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The receptor-interacting serine/threonine-protein kinases RIPK1 and RIPK3 play important roles in necroptosis that are closely linked to the inflammatory response. Although the activation of necroptosis is well characterized, the mechanism that tunes down necroptosis is largely unknown. Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase implicated in Parkinson's disease and as a tumour suppressor, regulates necroptosis and inflammation by regulating necrosome formation. Parkin prevents the formation of the RIPK1-RIPK3 complex by promoting polyubiquitination of RIPK3. Parkin is phosphorylated and activated by the cellular energy sensor AMP-activated protein kinase (AMPK). Parkin deficiency potentiates the RIPK1-RIPK3 interaction, RIPK3 phosphorylation and necroptosis. Parkin deficiency enhances inflammation and inflammation-associated tumorigenesis. These findings demonstrate that the AMPK-Parkin axis negatively regulates necroptosis by inhibiting RIPK1-RIPK3 complex formation; this regulation may serve as an important mechanism to fine-tune necroptosis and inflammation.

Genetic susceptibility explains 5-10% of all breast cancer cases. High-penetrance breast cancer susceptibility genes deliberate a greater than tenfold relative risk of breast cancer. BRCA1 and BRCA2 genes are the most common cause of hereditary breast cancer, and TP53, PTEN, and SKT11 (LKB1) are rarely present. The prevalence of BRCA1 and BRCA2 genetic alterations differ in various ethnic groups. The Korean Hereditary Breast Cancer (KOHBRA) Study, nationwide-scale study, was established to acquire evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea prospectively since 2007. In this chapter, we review previous research related to hereditary breast cancer and summarize the present concepts and research results centered on the Korean Hereditary Breast Cancer Research at this time.

Genetic susceptibility explains 5–10% of all breast cancer cases. High-penetrance breast cancer susceptibility genes deliberate a greater than tenfold relative risk of breast cancer. BRCA1 and BRCA2 genes are the most common cause of hereditary breast cancer, and TP53, PTEN, and SKT11 (LKB1) are rarely present. The prevalence of BRCA1 and BRCA2 genetic alterations differ in various ethnic groups. The Korean Hereditary Breast Cancer (KOHBRA) Study, nationwide-scale study, was established to acquire evidence for the accurate risk assessment and management of hereditary breast and ovarian cancer (HBOC) in Korea prospectively since 2007. In this chapter, we review previous research related to hereditary breast cancer and summarize the present concepts and research results centered on the Korean Hereditary Breast Cancer Research at this time.

Many studies have reported that Aldehyde dehydrogenase 1 (ALDH1) and tumor-infiltrating lymphocytes (TIL) are related to breast cancer prognosis. However, the clinical significance of ALDH1 and tumor-infiltrating immune cells in breast cancer has not been fully investigated in patients who received neoadjuvant chemotherapy (NAC). We studied the significance of the expression of ALDH1 and the population of TIL for predicting the prognosis and chemotherapeutic response of patients with breast cancer who had received NAC. Forty patients who underwent NAC were enrolled in this study. ALDH1 and TIL (T cells and tumor associated macrophages) were evaluated before and after NAC. The influences of ALDH1 expression status and TIL populations on both prognosis and chemotherapeutic response were evaluated. ALDH1 positivity was related to estrogen receptor (p = 0.026) and progesterone receptor negativity (p = 0.025). Positive change of ALDH1 after NAC tended to be associated with a poor NAC response (p = 0.078). Patients with more CD8+ T cells before NAC and fewer CD68 (+) macrophages after NAC tended to have better OS, respectively (p = 0.086, p = 0.096). The chemotherapeutic response and prognosis of patients with breast cancer who received NAC are thought to be determined by the tumor microenvironment. Further research with more patients and a longer study period is needed.

An overexpression of S-phase kinase-associated protein 2 (SKP2) is frequently observed in human cancer progression and metastasis, and evidence suggests that SKP2 plays a proto-oncogenic role both in vitro and in vivo. However, the function of SKP2 in gastric adenocarcinoma remains largely obscure. We investigated SKP2 expression in human gastric carcinomas. Tissue samples were acquired from 182 cases of gastric adenocarcinoma that were surgically resected from 2006 to 2012. Immunohistochemical staining for SKP2, Beclin-1, and forkhead box protein P3 (FOXP3) was performed. Pearson chi-square test was used to evaluate the associations among clinicopathological variables. The Kaplan–Meier method, the log-rank test, and the Cox proportional-hazards model were used in the analysis of the overall survival (OS) and disease-free survival (DFS). As a result, SKP2 overexpression in gastric adenocarcinomas showed a significant correlation with several favorable clinical factors, including the tumor size, T category, N category, lymphatic invasion, vascular invasion, OS, and DFS. SKP2 expression was positively correlated with the tumoral FOXP3, Beclin-1 expression, and regulatory T cell (Treg) infiltration. The difference in DFS between the SKP2 positive and negative group was attenuated by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration. Attenuation of the difference in OS by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration was not significant. In multivariable analysis, SKP2 expression was not correlated with OS and DFS. Our study showed a complex interrelationship between SKP2 and Beclin-1 and FOXP3 expression in gastric adenocarcinoma. The antioncogenic effect of Beclin-1 and FOXP3 expression in gastric adenocarcinoma is related to SKP2 expression.

