We compared the radiological and clinical outcomes between patients who underwent posterior fixation alone and supplemented with fusion following the onset of thoracolumbar burst fractures. In addition, we also evaluated the necessity of posterolateral fusion for patients treated with posterior pedicle screw fixation.
From January 2007 to December 2009, 46 consecutive patients with thoracolumbar burst fracture were included in this study. On the basis of posterolateral fusion, we divided our patients into the non-fusion group and the fusion group. The radiological assessment was performed according to the Cobb's method, and results were obtained at immediately, 3, 6, 12 months after surgery. The clinical outcomes were evaluated using the modified Mcnab criteria at the final follow-up.
The demographic data and the mean follow-up period were similar between the two groups. Patients of both groups achieved satisfactory clinical outcomes. The mean loss of kyphosis correction showed that patients of both groups experienced loss of correction with no respect to whether they underwent the posterolateral fusion. There was no significant difference in the degree of loss of correction at any time points of the follow-up between the two groups. In addition, we also compared the effect of fixed levels (i.e., short versus long segment) on loss of correction between the two groups and there was no significant difference. There were no major complications postoperatively and during follow-up period.
We suggest that posterolateral fusion may be unnecessary for patients with thoracolumbar burst fractures who underwent posterior pedicle screw fixation.
Thoracolumbar burst fracture; Posterior pedicle screw fixation; Posterolateral fusion; Loss of kyphosis correction
Superior sagittal sinus thrombosis (SSST) is an uncommon cause of stroke, whose symptoms and clinical course are highly variable. It is frequently associated with a variety of hypercoagulable states. Coagulation abnormalities are commonly seen in patients with hyperthyroidism. To the best of our knowledge, there are few reports on the association between hyperthyroidism and cerebral venous thrombosis. We report on a 31-year-old male patient with a six-year history of hyperthyroidism who developed seizure and mental deterioration. Findings on brain computed tomography (CT) showed multiple hemorrhages in the subcortical area of both middle frontal gyrus and cerebral digital subtraction angiography (DSA) showed irregular intra-luminal filling defects of the superior sagittal sinus. These findings were consistent with hemorrhagic transformation of SSST. Findings on clinical laboratory tests were consistent with hyperthyroidism. In addition, our patient also showed high activity of factors IX and XI. The patient received treatment with oral anticoagulant and prophylthiouracil. His symptoms showed complete improvement. A follow-up cerebral angiography four weeks after treatment showed a recanalization of the SSS. In conclusion, findings of our case indicate that hypercoagulability may contribute to development of SSST in a patient with hyperthyroidism.
Cerebral venous thrombosis; Superior sagittal sinus; Hyperthyroidism; Hypercoagulability
This survey was performed to analyze the usability of the third edition of the Korean breast cancer clinical practice guidelines (KBCCPG) in clinical practice. We made a questionnaire composed of 18 general and 82 specific questions regarding benign breast disease (B; 1 question); non-invasive disease (N; 12 questions); early-stage disease (E; 26 questions); advanced disease (A; 24 questions); and metastatic (M) breast cancer-related problems (19 questions). A total of 100 questionnaires, with a link to an online survey, were delivered via e-mail to over 700 members of the Korean Breast Cancer Society (KBCS), and associated academy members, over 20 days between 26th February and 16th May 2010. Out of 270 respondents who read the e-mail, 96 answered the questionnaire. Participants included 87 surgical oncologists, 5 radiation oncologists, 2 oncoplastic surgeons, 1 pathologist, and 1 medical oncologist. The third KBCCPG were perceived as differing from the second guidelines in terms of the level of clinical evidence required before choosing a recommendation. For the progress of the KBCCPG, the guideline committee should try to reinforce all courses of guideline development with several elements including data from clinical trials of Korean breast cancer patients, securing a multidisciplinary approach, developing consistent and reasonable processes for each step of the revision of the guidelines, induction of liberal scientific and ethical discussion about all issues with all KBCS members. The cost-effectiveness of healthcare and the logical development of the KBCCPG would also be ensured. Timely updates of the clinical guidelines for breast cancer treatment are essential to facilitate optimal decision-making in daily practice, and to ensure adequate patient feedback.
