Exploration of MELK as a downstream of Del-1 and druggable targets in triple-negative breast cancer.

PURPOSE: In our previous study, Developmental endothelial locus-1 (Del-1) was a promising predictive marker for breast cancer. However, the downstream targets of Del-1 remain unknown. Here, we sought to discover a druggable target downstream of Del-1 and investigate the mechanism by which it regulates the course of breast cancer. METHODS: To investigate Del-1 downregulation effect on breast cancer, we performed transcriptome analysis using RNA sequencing of Del-1 knockdowned MDA-MB-231 cell line Plus, to investigate the expression of Del-1 and Maternal embryonic leucine zipper kinase (MELK), mRNA levels in eight different triple-Negative Breast Cancer (TNBC) cell lines were analyzed. High-throughput sequencing was performed on total RNA isolated. OTS167 was used for MELK inhibition. The effects of MELK on cell proliferation and invasion were determined using the MTT and Matrigel transwell assays. Furthermore, we examined MELK expression in breast cancer tissue. RESULTS: Del-1 and MELK mRNA expression levels were significantly higher in the TNBC cell lines, MDA-MB-468, HCC-1806, and MBA-MB-231. Knocking down Del-1 with siRNA in HCC-1806 and MBA-MB-231 cells significantly decreased MELK expression and thus suggested a possible relationship between Del-1 and MELK. In MDA-MB-468 cells, a basal-like 1 TNBC cell line, OTS167 significantly inhibited breast cancer cell proliferation and promoted cell apoptosis. To further investigate the relationship between Del-1 and MELK, dual inhibition of both Del-1 and MELK was performed, which significantly reduced the viability of MDA-MB-468 and MBA-MB-231 cells. CONCLUSION: We found that MELK acts downstream of Del-1 and is a promising druggable target, especially in basal-like and mesenchymal stem-like subtype.

Ancistrocladus tectorius Extract Inhibits Obesity by Promoting Thermogenesis and Mitochondrial Dynamics in High-Fat Diet-Fed Mice.

Root extracts of Ancistrocladus tectorius (AT), a shrub native to China, have been shown to have antiviral and antitumor activities, but the anti-obesity effects of AT aerial parts, mainly the leaves and stems, have not been investigated. This study is the first to investigate the anti-obesity effects and molecular mechanism of AT 70% ethanol extract in 3T3-L1 adipocytes and high-fat diet (HFD)-fed C57BL/6J mice. Treatment with AT extract inhibited lipid accumulation in 3T3-L1 cells and decreased the expression of adipogenesis-related genes. AT extract also upregulated the mRNA expression of genes related to mitochondrial dynamics in 3T3-L1 adipocytes. AT administration for 12 weeks reduced body weight and organ weights, including liver, pancreas, and white and brown adipose tissue, and improved plasma profiles such as glucose, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and total cholesterol in HFD-fed mice. AT extract reduced HFD-induced hepatic steatosis with levels of liver TG and lipogenesis-related genes. AT extract upregulated thermogenesis-related genes such as Cidea, Pgc1α, Ucp1, Prdm16, Adrb1, and Adrb3 and mitochondrial dynamics-related genes such as Mff, Opa1, and Mfn2 in brown adipose tissue (BAT). Therefore, AT extract effectively reduced obesity by promoting thermogenesis and the mitochondrial dynamics of BAT in HFD-fed mice.

Ten-Year Oncologic Outcomes in T1-3N1 Breast Cancer After Targeted Axillary Sampling: A Retrospective Study.

