, and cribriform carcinoma presented with less node metastasis (p < 0.001), contrary to patients with micropapillary carcinoma. Patients with lobular, mucinous, tubular, papillary, and cribriform carcinoma presented as luminal A subtype much more often (p < 0.001). Micropapillary carcinoma included more luminal B subtype (p < 0.001). Typically, medullary and metaplastic carcinoma included more triple-negative subtypes (p < 0.001). In survival analysis, only medullary (Hazard Ratio (HzR) 0.542, 95% CI 0.345 to 0.852, p = 0.008) and metaplastic carcinoma (HzR 1.655, 95% CI 1.317 to 2.080, p < 0.001) showed significantly different overall survival from NST by multivariate analysis. CONCLUSION: Breast cancer had distinct clinicopathologic features according to histopathologic subtype. However, special types of breast cancer had similar survival outcomes compared to NST when adjusting for other prognostic factors, except for metaplastic carcinoma and medullary carcinoma.

Clinical Experience with Treatment of Aquafilling Filler-Associated Complications: A Retrospective Study of 146 Cases.

BACKGROUND: Aquafilling filler is used for breast and buttock augmentation, which are the most commonly performed cosmetic surgery procedures. However, complications after using Aquafilling filler for breast augmentation have been reported, and there are concerns regarding its use in large areas, such as the buttocks. We provide our experience with complications after breast augmentation and buttock augmentation using Aquafilling filler. METHODS: This observational cohort study analyzed the data of 399 patients treated for filler-related complications at our institutes from September 2015 to November 2019. Of these patients, 146 underwent surgery to remove Aquafilling filler from the breast or buttock. RESULTS: The mean time between Aquafilling filler use and complication onset was 38.5 ± 10.2 months. The average amount of filler material removed from one side of the breast or buttock was 285.5 ± 95.8 mL (range 150-750 mL). The most common complications were induration and masses (83.6%), followed by pain (52.1%), firmness (24.7%), asymmetry (10.3%), migration (8.2%), mastitis (6.8%), dimpling (6.2%), fever (3.4%), and sepsis (n = 1). After treatment, there was no recurrence of infection, and the patient satisfaction level based on the visual analogue scale was 8.0 ± 0.9. CONCLUSIONS: Although Aquafilling filler is easily injectable and has long-term clinical effects, complications can occur. Furthermore, there are concerns regarding its toxicity and influence on the surrounding tissues. Hence, further research studies on Aquafilling filler and evidence regarding its long-term safety are needed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

EGFR is a Therapeutic Target in Hormone Receptor-Positive Breast Cancer.

BACKGROUND/AIMS: Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models. METHODS: Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates. Levels of mRNA and protein expression were analyzed by real-time PCR and western blotting, respectively. Cell viability was analyzed by MTT assays and anchorage-independent growth by soft agar colony-formation assays. Efficacy of tamoxifen and/or gefitinib was analyzed using orthotopic xenograft mouse models. RESULTS: EGFR expression was significantly associated with more advanced stage and higher grade. EGFR expression was different in luminal A-like (Lum A, 1.3%) versus luminal B-like (Lum B, 11.4%) subtypes. On multivariate analyses for survival Lum B subtype EGFR+ tumors showed a hazard ratio (HR) of 5.22 (95% CI, 1.29-21.15, P = 0.020) for overall survival (OS) and HR of 2.91 (95% CI, 1.35-6.28, P = 0.006) for disease-free survival (DFS). Levels of EGFR inversely correlated with ER-α expression. Basal ER-α level was completely blocked by TGFA or EGF treatment. With TGFA pretreatment, ER+ breast cancer cells were resistant to 4-hydroxytamoxifen (4-OHT). Conversely, downregulation of ER-α by TGFA was reversed by gefitinib with recovered sensitivity to 4-OHT. Tumorigenicity of EGFR and ER+ breast cancer cells were significantly decreased by combined tamoxifen and gefitinib. CONCLUSION: Aberrant EGFR expression was associated with poor prognosis in ER+ breast cancers, especially the Lum B subtype. Loss of ER by EGFR activation induced tamoxifen resistance. Therefore, EGFR could be a therapeutic target for overcoming recurrence of ER+ breast cancer with high EGFR expression.

