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1.
Clin Breast Cancer ; 23(7): e424-e433.e3, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37438195

ABSTRACT

BACKGROUNDS: Tumor vascularity plays a fundamental role in cancer progression, including breast cancer. This study aimed to elucidate tumor vascularity and its impact on patient survival in the context of breast cancer subtypes using Hounsfield units (HU) on contrast-enhanced computed tomography (CT). MATERIALS AND METHODS: Patients with early-stage breast cancer who completed planned treatment between 2003 and 2013 were retrospectively assessed. RESULTS: The final cohort comprised 440 patients. Of the 440 patients, 262 had estrogen receptor (ER)-positive disease and 119 had human epidermal growth factor receptor 2 (HER2)-overexpressing disease. The tumor-to-aorta ratio of Hounsfield units (TAR) was related to significantly worse recurrence-free interval (RFI) (P < .001) and overall survival (OS) (P < .001) in patients with TAR > 0.33 for RFI and > 0.35 for OS than their counterparts. In the subgroup analysis, the survival disadvantage was limited only to patients with ER-positive and HER2-negative disease (P < .001 for both RFI and OS). CONCLUSION: This study showed that TAR, which reflects tumor vascularity, was significantly related to patients' RFI and OS, suggesting its capacity as a feasible biomarker. This study also showed that TAR was associated with the survival in patients with ER-positive and HER2-negative disease.

2.
Cancers (Basel) ; 14(14)2022 Jul 07.
Article in English | MEDLINE | ID: mdl-35884383

ABSTRACT

Breast cancer is a leading cause of death worldwide. Tumor vascularity and immune disturbances are hallmarks of cancer. This study aimed to investigate the reciprocal effect of tumor vascularity, assessed by the tumor-to-aorta ratio (TAR) of Hounsfield units (HU) on computed tomography (CT), and host immunity, represented by the serum neutrophil-to-lymphocyte ratio (NLR) from peripheral, complete blood cell counts and its impact on patient survival. Female patients with breast cancer who received primary treatment between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. The final cohort included 740 patients with a mean age of 54.3 ± 11.3 (22−89) years. The TAR was 0.347 ± 0.108 (range, 0.062−1.114) and the NLR was 2.29 ± 1.53 (0.61−10.47). The cut-off value for the TAR and NLR were 0.27 and 1.61, respectively. The patients with a TAR > 0.27 showed a poor recurrence free-interval (RFI) only when their NLR was larger than 1.61, and vice versa. The patients showed worse RFI when they had both high TAR and NLR. Our results suggest a dynamic reciprocal communication between tumor vascularity and systemic immunity.

3.
J Breast Cancer ; 24(5): 443-454, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34652080

ABSTRACT

PURPOSE: Triple-negative breast cancer (TNBC) has been associated with worse prognosis, and biomarkers are needed to identify high-risk patients who may benefit from clinical trials or escalated treatment after completion of standard treatment. We aimed to assess whether the post-treatment neutrophil-to-lymphocyte ratio (NLR) can reflect patient prognosis and determine the follow-up period that can provide the most feasible data. METHODS: In this retrospective analysis involving patients with TNBC, clinicopathological data, including those on peripheral complete blood cell count, were collected. The prognostic powers of serial NLRs obtained at baseline and after treatment completion were compared. Kaplan-Meier curves were generated to compare the overall survival (OS) and distant disease-free survival (DDFS). RESULTS: In total, 210 patients were enrolled. Forty-three (20.5%) events were detected. Two-thirds of the events (29/43) were related to breast cancer. Most recurrent breast cancer-related diseases (27/29) were detected within 5 years of the initial diagnosis. In contrast, half of the events due to secondary malignancies or non-breast-related diseases (7/14) occurred 5 years after the initial diagnosis. Comparison of the prognostic performance of NLRs at baseline and at 6, 12, and 24 months after treatment completion revealed the strongest prognostic performance at 6 months after treatment completion (area under the curve = 0.745). The high NLR group (NLR >2.47) showed worse OS (p = 0.006) and DDFS (p < 0.001) than low NLR group. CONCLUSION: Elevated post-treatment NLR was significantly associated with worse survival in patients with TNBC. We believe that it can be a useful surrogate marker for identifying high-risk patients with TNBC.