BACKGROUND: Targeted axillary sampling (TAS) is a new surgical concept for the assessment of axillary lymph node status in breast cancer that is hypothesized to be more effective at minimizing postoperative morbidities than axillary lymph node dissection (ALND), provided the metastatic axillary lymph node can be accurately detected without missing data; however, the oncologic outcomes over long-term follow-up have not been sufficiently investigated. This was a retrospective analysis to evaluate the 10-year oncologic outcomes in T1-3N1 breast cancer after TAS. METHODS: Between 2008 and 2013, 230 female patients with cT1-3N1 breast cancer underwent breast and axillary surgery (ALND, n = 171; TAS, n = 59) at our institute. After TAS was applied, additional axillary radiotherapy was performed. Various postoperative complications, including postoperative seroma, lymphedema, and 10-year oncological outcomes, were evaluated and compared between the ALND and TAS groups. RESULTS: Although overall survival during the 10-year follow-up period was better in the TAS group, there was no statistically significant difference in oncologic outcomes, including locoregional recurrence, distant metastasis, and overall survival (p = 0.395, 0.818, and 0.555, respectively). Furthermore, the incidence of lymphedema on the ipsilateral arm was significantly higher in the ALND group (p < 0.001). CONCLUSIONS: The 10-year oncological outcomes of TAS were not inferior to those of conventional ALND in T1-3N1 breast cancers; however, the incidence of lymphedema was significantly higher in the ALND group.

A Comparison Study of Nipple-Areolar Complex Measurement: Light Detection and Ranging (LiDAR) Camera Versus Photometry.

BACKGROUND: In breast surgery, achieving esthetic outcomes with symmetry is crucial. The nipple-areolar complex (NAC) plays a significant role in breast characteristic measurement. Various technologies have advanced measurement techniques, and light detection and ranging (LiDAR) technology using three-dimensional scanning has been introduced in engineering. Increasing effort has been exerted to integrate such technologies into the medical field. This study focused on measuring NAC using a LiDAR camera, comparing it with traditional methods, and aimed to establish the clinical utility of LiDAR for obtaining favorable esthetic results. METHODS: A total of 44 patients, who underwent breast reconstruction surgery, and 65 NACs were enrolled. Measurements were taken (areolar width [AW], nipple width [NW] and nipple projection [NP]) using traditional methods (ruler and photometry) and LiDAR camera. To assess correlations and explore clinical implications, patient demographics and measurement values were collected. RESULTS: NAC measurements using a periscope and LiDAR methods were compared and correlated. LiDAR measurement accuracy was found to be high, with values above 95% for AW, NW and NP. Significant positive correlations were observed between measurements obtained through both methods for all parameters. When comparing body mass index, breast volume with AW and NW with NP, significant correlations were observed. These findings demonstrate the reliability and utility of LiDAR-based measurements in NAC profile assessment and provide valuable insights into the relationship between patient demographics and NAC parameters. CONCLUSIONS: LiDAR-based measurements are effective and can replace classical methods in NAC anthropometry, contributing to consistent and favorable esthetic outcomes in breast surgery. LEVEL OF EVIDENCE II: 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 https://www.springer.com/00266 .

Anatomical View of Thoracodorsal Artery Variants Using Computed Tomography Angiography.

BACKGROUND: The latissimus dorsi (LD) muscle has a dominant pedicle with one thoracodorsal artery and receives sufficient blood by segmental circulation through several perforators. Thus, it is widely used in various reconstructive surgeries. We are reporting on the patterns of the thoracodorsal artery analyzed by chest computed tomography (CT) angiography. METHODS: We analyzed the preoperative chest CT angiography results of 350 patients scheduled to undergo LD flap breast reconstruction following complete mastectomy for breast cancer between October 2011 and October 2020. RESULTS: A total of 700 blood vessels were classified according to the Kyungpook National University Plastic Surgery-Thoracodorsal Artery (KNUPS-TDA) classification: 388 (185 right and 203 left), 126 (64 right and 62 left), 91 (49 right and 42 left), 57 (27 right and 30 left), and 38 (25 right and 13 left) vessels were classified as type I, type II, type III, type IV, and type V, respectively. Among 350 patients, 205 patients showed matching types for left and right vessels, whereas 145 patients showed mismatching types. For 205 patients with matching types, the distribution by type was 134, 30, 30, 7, and 4 patients with type I, type II, type III, type IV, and type V, respectively. For 145 patients with mismatching types, the distribution by different combinations was 48, 25, 28, 19, 2, 9, 7, 3, 1, and 3 patients with type I + type II, type I + type III, type I + type IV, type I + type V, type II + type III, type II + type IV, type II + type V, type III + type IV, type III + type V, and type IV + type V, respectively. CONCLUSION: While there is some diversity in the vascular anatomical structures of the LD flap, the dominant vessel can be found in a similar location in almost all cases and no flap had absence of a dominant vessel. Therefore, in surgical procedures using the thoracodorsal artery as the pedicle, preoperative radiological confirmation is not absolutely necessary; however, due to variants, performing the surgery with an understanding of this aspect should lead to good outcomes.

