Efficacy and safety of biosimilar trastuzumab (CT-P6) in routine clinical practice in the Republic of Korea: a real-world post-marketing surveillance study.

BACKGROUND: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers. RESEARCH DESIGN AND METHODS: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness. RESULTS: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response. CONCLUSIONS: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial.

PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.

Prognosis and Adjusting Factors in Elderly Patients With Triple-Negative Breast Cancer: Comparing With Young and Middle Age Groups.

PURPOSE: Proper breast cancer screening and treatment should be considered in the elderly population; however, some tend to be less proactive. Our study aimed to investigate the impact of old age on treatment and prognosis in triple-negative breast cancer (TNBC). METHOD: The study included patients with primary TNBC stage I-III diagnosed from 2002 to 2019 in single institution and retrospectively analyzed. We defined young (< 40 years), middle and old (> 70 years) groups. Clinicopathological factors, treatment, and prognosis were analyzed according to age group of TNBC patients. RESULT: TNBC patients aged 70 and above were 3.3 times more likely (P = .019) to have lymph node metastasis at the time of diagnosis compared to younger patients, but were found to be 0.24 times less likely to receive chemotherapy. (P = .003) Old TNBC patients have an expected likelihood 2.2 times higher of undergoing mastectomy rather than breast-conserving surgery. (P = .042) The 5-year prognosis is poorer in young and old group. (61%, 86%, and 65% in young, middle, and old groups). (P < .001). In subanalysis, old group of stages I and II received fewer chemotherapy compared to youngers (P < .05), but not in stage III. In Cox regression analysis, age and stage had significant impact on prognosis (hazard ratio 2-3), but treatment factors did not. However, in stratified analysis of adjuvant therapy and stage, prognosis of Old TNBC patients in stage II was improved when they underwent neo or adjuvant chemotherapy. CONCLUSION: TNBC presents challenges in older patients, who receive less aggressive treatment and have poorer outcomes. The primary cause of poor prognosis in old TNBC patients is the high disease stage at diagnosis, underscoring the need for promotion and education on early screening. Additionally, it is suggested that a more proactive approach to adjuvant chemotherapy is necessary for stage II old TNBC patients.

Obstetric and psychiatric history as predictors for psychosomatic symptoms among Korean perimenopausal women.

OBJECTIVES: Menopause presents various physical and psychological disturbances for women and comes at a high financial cost. Therefore, this study aimed to identify factors influencing menopause symptoms. STUDY DESIGN: Data of Korean perimenopausal women aged 40-60 (n = 1060; mean age, 46.03 ± 4.08) were collected by a research company. Participants were classified into a "functional" group (n = 716) or a "dysfunctional" group (n = 344) according to the severity of their perimenopausal psychosomatic symptoms. To investigate the association of obstetric and psychiatric history with membership of the "dysfunctional" group, a hierarchical logistic regression analysis was conducted. RESULTS: The outcomes of all three hierarchical logistic regression models presented significant overall model fit. Among the independent variables, family history of menopausal symptoms, menarcheal age, number of pregnancies, history of postpartum depression, postpartum psychosis, and other psychiatric disorders were positively associated with being in the "dysfunctional" group, whereas age and number of deliveries were negatively associated with being in the "dysfunctional" group. CONCLUSION: A short reproductive period and short exposure to estrogen due to late menarche and early menopausal transition may be related to severe perimenopausal symptoms. The relationship between the history of postpartum mental illness and severe perimenopausal symptoms may be associated with heightened sensitivity to hormonal triggers when a woman is exposed to fluctuating ovarian sex steroid levels. The relationship between parity or gravidity and the severity of menopausal symptoms in Korean women differed from that in studies conducted in other countries, possibly due to the low birth rate in Korea.

The effects of music therapy on the psychological status of women with perimenopause syndrome.

