• Journal of the Korean Society of Radiology
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• v.82 no.3
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• pp.670-681
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• 2021

Purpose This study aimed to investigate the optimal threshold value in Hounsfield units (HU) on CT to detect the solid components of pulmonary subsolid nodules using pathologic invasive foci as reference. Materials and Methods Thin-section non-enhanced chest CT scans of 25 patients with pathologically confirmed minimally invasive adenocarcinoma were retrospectively reviewed. On CT images, the solid portion was defined as the area with higher attenuation than various HU thresholds ranging from -600 to -100 HU in 50-HU intervals. The solid portion was measured as the largest diameter on axial images and as the maximum diameter on multiplanar reconstruction images. A linear mixed model was used to evaluate bias in each threshold by using the pathological size of invasive foci as reference. Results At a threshold of -400 HU, the biases were lowest between the largest/maximum diameter of the solid portion of subsolid nodule and the size of invasive foci of the pathological specimen, with 0.388 and -0.0176, respectively. They showed insignificant difference (p = 0.2682, p = 0.963, respectively) at a threshold of -400 HU. Conclusion For quantitative analysis, -400 HU may be the optimal threshold to define the solid portion of subsolid nodules as a surrogate marker of invasive foci.

• Journal of the Korean Society of Radiology
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• v.82 no.1
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• pp.128-138
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• 2021

Purpose We evaluated the risk factors for progression to chronic complicated bronchopleural fistula (BPF) after pulmonary resection using follow-up CT. Materials and Methods We retrospectively reviewed 45 cases with BPF that had undergone pulmonary resection during 2010-2018. We compared the clinical and radiological characteristics of those with complicated BPF (n = 24) and those without complicated (sterilized) BPF (n = 21). The clinical and radiological risk factors for progression to chronic complicated BPF were examined by logistic regression analysis. Results The thickness of the pleural cavity wall (p = 0.022), the size of the pleural cavity (p = 0.029), and the size increase of BPF on follow-up (p = 0.012) were significantly different between the two groups. The risk factors for progression to chronic complicated BPF were age > 70 years (odds ratio, 6.43; 95% confidence interval, 1.2-33.7), the thickness of the cavity wall > 5 mm (odds ratio, 52.5; 95% confidence interval, 5.1-545.4), and an increase in the size of the pleural cavity on follow-up CT (odds ratio, 12.5; 95% confidence interval, 2.1-73.5), only in the univariate analysis. Conclusion The risk factors for progression to chronic complicated BPF can be evaluated using follow-up CT.

• Journal of the Korean Society of Radiology
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• v.85 no.3
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• pp.566-578
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• 2024

Purpose This study investigated whether the respiratory phase during pleural puncture in CT-guided percutaneous transthoracic needle biopsy (PTNB) affects complications. Materials and Methods We conducted a retrospective review of 477 lung biopsy CT scans performed during free breathing. The respiratory phases during pleural puncture were determined based on the table position of the targeted nodule using CT scans obtained during free breathing. We compared the rates of complications among the inspiratory, mid-, and expiratory respiratory phases. Logistic regression analysis was performed to control confounding factors associated with pneumothorax. Results Among the 477 procedures, pleural puncture was performed during the expiratory phase in 227 (47.6%), during the mid-phase in 108 (22.6%), and during the inspiratory phase in 142 (29.8%). The incidence of pneumothorax was significantly lower in the expiratory puncture group (40/227, 17.6%; p = 0.035) and significantly higher in the mid-phase puncture group (31/108, 28.7%; p = 0.048). After controlling for confounding factors, expiratory-phase puncture was found to be an independent protective factor against pneumothorax (odds ratio = 0.571; 95% confidence interval = 0.360-0.906; p = 0.017). Conclusion Our findings suggest that pleural puncture during the expiratory phase may reduce the risk of pneumothorax during image guided PTNB.