Breast neoplasms; Guideline; Korea; Surveys
Breast cancer is the most common cancer in women worldwide. It is necessary to identify biomarkers for early detection, to make accurate prognoses, and to monitor for any recurrence of the cancer. In order to identify potential breast cancer biomarkers, we analyzed the plasma samples of women diagnosed with breast cancer and age-matched normal healthy women by mTRAQ-based stable isotope-labeling mass spectrometry. We identified and quantified 204 proteins including thrombospondin-1 (THBS1) and bromodomain and WD repeat-containing protein 3 (BRWD3) which were increased by more than 5-fold in breast cancer plasma. The plasma levels of the two proteins were evaluated by Western blot assay to confirm for their diagnostic value as serum markers. A 1.8-fold increase in BRWD3 was observed while comparing the plasma levels of breast cancer patients (n = 54) with age-matched normal healthy controls (n = 30), and the area under the receiver operating characteristic curve (AUC) was 0.917. THBS1 was detected in pooled breast cancer plasma at the ratio similar to mTRAQ ratio (> 5-fold). The AUC value for THBS1 was 0.875. The increase of THBS1 was more prominent in estrogen receptor negative and progesterone receptor negative patients than receptor-positive patients. Our results are evidence of the diagnostic value of THBS1 in detecting breast cancer. Based on our findings, we suggest a proteomic method for protein identification and quantification lead to effective biomarker discovery.
biological markers; breast neoplasms; BRWD3 protein, human; mass spectrometry; proteomics; thrombospondin 1
We investigated the clinical and radiological advantages of unilateral laminectomy in posterior lumbar interbody fusion (PLIF) procedure comparing with bilateral laminectomy, under the same procedural condition including bilateral instrumentation and insertion of two cages, in patients
with degenerative lumbar disease with unilateral leg symptoms.
We retrospectively reviewed 124 consecutive cases of PLIF via unilateral or bilateral approach between January 2006 and April 2010. In 80 cases (bilateral group), two cages were inserted via bilateral laminectomy, and in 44 cases (unilateral group), via unilateral laminectomy. The average
follow-up duration was 29.5 months. The clinical outcomes were evaluated with the Visual Analogue Scale (VAS) and the Oswestry disability index (ODI). The fusion rates and disc space heights were determined by dynamic standing radiographs and/or computed tomography. Operative times, intra-operative and post-operative blood losses and hospitalization periods were also evaluated.
In clinical evaluation, the VAS and ODI scores showed excellent outcomes in both groups. There were no significant differences in term of fusion rate, but the perioperative blood loss and the operative time of the unilateral group were lower than that of the bilateral group.
Unilateral laminectomy can minimize the operative time and perioperative blood loss in PLIF procedure. However, the different preoperative
disc height between two groups is a limitation of this study. Despite this limitation, solid fusion and satisfactory symptomatic improvement could be achieved uniquely by our surgical method. This surgical method can be an alternative surgical technique in patients with unilateral leg pain.
Posterior lumbar interbody fusion; Iatrogenic root injury; Unilateral approach; Unilateral leg symptoms
A core-sheath of multi-walled carbon nanotube (MWNT)-cellulose fibers of diameters from several hundreds nm to several µm were prepared by co-axial electrospinning from a non-valatile, non-flammable ionic liquid (IL) solvent, 1-methyl-3-methylimidazolium acetate ([EMIM][Ac]). MWNTs were dispersed in IL to form a gel solution. This gel core solution was electrospun surrounded by a sheath solution of cellulose disolved in the same IL. Electrospun fibers were collected in a coagulation bath containing ethanol-water to completely remove the IL and dried to form a core-sheath MWNT-cellulose fibers having a cable structure with a conductive core and insulating sheath. Enzymatic treatment of a portion of a mat of these fibers with cellulase selectively removed the cellulose sheath exposing the MWNT core for connection to an electrode. These MWNT-cellulose fiber mats demonstrated excellent conductivity due to a conductive pathway of bundleled MWNTs. Fiber mat conductivity increased with increasing ratio of MWNT in the fibers with a maximum conductivity of 10.7 S/m obtained at 45 wt% MWNT loading.