OBJECTIVE: Women experience many physical and psychological changes with the reduction of progesterone and estrogen as ovarian function gradually weakens. This study applied a music psychotherapy program as a nonpharmacological treatment method in addition to treatment using drugs such as hormone therapy for perimenopausal women. METHOD: This study's pre-post, control-experimental research compared 20 women in the music psychotherapy experimental group and 20 in the cognitive behavioral therapy (CBT) control group. The perimenopausal women aged between 40 and 60 years experienced no menstrual period for 1 year. We provided eight sessions of music psychotherapy, including CBT, each lasting 60 minutes. The study period was 4 months from the time of recruitment. RESULTS: The music therapy group showed a more significant decrease in the Menopause Rating Scale total (change over time, 9.2 points and 3.5 points, respectively; P = 0.008) and psychology subcategory (change over time, 6.5 points and 0.9 points, respectively; P = 0.004) of Menopause Rating Scale scores, compared with the CBT group. In addition, the music therapy group increased their quality of life psychological score, but the CBT group did not. CONCLUSIONS: These results suggest that music therapy can help the psychological and emotional symptoms of perimenopausal women and is effective for treatment. The study result provides a therapeutic basis for developing treatments for nonpharmacological mediation.

Diagnostic accuracy of a three-protein signature in women with suspicious breast lesions: a multicenter prospective trial.

BACKGROUND: Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. FINDINGS: This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. CONCLUSIONS: The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 ( https://cris.nih.go.kr ).

Mutational Analysis of Triple-Negative Breast Cancer Using Targeted Kinome Sequencing.

PURPOSE: Triple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC. METHODS: A kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three non-Asian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy). The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation. RESULTS: The significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively). CONCLUSION: Comprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.

The clinical impact of extrathyroidal extensions on prognoses in pediatric differentiated thyroid cancers.

BACKGROUND: The prognostic impact of extrathyroidal extensions (ETE) on clinical outcomes has not been well studied in pediatric thyroid cancers. The aim of this study was to analyze the clinicopathological characteristics and clinical outcomes according to the extent of ETE in pediatric and adolescent thyroid cancers. METHODS: This study retrospectively reviewed 89 papillary thyroid carcinoma (PTC) patients less than 19 years of age who underwent total thyroidectomy with central neck dissections (CND) between 1997 and 2018. We compared the clinicopathological features among three groups: no ETE, microscopic ETE, and gross ETE. RESULTS: The median follow-up time was 111 months. The mean age was 15.3 years and the mean tumor size was 2.4 cm. Tumor sizes larger than 2 cm (OR = 9.2, p = 0.001), exhibited bilaterality (OR = 4.3, p = 0.006), were an aggressive variant (OR = 5.8, p = 0.006), and exhibited central lymph node metastasis (OR = 1.3, p = 0.018), lateral lymph node metastasis (OR = 9.2, p = 0.001), recurrence (OR = 3.9, p = 0.038), and distant metastasis (OR = 4.4, p = 0.016) were associated with gross ETE. There was no remarkable difference in clinicopathological characteristics between the no ETE group and microscopic ETE group, except for aggressive variants (OR = 5.5, p = 0.008). There was a significant difference in recurrence-free survival (RFS) rates according to the extent of ETE (p = 0.025). Furthermore, the distant metastasis-free survival curve presented a significant difference among the three groups (p = 0.018). Both microscopic ETE and gross ETE were significantly associated with worse prognoses in pediatric thyroid cancers. CONCLUSIONS: We recommend that microscopic ETE should be included in the intermediate risk category and that gross ETE should be stratified in the high risk group in future revisions of ATA pediatric guidelines.

Clinicopathologic factors affecting discrepancies in HER2 overexpression between core needle biopsy and surgical biopsy in breast cancer patients according to neoadjuvant treatment or not.