The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients: data from the Korean Breast Cancer Society Registry.

PURPOSE: Tumor markers such as carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are widely used for monitoring breast cancer. However, the prognostic efficacy of preoperative elevations of CEA and CA15-3 levels in breast cancer patients remains controversial. METHODS: We retrospectively analyzed the clinicopathological parameters of 149,238 patients in the Korean Breast Cancer Society Registry Database who underwent surgery between January 2000 and December 2015. RESULTS: The patients with elevated CA15-3/CEA levels had worse overall survival (OS) than the patients with normal CA15-3/CEA levels. For the luminal A subtype, the CA15-3- and CEA-elevated group had a hazard ratio (HR) of 2.14 (95% CI 1.01-4.55). The CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68) compared to the normal group. For the luminal B subtype, the CA15-3- and CEA-elevated group had an HR of 3.99 (95% CI 2.23-7.16), whereas the CA15-3-elevated group had an HR of 2.38 (95% CI 1.58-3.58) and the CEA-elevated group had an HR of 1.79 (95% CI 1.20-2.68). For the HER2 subtype, elevated CEA level was the only independent prognostic factor. However, for the triple-negative breast cancer (TNBC) subtype, elevated preoperative CEA and CA15-3 levels were not significant prognostic factors for OS. CONCLUSION: Preoperative CEA and CA15-3 levels showed varying prognostic ability according to breast cancer subtype. Preoperative CA15-3 and CEA elevation are significant prognostic factors for luminal breast cancer, but they were not significant factors for TNBC.

Clinical subtypes and prognosis in breast cancer according to parity: a nationwide study in Korean Breast Cancer Society.

PURPOSE: We explored the association between parity and the risk of developing a specific subtype of breast cancer. We also assessed the association between parity and prognosis according to subtypes. METHODS: A total of 158,189 patients were enrolled in the Korean Breast Cancer Society Registry database between 1996 and 2015 in Korea. The database provided information on sex, age, number of parity, surgical method, stage, histological findings, presence of biologic markers, adjuvant therapy, and date and cause of death. RESULTS: The patients with higher parity showed a higher ratio of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) subtypes. In univariate analysis, women with TNBC who had more than three children had a worse prognosis compared to other groups (HR 1.83; 95% CI 1.34-2.49; P < 0.001). This association was also observed in women younger than 50 years (HR 1.63; 95% CI 1.07-2.48; P = 0.021). In multivariate analysis stratified by subtypes, women who had more than three children were associated with a worse prognosis in TNBC in the total population (HR 1.53; 95% CI 1.11-2.12; P = 0.011). This association was also observed in patients younger than 50 years of age (HR 1.53; 95% CI 1.09-2.61; P = 0.017). CONCLUSION: Women who had more than three children were more likely to develop hormone receptor-negative (HR-) subtypes. Women who had more than three children were associated with worse prognosis in patients younger than 50 years of age and in patients with TNBC.

Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases.

Bone metastasis is the terminal stage disease of prostate, breast, renal, and lung cancers, and currently no therapeutic approach effectively cures or prevents its progression to bone metastasis. One of the hurdles to the development of new drugs for bone metastasis is the complexity and heterogeneity of the cellular components in the metastatic bone microenvironment. For example, bone cells, including osteoblasts, osteoclasts, and osteocytes, and the bone marrow cells of diverse hematopoietic lineages interact with each other via numerous cytokines and receptors. c-Met tyrosine kinase receptor and its sole ligand hepatocyte growth factor (HGF) are enriched in the bone microenvironment, and their expression correlates with the progression of bone metastasis. However, no drugs or antibodies targeting the c-Met/HGF signaling axis are currently available in bone metastatic patients. This significant discrepancy should be overcome by further investigation of the roles and regulation of c-Met and HGF in the metastatic bone microenvironment. This review paper summarizes the key findings of c-Met and HGF in the development of novel therapeutic approaches for bone metastasis.

Clinical subtypes and prognosis of pregnancy-associated breast cancer: results from the Korean Breast Cancer Society Registry database.