Vitamin D deficiency may be an indicator of poor prognosis in patients with breast cancer before surgery. We investigated the association between serum vitamin D concentration and breast cancer prognosis according to intrinsic cancer subtypes.
From June to December 2006, serum 25-OHD was measured in 310 Korean women with breast cancer who were treated at the Asan Medical Center, Korea. Clinicopathologic data were examined to determine the prognostic effects of serum 25-OHD. Expression of estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (Her2) were measured using tissue microarrays. Patients were classified with luminal A, luminal B, Her2-enriched, or basal-like subtypes of breast cancer.
Mean patient age was 48.7 years, and mean serum 25-OHD concentration was 31.4 ± 16.1 ng/ml. The 25-OHD levels were deficient (< 20 ng/ml) in 75 patients (24.2%), insufficient (20–29 ng/ml) in 95 (30.6%), and sufficient (30–150 ng/ml) in 140 (45.2%). Women with deficient 25-OHD levels were at increased risk of recurrence compared with those with sufficient vitamin D levels (P = 0.002). The 25-OHD concentration was inversely associated with prognosis of patients with cancer of the luminal A (P = 0.012) and luminal B subtypes (P = 0.023), but not with the prognosis of patients with Her2/neu-enriched (P = 0.245) or triple-negative (P = 0.879) cancer subtypes. This association remained valid after adjustment for age, tumor size, nodal status, and estrogen receptor status (hazards ratio = 3.97; 95% confidence interval = 1.77–9.61).
Vitamin D deficiency may be associated with poor outcomes in patients with luminal-type breast cancer.
This study assessed the efficacy of anterior cervical discectomy and fusion (ACDF) with cage alone compared with ACDF with plate instrumentation for radiologic and clinical outcomes in two-level cervical degenerative disease.
Patients with cervical degenerative disc disease from September 2004 to December 2009 were assessed retrospectively. A total of 42 patients received all ACDF at two-level cervical lesion. Twenty-two patients who underwent ACDF with cage alone were compared with 20 patients who underwent ACDF with plate fixation in consideration of radiologic and clinical outcomes. Clinical outcomes were assessed using Robinson's criteria and posterior neck pain, arm pain described by a 10 point-visual analog scale. Fusion rate, subsidence, kyphotic angle, instrument failure and the degenerative changes in adjacent segments were examined during each follow-up examination.
VAS was checked during each follow-up and Robinson's criteria were compared in both groups. Both groups showed no significant difference. Fusion rates were 90.9% (20/22) in ACDF with the cage alone group, 95% (19/20) in ACDF with the plate fixation group (p = 0.966). Subsidence rates of ACDF with cage alone were 31.81% (7/22) and ACDF with plate fixation were 30% (6/20) (p = 0.928). Local and regional kyphotic angle difference showed no significant difference. At the final follow-up, adjacent level disease developed in 4.54% (1/22) of ACDF with cage alone and 10% (2/20) of ACDF with plate fixation (p = 0.654).
In two-level ACDF, ACDF with cage alone would be comparable with ACDF with plate fixation with regard to clinical outcome and radiologic result with no significant difference. We suggest that the routine use of plate and screw in 2-level surgery may not be beneficial.
ACDF with cage alone; ACDF with plate fixation; Fusion rate; Subsidence; Adjacent level degeneration
Breast cancer is one of the leading causes of women's death worldwide. It is important to discover a reliable biomarker for the detection of breast cancer. Plasma is the most ideal source for cancer biomarker discovery since many cells cross-communicate through the secretion of soluble proteins into blood.