Robot-Assisted Latissimus Dorsi Flap Harvest for Partial Breast Reconstruction: Comparison With Endoscopic and Conventional Approaches.

BACKGROUND: Latissimus dorsi muscle flaps are widely utilized in breast reconstruction. Several methods have been introduced. OBJECTIVES: The aim was to compare the outcomes of robot-assisted breast reconstruction with a latissimus dorsi muscle flap following partial mastectomy with the outcomes of conventional and endoscopic-assisted techniques. METHODS: In this prospective single-institution study, Korean females diagnosed with breast cancer who underwent partial mastectomy and breast reconstruction with a latissimus dorsi flap from March 2020 to December 2021 were included. The outcomes of surgery and patient satisfaction utilizing the conventional, endoscopic-assisted, and robot-assisted techniques were compared. RESULTS: In total, 57 patients were included in this study, among whom 20 underwent conventional reconstruction, and 17 and 20 patients underwent endoscopic and robotic surgery, respectively. There was no statistically significant difference between the 3 methods in postoperative opioid analgesic dosage (P = .459), hospitalization period (P = .225), or the average total amount of donor site drainage during hospitalization (P = .175). With regard to patient satisfaction after surgery, especially regarding the donor site scar, the conventional method showed a significantly lower score than the other 2 techniques. CONCLUSIONS: Robot-assisted breast reconstruction with a latissimus dorsi muscle flap after partial mastectomy showed higher patient satisfaction than that for the conventional open method. Because robotic surgery is more convenient than the endoscopic technique, it is potentially a good alternative to conventional open or endoscopic surgery.

Useful Reduction Mammoplasty Technique in Oncoplastic Breast Surgery and Reconstruction.

Background: A combination of the reduction mammoplasty technique and breast reconstruction allows surgeons to lift ptotic breasts through local flaps and skin reduction during surgery for breast cancer. This study presents a reliable course for the combination of partial and skin or nipple-sparing mastectomy with reduction-reconstruction surgery. Methods: Fifty-seven patients underwent a partial mastectomy before reduction mammoplasty of both breasts during the same time period between 2014 and 2021 at our institution and thirteen patients underwent skin or nipple-sparing mastectomy, breast reconstruction with an extended latissimus dorsi flap or silicone implant, and aesthetic reduction mammoplasty of the contralateral breast during the same time period. Additional photos were obtained preoperatively, immediately after the operation, and at one, three, six, and twelve months postoperatively. Patient satisfaction was evaluated preoperatively and postoperatively and postoperative complications were noted. Results: Among the patients who underwent a partial mastectomy, the mean age was 45.18 ± 11.05 years, the mean body mass index (BMI) was 26.74 ± 3.53 kg/m2, and the mean preoperative right and left breast volumes were 663.85 (±28.12) cc and 664.34 (±37.13) cc, respectively, and the mean excised mass weight was 177.74 (±213.93) g. Among the patients who underwent a skin-sparing mastectomy, the mean age was 51.62 ± 8.96 years, the mean BMI was 26.91 ± 4.34 kg/m2, and the mean preoperative right and left breast volumes were 624.17 (±98.52) cc and 562.31 (±80.81) cc, respectively, and the mean excised mass weight was 618.05 (±338.17) g. Four patients (5.3%) in the partial mastectomy group had fat necrosis. The mean patient satisfaction score was higher postoperatively in both groups. Conclusion: Patients with breast cancer and large and/or ptotic breasts can successfully undergo reduction mammoplasty for both breasts immediately following partial mastectomy and nipple or skin-sparing mastectomy.

