Many studies have shown a consistent association between ambient air pollution and an increase in death due to cardiovascular causes. An increase in blood pressure is a common risk factor for a variety of cardiovascular diseases. However, the association between air pollution and blood pressure has not been evaluated extensively.
In this cross‐sectional study, we measured blood pressure in 10 459 subjects who had a health examination from 2001 to 2003, and calculated individual's exposure to ambient levels of air pollutants. To evaluate the relationship between exposure to air pollutants and blood pressure with respect to season, we performed a multiple regression analysis, separately, according to season, controlling for individual characteristics and meteorological variables.
In the warm‐weather season (July–September), particulate air pollutant of <10 μm (PM10) and nitrogen dioxide (NO2) concentrations were significantly associated with measures of blood pressure. During cold weather (October–December), blood pressure was significantly associated with sulphur dioxide (SO2) and ozone (O3) concentrations. The significant association between PM10 or NO2 and blood pressure disappeared during the cold‐weather season.
We found a seasonal variation for the association between ambient air‐pollutant concentrations and blood pressure.
BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. We also observed intratumor heterogeneity for the loss of wild-type BRCA1 and increased cell proliferation and centrosome amplification in the normal breast epithelium of BRCA1 mutation carriers. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population.
Defining the temporal order of tumor-driving somatic events is critical for early detection, risk stratification, and the design of chemopreventive therapies. Our combined experimental and computational approach reveal that the loss of wild-type BRCA1 may not be the first event in the majority of BRCA1-associated breast tumors and may not be present in all cancer cells within tumors.
Although pandemic community-associated (CA-) methicillin-resistant Staphylococcus aureus (MRSA) ST30 clone has successfully spread into many Asian countries, there has been no case in Korea. We report the first imported case of infection caused by this clone in a Korean traveler returning from the Philippines. A previously healthy 30-yr-old Korean woman developed a buttock carbuncle while traveling in the Philippines. After coming back to Korea, oral cephalosporin was given by a primary physician without any improvement. Abscess was drained and MRSA strain isolated from her carbuncle was molecularly characterized and it was confirmed as ST30-MRSA-IV. She was successfully treated with vancomycin and surgery. Frequent international travel and migration have increased the risk of international spread of CA-MRSA clones. The efforts to understand the changing epidemiology of CA-MRSA should be continued, and we should raise suspicion of CA-MRSA infection in travelers with skin infections returning from CA-MRSA-endemic countries.
Staphylococcus aureus; Methicillin Resistance; Community-Acquired Infections; Carbuncle; Travel
To determine the prevalence of Y chromosome microdeletions in infertile Korean men with abnormal sperm counts and to assess the clinical features and frequency of chromosomal abnormalities in Korean patients with microdeletions.
A total of 1,306 infertile men were screened for Y chromosome microdeletions, and 101 of them had microdeletions. These 101 men were then retrospectively studied for cytogenetic evaluation, testicular biopsy and outcomes of IVF and ICSI.
The overall prevalence of Y chromosome microdeletions in infertile men was 7.7 % (101/1,306). Most microdeletions were in the AZFc region (87.1 %), including deletions of AZFbc (24.7 %) and AZFabc (8.9 %). All patients with AZFa, AZFbc and AZFabc deletions had azoospermia, whereas patients with an AZFc deletion usually had low levels of sperm in the ejaculate or in the testis tissues. Chromosomal studies were performed in 99 men with microdeletions, 36 (36.4 %) of whom had chromosomal abnormalities. Among the infertile men with Y chromosome microdeletions in this study, the incidence of chromosomal abnormality was 48.6 % in the azoospermic group and 3.7 % in the oligozoospermic group. Among the 69 patients with microdeletions and available histological results, 100.0 % of the azoospermic group and 85.7 % of the oligozoospermic group had histological abnormalities. The frequency of both chromosomal abnormalities and histological abnormalities was higher in the azoospermic group compared to the oligozoospermic group. Thirty-four ICSI cycles with either testicular (n = 14) or ejaculated spermatozoa (n = 20) were performed in 23 couples with men with AZFc microdeletion. Thirteen clinical pregnancies (39.4 %) were obtained, leading to the birth of 13 babies.