Plasma proteomes obtained from 6 breast cancer patients and 6 normal healthy women were analyzed by using the isotope-coded affinity tag (ICAT) labeling approach and tandem mass spectrometry. All the plasma samples used were depleted of highly abundant 6 plasma proteins by immune-affinity column chromatography before ICAT labeling. Several proteins showing differential abundance level were selected based on literature searches and their specificity to the commercially available antibodies, and then verified by immunoblot assays.
A total of 155 proteins were identified and quantified by ICAT method. Among them, 33 proteins showed abundance changes by more than 1.5-fold between the plasmas of breast cancer patients and healthy women. We chose 5 proteins for the follow-up confirmation in the individual plasma samples using immunoblot assay. Four proteins, α1-acid glycoprotein 2, monocyte differentiation antigen CD14, biotinidase (BTD), and glutathione peroxidase 3, showed similar abundance ratio to ICAT result. Using a blind set of plasmas obtained from 21 breast cancer patients and 21 normal healthy controls, we confirmed that BTD was significantly down-regulated in breast cancer plasma (Wilcoxon rank-sum test, p = 0.002). BTD levels were lowered in all cancer grades (I-IV) except cancer grade zero. The area under the receiver operating characteristic curve of BTD was 0.78. Estrogen receptor status (p = 0.940) and progesterone receptor status (p = 0.440) were not associated with the plasma BTD levels.
Our study suggests that BTD is a potential serological biomarker for the detection of breast cancer.
This study was conducted to investigate the correlation between the degrees of injury on brain magnetic resonance imaging (MRI) and the time interval to recovery of consciousness in patients with diffuse axonal injury.
From January 2004 to December 2008, 25 patients with diffuse axonal injury were treated at our hospital. We retrospectively investigated the patients' medical records and radiological findings. We divided the patients into three groups according to the grade of MRI finding : grade I, small scattered lesions on the white matter of the cerebral hemisphere; grade II, focal lesions on the corpus callosum; and grade III, additional focal lesions on the brain stem.
Seven patients belonged to the grade I group; 10 to the grade II group; and 8 to the grade III group. The mean Glasgow Coma Scale (GCS) score of all patients at the time of admission was 7.28. Recovery of consciousness was observed in 23 of the 25 patients; the remaining two patients never regained consciousness. The time interval to recovery of consciousness (awake status) ranged from 1 day to 125 days (mean 22.1 days) : grade I group patients, within approximately 1 week (mean 3.7 days); grade II group patients, within approximately 2 weeks (mean 12.5 days); and grade III group patients, within approximately 2 months (mean 59.5 days).
Our study results suggest a correlation between the mean time interval to recovery of consciousness in patients with diffuse axonal injuries and the degrees of brain injuries seen on MRI. Patients with grade I and II diffuse axonal injuries recovered consciousness within 2 weeks, while patients with grade III injuries required approximately 2 months.
Brain stem; Consciousness; Diffuse axonal injury; MRI
Breast cancer is the most common type of cancer seen in women in western countries. Thus, diagnostic modalities sensitive to early-stage breast cancer are needed. Antibody-based array platforms of a data-driven type, which are expected to facilitate more rapid and sensitive detection of novel biomarkers, have emerged as a direct, rapid means for profiling cancer-specific signatures using small samples. In line with this concept, our group constructed an antibody bead array panel for 35 analytes that were selected during the discovery step. This study was aimed at testing the performance of this 35-plex array panel in profiling signatures specific for primary non-metastatic breast cancer and validating its diagnostic utility in this independent population.
Thirty-five analytes were selected from more than 50 markers through screening steps using a serum bank consisting of 4,500 samples from various types of cancer. An antibody-bead array of 35 markers was constructed using the Luminex™ bead array platform. A study population consisting of 98 breast cancer patients and 96 normal subjects was analysed using this panel. Multivariate classification algorithms were used to find discriminating biomarkers and validated with another independent population of 90 breast cancer and 79 healthy controls.