PURPOSE: We analyzed the clinicopathologic characteristics and prognosis of pregnancy-associated breast cancer (PABC) according to clinical subtypes to better understand the characteristics of PABC. METHODS: A total of 83,792 female patients between the ages of 20 and 49 were enrolled in the Korean Breast Cancer Society Registry database from January 1, 1996 to December 31, 2015. 'PABC' is defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. Other patients were defined as 'non-PABC' patients. RESULTS: In non-PABC patients, luminal A subtype was the most common (50.2%). In PABC patients, TNBC was the most common (40.4%) subtype, while luminal A comprised 21.2% and HER2 subtype comprised 17.3%. There was a significant difference in overall survival (OS). In non-PABC patients, TNBC had the highest HR (HR 2.3, 95% CI 2.1-2.6). In PABC patients, the luminal B subtype (HR+ HER2-high Ki67) had the highest HR at 7.0 (95% CI 1.7-29.1). In multivariate analysis of OS by subtypes, PABC patients had significantly higher HR than non-PABC patients in the HER2 subtype (HR 2.0, 95% CI 1.1-3.7) and luminal B subtype (HR+ HER2-high Ki67) (HR 4.4, 95% CI 1.6-12.3). CONCLUSION: PABC showed different biologic features than non-PABC. PABC had a particularly poor prognosis in the luminal B (HR+ HER2-highKi67) and HER2 subtypes. To improve the prognosis of PABC, treatment should be considered according to subtype. Development of drugs that can be used during pregnancy is needed.

Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer.

PURPOSE: TP53 mutation is the most common mutation in breast cancer, and it is considered a target marker of triple-negative breast cancer (TNBC). We investigated whether expression of p53 detected by immunochemical staining predicts the chemotherapy response of TNBC. METHODS: A total of 11,393 TNBC patients who had between stage I and stage III enrolled in the Korean Breast Cancer Society Registry database from January 1, 2000 to December 31, 2015. There were 6,331 'p53-positive (+) TNBC' patients and 5062 'p53-negative (-) TNBC' patients. RESULTS: In univariate analysis, p53(+) TNBC had a worse prognosis than p53(-) TNBC in patients not receiving chemotherapy (P = 0.003). However, there was no difference in prognosis between p53(+) TNBC and p53(-) TNBC for patients receiving chemotherapy. In multivariate analysis adjusted for age and stage, the risk of p53(+) TNBC was 1.84 times higher than that of p53(-) TNBC in the non-chemotherapy group. However, there was no difference between p53(+) TNBC and p53(-) TNBC in patients receiving chemotherapy. In p53(+) TNBC, the risk was 0.6-fold lower when chemotherapy was administered than when chemotherapy was not administered. However, in p53(-) TNBC, there was no risk reduction effect by chemotherapy. CONCLUSION: The prognosis of p53(+) TNBC has worse than p53(-) TNBC, but the risk for survival was significantly reduced with chemotherapy. It suggests that p53(+) TNBC would be more sensitive to chemotherapy than p53(-) TNBC.

Incidence and risk factors for congestive heart failure in patients with early breast cancer who received anthracycline and/or trastuzumab: a big data analysis of the Korean Health Insurance Review and Assessment service database.

PURPOSE: We aimed to analyze the incidence, time to occurrence, and congestive heart failure (CHF) risk factors for early breast cancer patients treated with anthracycline (AC)-based chemotherapy and/or trastuzumab (T) therapy in Korea. METHODS: We included female patients > 19 years old from the Health Insurance Review and Assessment Service database who had no prior CHF history and had been diagnosed with early breast cancer between January 2007 and October 2016. RESULTS: We included 83,544 patients in our analysis. In terms of crude incidence for CHF, AC followed by T showed the highest incidence (6.3%). However, 3.1 and 4.2% of the patients had CHF due to AC-based chemotherapy and non-AC followed by T, respectively. The median times to occurrence of CHF were different according to adjuvant treatments, approximately 2 years (701.0 days) in the AC-based chemotherapy group vs 1 year (377.5 days) AC followed by T group. T therapy was associated with earlier development of CHF irrespective of previous chemotherapy, but late risk of CHF 1.2 years after T therapy rapidly decreased in both chemotherapy groups. Multivariate Cox regression analysis revealed that the adjusted hazard ratio for CHF was increased in the group of older patients (≥ 65 years old) who underwent AC followed by T therapy, with Charlson comorbidity index scores of ≥ 2. CONCLUSIONS: Our study showed that neo-/adjuvant chemotherapy using T irrespective of previous chemotherapy (AC or non-AC) was associated with significantly increased risk of CHF compared with AC-based chemotherapy in Korean patients with early breast cancer.