The study results revealed a close relationship between microdeletions and spermatogenesis, although IVF outcome was not significantly affected by the presence of the AZFc microdeletion. Nevertheless, Y chromosome microdeletions have the potential risk of being transmitted from infertile fathers to their offspring by ICSI. Therefore, before using ICSI in infertile patients with severe spermatogenic defects, careful evaluations of chromosomal abnormalities and Y chromosome microdeletions screening should be performed and genetic counseling should be provided before IVF-ET.
Y chromosome microdeletion; Chromosomal abnormality; Azoospermia factor (AZF); Intracytoplasmic sperm injection (ICSI)
Mediastinal ectopic thyroid is a very rare condition, with few reported cases in the literature and no reported cases in Korea. This report describes an asymptomatic 65-year-old man with a right paratracheal mass compressing the superior vena. Additionally, the epidemiology, clinical manifestation, diagnosis, and management of mediastinal ectopic thyroids are discussed. A mediastinal ectopic thyroid should be considered in the differential diagnosis of all mediastinal masses. Surgical excision is recommended for both the diagnosis and treatment of this condition, because of its potential for malignancy and compression of mediastinal structures. This case demonstrates the clinical importance of mediastinal etopic thyroid.
Thyroid dysgenesis; Mediastinum
Klinefelter syndrome is a chromosomal disorder present in 1 out of 400 to 1,000 male newborns in Western populations. Two-thirds of affected newborns show a karyotype of 47,XXY. Few studies have examined the incidence of Klinefelter syndrome in Korea. The aim of this study was to investigate the incidence of Klinefelter syndrome by use of prenatal screening tests.
Materials and Methods
From January 2001 to December 2010, 18,049 pregnant women who had undergone a chromosomal study for fetal anomalies were included. For fetuses that were diagnosed as having Klinefelter syndrome, the patients' medical records were retrospectively reviewed. Both parents' ages, the reason for the chromosomal studies, and karyotypes were investigated.
We found that 22 of 18,049 (0.12%) fetuses were diagnosed with Klinefelter syndrome. The incidence of this disorder in male fetuses was 22 of 9,387 (0.23%). Also, 19 of the newborns (86.4%) showed a karyotype of 47,XXY; the other newborns showed karyotypes of 48,XXY,+21; 48,XXY,+12/46,XY; and 47,XXY/45,X/46,XY. The mean age of the mothers was 36.1 years, and 2 women had a past history of a Down syndrome pregnancy. Nine mothers had a normal spontaneous delivery, 9 mothers underwent artificial abortion, and 2 fetuses were spontaneously aborted.
The incidence of Klinefelter syndrome as reported in this study is higher than in previous studies. Further studies with a broader population should be considered to confirm these results.
Karyotype; Klinefelter syndrome; Male infertility
To report the feasibility of magnetic resonance imaging (MRI)-guided intervention for diagnosing suspicious breast lesions detectable by MRI only, using the freehand technique with a 3.0-T closed-bore MRI scanner.
Materials and Methods
Five women with 5 consecutive MRI-only breast lesions underwent MRI-guided intervention: 3 underwent MRI-guided needle localization and 2, MRI-guided vacuum-assisted biopsy. The interventions were performed in a 3.0-T closed-bore MRI system using a dedicated phased-array breast coil with the patients in the prone position; the freehand technique was used. Technical success and histopathologic outcome were analyzed.
MRI showed that four lesions were masses (mean size, 11.5 mm; range, 7-18 mm); and 1, a nonmass-like enhancement (maximum diameter, 21 mm). The locations of the lesions with respect to the breast with index cancer were as follows: different quadrant, same breast - 3 cases; same quadrant, same breast - 1 case; and contralateral breast - 1 case. Histopathologic evaluation of the lesions treated with needle localization disclosed perilobular hemangioma, fibrocystic change, and fibroadenomatous change. The lesions treated with vacuum-assisted biopsy demonstrated a radial scar and atypical apocrine hyperplasia. Follow-up MRI after 2-7 months (mean, 4.6 months) confirmed complete lesion removal in all cases.