Prepectoral breast reconstruction with complete anterior implant coverage using a single, large, square-shaped acellular dermal matrix.

BACKGROUND: Several studies have discussed various methods of prepectoral direct-to-implant (DTI) breast reconstruction using an acellular dermal matrix (ADM) prosthesis to achieve full coverage. However, methods for anterior coverage have rarely been reported. In this study, prepectoral DTI breast reconstruction with complete anterior implant coverage was performed using a square piece of ADM. This study aimed to introduce our prepectoral DTI technique and determine its functional and cosmetic outcomes as well as compare them with those of existing subpectoral DTI techniques. METHODS: This prospective comparative study focused on 29 patients (35 breasts) and 34 patients (35 breasts) who underwent breast reconstruction via subpectoral implant insertion (control group) and anterior coverage prepectoral implant insertion (anterior coverage group), respectively. Postoperative complications were noted, and breast symmetry was evaluated using the Vectra H2 three-dimensional scanner. The modified Kyungpook National University Hospital Breast-Q (KNUH Breast-Q) scale was used to assess the patient's subjective satisfaction with the reconstruction and postoperative quality of life. RESULTS: No remarkable differences in terms of complications (seroma, skin necrosis, nipple-areola complex necrosis, hematoma, capsular contracture, and infection) were noted in both groups. Compared with controls, considerably better results were observed among those in the anterior coverage group in terms of the mean drain removal period. Furthermore, those in the anterior coverage group showed greater symmetry on three-dimensional scans than the controls; however, this was not statistically significant. Subjective satisfaction and postoperative quality of life measured using the KNUH Breast-Q scale were not significantly different between both groups. CONCLUSIONS: Considering its stability, faster recovery time, and cosmetic benefit, prepectoral breast reconstruction with anterior implant coverage using a single, large ADM is a good choice to perform breast reconstruction with implant insertion in patients who have undergone mastectomy. LEVEL OF EVIDENCE: II.

Useful vertical latissimus dorsi flap for partial breast reconstruction in every tumor location.

BACKGROUND: We conducted a prospective cohort study to evaluate effective techniques for breast reconstruction after partial mastectomy due to breast cancer. Determining the method of reconstruction is often difficult as it depends on the location of the cancer and the amount of tissue excised.. Here, we present a new technique, using the vertical latissimus dorsi (LD) flap, that can be used in all partial mastectomies and can almost conceal scarring. We also compared these results to those of the mini LD flap. METHODS: We analyzed the data of a total of 50 and 47 patients, who underwent breast reconstruction with the mini LD flap and the vertical LD flap, respectively. Immediately after tumor excision, breast reconstruction was initiated. The skin flap for vertical LD was designed in a planarian shape, such that it may be hidden as much as possible and minimize bulging during closure, and the LD muscle flap was designed with a sufficient distance in the inferior direction. RESULTS: Our finding showed that the vertical LD flap group required significantly less total operation time than the mini LD flap group. While the mini-LD flap resulted in a scar that was difficult to conceal, the donor site scar of the vertical LD flap could not be seen easily, and no scar was visible on the back. CONCLUSIONS: The vertical LD flap is useful for partial breast reconstruction, in all breast regions requires a rather small volume of the flap. Moreover, recovery was relatively fast with high patient satisfaction.

Effect of Topical Tranexamic Acid on Seroma Formation in a Rat Mastectomy Model.