• Journal of Chest Surgery
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• v.36 no.7
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• pp.472-482
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• 2003

Recent studies have demonstrated that cerebral desaturation during rewarming period of CPB was associated with postoperative neurologic dysfunction. The prevention of cerebral desaturation during CPB may reduce the incidences of neurologic and neuropsychological complications. The present study was prospectively undertaken to compare the clinical effects between two strategies (hypercapnic CPB and high flow CPB) to prevent cerebral desaturation for establishing a proper CPB technique. Material and Method: Thirty-six adult patients scheduled for elective cardiac surgery were randomized into either hypercapnic (Pa$CO_2$ 45~50mmHg, n＝18) or high flow group (flow rate 2.75 L/ $m^2$/min and Pa$CO_2$ 35~40mmHg, n＝18) during rewarming period of CPB. In each patient, middle cerebral artery blood flow velocity ( $V_{MCA}$), cerebral arteriovenous oxygen content difference (C(a-v) $O_2$), modified cerebral metabolic rate for oxygen (MCMR $O_2$), cerebral oxygen transport rate ( $T_{E}$ $O_2$), incidence of cerebral desaturation (internal jugular bulb blood oxygen saturation $\leq$ 50%), increased rate of S-100 $\beta$ concentration, and arterial and internal jugular bulb blood gas were measured during the five phases of the operation; Pre-CPB, CPB-10 min (steady-state CPB, nasopharyngeal temperature 29~3$0^{\circ}C$), Rewarm-1 (rewarming phase, nasopharyngeal temperature 33$^{\circ}C$), Rewarm-2 (nasopharyngeal temperature 37$^{\circ}C$), and CPB-off. Incidence of postoperative delirium and duration were assessed in all patients. All variables were compared between the two groups. Result: $V_{MCA}$ (157.88$\pm$10.87 vs 120.00$\pm$6.18%, p＝0.006), internal jugular bulb $O_2$ saturation (68.01$\pm$2.75 vs 61.28$\pm$2.87%, p＝0.03) and $O_2$ tension (41.01$\pm$2.25 vs 32.02$\pm$ 1,67 mmHg, p＝0.03), and $T_{E}$ $O_2$(110.84$\pm$7.41 vs 81.15$\pm$8.11%, p＝0.003) at rewarming periods were higher in the hypercapnic group than in the high flow group. C(a-v) $O_2$ (4.0$\pm$0.30 vs 4.84$\pm$0.38 mg/dL, p＝0.04), COE (0.36$\pm$0.03 vs 0.42$\pm$0.03, p＝0.04), increased rate of S- 100$\beta$ (391.67$\pm$23.40 vs 940.0$\pm$17.02%, p＝0.003), and incidence of cerebral desaturation (2 vs 4 patients, p＝0.04) at rewarming periods, and duration of postoperative delirium (18 vs 34 hr, p＝0.02) were low in the hypercapnic group compared to the high flow group. Conclusion: These results indicate that hypercapnic CPB may provide relatively diminished cerebral injury and beneficial effects for cerebral metabolism relatively compared to high flow CPB.low CPB.

• Journal of Chest Surgery
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• v.37 no.12
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• pp.967-977
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• 2004

Background: DNA methylation is one of the important gene expression mechanisms of the cell. When cytosine of CpG dinucleotide in promotor is hypomethylated, expression of some genes that is controlled by this promoter is altered. In this study, the author investigated the effect of DNA demethylating agent, 5-aza-2'-deoxycytidine (ADC), on the expressions of cancer antigen genes, MHC and B7 in 4 lung cancer cell lines, NCIH1703, NCIH522, MRC-5, and A549. Material and Method: After treatment of cell lines, NCIH1703, NCIH522, MRC-5 and A549 with ADC (1 uM) for 48 hours, RT-PCR was performed by using the primers of MAGE, GAGE, NY-ESO-1, PSMA, CEA, and SCC antigen gene. In order to find the optimal ADC treatment condition for induction of cancer antigen, we studied the effect of ADC treatment time and dose on the cancer antigen gene expression. To know the effect of ADC on the expression of MHC or B7 and cell growth, cells were treated with 1 uM of ADC for 72 hours for FACS analysis or cells were treated with 0.2, 1 or 5 uM of ADC for 96 hours for cell counting. Result: After treatment of ADC (1 uM) for 48 hours, the expressions of MAGE, GAGE, NY-ESO-1, and PSMA genes increased in some cell lines. Among 6 MAGE isotypes tested, and gene expression of MAGE-1, -2, -3, -4 and -6 could be induced by ADC treatment. However, CEA gene expression did not change and SCC gene expression was decreased by ADC treatment. Gene expression was generally induced 24 - 28 hours after ADC treatment and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC ADC teatment, and expression of MAGE, GAGE, and NY-ESO-1 was maintained at least 14 days after ADC teatment in ADC-Free medium. Most gene expression could be induced at 0.2 uM of ADC, but gene expression increased dependently on ADC treatment dose. The expression of MHC and B7 was not increased by ADC treatment in all four cell lines, and the growth rate of 4 cell lines decreased significantly with the increase of ADC concentrations. Conclusion: Treatment of lung cancer cell lines with ADC increases the gene expression MAGE, GAGE and NY-ESO-1 that are capable of induction of cytotoxic T lymphocyte response. We suggest that treatment with 1 uM of ADC for 48 hours and then culturing in ADC-free medium is optimal condition for induction of cancer antigen. However, ADC has no effect on MHC and B7 induction, additional modification for increase of expression of MHC, B7 and cytokine will be needed for production of efficient cancer cell vaccine.

