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.

Importance of multimodal resident education curriculum for general surgeons: perspectives of trainers and trainees.

PURPOSE: Satisfaction should be prioritized to maximize the value of education for trainees. This study was conducted with professors, fellows, and surgical residents in the Department of general surgery (GS) to evaluate the importance of various educational modules to surgical residents. METHODS: A questionnaire was administered to professors (n = 28), fellows (n = 8), and surgical residents (n = 14), and the responses of the three groups were compared. Four different categories of educational curricula were considered: instructor-led training, clinical education, self-paced learning, and hands-on training. RESULTS: The majority of surgeons regarded attending scrubs as the most important educational module in the training of surgical residents. However, while professors identified assisting operators by participating in surgery as the most important, residents assessed the laparoscopic training module with animal models as the most beneficial. CONCLUSIONS: The best educational training course for surgical residents was hands-on training, which would provide them with several opportunities to operate and perform surgical procedures themselves.

Genomic and Spectroscopic Signature-Based Discovery of Natural Macrolactams.

The logical and effective discovery of macrolactams, structurally unique natural molecules with diverse biological activities, has been limited by a lack of targeted search methods. Herein, a targeted discovery method for natural macrolactams was devised by coupling genomic signature-based PCR screening of a bacterial DNA library with spectroscopic signature-based early identification of macrolactams. DNA library screening facilitated the efficient selection of 43 potential macrolactam-producing strains (3.6% of 1,188 strains screened). The PCR amplicons of the amine-deprotecting enzyme-coding genes were analyzed to predict the macrolactam type (α-methyl, α-alkyl, or ß-methyl) produced by the hit strains. 1H-15N HSQC-TOCSY NMR analysis of 15N-labeled culture extracts enabled macrolactam detection and structural type assignment without any purification steps. This method identified a high-titer Micromonospora strain producing salinilactam (1), a previously reported α-methyl macrolactam, and two Streptomyces strains producing new α-alkyl and ß-methyl macrolactams. Subsequent purification and spectroscopic analysis led to the structural revision of 1 and the discovery of muanlactam (2), an α-alkyl macrolactam with diene amide and tetraene chromophores, and concolactam (3), a ß-methyl macrolactam with a [16,6,6]-tricyclic skeleton. Detailed genomic analysis of the strains producing 1-3 identified putative biosynthetic gene clusters and pathways. Compound 2 displayed significant cytotoxicity against various cancer cell lines (IC50 = 1.58 µM against HCT116), whereas 3 showed inhibitory activity against Staphylococcus aureus sortase A. This genomic and spectroscopic signature-based method provides an efficient search strategy for new natural macrolactams and will be generally applicable for the discovery of nitrogen-bearing natural products.

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.

Mastectomy with Reconstruction Including Robotic Endoscopic Surgery (MARRES): a prospective cohort study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) and Korean Breast Cancer Study Group (KBCSG).

BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) has emerged as a new treatment option for breast cancer and risk-reducing mastectomy (RRM) for women who have a high risk of pathogenic variants. Even though several studies have reported that RNSM is a feasible procedure, some argue that it should only be performed by specialized surgeons, and data on oncologic outcomes and patient-reported outcomes (PROs) are limited. Recently, the United States Food and Drug Administration and several surgeons warned that robotic breast surgery should be performed only by specialized surgeons and recommended that the benefits, risks, and alternatives of all available treatment options be discussed with patients so they can make informed treatment decisions. The Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) has been established to evaluate, standardize, and teach this state-of-the-art procedure. We have designed a multicenter prospective cohort study entitled Mastectomy with Reconstruction Including Robot Endoscopic Surgery (MARRES) to report surgical, PRO, and oncologic outcomes. METHODS: MARRES is a multi-institution cohort study prospectively collecting data from patients undergoing mastectomy and reconstruction. The patient inclusion criteria are adult women older than 19 with breast cancer or a high risk of breast cancer (patients with BRCA1/2, TP53, PALB2 mutations, etc.), who have scheduled therapeutic or RRM and want immediate reconstruction. Surgical outcomes, including pre- and postoperative photos, oncologic outcomes, cost-effectiveness, and PRO, are collected. The primary endpoints are postoperative complication rates within 30 postoperative days and the Clavien-Dindo grade of postoperative complications within 180 postoperative days. The secondary endpoints are 5-year postoperative recurrence-free survival and cancer incidence rate (for those who underwent RRM), patient satisfaction with reconstruction expectations preoperative (baseline) and results within 6 to 12 postoperative months, surgeon satisfaction with postoperative results in 6 postoperative months, and cost-effectiveness of the definitive surgery. Patient recruitment will be completed in April 2025, and the target number of enrolled patients is 2000. DISCUSSION: This study will provide evidence about the surgical outcomes, oncologic outcomes, and patient satisfaction with RNSM and endoscopic nipple-sparing mastectomy (NSM), compared with conventional NSM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04585074. Registered April 8, 2020.

A Comprehensive Landscape of De Novo Malignancy After Double Lung Transplantation.

Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.

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.

Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society.

BACKGROUND: There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody-drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. METHODS: Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan-Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups. RESULTS: HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49-0.93; P = 0.019). CONCLUSIONS: These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

Robot-assisted Nipple-sparing Mastectomy With Immediate Breast Reconstruction: An initial Experience of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG).