Clinical Characteristics and Prognosis of Pregnancy-Associated Breast Cancer: Poor Survival of Luminal B Subtype.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is rare and is generally defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. The average ages of marriage and childbearing are increasing, and PABC is expected to also increase. This study is intended to increase understanding of the characteristics of PABC. METHODS: A database of 2,810 patients with breast cancer diagnosed when they were less than 40 years of age was reviewed. The clinicopathological factors and survival of PABC (40 patients) were compared to those of patients with young breast cancer (YBC, non-pregnant or over 12 months after delivery; 2,770 patients). RESULTS: PABC had significantly lower estrogen receptor (ER) and progesterone receptor (PR) expression (ER-positive 50.0%, PR-positive 45.0%) and higher HER2 overexpression (38.5%) than YBC. The most common subtype of PABC was triple-negative breast cancer (TNBC; 35.9%), and luminal A subtype represented only 7.7% of cases. In univariate analysis, PABC had significantly worse disease-free survival (DFS) and breast cancer-specific survival (BCSS) compared to YBC. In multivariate analysis, PABC was associated with worse BCSS (HR 4.0, 95% CI 1.2-12.9, p = 0.019) and survival, but there was no difference in DFS between PABC and YBC. In subgroup analysis by subtype, luminal B subtype of PABC showed worse DFS (HR 3.5; 95% CI 1.1-11.2, p = 0.039) and BCSS (HR 10.2, 95% CI 1.2-87.1, p = 0.035), especially with high Ki67. However, no differences were demonstrated in other subtypes. CONCLUSION: In this study, PABC showed lower expression of ER/PR, higher overexpression of HER2, fewer luminal A subtype, and more TNBC subtype compared to YBC. PABC had worse BCSS, especially luminal B subtype, compared to YBC.

Additional value of diffusion-weighted imaging to evaluate multifocal and multicentric breast cancer detected using pre-operative breast MRI.

OBJECTIVES: To investigate whether diffusion-weighted imaging (DWI) aids pre-operative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate additional lesions in breast cancer patients. METHODS: DCE-MRI and DWI were performed on 131 lesions, with available histopathological results. The apparent diffusion coefficient (ADC) of each lesion was measured, and the cut-off value for differentiation between malignant and benign lesions was calculated. A protocol combining the ADC cut-off value with DCE-MRI was validated in a cohort of 107 lesions in 77 patients. RESULTS: When an ADC cut-off value of 1.11 × 10-3 mm2/s from the development cohort was applied to the additional lesions in the validation cohort, the specificity increased from 18.9% to 67.6% (P < 0.001), and the diagnostic accuracy increased from 61.7% to 82.2% (P = 0.05), without significant loss of sensitivity (98.6% vs. 90.0%, P = 0.07). The negative predictive values of lesions in the same quadrant had decreased, as had those of lesions ≥1 cm in diameter. The ADC cut-off value in the validation cohort was 1.05 × 10-3 mm2/s. CONCLUSIONS: Additional implementation of DWI for breast lesions in pre-operative MRI can help to obviate unnecessary biopsies by increasing specificity. However, to avoid missing cancers, clinicians should closely monitor lesions located in the same quadrant or lesions ≥1 cm. KEY POINTS: • DWI can be used to further differentiate lesions during pre-operative cancer staging. • ADC cut-off values were similar in the development and validation cohorts. • DWI improves both PPV and NPV in cases of multicentric lesions. • DWI improves both PPV and NPV in lesions <1 in diameter. • NPVs are decreased in multifocal lesions and lesions ≥1 cm in diameter.

Comparison of skin-sparing mastectomy using LigaSure™ Small Jaw and electrocautery.