Serum concentrations of epidermal growth factor, soluble CD40-ligand and proapolipoprotein A1 were increased in breast cancer patients. High-molecular-weight-kininogen, apolipoprotein A1, soluble vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, vitamin-D binding protein and vitronectin were decreased in the cancer group. Multivariate classification algorithms distinguished breast cancer patients from the normal population with high accuracy (91.8% with random forest, 91.5% with support vector machine, 87.6% with linear discriminant analysis). Combinatorial markers also detected breast cancer at an early stage with greater sensitivity.
The current study demonstrated the usefulness of the antibody-bead array approach in finding signatures specific for primary non-metastatic breast cancer and illustrated the potential for early, high sensitivity detection of breast cancer. Further validation is required before array-based technology is used routinely for early detection of breast cancer.
This randomized prospective study investigated the effect of fibrin glue use on drainage duration and overall drain output after lumpectomy and axillary dissection in breast cancer patients. A total of 100 patients undergoing breast lumpectomy and axillary dissection were randomized to a fibrin glue group (N=50; glue sprayed onto the axillary dissection site) or a control group (N=50). Outcome measures were drainage duration, overall drain output, and incidence of seroma. Overall, the fibrin glue and control groups were similar in terms of drainage duration, overall drain output, and incidence of seroma. However, subgroup analysis showed that fibrin glue use resulted in a shorter drainage duration (3.5 vs. 4.7 days; p=0.0006) and overall drain output (196 vs. 278 mL; p=0.0255) in patients undergoing level II or III axillary dissection. Fibrin glue use reduced drainage duration and overall drain output in breast cancer patients undergoing a lumpectomy and level II or III axillary dissection.
Fibrin Tissue Adhesive; Axillary Lymph Node Excision; Lymphatic Drainage; Breast Neoplasms
The incidence of Brucellosis is increasing in Korea. Spondylitis is the most frequent complication, but it is difficult to diagnose because its clinical symptoms are non-specific. It should therefore be included in the differential diagnosis of back pain. We report three rare cases of brucellar spondylitis successfully treated by medical and surgical therapy.
The biological effects of CD24 (FL-80) cross-linking on breast cancer cells have not yet been established. We examined the impact of CD24 cross-linking on human breast cancer cell line MCF-7.
MCF-7 and MDA-MB-231 cells were treated with anti-rabbit polyclonal IgG or anti-human CD24 rabbit polyclonal antibodies to induce cross-linking, and then growth was studied. Changes in cell characteristics such as cell cycle modulation, cell death, survival in three-dimensional cultures, adhesion, and migration ability were assayed after CD24 cross-linking in MCF-7.
Expression of CD24 was analyzed by flow cytometry in MDA-MB-231 and MCF-7 cells where 2% and 66% expression frequencies were observed, respectively. CD24 cross-linking resulted in time-dependent proliferation reduction in MCF-7 cells, but no reduction in MDA-MB-231 cells. MCF-7 cell survival was reduced by 15% in three-dimensional culture after CD24 cross-linking. Increased MCF-7 cell apoptosis was observed after CD24 cross-linking, but no cell cycle arrest was observed in that condition. The migration capacity of MCF-7 cells was diminished by 30% after CD24 cross-linking.
Our results showed that CD24 cross-linking induced apoptosis and inhibited migration in MCF-7 breast cancer cells. We conclude that CD24 may be considered as a novel therapeutic target for breast cancer.
Most posttraumatic cerebrospinal fluid (CSF) leakage is noticed by the patients with the first symptom, rhinorrhea. A 38-year-old woman presented with frequent clear continuous rhinorrhea and otorrhea for 5 years after basilar skull fracture. After this, meningitis was developed with subsequent CSF fistula. Her clinical symptom was improved by medical treatment. The dural defect and CSF leakage were not detected by computerized tomography (CT) cisternography. We report a rare case of persistent posttraumatic CSF fistula that continued for five years.
Traumatic CSF fistula; Meningitis; CT cisternography
Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis.
Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07–1.14) (P-value for trend = 5.87 × 10−9). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.
Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.
To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.
In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).
This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.