Background: Accurate determination of human epidermal growth factor receptor 2 (HER2) status on breast core needle biopsy (CNB) tissue is important for determining neoadjuvant chemotherapies (NACs) for primary breast cancer. However, HER2 discrepancies occur before and after surgery, creating difficulties in the administration of appropriate NAC. This study aimed to identify the clinical factors affecting these discrepancies. Methods: This study was conducted on patients with primary breast cancer who underwent breast surgery from January 2012 to December 2018 at the Chung-Ang University Hospital. HER2 status was analyzed using immunohistochemistry. HER2 was graded as 0 to +3, and all 2+ cases were evaluated for gene amplification. The patients were divided into two groups based on whether or not they received chemotherapy. Patient and clinical characteristics between the two groups were compared using the χ2 test and a logistic regression model. Results: A total of 443 patients were evaluated; 384 patients (86.7%) did not receive NAC, and 59 patients (13.3%) received NAC. The HER2 discordance rate was 12.5% in the no NAC group and 23.7% in the NAC group. Most cases showed a change in HER2 status from negative in CNB to positive in surgical biopsy (SB). Clinicopathological factors affecting HER2 change in the no NAC group were larger tumor size and higher histologic grade. Meanwhile, poor response to prior chemotherapy affected HER2 change in NAC. Conclusion: The overall accuracy of CNB in determining HER2 status was lower in the NAC group than in the no NAC group. Some clinicopathological factors may affect HER2 changes in each group at different levels. Based on the HER2 status at the time of diagnosis, the choice of HER2-targeted therapy may vary, even if this is not true. Future research on the effects of changes in HER2 status between CNB and SB on prognosis is needed.

Considerations in Oncoplastic Surgery.

The development of oncoplastic surgery (OPS) is one of the greatest achievements for the treatment of breast cancer. OPS combines oncological resection with plastic surgery techniques in a single procedure to allow the excision of tumors without compromising cosmetic outcome. It allows better aesthetic-functional outcomes and consequently an improvement of the psychological aspects of patients with breast cancer.OPS begins with preoperative design considering breast volume, tumor size, and location and distance from nipple of the tumor, with clinical breast examination and image studies. Various techniques of volume replacement and volume displacement methods described here can help the decision-making process so the best results concerning the aesthetic-functional aspects can be achieved.The outcome measurement of the oncoplastic breast surgery consisted of local recurrence, cosmesis, and patients satisfaction. In OPS for breast cancer patients, aesthetic assessment could be performed by various methods. And questionnaires on quality of life can be applied as a scientific method to assess results. In this chapter, we introduced our results of assessment of both aesthetic and QOL outcomes in OPS patients.

Target Calorie Intake Achievements for Patients Treated in the Surgical Intensive Care Unit.

Adequate nutritional support in critically ill patients is important, however, sometimes it has been neglected in perioperative period of patients at surgical intensive care units (SICU). The aim of this study was to investigate whether approaching target calorie intake of surgical patients influences on their clinical outcomes. A total of 279 patients who admitted at SICU in perioperative period from August 2014 to July 2016 at our hospital were analyzed. Demographics, supplied calorie amount and its method, lengths of SICU and hospital stay, and mortality of study population were collected. Among 279 patients, 103 patietns (36.9%) approached target calorie intake during SICU stay. Patients who approached target calorie intake had significantly decreased length of stay in SICU (10.78 ± 11.5 vs. 15.3 ± 9.9, p = 0.001) and hospital (54.52 ± 40.6 vs. 77.72±62.2, p < 0.001), than those did not, however there was no significant difference of mortality (9.7% vs. 8.5%, p = 0.829). Enteral feeding was a significant factor for target calorie achievement (odd ratio [OR], 2.029; 95% confidence interval [CI], 1.096-3.758; p = 0.024) and especially in patients with ≤ 7 days of SICU stay (OR, 4.13; 95% CI, 1.505-11.328; p = 0.006). Target calorie achievement in surgical patients improves clinical outcomes and enteral feeding, especially in early postoperative period would be an effective route of nutrition.