BACKGROUND: Skin-sparing mastectomy (SSM) is increasingly used in patients with breast cancer. We compared the differences between use of electrocautery and LigaSure™ Small Jaw in patients with breast cancer who underwent SSM. METHODS: Between January 2012 and December 2015, 81 patients with breast cancer who underwent SSM were selected and were divided into the electrocautery group and the LigaSure™ Small Jaw group based on the devices that were used. Clinicopathological characteristics, body mass index, operative time, and weight of removed breast were obtained from medical records. Total amount and days of drain use, until removal, and postoperative skin necrosis, requiring debridement, were also analyzed. RESULTS: The study population consisted of 50 patients in the electrocautery group and 31 in the LigaSure™ Small Jaw group. The latter group has significantly shorter operative time (117.5 ± 16.9 vs. 104.0 ± 23.6 min, P = 0.004). The mean total volume of drainage was less (805 ± 278 vs. 694 ± 131 mL, P = 0.017) and mean duration of drainage was also significantly shorter in the LigaSure™ Small Jaw group (11.3 ± 2.5 vs. 10.1 ± 2.0 days, P = 0.029). CONCLUSIONS: The use of LigaSure™ Small Jaw during skin-sparing mastectomy shortened the operative time and duration of drainage and reduced the total volume of drainage.

Pre-ablation stimulated thyroglobulin is a better predictor of recurrence in pathological N1a papillary thyroid carcinoma than the lymph node ratio.

BACKGROUND: Papillary thyroid carcinomas (PTC) with lymph node metastases have a high recurrence rate. We analyzed the potential of lymph node ratio (LNR) and the level of pre-ablation stimulated thyroglobulin (sTg) as risk factors predicting recurrence in patients with pathological N1a PTC. MATERIALS AND METHODS: This study involved 192 patients with pathologically confirmed PTC and central neck lymph node metastases who underwent total thyroidectomy with central lymph node dissection (CLND). The clinico-pathological characteristics, the pre-ablation sTg level and post-treatment recurrences were examined. Univariate and multivariate analyses were performed to identify factors associated with recurrence in these patients. RESULTS: During a median follow-up of 63 months, 17 patients had loco-regional recurrences. Receiver operating characteristic curve analysis showed that the appropriate cut-off values for LNR and the pre-ablation sTg level was 0.48 and 9.3 ng/mL, respectively. Patients with LNR values of ≥0.48 had a significantly worse disease-free survival (DFS) than those with LNR values of <0.48 (P = 0.015), and patients with pre-ablation sTg level values of ≥9.3 ng/mL had significantly worse DFS than those with pre-ablation sTg level values <9.3 ng/mL (P < 0.001). Relative to patients with LNR values of <0.48, those with LNR values of ≥0.48 had higher median pre-ablation sTg level values (0.55 vs. 4.20; P < 0.001). The correlation covariant between the LNR value and the pre-ablation sTg level value was r = 0.454 (P < 0.001). Multivariate analysis showed that a LNR value of ≥0.48 (P = 0.386) was not an independent risk factor for recurrence. To the contrary, a pre-ablation sTg level value of ≥9.3 ng/mL (P < 0.001) was an independent risk factor for recurrence. CONCLUSION: A high pre-ablation sTg level is a better predictor of recurrence in pathological N1a PTC than a high LNR value. Careful follow-up of patients with this risk factor is recommended.

Robotic thyroidectomy using bilateral axillo-breast approach: Comparison of surgical results with open conventional thyroidectomy.

BACKGROUND: The aim of the present study was to compare the surgical outcomes of robotic thyroidectomy using the bilateral axillo-breast approach (BABA) with open conventional thyroidectomy. METHODS: Database of patients who underwent thyroidectomy with cervical lymph node dissection after diagnosed as papillary thyroid carcinoma between July 2008 and February 2013 were examined. Clinicopathologic characteristics, surgical outcomes, and postoperative morbidities of robot group and open group were investigated. RESULTS: The dominant tumor size (P=0.974), body mass index (BMI) (P=0.426), and the mean number of metastatic lymph nodes in central compartment neck dissection (P=0.269) were comparable between the two groups. The mean number of retrieved central lymph nodes was higher in the open group than in the robot group (P=0.001). Postoperative complications were comparable: hypoparathyroidism in 2 weeks (P=0.296) and 3 months (P=0.446) after the surgery; vocal cord palsy in 2 weeks (P=0.363) and 3 months (P=0.312); hematoma (P=0.162); and wound infection (P=0.421). CONCLUSIONS: Robotic thyroidectomy using BABA may be a technically feasible and safe procedure comparable to conventional open surgery especially in node-negative patients.