BACKGROUND: Seroma is the most common complication after mastectomy and reconstruction surgery. Therefore, this study aimed to determine whether the topical application of tranexamic acid would be useful to reduce seromas in a rat mastectomy model. METHODS: Forty-eight Sprague-Dawley rats were divided into four groups. After mastectomy and axillary lymph node dissection, 0.4 mL of normal saline was administered to group A in the dead space. In group B, 0.4 mL of a triamcinolone mixed solution was administered. In group C, 0.4 mL of a tranexamic acid (10 mg/kg) mixed solution was administered. In group D, 0.4 mL of a tranexamic acid (50 mg/kg) mixed solution was administered. Gross examination, assessment with micro-computed tomography (CT), quantitative analysis via aspiration, and histopathologic assessment were implemented 7 and 14 days postoperatively. RESULTS: No other complications such as wound infection and skin necrosis were observed. At postoperative week 1, groups B and C showed significantly lower seroma volume values on micro-CT (P < 0.001 and P < 0.05, respectively) and seroma volume values at aspiration (P < 0.01 and P < 0.001, respectively) than group A. According to histopathologic analysis, inflammation was observed more frequently in groups A and D than in the other groups, and angiogenesis was more active in groups B and C than in the other groups. CONCLUSIONS: Topical application of tranexamic acid was as effective as topical application of triamcinolone to prevent seroma formation. The stability of tranexamic acid was confirmed when the high dose of tranexamic acid was used. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Influence of Irradiation on Capsules of Silicone Implants Covered with Acellular Dermal Matrix in Mice.

BACKGROUND: In advanced breast cancer, radiotherapy is recommended as adjuvant therapy following breast reconstructive surgery. This inevitably led to growing concerns over possible complications of radiotherapy on implants. In this experimental animal study, we investigated the utility of acellular dermal matrix (ADM) wraps around implants as preventive management for radiotherapy complications. METHODS: Black mice (C57NL6; n = 32) were assigned to groups that either received radiation or did not: groups A and B underwent surgery using implants without radiotherapy; while groups C and D underwent surgery using implants with radiotherapy for one and three months, respectively. The hemispheric silicone implants with an 0.8-cm-diameter were inserted on the left back of each mouse, and implants wrapped by ADM were inserted on the right back. The Clinic 23EX LINAC model was used for irradiation at 10 Gy. The samples were evaluated by gross assessment, histological analysis, immunohistochemical analysis, and the Western blotting test. RESULTS: The H&E staining analysis showed that membrane thickness is smallest in group A, followed by groups C, D, and B. In a Masson trichrome histological analysis, collagen fibers became less dense and more widespread over time in the groups that received an ADM. Immunohistochemistry findings were similarly constant. However, the expression of TGF-ß1 was increased in the irradiated groups, whereas it was decreased in the non-irradiated groups as observed over time. CONCLUSIONS: Radiotherapy was shown to increase risk factors for capsular contracture, including inflammatory response, pseudoepithelium, thinning of membrane, and TGF-ß1 expression over time; however, the accompanying framework using an ADM as a barrier between implant and tissue was shown to be effective in alleviating these risks. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Survival of Breast-Conserving Surgery Plus Radiotherapy versus Total Mastectomy in Early Breast Cancer.

BACKGROUND: Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM. METHODS: In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database. RESULTS: In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392-1.707, p < 0.001) and 1.405 (95% CI 1.183-1.668, p < 0.001), respectively, favoring the BCS + RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476-2.328, p < 0.001) and 1.807 (95% CI 1.186-2.752, p = 0.006), respectively. CONCLUSIONS: Our results suggest that BCS + RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients.

Short-term serial assessment of electronic patient-reported outcome for depression and anxiety in breast Cancer.

PURPOSE: The incidence of depression and anxiety is higher in patients with breast cancer than in the general population. We evaluated the degree of depression and anxiety and investigated the changes in patients with breast cancer during the treatment period and short-term follow-up period. METHODS: Overall, 137 patients with breast cancer were evaluated using the Patient Health Questionnaire 9-item depression scale (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7). The scales were developed as a web-based electronic patient-reported outcome measure, and serial results were assessed before the operation, after the operation, in the post-treatment period, and in the 6-month follow-up period after surgery. RESULTS: The degree of depression and anxiety increased during treatment and decreased at 6-month follow-up, even if there were no statistical differences among the four periods (PHQ-9: p = 0.128; GAD-7: p = 0.786). However, daily fatigue (PHQ-9 Q4) and insomnia (PHQ-9 Q3) were the most serious problems encountered during treatment and at 6-month follow-up, respectively. In the GAD-7, worrying too much (Q3) consistently showed the highest scores during the treatment and follow-up periods. Of the patients, 7 (5.11%) and 11 (8.03%) patients had a worsened state of depression and anxiety, respectively, after treatment compared with before treatment. CONCLUSION: Most factors associated with depression and anxiety improved after treatment. However, factors such as insomnia and worrying too much still disturbed patients with breast cancer, even at 6-month follow-up. Therefore, serial assessment of depression and anxiety is necessary for such patients.