MRI-guided intervention for breast lesions using the freehand technique with a 3.0-T closed-bore MRI scanner is feasible and accurate for diagnosing MRI-only lesions.
Breast neoplasms; Magnetic resonance imaging; Biopsy; High field; Freehand technique; Needle localization
Cholesterol granuloma of the breast is a rare, benign disease. Here, we present the unique ultrasonographic findings of breast cholesterol granuloma manifesting as an intracystic mass. The findings of this case report may help expand existing knowledge regarding differential diagnosis of intracystic breast masses, which are found on ultrasonographic examination.
Breast; Cholesterol granuloma; Ultrasonography
Cell-free fetal DNA and cell-free total DNA in maternal circulation have been proposed as potential markers for noninvasive monitoring of the placental condition during the pregnancy. However, the correlation of and change in cell-free fetal DNA and cell-free total DNA in spontaneous abortion (SA) with fetal chromosomal aneuploidy have not yet been reported. Therefore, we investigated cell-free fetal DNA and cell-free total DNA levels in SA women with fetal chromosomal aneuploidy.
A nested case-control study was conducted with maternal plasma collected from 268 women in their first trimester of pregnancy. Subjects included 41 SA with normal fetal karyotype, 26 SA with fetal chromosomal aneuploidy, and 201 normal controls. The unmethylated PDE9A gene was used to measure the maternal plasma levels of cell-free fetal DNA. The GAPDH gene was used to measure the maternal plasma levels of cell-free total DNA. The diagnostic accuracy was measured using receiver-operating characteristic (ROC) curves. Levels of cell-free fetal DNA and cell-free total DNA were significantly higher in both SA women with normal fetal karyotype and SA women with fetal chromosomal aneuploidy in comparison with the normal controls (P<0.001 in both). The correlation between cell-free fetal DNA and cell-free total DNA levels was stronger in the normal controls (r = 0.843, P<0.001) than in SA women with normal karyotype (r = 0.465, P = 0.002) and SA women with fetal chromosomal aneuploidy (r = 0.412, P = 0.037). The area under the ROC curve for cell-free fetal DNA and cell-free total DNA was 0.898 (95% CI, 0.852–0.945) and 0.939 (95% CI, 0.903–0.975), respectively.
Significantly high levels of cell-free fetal DNA and cell-free total DNA were found in SA women with fetal chromosomal aneuploidy. Our findings suggest that cell-free fetal DNA and cell-free total DNA may be useful biomarkers for the prediction of SA with fetal chromosomal aneuploidy, regardless of fetal gender.
We describe the first reported case of endocarditis due to Neisseria skkuensis. The organism from the blood cultures taken on admission day was identified initially as unidentified Gram-negative cocci by Vitek2. Finally, it was identified as Neisseria skkuensis by 16 rRNA gene sequence analysis.
Successful cecal intubation (SCI) is not only a quality indicator but also an important marker in a colonoscopy trainee’s progress. We conducted this study to determine factors predicting SCI in colonoscopy trainees, and to compare these factors before and after trainees achieve technical competence.
Design of this study was a cross-sectional studies of two time series design for one year at a single center. From March 2011 to February 2012, a total 2,050 subjects who underwent colonoscopy by four first-year gastrointestinal fellows were enrolled at Christian hospital, Wonju, Republic of Korea. Four gastrointestinal fellows have filled out the colonoscopic documentation. Main outcome measurement was predictive factors affecting cecal intubation failure and learning curves.
Colonoscopy was successfully completed to the cecum in 1,720 patients (83.9%). Success rates gradually increased as trainees performed more colonoscopies: the rate of SCI was 62% in the first 50 cases, and grew to 93% by the 250th case. Logistic regression analysis of factors affecting cecal intubation failure showed that female gender, low BMI (BMI < 18.5 kg/m2), poor bowel preparation, and past history of stomach surgery were more often associated with cecal intubation failure, particularly before the trainees achieved technical competence.