The Korean clinical practice guideline recently developed by the Korean Breast Cancer Society to address the national clinical situation is currently under revision ahead of a seventh recommendation. A second consensus conference was held to further develop this guideline by soliciting opinions regarding important issues related to surgery, radiotherapy, and medical oncology. Several issues were discussed, and the discussion progressed to pros and cons in the context of cases in various clinical situations. The panels discussed and voted on issues regarding surgical treatment for non-axillary regional lymph nodes, regional nodal irradiation of pN1 disease, and ovarian functional suppression (OFS) as an adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Regarding the surgical treatment of non-axillary regional lymph node, most panelists agreed with the recommendation of preoperative chemotherapy and postoperative radiotherapy for patients with biopsy-diagnosed metastases, whereas surgery or radiotherapy of non-axillary regional lymph nodes was suggested for clinical partial responders. Discussions on radiotherapy addressed the need for adjuvant radiotherapy and radiation field of regional lymph node in the context of various N1 breast cancer cases. The participants reached a consensus to recommend that N1 patients should receive regional nodal irradiation for a large tumor burden (e.g., three positive nodes, perinodal extension, or large primary tumor). Finally, the panels favored OFS in addition to endocrine therapy for premenopausal women with high risk factors such as a large tumor size, involvement of more than three nodes, and a high histologic grade.

We hypothesized that cancer stem cells (CSCs) are responsible for the poor outcome and aggressive clinicopathological factors. We surveyed the expression of selected CSC markers that are specifically expressed in thyroid papillary carcinoma (PTC). A total of 80 patients with PTC from 2011 to 2012 were enrolled. We selected CD24, CD44, CD133, and dehydrogenase 1 (ALDH1), as they have been suggested to be candidate CSC markers. Expression of these markers was investigated by immunohistochemical (IHC) staining. IHC staining for CD24, CD44, CD133 and ALDH1 was evaluated according to staining intensity and proportion. The intensity and proportion scores were multiplied together for a total score, which was either 0-2 (negative) or 3-7 (positive). IHC for CD133 in PTC was positive in 49 (61.3%) patients, and CD24 was positive in 28 (35.0%). Seventy-eight (97.5%) patients were CD44 positive and 79 (98.8%) were ALDH1 positive. When we assessed the relationship between CSC markers and clinicopathological factors in PTC, CD24 expression was inversely correlated with multifocality (p=0.045; odds ratio [OR], 0.370; 95% confidence interval [CI], 0.138-0.991) and CD44 expression was significantly correlated with a BRAF mutation (p=0.001; OR, 7.091; 95% CI, 4.101-12.262). However, CD133 and ALDH1 were not associated with any of the clinicopathological parameters. CD24 expression was inversely correlated with multifocality, and CD44 expression was significantly correlated with a BRAF mutation. Therefore, CD24 and CD44 are related to clinicopathological aggressive features and important for determining surgical extent in patients with PTC.

Ultrasound can be an effective alternative to computed tomography for surveillance following endovascular aneurysm repair (EVAR). Recently, ultrasound fusion imaging with the real-time navigation system was introduced. Here we described 3 patients who underwent post-EVAR surveillance using this novel technique. Complete coregistration was achieved in all patients. The origin of left renal artery was selected for the target of coregistration. Ultrasound fusion imaging was useful to differentiate the confusing lesion and to evaluate the complete resolution of endoleak and newly developed delayed endoleak. Ultrasound fusion image with real-time navigation system can be a feasible imaging tool for post-EVAR surveillance.

Inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) and antioxidant activity were evaluated for 195 extracts from Ukraine-derived endogenous lichen fungi (ELF). Among them, an ELF13 (identified as Daldinia fissa) extract showed the highest inhibitory activity against MAO-B, and 5-hydroxy-2-methyl-chroman-4-one (HMC) was isolated as a ~ 4-fold selective inhibitor of MAO-B (IC50 = 3.23 &micro, M) compared to MAO-A (IC50 = 13.97 &micro, M). HMC is a reversible competitive inhibitor with a Ki value of 0.896 &micro, M. No cytotoxicity was observed in normal and cancer cells at 50 &micro, M of HMC. HMC showed blood&ndash, brain barrier permeability and high gastrointestinal absorption in silico pharmacokinetics. The docking simulation results showed that the binding affinity of HMC for MAO-B (&minus, 7.3 kcal/mol) was higher than that of MAO-A (&minus, 6.1 kcal/mol) and that HMC formed a hydrogen bond interaction with Cys172 of MAO-B (distance: 3.656 &Aring, ), whereas no hydrogen bonding was predicted with MAO-A. These results suggest that HMC can be considered a candidate for the treatment of neurodegenerative diseases, such as Alzheimer&rsquo, s disease and Parkinson&rsquo, s disease.