A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial).

PURPOSE: Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. METHODS: This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the "frozen section biopsy" or "frozen section biopsy omission" group after lumpectomy. Patients with clinical stage T1-T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness. DISCUSSION: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy. We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03975179; Clinical Research Information Service Identifier: KCT0004606.

Programmed cell death-ligand 1 expression in stromal immune cells is a marker of breast cancer outcome.

Purpose: The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in antitumor immune responses. However, there is considerable inconsistency regarding the prognostic value of PD-L1 expression status in breast cancer. We sought to evaluate the differential prognostic impacts of tumoral versus stromal immune cell PD-L1 expression in primary breast cancer. Materials & Methods: Both tumoral and stromal immune PD-L1 expression in formalin-fixed, paraffin-embedded tumor samples from 233 breast cancer patients without initial stage IV metastases were evaluated by immunohistochemistry using a mouse monoclonal anti-PDL1 antibody. Clinicopathological variables were also documented. A Cox regression model was used to assess the association of tumoral/stromal immune PD-L1 expression with clinical outcome using disease-free survival (DFS) as the primary end point. Results: Both tumoral and stromal immune PD-L1 expression were associated with aggressive tumor characteristics, including higher histologic grade, as well as negative estrogen receptor, negative progesterone receptor, and positive human epithelial growth factor receptor 2 (HER2) status Multivariate analyses further demonstrated that stromal immune cell, but not tumoral, PD-L1 expression was a favorable prognostic factor for survival. Conclusions: Despite its association with aggressive tumor features, PD-L1 expression on stromal immune cells emerged as a positive prognostic biomarker in breast cancer. This pro-survival effect might reflect the presence of a strong antitumor immune response that leads to PD-L1 expression.

Effects of Steady Low-Intensity Exercise on High-Fat Diet Stimulated Breast Cancer Progression Via the Alteration of Macrophage Polarization.

Physical inactivity and high-fat diet, especially high saturated fat containing diet are established risk factors for breast cancer that are amenable to intervention. High-fat diet has been shown to induce tumor growth and metastasis by alteration of inflammation but steady exercise has anti-tumorigenic effects. However, the mechanisms underlying the effects of physical activity on high-fat diet stimulated breast cancer initiation and progression are currently unclear. In this study, we examined how the intensity of physical activity influences high fat diet-stimulated breast cancer latency and progression outcomes, and the possible mechanisms behind these effects. Five-week-old female Balb/c mice were fed either a control diet or a high-fat diet for 8 weeks, and then 4T1 mouse mammary tumor cells were inoculated into the mammary fat pads. Exercise training occurred before tumor cell injection, and tumor latency and tumor volume were measured. Mice with a high-fat diet and low-intensity exercise (HFLE) had a longer tumor latency period, slower tumor growth, and smaller tumor volume in the final tumor assessment compared with the control, high-fat diet control (HFDC), and high-fat diet with moderate-intensity exercise (HFME) groups. Steady low- and moderate-intensity exercise had no effect on cell proliferation but induced apoptosis by activating caspase-3 through the alteration of Bcl-2, Bcl-xL, and Bax expression. Furthermore, steady exercise reduced M2 macrophage polarization in breast tumor tissue, which has been linked to tumor growth. The myokine, myostatin, reduced M2 macrophage polarization through the inhibition of the JAK-STAT signaling pathway. These results suggest that steady low-intensity exercise could delay breast cancer initiation and growth and reduce tumor volume through the induction of tumor cell apoptosis and the suppression of M2 macrophage polarization.

High Endothelial Venule with Concomitant High CD8+ Tumor-Infiltrating Lymphocytes Is Associated with a Favorable Prognosis in Resected Gastric Cancer.