Natural course of fat necrosis after breast reconstruction: a 10-year follow-up study.

BACKGROUND: Although fat necrosis is a minor postoperative complication after breast reconstruction, occasionally it mimics to tumor recurrence in patients with breast cancer. Therefore, the surgeon should distinguish between benign fat necrosis and true local recurrence. The authors evaluated the clinical characteristics of fat necrosis after breast reconstruction and investigated the natural course of fat necrosis. METHODS: Between 2007 and 2013, a total of 362 patients underwent breast reconstruction after partial or total mastectomy for breast cancer in Kyungpook National University Hospital. Clinicopathologic characteristics and the occurrence of fat necrosis were assessed during surveillance for 10 years of mean follow-up period. RESULTS: There were 42 cases (11.6%) of fat necrosis after breast reconstruction with partial or total mastectomy which were confirmed by needle or excision biopsy. The fat necrosis was resolved after a mean period of 45.9 months (SD, ± 42.1) and 26 cases (61.9%) of fat necrosis were almost completely resolved (less than 5 mm) during 10-year follow-up period. CONCLUSION: Based on the natural course of fat necrosis, the fat necrosis after breast reconstruction can be only monitored, if pathologic confirmation was done. More than half of the cases will be resolved within 2-3 years.

The Usefulness of Endoscopic Harvesting of the Latissimus Dorsi Flap for Breast Reconstruction Using a Single-Port and CO2 Gas Insufflation Technique.

BACKGROUND: In the recent trend toward less aggressive approaches to breast reconstruction, minimally invasive harvesting of the latissimus dorsi (LD) flaps has long been a desirable goal. Endoscopically-assisted LD flap harvesting was reported as a method for minimizing scar formation and reducing donor-site morbidity. This study investigates the surgical outcomes of endoscopically-assisted immediate breast reconstruction with LD muscle flaps. MATERIALS AND METHODS: This prospective study included 21 patients who underwent endoscopically-assisted breast reconstruction with LD muscle flap and 20 patients who underwent breast reconstruction with conventional harvesting LD musculocutaneous flap. In patients with nonexcised skin or possible primary closure, the reconstruction was performed with endoscopically-assisted LD muscle flaps using the single-port and CO2 gas insufflation technique. The patients were classified into groups according to the location of the defect and mastectomy type. Moreover, patient satisfaction was investigated 6 months after surgery. RESULTS: In patients who underwent endoscopically-assisted breast reconstruction with LD muscle flaps, the scar of the donor-site was vertical, and the size was 4 cm to be obscured when lowering the arms. In comparison with patients who underwent breast reconstruction with conventional LD flaps, those who underwent endoscopically-assisted breast reconstruction with LD muscle flaps showed shorter hospital stay and no difference in patient satisfaction. CONCLUSION: Endoscopically-assisted breast reconstruction with LD flaps showed no difference in patient satisfaction with good esthetic results compared with conventional LD flaps. The endoscopic LD muscle flap harvest technique using a single-port and CO2 insufflation technique can be very useful in breast reconstruction that does not require a skin paddle. 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 .

A Prospective Study of the Efficacy of Cell-Assisted Lipotransfer with Stromal Vascular Fraction to Correct Contour Deformities of the Autologous Reconstructed Breast.