Purpose Receptor-interacting protein 3 (RIP3) is the main initiator of necroptosis. Parkin prevents the formation of the RIP1-RIP3 complex by promoting polyubiquitination of RIP3. However, the mechanism by which necroptosis affects the clinical features of breast cancer and prognosis is not known. Here, we aimed to study the effect of necroptosis on the clinical features and prognosis of breast cancer by assessing the expression of RIP3 and Parkin. Methods Tissue microarrays (TMAs) were constructed from 257 cases of breast cancer. Immunohistochemistry was performed on 4-μm tissue sections from each TMA block. The χ² test, Kaplan-Meier survival analysis with log-rank test, and Cox regression proportional hazard model were used for statistical analysis. Results Low RIP3 expression resulted in a large tumor size and high nuclear grade. Low RIP3 expression was correlated with human epidermal growth factor receptor 2 positivity, short overall survival (OS), and short disease-free survival (DFS). The triple negative breast cancer group with low RIP3 expression and lymph node (LN) positive group with low RIP3 expression had the shortest OS. High Parkin expression was associated with high histological grade, estrogen and/or progesterone receptor negativity, and lymphatic emboli, but was not correlated with OS and DFS. OS was correlated with LN metastasis and RIP3 loss and DFS with large tumor size, LN metastasis, and RIP3 loss. Conclusion Low RIP3 and high Parkin expression are associated with aggressive clinical features in breast cancer. RIP3, a molecular marker of necroptosis, is an independent factor associated with survival in breast cancer. Further in-depth studies are needed to investigate the role of necroptosis in breast cancer development, metastasis, and treatment in the future.

Cancer stem cells (CSCs) contribute to chemoresistance and tumor relapse. By using the distinct metabolic phenotype of CSC, we designed novel PET parameters for CSC metabolism and investigated their clinical values. Patients with breast cancer who underwent 18F-FDG PET/CT before neoadjuvant chemotherapy (NAC) were retrospectively included. We developed a method to measure CSC metabolism using standardized uptake value histogram data. The predictive value of novel CSC metabolic parameters for pathologic complete response (pCR) was assessed with multivariable logistic regression. The association between the CSC parameter and disease-free survival (DFS) was also determined. We identified 82 patients with HER2-positive/triple-negative subtypes and 38 patients with luminal tumors. After multivariable analysis, only metabolic tumor volume for CSC (MTVcsc) among metabolic parameters remained the independent predictor of pCR (OR, 0.12, p = 0.022). MTVcsc successfully predicted pathologic tumor response to NAC in HER2-positive/triple-negative subtypes (accuracy, 74%) but not in the luminal subtype (accuracy, 29%). MTVcsc was also predictive of DFS, with a 3-year DFS of 90% in the lower MTVcsc group (&lt, 1.75 cm3) versus 72% in the higher group (&gt, 1.75 cm3). A novel data-driven PET parameter for CSC metabolism provides early prediction of pCR after NAC and DFS in HER2-positive and triple-negative subtypes.

Purpose BRCA1/2 mutations are associated with risks of breast and ovarian cancer. In Korea, incidences of BRCA1/2 genetic testing and risk-reducing surgery (RRS) have increased with insurance coverage and the Angelina Jolie effect. The aim of this study was to identify trends in RRS performed in Korean women with the BRCA1/2 mutation. Methods We retrospectively reviewed the medical records of BRCA1/2 mutation carriers with (affected carriers) and without (unaffected carriers) breast cancer until August 2018 from 25 Korean Hereditary Breast Cancer (KOHBRA)-affiliated hospitals. Results The numbers of contralateral risk-reducing mastectomy (RRM) and risk-reducing bilateral salpingo-oophorectomy (RRBSO) in affected carriers have increased 5.8- and 3.6-fold, respectively, since 2013. The numbers of RRBSO in unaffected carriers has increased 8-fold since 2013. The number of institutions that perform RRS has increased gradually. The number of hospitals that perform contralateral RRM on affected carriers increased from 3 in 2012 to 11 in 2018, and that of those that perform RRBSO increased from 7 to 17. The number of hospitals that perform bilateral RRM on unaffected carriers increased from 1 in 2012 to 2 in 2018, and that of those that perform RRBSO increased from 1 to 8. However, the hospitals showed differences in the rates of RRM or RRBSO performed. Conclusion The incidence of RRS increased each year throughout the study period. However, in Korea, the rate of RRS procedures depended on the hospital.

The von Hippel-Lindau tumor suppressor pVHL is an E3 ligase that targets hypoxia-inducible factors (HIFs). Mutation of VHL results in HIF up-regulation and contributes to processes related to tumor progression such as invasion, metastasis, and angiogenesis. However, very little is known with regard to post-transcriptional regulation of pVHL. Here we show that WD repeat and SOCS box-containing protein 1 (WSB1) is a negative regulator of pVHL through WSB1's E3 ligase activity. Mechanistically, WSB1 promotes pVHL ubiquitination and proteasomal degradation, thereby stabilizing HIF under both normoxic and hypoxic conditions. As a consequence, WSB1 up-regulates the expression of HIF-1α’s target genes and promotes cancer invasion and metastasis through its effect on pVHL. Consistent with this, WSB1 protein level negatively correlates with pVHL level and metastasis-free survival in clinical samples. This work reveals a new mechanism of pVHL's regulation by which cancer acquires invasiveness and metastatic tendency.