Several patient characteristics were identified that may predict difficulty of cecal intubation in colonoscopy trainees. Particularly, low BMI, inadequate bowel cleansing, and previous stomach operation were predictors of cecal intubation failure before the trainees have reached technical competency. The results could be informative so that trainees enhance the success rate regarding better colonoscopy training programs.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected p-value of p < 2.03 × 10−3 were observed between LN and MYH9 in EAs (N=4620), with the most pronounced association at rs2157257 (p = 4.7 × 10−4; odds ratio [OR]=1.205). A modest effect with MYH9 was also detected in Gullah (rs8136069, p = 0.0019, OR = 2.304). No association between LN and MYH9 was found in AAs, Asians, Amerindians or Hispanics. This study provides the first investigation of MYH9 in LN in non-Africans and of APOL1 in LN in any population and presents novel insight into the potential role of MYH9 in LN in EAs.
MYH9; APOL1; lupus nephritis; systemic lupus erythematosus; multiethnic association study
Phyllodes tumor is an uncommon fibroepithelial neoplasm of the breast. And it is characterized by expanded stroma with increased cellularity and elongated epithelium-lined clefts. Mammary carcinomas within phyllodes tumors have been rarely reported. To date, however, no reports have described the invasive cribriform carcinoma arising in malignant phyllodes tumor. Here, we report a 62-year-old woman who presented with a large breast mass. Microscopically, the mass was a typical malignant phyllodes tumor showing well developed leaf-like architecture and stromal overgrowth with high cellularity and nuclear pleomorphism. In a portion of the tumor, however, the epithelial component showed a cribriform pattern of proliferation in the absence of myoepithelial cells, suggestive of the invasive cribriform carcinoma. To our knowledge, this is rare and it is difficult to make a differential diagnosis of it. Here, we report our case with a review of literatures.
Invasive carcinoma; Phyllodes tumor; Breast; Cribriform
Villoglandular adenocarcinoma (VGA) is a rare subtype of cervical adenocarcinoma with a more favorable prognosis compared to conventional adenocarcinomas. Although the tumors are usually recognized on colposcopic examination due to the mainly exophytic growth pattern, they may be underdiagnosed as benign lesions by cytology because of their minimal cytologic atypia. We report the liquid-based cytology (LBC) findings of three histologically confirmed VGAs which we have recently identified. They were characterized by hypercellular smears on low-power examination with smooth-bordered three-dimensional papillary fragments. The nuclei were relatively uniform with irregular nuclear membranes. Nucleoli were small but distinct and macronucleoli were also seen. The abnormal architectural patterns such as papillary structures and nuclear overlapping and nuclear hyperchromasia are important clues to the diagnosis of VGA. In addition, nuclear membrane irregularity and prominent nucleoli can be recognized on LBC specimens, further facilitating its diagnosis.
Villoglandular adenocarcinoma; Uterine cervical neoplasms; Liquid-based cytology
Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs). Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma.
Lymphoma; Hemolytic anemia; Coombs' test; Idiopathic thrombocytopenic purpura
To perform a reliable non-invasive detection of the fetal achondroplasia using maternal plasma.
We developed a quantitative fluorescent-polymerase chain reaction (QF-PCR) method suitable for detection of the FGFR3 mutation (G1138A) causing achondroplasia. This method was applied in a non-invasive detection of the fetal achondroplasia using circulating fetal-DNA (cf-DNA) in maternal plasma. Maternal plasmas were obtained at 27 weeks of gestational age from women carrying an achondroplasia fetus or a normal fetus.
Two percent or less achondroplasia DNA was reliably detected by QF-PCR. In a woman carrying a normal fetus, analysis of cf-DNA showed only one peak of the wild-type G allele. In a woman expected an achondroplasia fetus, analysis of cf-DNA showed the two peaks of wild-type G allele and mutant-type A allele and accurately detected the fetal achondroplasia.
The non-invasive method using maternal plasma and QF-PCR may be useful for diagnosis of the fetal achondroplasia.
Achondroplasia; Non-invasive prenatal diagnosis; Maternal plasma; QF-PCR
To investigate associations between the androgen receptor (AR) polymorphisms as CAG repeats, GGC repeats and c.211G>A polymorphism and the risk of preeclampsia.