CD8+ tumor-infiltrating lymphocytes (TILs) play a major role in antitumor immunity. High endothelial venules (HEVs) are related to diverse immune cells in solid tumors. We analyzed CD8+ and Foxp3+ TILs in combination with HEVs to determine their prognostic role in advanced gastric cancer (AGC). We enrolled 157 patients with AGC in this study. The densities of CD8+ TILs and Foxp3+ TILs were calculated using immunohistochemical staining. HEVs were evaluated by MECA-79 expression. HEVs were identified in 60 (38.2%) cases and was significantly associated with an increased number of CD8+ TILs (p = 0.027) but not of Foxp3+ TILs (p = 0.455) and CD20+ TILs (p = 0.163). A high CD8+/HEV+ level was significantly associated with nodal metastasis (p = 0.048). In survival analysis, patients with high CD8+/HEV+ levels demonstrated the longest overall survival (OS) (p = 0.015). Furthermore, a high CD8+/HEV+ level was an independent prognostic factor in AGC (p = 0.011; hazard ratio (HR) = 0.435; 95% confidence interval (CI) = 0.245-0.837). HEVs were found to play an important role in antitumor immunity associated with CD8+ TILs in AGC. This analysis of HEVs and CD8+ TILs helps stratify patients with AGC and sheds light on tumor immunity.

Risk Factors for Tamoxifen-Induced Ovarian Hyperstimulation in Breast Cancer Patients.

INTRODUCTION: Adjuvant endocrine therapy is an integral component of care for hormone-dependent breast cancer. Tamoxifen is a potent inducer of ovarian function and consequent hyperestrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenon remain unclear. PATIENTS AND METHODS: Data of patients younger than 60 years who received adjuvant tamoxifen therapy for hormone-dependent breast cancer (stages 0-III) and who underwent regular follow-up of laboratory results for follicle-stimulating hormone and estradiol levels were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinicopathologic factors related to ovarian hyperstimulation. RESULTS: Among 205 patients, 19 (9.3%) showed high values of serum estradiol during tamoxifen therapy. The mean (± SD) serum concentrations of estradiol and follicle-stimulating hormone were 1047.97 ± 638.8 pg/mL and 11.5 ± 7.3 mIU/mL, respectively. A mean of 400.83 days elapsed from the start of the single administration of tamoxifen to the initial detection of a high concentration of estradiol. Univariate and multivariate analyses showed that younger age (< 40 years) and only endocrine therapy without chemotherapy were significantly related to a higher prevalence of ovarian hyperstimulation (P = .015, relative risk = 7.49 for age < 40 years; P = .017, relative risk = 32.9 for no chemotherapy). Pathologic stages and tumor characteristics were not related to the manifestation of ovarian hyperstimulation. CONCLUSION: Young age (< 40 years) and endocrine treatment without chemotherapy were risk factors for the incidence of ovarian hyperstimulation during tamoxifen treatment. Close monitoring of endocrine parameters during treatment with tamoxifen especially in this patient group is essential.

Radiologic and Pathologic Findings of Atypical Ductal Hyperplasia in the Male Breast: Case Report and Literature Review.

In this case report, we present the radiologic and pathologic findings of atypical ductal hyperplasia (ADH) in the male breast. It is well known that a high-risk lesion such as ADH is a precursor of breast cancer in females. However, the clinical significance of these lesions in the male breast is still uncertain because male breasts mainly consist of ducts without lobule formation, unlike the female breast. To our knowledge, imaging findings of ADH in the male breast have not been reported previously, except for a few studies on the pathologic findings of these lesions. Through this paper, we would like to present the possible imaging features of this high-risk lesion in the male breast and review the related literature.

Less Pain and Reduced Risk of Early Postoperative Ileus After Clipless Versus Conventional Laparoscopic Appendectomy.