The Korean Hereditary Breast Cancer (KOHBRA) study was established to evaluate the prevalence and spectrum of BRCA1/2 mutations in Korean breast cancer patients at risk for hereditary breast and ovarian cancer. A total of 2953 subjects (2403 index patients and 550 family members of affected carriers) from 36 centers participated in this study between May 2007 and December 2013. All participants received genetic counseling and BRCA genetic testing. In total, 378 mutation carriers among 2403 index patients were identified. The prevalence of BRCA mutations in specific subgroups was as follows: 22.3 % (274/1228) for breast cancer patients with a family history of breast/ovarian cancers, 8.8 % (39/441) for patients with early-onset (

Multiple symmetric lipomatosis (MSL), or Madelung's disease, is a rare disease of unknown etiology. It is characterized by the presence of loose adipose tissue deposits localized in the cervical region and upper body. MSL presenting as bilateral huge gynecomastia is an extremely rare phenomenon. The present report describes a case of MSL in a 66-year-old man. The patients presented with bilateral breast bulging. He had a history of cigarette and alcohol use. His condition was treated with a bilateral nipple-sparing mastectomy. MSL can present as a form of gynecomastia, for its accurate diagnosis and proper treatment of MSL, increasing awareness of the clinical characteristics of the disease is required, especially amongst breast surgeons. Herein, we review the literature and discuss the clinical characteristics, pathology, and surgical treatment of MSL.

Background The purpose of this study was to compare the surgical outcomes of robotic thyroidectomy (RT) using bilateral axillo-breast approach (BABA) with conventional open thyroidectomy (OT) in papillary thyroid carcinoma patients. Methods Between January 2009 and December 2013, 815 patients who had received thyroidectomy for papillary thyroid carcinoma were enrolled. Of these, 126 patients received RT and 689 patients underwent OT. Age, gender, body mass index, extent of surgery, tumor size, multiplicity, bilaterality, extrathyroidal extension, and tumor stage were used for the propensity score matching analysis. One hundred and nine patients were selected in each group, and surgical outcomes were compared between the two groups. Results The RT group showed a significantly longer operating time (290.6 ± 74.4 vs. 107.9 ± 30.8 min, P

Oncogene-induced senescence (OIS) or apoptosis through the DNA-damage response is an important barrier of tumorigenesis. Overcoming this barrier leads to abnormal cell proliferation, genomic instability, and cellular transformation, and finally allows cancers to develop. However, it remains unclear how the OIS barrier is overcome. Here, we show that the E3 ubiquitin ligase WD repeat and SOCS box-containing protein 1 (WSB1) plays a role in overcoming OIS. WSB1 expression in primary cells helps the bypass of OIS, leading to abnormal proliferation and cellular transformation. Mechanistically, WSB1 promotes ATM ubiquitination, resulting in ATM degradation and the escape from OIS. Furthermore, we identify CDKs as the upstream kinase of WSB1. CDK-mediated phosphorylation activates WSB1 by promoting its monomerization. In human cancer tissue and in vitro models, WSB1-induced ATM degradation is an early event during tumorigenic progression. We suggest that WSB1 is one of the key players of early oncogenic events through ATM degradation and destruction of the tumorigenesis barrier. Our work establishes an important mechanism of cancer development and progression in premalignant lesions.

Background Ultrasound screening shows a clinical benefit in reducing abdominal aortic aneurysm (AAA)–related mortality. However, its cost-effectiveness remains unclear. Understanding the relationship between risk factors and AAA is important to maximize the benefit of AAA screening. However, risk factors for AAA have not been reported in Korea. The purpose of this study is to determine the prevalence of, and risk factors for, AAA among the Korean population. Methods The study population consisted of patients >50 years of age who consented for AAA screening. Screening was performed as follows for all participants: collection of demographic information, including risk factors, physical examination, and ultrasound screening. We measured the maximal diameter of the aorta from the outer to outer layer at 5 levels: suprarenal, renal, and infrarenal aorta, and bilateral common iliac arteries. AAA was defined as maximal aortic diameter >3 cm. The risk factors and risk ratio for AAA were determined. Chi-square test and a logistic regression model were used for statistical analysis. All P-values

The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.