4.
Cancer Res ; 81(24): 6259-6272, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34711608

ABSTRACT

Genomic analysis has recently identified multiple ESR1 gene translocations in estrogen receptor alpha-positive (ERα+) metastatic breast cancer (MBC) that encode chimeric proteins whereby the ESR1 ligand binding domain (LBD) is replaced by C-terminal sequences from many different gene partners. Here we functionally screened 15 ESR1 fusions and identified 10 that promoted estradiol-independent cell growth, motility, invasion, epithelial-to-mesenchymal transition, and resistance to fulvestrant. RNA sequencing identified a gene expression pattern specific to functionally active ESR1 gene fusions that was subsequently reduced to a diagnostic 24-gene signature. This signature was further examined in 20 ERα+ patient-derived xenografts and in 55 ERα+ MBC samples. The 24-gene signature successfully identified cases harboring ESR1 gene fusions and also accurately diagnosed the presence of activating ESR1 LBD point mutations. Therefore, the 24-gene signature represents an efficient approach to screening samples for the presence of diverse somatic ESR1 mutations and translocations that drive endocrine treatment failure in MBC. SIGNIFICANCE: This study identifies a gene signature diagnostic for functional ESR1 fusions that drive poor outcome in advanced breast cancer, which could also help guide precision medicine approaches in patients harboring ESR1 mutations.


Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Biomarkers, Tumor/genetics , Breast Neoplasms/pathology , Drug Resistance, Neoplasm , Estrogen Receptor alpha/genetics , Mutation , Oncogene Proteins, Fusion/genetics , Animals , Apoptosis , Biomarkers, Tumor/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Proliferation , Estrogen Receptor alpha/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Nude , Oncogene Proteins, Fusion/metabolism , Prognosis , Survival Rate , Transcriptome , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
5.
Cancer Control ; 28: 10732748211037914, 2021.
Article in English | MEDLINE | ID: mdl-34406898

ABSTRACT

BACKGROUND: The incidence of breast cancer in Asia, including Korea, has rapidly increased. Each country has shown different clinical features. This study presents a comprehensive understanding of breast cancer in different age groups in Korea and determines potential measures for improving patient survival. METHODS: Patients diagnosed with invasive breast cancer stages I to III with available clinicopathologic and follow-up data were included in the study. Kaplan-Meier survival graphs were generated for each group and compared using log-rank test. The hazard ratio for each risk factor was calculated using the Cox regression model and the 95% confidence interval. RESULTS: The final cohort included 833 patients with a mean age of 51.3±11.3 years (range, 22-89 years), and 191 (22.9%) of them were aged >60 years. Patients aged ≥60 years had worse overall survival (OS) and distant disease-free survival than those aged <60 years. Although no difference was observed in the tumor biology, elderly patients showed significant differences in practice patterns: they tended to undergo mastectomy (40.2% vs 62.8%, P<0.001), did not receive the standard chemotherapy (88.4% vs 69.3%, P < 0.001), and had a higher risk of developing second primary cancer or diseases other than breast cancer (1.2% vs 6.8%, P < 0.001), which significantly correlated with poor survival in elderly patients. CONCLUSION: Less-than-the-standard treatment of care or development of a second primary disease resulted in poor prognosis in elderly patients in Korea. A multi-institutional and multinational study is warranted to elucidate the clinical features of breast cancer in Asian patients.


Subject(s)
Breast Neoplasms/mortality , Mastectomy/methods , Neoplasm Staging , Risk Assessment/methods , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Disease-Free Survival , Female , Humans , Middle Aged , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Survival Rate/trends , Young Adult
6.
Breast Cancer ; 27(5): 871-879, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32221862