BACKGROUND: Autologous lipotransfer has increasingly become popular for breast reconstruction. Moreover, owing to the emergence of information regarding the efficacy of stromal vascular fraction (SVF) in terms of oncological safety and survival rate, procedures based on cell-assisted lipotransfer (CAL) have been widely employed recently. However, quantitative data of CAL with SVF are lacking. We evaluated the efficacy of CAL using SVF on survival rate in breast reconstruction. METHODS: A 12-month prospective study was conducted for 20 patients (20 breasts) requiring breast asymmetry correction due to volume deficit following autologous breast reconstruction using a transverse rectus abdominis myocutaneous flap or latissimus dorsi flap after total mastectomy. After the patients were equally divided into two groups-fat graft with SVF (Group 1, n = 10) and without SVF (Group 2, n = 10)-, the variance of breast volume was measured using three-dimensional scanning to analyze fat graft retention rate. Moreover, patient satisfaction and complications were investigated. RESULTS: Fat graft retention rate was higher in Group 1 than in Group 2 at both postoperative 6 months (73.8% vs. 62.2%; p = 0.03) and 12 months (65.4% vs. 48.4%; p = 0.03). Group 1 showed higher patient satisfaction. Regarding complications, fat necrosis occurred in 1 patient each in both groups. However, locoregional recurrence was not observed in any patient during follow-up. CONCLUSIONS: CAL with SVF is effective in increasing survival rates of autologous fat grafts for correction of volume deficit after breast reconstruction. Moreover, it is associated with improved patient satisfaction in terms of the esthetic aspect. 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.

Viburnum stellato-tomentosum Extract Suppresses Obesity and Hyperglycemia through Regulation of Lipid Metabolism in High-Fat Diet-Fed Mice.

The potential biological activities of Viburnum stellato-tomentosum (VS), a plant mainly found in Costa Rica, have yet to be reported. Supplementation of VS extract for 17 weeks significantly decreased body weight gain, fat weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride levels in high-fat diet (HFD)-fed C57BL/6J mice. The molecular mechanisms underlying the anti-obesity and glucose-lowering effects of VS extract were investigated. VS extract suppressed adipocyte hypertrophy by regulating lipogenesis-related CCAAT/enhancer-binding protein α (C/EBPα) and insulin sensitivity-related peroxisome proliferator-activated receptor γ (Pparg) expression in adipose tissue (AT) and hepatic steatosis by inhibiting C/EBPα and lipid transport-related fatty acid binding protein 4 (FABP4) expression. VS extract enhanced muscular fatty acid ß-oxidation-related AMP-activated protein kinase (AMPK) and PPARα expression with increasing Pparg levels. Furthermore, VS extract contained a much higher content of amentoflavone (AMF) (29.4 mg/g extract) compared to that in other Viburnum species. AMF administration decreased Cebpa and Fabp4 levels in the AT and liver, as well as improved insulin signaling-related insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1) levels in the muscle of HFD-fed mice. This study elucidated the in vivo molecular mechanisms of AMF for the first time. Therefore, VS extract effectively diminished obesity and hyperglycemia by suppressing C/EBPα-mediated lipogenesis in the AT and liver, enhancing PPARα-mediated fatty acid ß-oxidation in muscle, and PPARγ-mediated insulin sensitivity in AT and muscle.

Development of a novel denture care agent with highly active enzyme, arazyme.

BACKGROUND: The importance of efficient denture deposit removal and oral hygiene has been further underscored by the continuous increase of denture wearers. Denture hygiene management has also become an important aspect associated with denture-induced stomatitis. This study aims to evaluate the denture cleaning effect of arazyme, the metalloprotease produced from the Serratia proteamaculans HY-3. We performed growth inhibition tests against oral opportunistic pathogens to be used as a potential oral health care agent. METHODS: The proteolytic activities of arazyme was evaluated over broad ranges of temperature, pH, and denture components compared to those of subtilisin in commercially available denture cleansers. The washing effects of arazyme were also measured by using homogeneously soiled EMPA 105 cottons. To investigate the denture cleaning capability of arazyme, artificially contaminated dentures were treated with arazyme, subtilisin (Everlase 6.0T), and Polident®, respectively. The growth kinetics of Candida albicans, Enterococcus faecalis, Staphylococcus epidermis, and Streptococcus mutans were evaluated in the presence of different concentrations of arazyme to estimate the prevention effects of arazyme against major oral opportunistic pathogens. RESULTS: Arazyme showed strong proteolytic activities over wide temperature and pH ranges compared with the serine protease of the subtilisin family. Arazyme demonstrated efficient removal and decomposition of artificially contaminated dentures and showed explicit washing effects against soiled cottons. Moreover arazyme inhibited the growth of oral opportunistic pathogens, including C. albicans, E. faecalis, S. epidermis, and S. mutans, with more than 80% inhibition against C. albicans, the major cause of denture stomatitis, with 250 mg/mL arazyme. CONCLUSIONS: Arazyme shows promise as a biological oral health care agent with effective cleaning and antimicrobial activities and is a potential source for developing novel denture care agents.