The FOSB gene is involved in cell proliferation, differentiation and transformation in several tumor types. We investigated whether coding single-nucleotide polymorphisms (cSNPs) and promoter SNPs of FOSB contribute to the development of papillary thyroid cancer (PTC). We also assessed the associations between FOSB SNPs and the clinicopathological characteristics of PTC. One coding SNP (rs2282695, Ala39Ala) and one promoter SNP (rs12373539, -158) in the FOSB gene were genotyped using direct sequencing in 94 PTC patients and 213 healthy controls. Genetic data were analyzed using SNPStats, HelixTree and SNPAnalyzer. PTC patients were dichotomized and compared with respect to clinicopathological characteristics of PTC. We detected an association between PTC and cSNP (rs2282695) in FOSB [codominant model 1 (C/C vs. G/C); OR=1.75; 95% CI, 1.04-2.94; P=0.024; codominant model 2 (C/C vs. G/G): OR=2.55; 95% CI, 1.15-5.64; P=0.045; dominant model: OR=1.89; 95% CI, 1.16-3.08; P=0.010; Log-additive model: OR=1.64; 95% CI, 1.15-2.35; P=0.007]. The G allele was a risk allele in the geno-type and allele analyses of cSNP (rs2282695) in the FOSB gene (OR=1.57; 95% CI, 1.10-2.24; P=0.012). A promoter SNP (rs12373539) in FOSB was associated with cervical lymph node metastasis of PTC [codominant model 1 (G/G vs. A/G): OR=0.23; 95% CI, 0.07-0.72; P=0.016; codominant model 2 (G/G vs. A/A): OR=0.21; 95% CI, 0.02-1.96; P=0.0.05; dominant model: OR=0.22; 95% CI, 0.08-0.66; P=0.004; overdominant model: OR=0.27; 95% CI, 0.09-0.84; P=0.02; log-additive model: OR=0.31; 95% CI, 0.12-0.78; P=0.006]. The A allele was a protective allele in the genotype and allele analyses of SNP (rs12373539) in the FOSB gene promoter (OR=0.34; 95% CI, 0.14-0.83; P=0.017). Variation in a FOSB cSNP (rs2282695) may be associated with risk of PTC. The FOSB promoter SNP (rs12373539) may be associated with lymph node metastasis of PTC.

Cancer cells show a higher rate of anaerobic respiration than normal cells. The exact mechanisms for this higher glycolysis rate in cancer cells remain to be elucidated. The results of recent studies have indicated that p53, the most commonly mutated tumor suppressor gene, may have important functions in the regulation of energy-generating metabolic pathways that switch from oxidative phosphorylation to glycolysis via the synthesis of cytochrome c oxidase 2 (SCO2), p53-transactivated TP53-induced glycolysis (TIGAR), and apoptosis regulator. We evaluated the expression of p53, SCO2, TIGAR, and COX in 113 cases of invasive breast cancer using immunohistochemistry. A high expression of p53, SCO2, TIGAR, and COX was noted in 27.5% (31 cases), 84.1% (95 cases), 74.3% (84 cases), and 73.4% (83 cases) of the breast tumors, respectively. A high p53 expression was significantly associated with low expression levels of SCO2 (P = .008), COX (P < .0001), and TIGAR (P = .007). On the survival analysis, the low SCO2-expressing breast cancer patients showed a significantly poorer prognosis than that of the high SCO2-expressing breast cancer patients (P = .0078). These results suggest that p53 can modulate the metabolic pathways via the proteins SCO2 and TIGAR in human breast cancer.

PURPOSE: Primary systemic therapy (PST) downstages up to 40% of initial documented axillary lymph node (ALN) metastases in breast cancer. The current surgical treatment after PST consists of breast tumor resection and axillary lymph node dissection (ALND). This strategy, however, does not eliminate unnecessary ALND in patients with complete remission of axillary metastases. The aim of this study was to examine the accuracy of sentinel lymph node biopsy (SLNB) after PST among patients with documented ALN metastasis at presentation and to identify the rate of pathologic complete-remission (CR) with ALN after PST. METHODS: We analyzed 66 patients with ALN metastasis that was pathologically proven preoperatively who underwent SLNB and concomitant ALND after PST. Axillary ultrasound (AUS) was used to evaluate the clinical response of initially documented ALN metastasis after PST. Intraoperative lymphatic mapping was performed using blue dye with or without radioisotope. RESULTS: After PST, 34.8% of patients had clinical CR of ALN on AUS and 28.8% patients had pathologic CR of ALN. The overall success rate of SLNB after PST was 87.9%, and the sentinel lymph node identification rate in patients with clinical CR was 95.7%. In patients with successful lymphatic mapping, 70.7% of patients had residual axillary metastases. The overall accuracy and false-negative rate were 87.9% and 17.1% in all patients: 95.5% and 10.0% in patients with clinical CR of ALN, and 83.3% and 19.4% in patients with residual axillary disease after PST. CONCLUSION: Our findings suggest that SLNB may be feasible in patients with initial documented ALN metastasis who have clinical CR for metastatic ALN after PST. Further investigation in a prospective setting should be performed to confirm our results.