The AR polymorphisms were experienced in 184 preeclamptic patients and 190 normal pregnancies and analyzed by multiple logistic regression.
Women with GGC repeats>16 were more frequently observed in preeclampsia, compared to those with GGC repeats≤16 [adjOR (95% CI): 3.64 (1.71–6.23)]. However, no significant differences were observed between the two groups with respect to CAG repeats. The genotypic and allelic frequencies of c.211G>A variant were significantly higher in cases than in controls (P < 0.05 for both). In the combined distribution of these polymorphisms, the highest risk of preeclampsia was found among women with the haplotype as CAG > 20/GA/GGC>16 [adjOR (95% CI): 4.26 (1.92–12.23)].
Our findings suggest that longer GGC repeats and c.211G>A variant in the AR gene are associated with increased susceptibility to the risk of preeclampsia.
Androgen receptor; CAG repeats; GGC repeats; c.211G>A polymorphism; Preeclampsia
To assess the relationship between apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance (MR) imaging and pathologic measures of a tumor using a prostate cancer xenograft model.
Materials and Methods
Eighteen athymic nude mice with 36 PC-3-induced tumors were sacrificed to obtain specimens immediately after MR imaging in order to compare the findings on MR images with those seen on pathological specimens. Using a high-field small-animal MR scanner, T1- and T2-weighted imaging and DW MR imaging was performed. Tumors were then processed for Hematoxylin and Eosin staining to evaluate tumor cellularity, intratumoral necrosis and immunostaining using antibodies directed against CD31 and vascular endothelial growth factor (VEGF) to determine the levels of microvessel density (MVD). Mean ADC values that were measured on the solid portion within each tumor were compared with tumor volume, cellularity, degree of necrosis, VEGF expression, and MVD in the corresponding section of the pathological specimen.
Mean ADC values of the solid portion within the PC-3-induced high-grade tumors were significantly correlated with the degree of intratumoral necrosis (r = 0.63, p < 0.0001) and MVD (r = -0.44, p = 0.008) on pathologic slides. The ADC values were not significantly correlated with tumor cellularity, VEGF expression, or tumor volume in high-grade prostate cancer tissues.
In the xenografted prostate cancer model, the ADC values of the solid portion of the tumors are significantly correlated with tumor necrosis and MVD of the pathologic specimens. The ADC values may be utilized as surrogate markers for the noninvasive assessment of tumor necrosis and MVD in high-grade prostate cancer.
PC3; Prostate; Diffusion weighted imaging; MR; Necrosis; MVD
A 35-year-old man with infertility was referred for chromosomal analysis. In routine cytogenetic analysis, the patient was seen to have additional material of unknown origin on the terminal region of the short arm of chromosome 4. To determine the origin of the unknown material, we carried out high-resolution banding, comparative genomic hybridization (CGH), and FISH. CGH showed a gain of signal on the region of 4q32→q35. FISH using whole chromosome painting and subtelomeric region probes for chromosome 4 confirmed the aberrant chromosome as an intrachromosomal insertion duplication of 4q32→q35. Duplication often leads to some phenotypic abnormalities; however, our patient showed an almost normal phenotype except for congenital dysfunction in spermatogenesis.
Chromosome 4; Insertion 4p; Duplication 4q; Comparative genomic hybridization; Fluorescent in situ hybridization; Human
Down syndrome (DS) is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A). Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A.
A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling). All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8–151.6] and 63.7 [95% confidence interval: 23.2–206.7], respectively.
Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal gender.
Although the nodal ratio (NR) has been recognized as a prognostic factor in breast cancer, its clinical implication in patients with 1-3 positive nodes (N1) remains unclear. Here, we evaluated the prognostic value of the NR and identified other clinico-pathologic variables associated with poor prognosis in these patients.
We analyzed 130 patients with N1 invasive breast cancer who were treated at Seoul National University Bundang Hospital from March 2003 to December 2007. Disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were compared according to the NR with a cut-off value of 0.15.