Axillary Nodal Burden Assessed with Pretreatment Breast MRI Is Associated with Failed Sentinel Lymph Node Identification after Neoadjuvant Chemotherapy for Breast Cancer.

Background After publication of the findings of the American College of Surgeons Oncology Group Z1071 trial, sentinel lymph node biopsy (SLNB) has been increasingly performed in patients with breast cancer after neoadjuvant chemotherapy (NAC). Purpose To investigate the pretreatment breast MRI and clinical-pathologic characteristics associated with failed sentinel node identification after NAC in patients with breast cancer. Materials and Methods Patients who underwent SLNB after NAC between January 2015 and January 2019 were retrospectively identified. Two radiologists independently reviewed the characteristics of axillary nodes (number, perinodal infiltration, cortical thickness, and maximal diameter) at pretreatment breast MRI. The associations of the clinical-pathologic and imaging characteristics of the axillary nodes with sentinel node identification were assessed by using the χ2 test and/or the χ2 test for trend and multivariable logistic regression with odds ratio (OR) calculation. Results A total of 276 women (mean age ± standard deviation, 48 years ± 9; range, 27-68 years) were included. Sentinel nodes were identified in 252 of the 276 patients (91%). Multivariable analysis showed that higher (stage 3 or 4) clinical T stages (OR = 5.2, P = .004 for radiologist 1; OR = 4.6, P = .01 for radiologist 2), use of a single tracer (OR = 4.3, P = .04 for radiologist 1; OR = 3.9, P = .046 for radiologist 2), a greater number (10 or more) of suspicious axillary nodes (OR = 11.5, P = .002 for radiologist 1; OR = 8.3, P = .01 for radiologist 2), and the presence of perinodal infiltration (OR = 7.0, P = .002 for radiologist 1; OR = 7.5, P = .003 for radiologist 2) were associated with failed sentinel node identification. Conclusion A greater number of suspicious axillary nodes and the presence of perinodal infiltration at pretreatment MRI, higher clinical T stages, and use of a single tracer were independently associated with failed sentinel node identification after neoadjuvant chemotherapy in patients with breast cancer. © RSNA, 2020 See also the editorial by Imbriaco in this issue.

Utility of 18F-FDG PET/CT for predicting pathologic complete response in hormone receptor-positive, HER2-negative breast cancer patients receiving neoadjuvant chemotherapy.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is a predictor of improved outcomes in breast cancer. In patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative breast cancer, the response to NAC is variable and mostly limited. This study was an investigation of the predictive relevance of parameters of 18F-FDG PET/CT for the pCR to NAC in patients with HR-positive, HER2-negative breast cancer. METHODS: AH total of 109 consecutive HR-positive and HER2-negative breast cancer patients who were treated with NAC were enrolled in this prospective cohort study. The relationships between pretreatment 18F-FDG PET/CT and clinical outcomes including pathologic response to NAC were evaluated. RESULTS: All patients finished their planned NAC cycles and eight patients (7.3%) achieved pCR. In the receiver operating characteristic (ROC) curve analysis, pSUVmax exhibited high sensitivity and specificity for predicting pCR. Furthermore, multivariate logistic regression analysis revealed pSUVmax as a predictive factor for pCR (hazard ratio = 17.452; 95% CI = 1.847-164.892; p = 0.013). CONCLUSION: The results of this study suggest that 18F-FDG PET/CT pSUVmax is a predictive factor for pCR of HR-positive, HER2-negative breast cancer to NAC.