The worldwide use of complementary and alternative medicine (CAM) among cancer patients has increased, with breast cancer patients being more likely to use CAM compared with any other cancer patients. However, few surveys have systematically described CAM use among Korean breast cancer patients. This study investigated the use of CAM among patients who were diagnosed with breast cancer, along with the relevant demographic and clinical factors related to CAM use. We also compared the difference in quality of life between CAM users and nonusers. A total of 661 patients were invited to participate in this study during routine clinic visits, with 425 patients ultimately participating. Three hundred ninety-nine questionnaires were completed and used in the final analysis. Quality of life was evaluated based on the Korean versions of the EORTC QLQ-C30 and EORTC QLQ-BR23. Previous or current CAM usage was reported by 229 patients (57.4%). Independent factors related to CAM use were marital status, cancer stage, and coexisting illness. The common types of CAM use included exercise therapy (43.2%) and ingestion of vitamins and minerals (41.9%). The reasons for CAM use were to boost the immune system (53.2%), promote health (46.8%) and prevent recurrence (37.7%). Large proportions (70.4%) of CAM users did not discuss their CAM use with their physicians. Only a small number of CAM users (2.5%) answered that they were unsatisfied with their CAM use, with most CAM users reporting that they would continue their CAM use. Quality of life was not significantly different between CAM users and nonusers. A significant number of patients with breast cancer have used CAM, and health care providers should be aware of the variety of CAM methods and their patients’ CAM uses for the proper management of breast cancer.

Purpose: The aims of this study are to evaluate psychological impact and quality of life according to the cancer diagnosis and mutation status in Korean families with BRCA mutations. Materials and Methods: Seventeen affected carriers (AC), 16 unaffected carriers (UC) and 13 healthy non carriers (NC) from 13 BRCA mutation families were included in the study. Outcomes were compared with regard to depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory, STAI), optimism (Reevaluation of the Life Orientation test, LOT-R), knowledge of hereditary ovarian cancer, and quality of life (QoL) (SF-36v2 Health Survey, physical component score (PCS), mental component score (MCS)) among three groups. Result: Level of depression, optimism, and PCS were similar in AC, UC, and NC. Anxiety score was elevated in all three groups. MCS was significantly low in AC than in UC and NC (P=0.009, P=0.017). Knowledge of hereditary breast and ovarian cancer was high in AC than NC (P=0.001). MCS was significantly related to whether patient was affected by cancer (P=0.043) and has occupation (P= 0.008) or not in multivariable analysis. Conclusion: From this cross sectional study, psychological adverse effect was not related to the carrier status of BRCA mutation. Elevated anxiety in BRCA family members was observed but, inde- pendent to affection and the type of genetic mutation. AC showed low mental QoL. Further effort to understand psychological impact and QoL of genetic testing in BRCA family members is required for follow-up in clinical aspects.

Improved survival in patients with stage III colon cancer after a laparoscopic colectomy (LC) has been reported by Lacy et al. (Lancet 359:2224-2229, 6), and preserved immunity was suggested as the reason for the survival advantage. The aim of our study was to clarify the existence of an immunological benefit after laparoscopic colon cancer surgery (LC) compared to open colon surgery (OC).From January 2006 to November 2007, 74 patients with clinical stage III colon cancer were prospectively assigned to undergo a LC (n = 35) or an OC (n = 39). The immune factors were examined preoperatively, and on the first and fifth days postoperatively (POD1 and POD5).The cellular immune factors were significantly decreased; however, there was no significant difference between the LC and OC groups except for the mHLA-DR. The LC group had a better preserved mHLA-DR on POD5 than did the OC group (p = 0.015), in addition to a faster recovery (p0.005).The mHLA-DR on POD5 was affected less by the LC compared to the OC. The LC demonstrated minimal immunological advantage when compared to the OC. However, further study is required to clarify the immunological benefits of the LC on colorectal cancer prognosis.

To evaluate the clinical course and outcomes of patients with T2 or T3 rectal cancer treated by transanal local excision after preoperative chemoradiation therapy (CRT).Between June 2000 and August 2004, seven patients underwent local excision of T2 or T3 rectal cancer after preoperative CRT. Preoperative clinical staging was on the basis of the findings of endorectal ultrasound. Computed tomography (CT) and digital rectal examination consisted of radiation therapy with 4 500 cGy/25 fractions, given over 5 weeks with 5-FU-based chemosensitization. Local excision was performed 4-7 weeks later.The mean age of the patients was 54.9 (35-70) years and the median follow-up period was 23 (5-57) months. The lesions were located 2-6 cm above the anal verge (median 3.0 cm). Pretreatment T staging was estimated as T3 in one patient, and T2 in six patients. Post-treatment T staging was estimated as complete remission (CR) in two patients, T1 in three patients, and T2 in two patients. Pathologic evaluation revealed tumor downstaging in six patients, including three (42.9%) with CR. No tumor cells were seen in the resection margin and there was no sign of recurrence in any of the patients.These findings support local excision after preoperative CRT as an effective alternative to radical resection in carefully selected patients with T2 and T3 distal rectal cancer.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that can be benign or malignant. SFTs have been most often documented in the pleura. Recently, involvement of extrapleural sites such as the abdomen, musculoskeletal soft tissue, upper respiratory tract, mediastinum, and head and neck were reported. Less than 15 cases of SFT of the breast have been reported. Here, we report a case of a pathologically proven SFT of the breast and review the literature on the radiologic findings. US imaging showed an oval, well-circumscribed, hypoechoic solid mass. A solitary fibrous tumor of the breast is a very rare lesion.