OBJECTIVE: The aim of this study was to present the results of early experience of robot-assisted nipple sparing mastectomy (RANSM). BACKGROUND: RANSM improves cosmetic outcomes over conventional nipple-sparing mastectomy. However, data on the feasibility and safety of the RANSM are limited. METHODS: Patients who underwent RANSM with immediate breast reconstruction as part of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) from November 2016 to January 2020 were enrolled. clinicopathologic characteristics, perioperative complications, and operation time were collected. RESULTS: Overall, 73 women underwent 82 RANSM procedures conducted by 11 breast surgeons at 8 institutions. The median patient age was 45.5 years old (20-66 years), and 52 (63.4%) patients were premenopausal. Invasive breast cancer was noted in 55 cases (40 cases were stage i, 11 cases were stage ii, and 4 cases were stage iii, respectively) and ductal carcinoma in-situ was recorded in 20 cases. Of those, 3 patients with BRCA1/2 mutation carriers underwent contralateral risk-reducing RANSM. The median length of hospitalization was 12.0 days (5.0-24.0 days). The incision location was the mid-axillary line and the median incision length was 50.0 mm (30.0-60.0 mm). Median total operation time, median total mastectomy time, and median reconstruction time was 307.0 minutes (163.0-796.0 minutes), 189.5 minutes (97.5-325.0 minutes), and 119.5 minutes (45.0-689.0 minutes). Only 2 cases (2.5%) required reoperation. Nipple ischemia was found in 9 cases (10.9%) but only 1 case (1.2%) required nipple excision given that 8 cases (9.7%) resolved spontaneously. Skin ischemia was observed in 5 cases (6.1%) and only 2 (2.4%) cases needed skin excision whereas 3 cases (3.6%) resolved spontaneously. There was no conversion to open surgery orcases of mortality. The mean time for mastectomy among surgeons who performed more than 10 cases was 182.3 minutes (± 53.7, minutes) and 195.4 minutes (± 50.4, minutes). CONCLUSION: This was the first report of RANSM conducted in the KoREa-BSG. RANSM is technically feasible and acceptable with a short learning curve. Further prospective research to evaluate surgical and oncologic outcomes is needed.

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.

Development of PD3 and PD3-B for PDEδ inhibition to modulate KRAS activity.

Despite extensive efforts over 40 years, few effective KRAS inhibitors have been developed to date, mainly due to the undruggable features of KRAS proteins. In addition to the direct approach to KRAS via covalent inhibition, modulation of the prenyl-binding protein PDEδ that binds with farnesylated KRAS has emerged as an alternative strategy to abrogate KRAS activity. For the verification of new therapeutic strategies, chemical probes with the dual functions of visualisation and pharmacological inhibition against oncogenic proteins are enormously valuable to understand cellular events related to cancer. Here, we report indolizino[3,2-c]quinoline (IQ)-based fluorescent probes (PD3 and PD3-B) for PDEδ inhibition. By using the unique fluorescent characteristics of the IQ scaffold, a fluorescence polarisation (FP)-based binding assay identified PD3 as the most effective PDEδ probe among the tested PD analogues, with a low Kd value of 0.491 µM and long retention time in the binding site of PDEδ. In particular, a FP-based competition assay using deltarasin verified that PD3 occupies the farnesylation binding site of PDEδ, excluding the possibility that the FP signals resulted from non-specific hydrophobic interactions between the ligand and protein in the assay. We also designed and synthesised PD3-B (5), an affinity-based probe (ABP) from the PD3 structure, which enabled us to pull down PDEδ from bacterial lysates containing a large number of intrinsic bacterial proteins. Finally, KRAS relocalization was verified in PANC-1 cells by treatment with PD3, suggesting its potential as an effective probe to target PDEδ.

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.

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 .

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 .

Response to neoadjuvant chemotherapy based on pathologic complete response in very young patients with ER-positive breast cancer: a large, multicenter, observational study.

BACKGROUND: In estrogen receptor (ER)-positive breast cancer (BC), young age is associated with poor prognosis. While very young patients respond better to chemotherapy, chemotherapy is less effective in ER-positive tumors than in ER-negative tumors. The authors tried to evaluate chemotherapy response of very young patients with ER-positive BC by pathologic complete response (pCR) after neoadjuvant chemotherapy excluding the effect of endocrine treatment to the extent possible. METHODS: We collected individual patient data from 1992 to 2013 from the Korean Breast Cancer Society (KBCS). Total 1048 ER-positive and 797 ER-negative patients aged < 50 years who had been treated with neoadjuvant chemotherapy were included for analysis. We compared pCR rate between patients aged < 35 years with ER-positive tumors and the other groups. RESULTS: The proportion of patients aged < 35 years was 14.0% of patients with ER-positive BC in this cohort of under 50 years old, and 16.8% of patients with ER-negative BC in this cohort of under 50 years old. Although most characteristics of tumors according to age were comparable, tumors with high Ki-67 expression were more common in patients aged < 35 years than in patients aged 35-49 years in both ER-positive and -negative group (P = 0.001). Breast conservation rates were not significantly different according to age (44.2% vs. 46.8% in ER-positive group, 55.2% vs. 48.0% in ER-negative group). pCR rate was not different according to age in ER-positive group (P = 0.71) but significantly better in patients aged < 35 years in ER-negative group (P = 0.009). After adjusting for confounding variables, young patients maintained the higher probability of pCR than older patients in ER-negative tumors. However, pCR rate did not differ according to age in ER-positive tumors. In multivariate analysis, young age (< 35 years) was correlated with poor overall survival (P = 0.003, HR = 1.98) and there was only one event in a few patients achieved pCR in ER-positive group. CONCLUSIONS: Chemotherapy response based on pCR was not better in young patients (< 35 years) with ER-positive BC than in older premenopausal patients with non-metastatic ER-positive BC. Young age cannot be a predictive factor of response to neoadjuvant chemotherapy in ER-positive BC. Different biological characteristics such as high proliferative index should be considered. TRIAL REGISTRATION: Retrospectively registered.

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.