ABSTRACT

INTRODUCTION: Neoadjuvant treatment has been widely used for patients with advanced breast cancer, and pathological complete response (pCR) has been proposed as a surrogate marker. However, more than 50% of patients will not achieve pCR and an appropriate, practical prognostic marker is required for these patients. MATERIALS AND METHODS: A retrospective analysis of patients treated with neoadjuvant treatment for stage I-III disease was performed. Clinicopathological data including the neutrophil-to-lymphocyte ratio (NLR) were collected. NLRs were collected serially according to the treatment schedule. Changes in NLRs were calculated, of which the performance capacity as a prognostic factor was evaluated, and a Kaplan-Meier plot was developed and compared with the log rank test RESULTS: Changes in NLRs of each time points of 148 patients were used to assess performance capacity as a prognostic factor for invasive disease-free survival (IDFS), overall survival (OS) and distant disease-free survival (DDFS), and that of shortly prior to the third cycle treatment showed statistical significance. With a cut off value of 0.1258, patients could be divided into high- and low-risk of invasive disease recurrence. Kaplan-Meier curves were developed and the log rank test showed that patients in high-risk group after 2 cycles of neoadjuvant treatment were significantly correlated with worse survival outcomes than those in low-risk group. CONCLUSION: Changes in NLRs after neoadjuvant treatment showed statistically significant correlation with patient survival and could categorize patients into high- and low-risk groups. Larger, prospectively designed clinical trials are required to substantiate findings of this study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/therapy , Lymphocytes , Neoadjuvant Therapy , Neoplasm Recurrence, Local/epidemiology , Neutrophils , Adult , Aged , Breast Neoplasms/blood , Breast Neoplasms/diagnosis , Breast Neoplasms/mortality , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Mastectomy , Middle Aged , Neoplasm Staging , Prognosis , Reference Values , Registries/statistics & numerical data , Republic of Korea/epidemiology , Retrospective Studies , Risk Assessment/methods
7.
Breast Cancer ; 27(1): 54-61, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31280452

ABSTRACT

BACKGROUND: Late recurrence accounts for nearly half of the recurrences in estrogen receptor (ER)-positive breast cancer and decreases post-recurrence survival in patients with ER-negative breast cancer. Clinicopathological factors and multigene assays have been used for various purposes but their prognostic capacity for late recurrence was limited. This study aimed to determine whether neutrophil to lymphocyte ratio (NLR) taken after primary treatment can be a feasible prognostic factor for late recurrence. METHODS: Patients who were diagnosed with primary breast cancer and completed planned treatment were enrolled; data were retrospectively collected from the Wonju Severance Hospital database of Yonsei University. RESULTS: 496 patients completed planned treatment for their primary breast cancer. 385 were disease free after 5 years of the primary diagnosis and 330 were enrolled for second-look NLR analysis. NLR analysis performed approximately 5 years after the primary diagnosis categorized patients into high and low risk of late recurrence with p < 0.001 and an elevated NLR was found as an independent risk factor for late recurrence (HR 1.448, CI 1.168-1.795, p < 0.001). CONCLUSION: A clinically valid biomarker to determine late recurrence is urgently needed to prevent patients from treatment extension with little benefit. Elevated NLR is found as an independent prognostic factor for late recurrence and could be utilized as a reliable, easily accessible, and cost-effective test.


Subject(s)
Breast Neoplasms/blood , Lymphocytes/pathology , Neutrophils/pathology , Adult , Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Leukocyte Count , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Proportional Hazards Models , Retrospective Studies
8.
Proc Natl Acad Sci U S A ; 115(51): E11978-E11987, 2018 12 18.
Article in English | MEDLINE | ID: mdl-30498031

ABSTRACT

A Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomic analysis prioritized dihydropyrimidinase-like-3 (DPYSL3) as a multilevel (RNA/protein/phosphoprotein) expression outlier specific to the claudin-low (CLOW) subset of triple-negative breast cancers. A PubMed informatics tool indicated a paucity of data in the context of breast cancer, which further prioritized DPYSL3 for study. DPYSL3 knockdown in DPYSL3-positive ([Formula: see text]) CLOW cell lines demonstrated reduced proliferation, yet enhanced motility and increased expression of epithelial-to-mesenchymal transition (EMT) markers, suggesting that DPYSL3 is a multifunctional signaling modulator. Slower proliferation in DPYSL3-negative ([Formula: see text]) CLOW cells was associated with accumulation of multinucleated cells, indicating a mitotic defect that was associated with a collapse of the vimentin microfilament network and increased vimentin phosphorylation. DPYSL3 also suppressed the expression of EMT regulators SNAIL and TWIST and opposed p21 activated kinase 2 (PAK2)-dependent migration. However, these EMT regulators in turn induce DPYSL3 expression, suggesting that DPYSL3 participates in negative feedback on EMT. In conclusion, DPYSL3 expression identifies CLOW tumors that will be sensitive to approaches that promote vimentin phosphorylation during mitosis and inhibitors of PAK signaling during migration and EMT.