Laparoscopic appendectomy (LA) is perceived as a procedure requiring a short hospital stay; however, some patients require prolonged hospitalization because of postoperative ileus and pain; therefore, we introduced clipless LA, using only an ultrasonic energy device only for coagulation. A total of 1013 patients (clipless LA; n=290 and conventional LA; n=723) who underwent LA at our hospital between January 2015 and February 2018 were analyzed. The mean operative time was shorter (P<0.001), and postoperative pain score at 24 hours was lower (P<0.001) for clipless than for conventional LA. There were no significant differences in postoperative complications, except with regard to early postoperative ileus (clipless LA; 18.1% vs. conventional LA; 31.6%, P=0.025), and the operative method had significantly influenced early postoperative ileus (relative risk, 0.505; 95% confidence interval, 0.257-0.994; P=0.048). Clipless LA is comparable to conventional LA with regard to operative safety but results in significantly less pain and postoperative ileus.

Asprosin attenuates insulin signaling pathway through PKCδ-activated ER stress and inflammation in skeletal muscle.

It has been reported that asprosin is a novel adipokine which is augmented in mice and humans with type 2 diabetes (T2DM). Asprosin stimulates hepatic gluconeogenesis under fasting conditions. However, the roles of asprosin in inflammation, endoplasmic reticulum (ER) stress, and insulin resistance in skeletal muscle has not been studied. In the currents study, elevated levels of asprosin expression were observed in adipocytes under hyperlipidemic conditions. Treatment of C2C12 myocytes with asprosin-induced ER stress markers (phosphorylated inositol-requiring enzyme 1 and eukaryotic initiation factor 2, and CHOP expression) as well as inflammation markers (interleukin-6 expression, phosphorylated IκB, and nuclear translocated nuclear factor-κß). Finally, asprosin treatment promoted exacerbation of insulin sensitivity as determined by levels of insulin receptor substrate 1 and Akt phosphorylation as well as glucose uptake. Moreover, treatment of asprosin augmented protein kinase C-δ (PKCδ) phosphorylation and nuclear translocation, but suppressed messenger RNA expression of sarcoplasmic reticulum Ca2+ ATPase 2b in both C2C12 myocytes and in mouse soleus skeletal muscle. These asprosin-induced effects were markedly decreased in small interfering (si) RNA-mediated PKCδ-knockdown in C2C12 myocytes. These results suggest that asprosin results in impairment of insulin sensitivity in skeletal muscle through PKCδ-associated ER stress/inflammation pathways and may be a valuable strategy for management of insulin resistance and T2DM.

Management of benign papilloma without atypia diagnosed at ultrasound-guided core needle biopsy: Scoring system for predicting malignancy.

BACKGROUND: The management of benign intraductal papilloma diagnosed on core needle biopsy (CNB) remains unclear. This study was designed to evaluate factors predicting malignancy in patients diagnosed with benign papilloma without atypia at ultrasound-guided CNB and to develop a scoring system predicting malignancy based on clinical, radiological and pathological factors on further excisional biopsy. METHODS: The study enrolled patients diagnosed with benign papillomas (including benign and atypical papillary lesions) at CNB. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict malignancy. RESULTS: A total of 520 CNBs were diagnosed with benign or atypical papilloma. Of these, 452 were benign papilloma without atypia. Of the 250 lesions subsequently excised surgically from 234 women, 17 (6.8%) were diagnosed with malignancy. Multivariate analysis revealed that bloody nipple discharge, size on imaging ≥15 mm, BI-RADS≥4b, peripheral location and palpability were independent predictors of malignancy. A scoring system was developed based on logistic regression models and beta coefficients for each variable. The area under the ROC curve was 0.947 (95% CI: 0.913-0.981, p < 0.001) and a negative predictive value was 100%. In a validation set of 62 patients, an area under the ROC curve was 0.926 (95% CI: 0.857-0.995, p < 0.001). CONCLUSIONS: A scoring system predicting malignancy in patients diagnosed by CNB with benign papilloma without atypia was developed. This system was able to identify a subset of patients with lesions likely to be benign, indicating that imaging follow-up rather than surgical excision may be appropriate.