Atherosclerotic carotid stenosis (ACS) is a major cause of ischemic stroke. Screening for asymptomatic ACS is important to identify the patients who require longitudinal surveillance, medication, or endovascular surgery. The aim of this study was to assess the prevalence and risk factors for ACS and carotid plaque (CP) in Korea using a population-based screening study. We recruited participants during visits to several community welfare centers in Korea. The baseline characteristics of the study population were collected. All patients underwent duplex ultrasonography to examine their bilateral carotid arteries. ACS was defined as the presence of plaque with ≥50% vessel diameter reduction and peak systolic velocity (PSV) ≥125 cm/s or PSV ratio ≥2.0. CP was defined as the presence of plaque with

The classical triad of abdominal pain, vomiting, and bloody stool is absent in chronic intussusception for more than 2 weeks. Here, we report a 6-year-old female with recurrent abdominal pain for 2 months. Ultrasonography of the abdomen revealed an ileocolic-type intussusception. The lesion accompanying the tight fibrous adhesion was treated by resection and ileocolic anastomosis. It was diagnosed as intussusception with diffuse large B-cell lymphoma. A high index of suspicion for abdominal pain in children should result in the correct diagnosis and appropriate management., Graphical Abstract

Purpose: Intraoperative assessment of tissue perfusion is important to predict wound healing or improvement of symptoms in patients with peripheral arterial disease (PAD) or vascular trauma. There is no widely accepted standard for intraoperative measurement of tissue perfusion. Here, we report the use of indocyanine green (ICG)-based angiography to determine the blood flow in patients with PAD and vascular trauma. Methods: The SPY fluorescent imaging system was utilized. A dose of 3–5 mL of ICG (2.5 mg/mL) was injected intravenously followed by a 10-mL normal saline flush. The SPY imaging system was used to quantitatively assess perfusion. During the study period, the SPY imaging system was applied in 4 patients with PAD and one patient with vascular trauma. Results: In 3 patients with PAD associated with an ischemic wound, complete wound healing was achieved with the indication of viable tissue by the SPY system. In one patient with severe claudication in both lower extremities, the ICG angiography was used to determine the increased blood flow after revascularization. In the case of vascular trauma, this imaging system enabled the delineation of viability of the injured tissue. Conclusion: ICG angiography can determine the surface tissue viability in PAD patients. In cases of severe vascular trauma, the SPY system can be used to determine tissue perfusion. Further study is warranted to define the definite utility of this technology to assess perfusion, response to revascularization, and potentially, to predict the likelihood of wound healing.

The primary aims of the Korean Hereditary Breast Cancer (KOHBRA) study are to estimate the prevalence of BRCA1/2 mutations and ovarian cancer among a high-risk group of patients with hereditary breast cancer and their families.The KOHBRA study is a prospective multicentre cohort identifying cases and their families. Between May 2007 and May 2010, the KOHBRA study enrolled up to 2000 subjects. All participants received genetic counselling and BRCA genetic testing; the clinical information and blood samples for blood banking were collected. An interim analysis of the prevalence of BRCA1/2 mutations and ovarian cancer in Korean subjects was determined from the initial 975 patients who presented to 33 centres.By April 2009, a total of 167 mutation carriers among 853 probands were identified. The prevalence of the BRCA mutation was as follows: 24.8% (106/428) for breast cancer patients with a family history of breast/ovarian cancers; 11.3% (24/212) for patients with early-onset (35 years) breast cancer without a family history; 22.1% (15/68) for patients with bilateral breast cancer; male breast cancer in 8.3% (1/12); and 33.4% (1/3) for patients with breast and ovarian cancer.The results of this study suggest that the prevalence of BRCA mutations in Korean subjects is similar to the prevalence reported among Western cohorts. However, weak family history and non-familial early-onset of breast cancer were significant factors associated with carrying the BRCA mutation in Korean breast cancer patients. Completion of the KOHBRA study is needed to confirm these findings.

Purpose: Peripheral arterial disease (PAD) has been a major public health issue in the elderly. Advances in endovascular surgery have led to a substantial shift in the management of PAD. Although the nationwide trend of PAD treatment in the Western countries was reported, limited data have been available on this in Korea. This study examined the national trend in the treatment of PAD in Korea over the past decade. Methods: Health Insurance Review and Assessment Service data were used. We sought to analyze trends in the open and endovascular surgery for the treatment of PAD in Medicare beneficiaries between 2004 and 2013. We also analyzed trends in each types of surgery in the lower extremity. A linear-by-linear association was performed to determine the changes of PAD treatment for this period. Results: The rate of open surgery per 100,000 Medicare beneficiaries decreased significantly from 8 procedures in 2004 to 6 in 2013. At the same time, endovascular surgery increased from 23 procedures in 2004 to 59 in 2013. Endovascular surgery in the lower extremity increased more than twofold, while the open surgery decreased by 39%. The rate of balloon angioplasty among endovascular surgery was increased by almost threefold, while the bypass surgery using artificial graft decreased by half. Conclusion: Endovascular surgery is now performed more commonly than open surgery for PAD treatment. Balloon angioplasty increased by almost threefold, while the bypass surgery using artificial graft decreased by about 50%.