Subject(s)
Breast Neoplasms/metabolism , Cell Movement/physiology , Claudins/metabolism , Epithelial-Mesenchymal Transition/physiology , Gene Expression Regulation, Neoplastic , Mitosis/physiology , Muscle Proteins/metabolism , Animals , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Epithelial-Mesenchymal Transition/genetics , Feedback, Physiological , Female , Gene Knockdown Techniques , Heterografts , Humans , Male , Mice , Mice, Nude , Muscle Proteins/genetics , Nuclear Proteins/metabolism , Phosphorylation , Proteogenomics , Proteomics , Repressor Proteins/metabolism , Signal Transduction , Snail Family Transcription Factors/metabolism , Triple Negative Breast Neoplasms/metabolism , Twist-Related Protein 1/metabolism , Vimentin/metabolism , Zinc Finger E-box Binding Homeobox 2/metabolism , Zinc Finger E-box-Binding Homeobox 1/metabolism , p21-Activated Kinases/metabolism
9.
J Breast Cancer ; 17(4): 308-13, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25548577

ABSTRACT

The first Korean Breast Cancer Treatment Consensus Conference Expert Panel reviewed and endorsed new evidence on aspects of local and regional therapies and diagnostic procedures that support the conservative application of results from recent clinical trials. This conference clarified the barriers that limit the application of recent clinical trial results, such as questions about level of evidence, differences between the setting of clinical trials and that of daily clinical practice, and medical necessities and environment. Detailed decisions recommended for the treatment and diagnosis, according to the from the consensus conference, are recorded including details of the votes. These recommendations differed in the degree of support for clinical consideration of disease extent and host factors, medical necessities, and environment.

10.
J Breast Cancer ; 17(1): 47-53, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24744797

ABSTRACT

PURPOSE: The effect of cyclin D1 overexpression on breast cancer outcomes and prognosis is controversial, even though amplification of the cyclin D1 gene, CCND1, has been shown to be associated with early relapse and poor prognosis. In this study, we examined the relationship between cyclin D1 overexpression and disease-specific survival (DSS). We also analyzed survival in patients who experienced recurrence. METHODS: We retrospectively analyzed data from patients diagnosed with ductal carcinoma between April 2005 and December 2010. We examined clinicopathologic factors associated with cyclin D1 overexpression and analyzed the influence of cyclin D1 on recurrence-free survival and DSS. RESULTS: We identified 236 patients diagnosed with primary breast cancer who completed all phases of their primary treatment. Cyclin D1 overexpression was significantly associated with longer DSS (5-year DSS, 89.9% in patients without cyclin D1 overexpression vs. 98.9% in patients with cyclin D1 overexpression; p=0.008). Multivariate analysis also found that patients with cyclin D1 overexpressing tumors had significantly longer disease-specific survival than patients whose tumors did not overexpress cyclin D1, with a hazard ratio for disease-specific mortality of 7.97 (1.17-54.22, p=0.034). However, in the group of patients who experienced recurrence, cyclin D1 overexpression was not significantly associated with recurrence-free survival. Cyclin D1 overexpression was significantly associated with increased survival after disease recurrence, indicating that cyclin D1 overexpression might be indicative of more indolent disease progression after metastasis. CONCLUSION: Cyclin D1 overexpression is associated with longer DSS, but not recurrence-free survival, in patients with breast cancer. Longer postrecurrence survival could explain the apparent inconsistency between DSS and recurrence-free survival. Patients with cyclin D1-overexpressing tumors survive longer, but with metastatic disease after recurrence. This information should spark the urgent development of tailored therapies to cure these patients.

11.
Yonsei Med J ; 54(3): 650-7, 2013 May 01.
Article in English | MEDLINE | ID: mdl-23549810

ABSTRACT

PURPOSE: ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression patterns and to verify the association with prognostic factors in invasive ductal carcinoma (IDC) of the breast. MATERIALS AND METHODS: Tissue samples from 203 patients were used. Forty-six cases were available for fresh tissue. We performed immunohistochemical staining and real-time polymerase chain reaction (PCR). RESULTS: ROS1 expression was significantly lower in proportion to higher histologic grade, higher mitotic counts, lower estrogen receptor expression, and a higher Ki-67 proliferation index, although ROS1 expression was not significantly associated with the survival rate. The result of real-time PCR revealed similar trends, however not statistically significant. CONCLUSION: Higher ROS1 expression may be associated with favorable prognostic factors of IDC and its expression in IDC is related to the proliferation of tumor cells.


Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Cell Proliferation , Female , Humans , Immunohistochemistry , Middle Aged , Neoplasm Grading , Prognosis , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Survival Analysis
12.
J Breast Cancer ; 16(1): 55-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23593082

ABSTRACT

PURPOSE: The purpose of this study was to investigate the prognostic impact of pretreatment neutrophil to lymphocyte ratio (NLR) on breast cancer in view of disease-specific survival and the intrinsic subtype. METHODS: We retrospectively studied patients diagnosed with primary breast cancer that had completed all phases of primary treatment from 2000 to 2010. The association between pretreatment NLR and disease-specific survival was analyzed. RESULTS: A total of 442 patients were eligible for analysis. Patients with higher NLR (2.5 ≤NLR) showed significantly lower disease-specific survival rate than those with lower NLR (NLR <2.5). Higher NLR along with negative estrogen receptor status and positive nodal status were independently correlated with poor prognosis, with hazard ratio 4.08 (95% confidence interval [CI], 1.62-10.28), 9.93 (95% CI, 3.51-28.13), and 11.23 (95% CI, 3.34-37.83), respectively. Luminal A subtype was the only intrinsic subtype in which higher NLR patients showed significantly poor prognosis (87.7% vs. 96.7%, p=0.009). CONCLUSION: Patients with an elevated pretreatment NLR showed poorer disease-specific survival than patients without elevated NLR, most evident in the luminal A subtype. Further validation and a feasibility study are required before it can be considered for clinical use.

13.
Korean J Pathol ; 46(4): 311-7, 2012 Aug.
Article in English | MEDLINE | ID: mdl-23110022

ABSTRACT

BACKGROUND: Histone deacetylase 1 (HDAC1) is associated with the expression and function of estrogen receptors and the proliferation of tumor cells, and has been considered a very important factor in breast tumor progression and prognosis. Several studies have reported an association between HDAC1 expression and poorer prognosis in cancers including breast cancer, with a few exceptions. However, because of the dearth of studies on HDAC1 expression in breast cancer, its significance for breast cancer prognosis has not been well defined. Therefore, we examined HDAC1 expression in invasive ductal carcinoma (IDC), the most common breast cancer, and investigated its potential prognostic significance. METHODS: We used 203 IDC tissue samples. Immunohistochemical stains for HDAC1 and real-time polymerase chain reaction for HDAC1 mRNA were performed and the results were compared to generally well-established prognostic factors in breast cancer and patient survival rates. RESULTS: HDAC1 expression was significantly reduced in proportion to higher histologic grade, higher nuclear pleomorphism score, and higher mitotic counts, and with lower estrogen receptor expression. Furthermore, it was significantly associated with the survival rate. CONCLUSIONS: HDAC1 expression is a good prognostic indicator in IDC.

14.
Korean J Pathol ; 46(4): 324-30, 2012 Aug.
Article in English | MEDLINE | ID: mdl-23110024

ABSTRACT

BACKGROUND: Fibroadenoma (FA) and phyllodes tumor (PT) are stromal tumors of breast and are histologically similar. There are no established differences in tumorigenesis and oncogene expression among them. Ras homolog enriched in brain (RHEB) plays an important role in cell growth and cell-cycle control, histone deacetylase 1 (HDAC1) is an important factor in breast tumor progression and prognosis, and WEE1 homolog (WEE1) functions as a tumor suppressor. No studies on the expressional differences of these proteins in FA and PT have been reported to date. METHODS: The expression of these proteins in FA, PT, and normal breast was compared. We used 102 cases of FA and 25 cases of benign PT. RESULTS: In epithelial cells, the expression of RHEB, HDAC1, and WEE1 was lowest in PT, higher in FA, and most enhanced in normal breast. In addition, the expression of RHEB and HDAC1 was higher in the stromal cells of PT than in FA and normal breast. CONCLUSIONS: Both epithelial and stromal cells of FA and PT express these proteins, which indicates that epithelial cells play an important role in the development of stromal tumors. In addition, the expressional differences of these proteins may be associated with the tumorigenesis of breast stromal tumors.