We followed patients' recovery for a median duration of 59 months. An NR > 0.15 was found in 23.1% of patients, and a median of 18 nodes were dissected per patient (range 1-59). The NR was statistically independent from other prognostic variables, such as patient age, T stage, extent of surgery, pathologic factors in the chi square test. On univariate analysis, patients with a NR > 0.15 had significantly lower 5-year LRRFS (88.7% vs. 97.9%, p = 0.033) and 5-year DMFS (81.3% vs. 96.4%, p = 0.029) and marginally lower 5-year DFS (81.3% vs. 94.0%, p = 0.069) than those with a NR ≤0.15, respectively. Since the predictive power of the NR was found to differ with diverse clinical and pathologic variables, we performed adjusted analysis stratified by age, pathologic characteristics, and adjuvant treatments. Only young patients with a NR > 0.15 showed significantly lower DFS (p = 0.027) as well as those presenting an unfavorable pathologic profile such as advanced T stage (p = 0.034), histologic grade 3 (p = 0.034), positive lymphovascular invasion (p = 0.037), involved resection margin (p = 0.007), and no chemotherapy (p = 0.014) or regional radiotherapy treatment (p = 0.039). On multivariate analysis, a NR > 0.15 was significantly associated with lower DFS (p = 0.043) and DMFS (p = 0.012), but not LRRFS (p = 0.064).
A NR > 0.15 was associated with an increased risk of recurrence, especially in young patients with unfavorable pathologic profiles.
breast cancer; N1; nodal ratio; prognostic factor
A 36-year-old male patient with no remarkable medical history was admitted to our hospital for a health check up. On chest radiography, bilateral aortic notches at the level of aortic arch were shown suggesting aortic arch anomaly without any clinical symptoms. Two aortic arches were almost same-in-size on suprasternal view of transthoracic echocardiography. In addition, multidetector computed tomography showed balanced type double aortic arch forming a complete vascular ring which encircled the trachea and esophagus. The trachea was slightly compressed by the vascular ring whereas the esophagus was intact. Nevertheless, the pulmonary function test was normal. The patient was discharged from hospital with instructions for periodic follow-up.
Double aortic arch; Echocardiography; Vascular ring
To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells.
A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group.
No differences were found between the two groups' mean plasma homocysteine levels (7.6±1.5 µmol/L vs. 7.1±2.1 µmol/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant (7.7±1.1 µmol/L) had higher homocysteine levels than those with the CC and CT variants (7.4±1.9 µmol/L and 7.4±1.2 µmol/L) and those with the CT variant (19.2±8.1%) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants (17.7±6.6% and 17.9±7. 0%), but the results of both comparisons were statistically insignificant.
These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.
Methylenetetrahydrofolate Reductase Polymorphism; Habitual Abortion; Natural Killer Cells; Human
The PIK3 signaling pathway has been identified as one of the most important and most frequently mutated pathways in breast cancer. Somatic mutations in the catalytic subunit of PIK3CA have been found in a significant fraction of breast carcinomas, and it has been proposed that mutant PIK3CA plays a role in tumor initiation. However, the majority of primary human tumors analyzed for genetic alterations in PIK3CA have been invasive breast carcinomas and the frequency of PIK3CA mutations in pre-invasive lesions has not been explored. To investigate this, we sequenced exons 9 and 20 of PIK3CA in pure ductal carcinoma in situ (DCIS), DCIS adjacent to invasive carcinoma, and invasive ductal breast carcinomas (IDC). In a subset of cases both in situ and invasive areas were analyzed from the same tumor. We found that the frequency of PIK3CA mutations was essentially the same (~30%) in all three histologic groups. In some cases in situ and invasive areas of the same tumor were discordant for PIK3CA status and in two cases where multiple invasive and adjacent in situ areas within the same tumor were analyzed independently, we detected intra-tumor heterogeneity for PIK3CA mutations. Our results suggest that mutation of PIK3CA is an early event in breast cancer that is more likely to play a role in breast tumor initiation than in invasive progression, although a potential role for exon 9 mutations in the progression of a subset of DCIS cases cannot be excluded.
DCIS; PIK3CA; tumor progression; invasion; breast cancer
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.
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.
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.
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.
Breast neoplasms; Primary systemic therapy; Sentinel lymph node biopsy