제의개발은유방암환자의생존율에유의한향상을가져왔을뿐 Purpose: This study is to review the initial 5-years of breast cancer management in a single hospital using the clinical data warehouse (CDW). Methods: We reviewed the electronic medical records of 754 patients with breast cancer who were treated by a single surgeon between June 2003 and December 2007 in Seoul National University Bundang Hospital. We analyzed the epidemiological, clinical and therapeutic profiles of the breast cancer patients which were encoded and stored at the CDW. Results: The mean age of the patients was 49.3 years and the peak incidence was in the fifth decade (36.6%). Symptomatic breast cancer was 74.6% and screening-detected breast cancer was 25.4%. Breast conserving surgery (BCS) was performed in 54.1% of all cases and the BCS rate increased annually. Immediate reconstruction after mastectomy was performed in 62 cases (17.7%). Sentinel lymph node (SLN) biopsy for nodal staging was performed in 501 cases (72.1%) and 160 cases (23.0%) underwent complete axillary lymph node dissection. The proportion of in situ and early stage invasive breast cancer was 85.0%. Six hundred and ninety three patients (92.5%) received more than one adjuvant therapy. Thirty one patients experienced local or systemic relapse after surgery and ipsilateral breast tumor recurrence (IBTR) occurred in 6 cases. The median follow-up period was 29.5 months. Two-year and 3-year disease-free survival rates were 95.9% and 94.4%. Conclusion: BCS and SLN biopsy continuously increased and immediate reconstruction after mastectomy was performed widely. Most patients received more than one adjuvant therapy. Moreover, we saved the time and human power to review the medical record by using the CDW.

trance) of breast and ovarian cancers among female family members with BRCA1 and BRCA2 mutation. Methods: Among the 61 BRCA1 mutation carriers in the 42 families and 47 BRCA2 mutation carriers in 31 families identified at 5 academic breast clinics, the probands were excluded to estimate the cumulative risk till each age of breast cancer in the Korean BRCA1 and BRCA2 carriers. Using Kaplan-Meier analyses, cumulative cancer risk estimates were determined. Results: By the age 70, the female breast cancer risk for the BRCA1 and BRCA2 mutation carriers was 72.1% (95% confidence interval [CI]=59.5% to 84.8%) and 66.3% (95% CI=41.2% to 91.5%), respectively, and the ovarian cancer risk was 24.6% (95% CI=0% to 50.3%) and 11.1% (95% CI= The Breast and Ovarian Cancer Risks in Korea Due to Inherited Mutations in BRCA1 and BRCA2: A Preliminary Report

Adenoma of the nipple (AN) is an uncommon benign tumor of the breast. This tumor usually arises from the lactiferous ducts of the nipple. The common clinical findings are unilateral serosanguinous discharge with crust and a palpable nodule in the nipple. The symptoms and signs of AN are similar to those of Paget’s disease and this confusion sometimes leads to unnecessary mastectomy. Thus performing careful clinical and histological examinations along with radiologic investigations are very important for the proper management of AN. This tumor is usually treated by total excision of the nipple. We report here on two cases of AN in two women who presented with red swelling, serosanguinous discharge and erosion of the nipple. We successfully managed them with partial excision or total excision along with reconstruction. Although AN is a relatively rare disease, surgeons should keep the diagnosis in mind for the proper management of this disease. (J Korean Surg Soc 2009;77:134-137)

Risk-reducing surgery is known as the most powerful preventive strategy for BRCA mutation carriers. This current case report represents the first documentation of the contralateral prophylactic mastectomy (CPM) and bilateral salphingooophorectomy (BSO) in a carrier of BRCA mutation in Korea. The patient was a 39-year-old woman who was seen in at a genetic counseling clinic for discussing of risk-reducing strategies for the breast and ovarian cancer. She presented at the age of 38 year with a 1.5 cm sized, grade 3, and ER/PR/HER2 negative infiltrating ductal carcinoma of the right breast. She was treated with wide local excision of the right breast and sentinel lymph node biopsy of the axilla. She was then treated with CAF (Cyclophosphamide+Doxorubicin+5-Fluorouracil) chemotherapy and radiation therapy. She was initially counseled at the time of surgery due to the family history of her mother, who suffered with breast cancer at the age of 58. After the completion of chemotherapy, we received the genetic test results and it was positive for the BRCA1 mutation (3746_ 3747insA). After a long discussion of cancer surveillance and risk-reducing options, she decided to undergo ipsilateral mastectomy and CPM and BSO. Before surgery, psychiatric consultation was done and questionnaires evaluating her depression, anxiety, body image, quality of life, and psychological distress were filled out. After discussion with the plastic surgeon, she decided to undergo delayed reconstruction of the breast. We performed endoscopic bilateral skin-sparing mastectomy and a laparoscopic bilateral salphingo-oophorectomy. There was no complication after surgery and the pathologic examination revealed no evidence of cancer in both breasts and ovaries. We think that CPM and BSO are feasible risk-reducing options for the breast cancer patients with the BRCA mutation in Korea.