15.
J Korean Surg Soc ; 83(4): 237-41, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23091796

ABSTRACT

PURPOSE: Accurate diagnosis and optimal management of acute appendicitis, despite being the most common surgical emergency encountered in emergency departments, is often delayed in pediatric patients due to nonspecific symptoms and communication barriers, often leading to more complicated cases. The aim of this study is to investigate the diagnostic significance of common laboratory markers. METHODS: A total of 421 patients aged 15 and younger underwent surgical treatment for acute appendicitis. We conducted a retrospective analysis for white blood cell (WBC), C-reactive protein (CRP) and bilirubin. All patients were classified into simple or complicated appendicitis groups based on postoperative histology. RESULTS: The mean age of the patients in the complicated appendicitis group was younger than that in the simple group (P = 0.005). WBC, CRP and bilirubin levels were significantly higher in the complicated appendicitis group (P < 0.001, <0.001, 0.002). The relative risk for complicated appendicitis was calculated using age, WBC, CRP and bilirubin. Elevated CRP levels were associated with the highest risk for complicated appendicitis (hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.38 to 4.65) followed by WBC (HR, 2.42; 95% CI, 1.07 to 5.46) and bilirubin (HR, 2.04; 95% CI, 1.09 to 3.82). The most sensitive markers for diagnosing complicated appendicitis were WBC (95.2%) and CRP (86.3%). Bilirubin levels showed the highest specificity at 74.8%. CONCLUSION: The risk of complicated appendicitis was significantly higher in patients younger than 10 years old. Preoperative WBC, CRP and bilirubin have clinical value in diagnosing complicated appendicitis with a HR of 2.0 to 2.5. Our results suggest that the utilization of WBC, CRP, and bilirubin can assist in the diagnosis of complicated appendicitis in pediatric patients, allowing prompt diagnosis and optimal management.

16.
Pathol Int ; 58(4): 226-32, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18324915

ABSTRACT

Although fibroadenoma is one of the most common types of benign breast tumor, genes specific to the tumor have not been identified. Microarrays were used to identify differentially expressed genes between fibroadenoma and infiltrating ductal carcinoma. The comparative expression of one of the identified genes, RAS homolog enriched in the brain (RHEB), was further explored using reverse transcriptase-polymerase chain reaction (RT-PCR). Microarray analysis was performed on tissue samples from five patients with fibroadenoma. In the fibroadenoma samples, the genes HDAC1, ROS1, TNFRSF10A, WASP2, TYRP1, WEE1, and RHEB were expressed at levels more than twofold higher than in the normal tissues. RT-PCR for RHEB indicated increased expression of RHEB in fibroadenoma compared to breast cancer. When studied with real-time PCR, the average RHEB/beta-actin ratio in fibroadenoma samples was 1.99, 2.46-fold greater than the average RHEB/beta-actin ratio in breast carcinoma of 0.81 (P < 0.01). Immunohistochemistry and PCR followed by microdissection shows increased expression of RHEB in epithelial cells compared to the stromal cells of fibroadenoma. Therefore, RHEB could be used cytopathologically to distinguish fibroadenoma from malignant breast carcinomas as a secondary diagnostic tool.


Subject(s)
Breast Neoplasms/genetics , Fibroadenoma/genetics , Gene Expression Regulation, Neoplastic , Monomeric GTP-Binding Proteins/genetics , Neuropeptides/genetics , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Female , Fibroadenoma/metabolism , Fluorescent Antibody Technique, Indirect , Humans , Immunoenzyme Techniques , Mastectomy , Microdissection , Monomeric GTP-Binding Proteins/metabolism , Neuropeptides/metabolism , Oligonucleotide Array Sequence Analysis , RNA, Messenger/metabolism , Ras Homolog Enriched in Brain Protein , Reverse Transcriptase Polymerase Chain Reaction
17.
Pediatr Surg Int ; 23(3): 225-31, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17021737

ABSTRACT

Anomalous union between the pancreatic and biliary systems (APBDU) has been reported to produce choledochal cyst. The aim of this experiment was to evaluate the role of sphincteroplasty to adverse effect of APBDU in an animal model. Twelve mongrel puppies were randomly divided into a control group (n = 5) and an experimental group (n = 7). A well-established model of APBDU was produced in both groups. Transduodenal sphincteroplasty was performed only on the experimental group. For all animals, serial chemical analyses of serum were performed, and biliary tree sizes were measured by magnetic resonance cholangiography 2.5 months after the experimental surgery. At the time of animal sacrifice, 3 months after the experimental surgery, operative cholangiography was performed, and bile juice and tissues were obtained for chemical analysis and histologic examination. Dilatation of the bile duct and thickening of the wall of the bile duct were observed less frequently in the experimental group than in the control group. There were no significant differences found in pancreatic enzyme activity in the bile juice between the two groups. Denudation of the mucosa was the predominant mucosal change seen in the experimental group, while epithelial hyperplasia was the predominant mucosal change found in the control group. Our experiment shows that sphincteroplasty is not effective to prevent the pancreaticobiliary reflux, but may be effective to reduce the degree of both bile duct dilatation and mural thickening in the APBDU puppy model.