Effect of Antiadhesion Barrier Solution and Fibrin on Capsular Formation After Silicone Implant Insertion in a White Rat Model.

INTRODUCTION: One of the most serious complications of breast reconstruction and augmentation using silicone implants is capsular contracture. Several preventive treatments, including vitamin E, steroids, antibiotics, and cysteinyl leukotriene inhibitors, have been studied, and their clinical effects have been reported. However, the problem of capsular contracture has not yet been completely resolved. This study was performed to compare anti-adhesion barrier solution (AABS) and fibrin in their ability to prevent fibrotic capsule formation and simultaneously evaluated their effect when used in combination by capsular thickness analysis and quantitative analysis of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and type I collagen within the fibrous capsule. MATERIALS AND METHODS: This study used female six-week-old Sprague-Dawley rats. Eighty rats were equally subdivided into the four following groups: AABS-treated, fibrin-treated, AABS and fibrin combined-treated, and untreated control groups. Each rat received two silicone chips under the panniculus carnosus muscle layer. The test materials were applied around the silicon chips. Four weeks later, the implantation sites including the skin and muscle were excised to avoid the risk of losing the fibrous capsule around the implants. The capsular thickness was analyzed by Masson's trichrome stain. Quantitative analysis of type I collagen, MMPs, and TIMPs was performed by real-time PCR, Western blot, and zymography. RESULTS: The mean capsular thickness was 668.10 ± 275.12 µm in the control group, 356.97 ± 112.11 µm in the AABS-treated group, 525.96 ± 130.97 µm in the fibrin-treated group, and 389.24 ± 130.51 µm in the AABS and fibrin combined-treated group. Capsular thickness was significantly decreased in all experimental groups (p < 0.05). Capsular thickness was greater in the fibrin-treated group than in the AABS-treated group (p < 0.05). There was no statistically significant difference in capsular thickness between the AABS and fibrin combined-treated group and the AABS- or fibrin-treated group (p > 0.05). Compared to the control group, the experimental groups had significantly lower expressions of type I collagen and MMP-1 (p < 0.05), but there was no statistically significant difference in expressions of type I collagen and MMP-1 between the AABS-, fibrin-, and AABS and fibrin combined-treated groups (p > 0.05). The expressions of MMP-2 and TIMP-2 were not significantly different between the control and the experimental groups (p > 0.05). CONCLUSION: AABS is more effective in reducing capsular thickness compared with fibrin treatment in a white rat model.

HER3 status by immunohistochemistry is correlated with poor prognosis in hormone receptor-negative breast cancer patients.

Breast cancer is a highly heterogeneous malignancy. The triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer subtypes are highly aggressive and are associated with a poor prognosis. The therapeutic targets for TNBC remain undefined, and many patients with the HER2 subtype acquire resistance to therapy after prolonged treatment. The objective of this study was to evaluate the prognostic significance of HER3 expression in invasive breast carcinoma. We established matched tissue microarray (TMA) blocks and clinical data from 950 cases of invasive breast carcinoma with long-term clinical follow-up data (median 109.7 months). Using the TMAs, we characterized the expression of ER, PR, HER2, EGFR, and HER3 by immunohistochemistry. Each case was classified as one of four IHC-based subtypes based on the expression of hormonal receptor (HR) and HER2. The clinicopathological characteristics and survival of 950 patients were analyzed by subtype. In the TNBC subtype, the HER3(+) group showed poorer disease-free survival (DFS, P = 0.010) and overall survival (OS, P = 0.015) than the HER3(-) group. In the HER2 subtype, the HER3(+) group also showed poorer DFS (P = 0.022) and OS (P = 0.077) than the HER3(-) group. However, there was no difference in patients with HR-positive breast cancer. HER3 expression was associated with poor DFS in both the TNBC and HER2 subtypes and poor OS in the TNBC subtype. HER3 overexpression is an important prognostic marker in hormone receptor-negative breast cancer, and further study is needed to clarify the role of HER-3 targeted treatment.