Subject(s)
Bile Ducts, Extrahepatic/abnormalities , Pancreatic Ducts/abnormalities , Sphincterotomy, Transduodenal , Amylases/blood , Animals , Bile Ducts, Extrahepatic/pathology , Cholangiopancreatography, Magnetic Resonance , Choledochal Cyst/etiology , Choledochal Cyst/pathology , Choledochal Cyst/prevention & control , Dilatation, Pathologic , Dogs , Lipase/blood , Pancreatic Ducts/pathology
18.
Yonsei Med J ; 45(1): 177-9, 2004 Feb 29.
Article in English | MEDLINE | ID: mdl-15004890

ABSTRACT

Giant Meckel's diverticulum is a very rare lesion and its association with a congenital diaphragmatic hernia has not been reported previously. We report a case of newborn with a giant Meckel's diverticulum and congenital diaphragmatic hernia. A large round atypical air-filled bowel segment was found by chest radiography preoperatively, and a giant Meckel's diverticulum was located within the left hemithorax during surgery.


Subject(s)
Hernia, Diaphragmatic/complications , Hernia, Diaphragmatic/pathology , Meckel Diverticulum/complications , Meckel Diverticulum/pathology , Hernias, Diaphragmatic, Congenital , Humans , Infant, Newborn , Male , Meckel Diverticulum/surgery
19.
J Pediatr Surg ; 37(12): 1758-61, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12483650

ABSTRACT

BACKGROUND/PURPOSE: The etiology of meconium obstruction without cystic fibrosis is unclear. Interstitial cells of Cajal (ICC) function as pacemakers in gut motility and may play a role in the pathophysiology of the disease. METHODS: The ICC were examined by immunohistochemical staining with anti-c-kit antibody in the bowel walls of 6 neonates who had meconium obstruction without cystic fibrosis, and the results were compared with specimens from normal neonates (n = 2). RESULTS: Six patients underwent ileostomy between 2 and 15 days after birth, and 5 of them presented with microcolon. Ganglion cells were present in the ileum and colon. Whereas ICC were evenly distributed in the control specimens, they were not seen at the time of ileostomy in the colons of 2 patients, and the other 4 showed scanty distribution in muscle layers. However, ileum showed normal distribution of ICC in all patients. The ileostomies were closed between 39 and 104 days of age, and the ICC distribution was changed to a normal pattern in the colons of all 6 patients. Their bowel movements were restored to normal after closure. CONCLUSION: The findings of this study suggest that delayed maturity of ICC may be a cause of meconium obstruction without cystic fibrosis.


Subject(s)
Coiled Bodies/pathology , Colonic Diseases/pathology , Ileal Diseases/pathology , Infant, Newborn, Diseases/pathology , Intestinal Obstruction/pathology , Colonic Diseases/etiology , Colonic Diseases/surgery , Female , Gastrointestinal Motility , Humans , Ileal Diseases/etiology , Ileal Diseases/surgery , Ileostomy , Immunohistochemistry , Infant, Newborn , Infant, Newborn, Diseases/etiology , Infant, Newborn, Diseases/surgery , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Male , Meconium
20.
J Pediatr Surg ; 37(11): E36, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12407566

ABSTRACT

PURPOSE: The aim of this study was to introduce a new surgical technique for the correction of congenital cricotracheal stenosis. METHODS: A 5-day-old girl presented with esophageal atresia and congenital cricotracheal stenosis. After successfully correcting her esophageal atresia, the authors chose to use a type of slide cricotracheoplasty, which was a modification of slide tracheoplasty and anterior cricoid split. RESULTS: The postoperative period was remarkably uneventful except for minor subcutaneous emphysema, and the midterm results were excellent. CONCLUSIONS: Slide cricotracheoplasty produced a good result and offered the same advantages as slide tracheoplasty. The authors believe that the described technique offers an efficient surgical procedure for the single-staged correction of congenital cricotracheal stenosis.


Subject(s)
Cricoid Cartilage/abnormalities , Cricoid Cartilage/surgery , Tracheal Stenosis/congenital , Tracheal Stenosis/surgery , Bronchoscopy , Female , Humans , Infant, Newborn , Suture Techniques , Trachea/surgery
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