• Journal of Chest Surgery
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• v.37 no.3
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• pp.210-219
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• 2004

Extracellular $K^{+}$ concentration ([ $K^{+}$]$_{0}$ ) can be increased within several mM by the efflux of intracellular $K^{+}$. To investigate the effect of an increase in [ $K^{+}$]$_{0}$ on vascular contractility, we attempted to examine whether extracellular $K^{+}$ might modulate vascular contractility, endothelium-dependent relaxation (EDR) and intracellular $Ca^2$$^{+}$ concentration ([C $a^2$$^{+}$]$_{i}$ ) in endothelial cells (EC). We observed isometric contractions in rabbit carotid, superior mesenteric, basilar arteries and movse aorta. [C $a^2$$^{+}$]$_{i}$ was recorded by microfluorimeter using Fura-2/AM in EC. No change in contractility was recorded by the increase in [ $K^{+}$]$_{0}$ from 6 to 12 mM in conduit artery such as rabbit carotid artery. whereas resistant vessels, such as basilar and branches of superior mesenteric arteries (SMA), were relaxed by the increase. In basilar artery, the relaxation by the increase in [ $K^{+}$]$_{0}$ to from 1 to 3 mM was bigger than that by the increase from 6 to 12 mM. In contrast, in branches of SMA, the relaxation by the increase in [ $K^{+}$]$_{0}$ to from 6 to 12 mM is bigger than that by the increase from 1 to 3 mM. $Ba^2$$^{+}$ (30 $\mu$M) did not inhibit the relaxation by the increase in [ $K^{+}$]$_{0}$ from 1 to 3 mM but did inhibit the relaxation by the increase from 6 to 12 mM. In the mouse aorta without the endothelium or treated with $N^{G}$_nitro-L-arginine (30 $\mu$M), nitric oxide synthesis blocker, the increase in [ $K^{+}$]$_{0}$ from 6 to 12 mM did not change the magnitude of contraction induced either norepinephrine or prostaglandin $F_2$$_{\alpha}$. The increase in [ $K^{+}$]$_{0}$ up to 12 mM did not induce contraction of mouse aorta but the increase more than 12 mM induced contraction. In the mouse aorta, EDR was completely inhibited on increasing [ $K^{+}$]$_{0}$ from 6 to 12 mM. In cultured mouse aorta EC, [C $a^2$$^{+}$]$_{i}$ , was increased by acetylcholine or ATP application and the increased [C $a^2$$^{+}$]$_{i}$ , was reduced by the increase in [ $K^{+}$]$_{0}$ reversibly and concentration-dependently. In human umbilical vein EC, similar effect of extracellular $K^{+}$ was observed. Ouabain, a N $a^{+}$ - $K^{+}$ pump blocker, and N $i^2$$^{+}$, a N $a^{+}$ - $Ca^2$$^{+}$ exchanger blocker, reversed the inhibitory effect of extracellular $K^{+}$. In resistant arteries, the increase in [ $K^{+}$]$_{0}$ relaxes vascular smooth muscle and the underlying mechanisms differ according to the kinds of the arteries; $Ba^2$$^{+}$-insensitive mechanism in basilar artery and $Ba^2$$^{+}$ -sensitive one in branches of SMA. It also inhibits [C $a^2$$^{+}$]$_{i}$ , increase in EC and thereby EDR. The initial mechanism of the inhibition may be due to the activation of N $a^{+}$ - $K^{+}$pump. activation of N $a^{+}$ - $K^{+}$pump.p.p.p.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.853-860
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• 1997

Background : Chronic cough, defined as a cough persisting for three weeks or longer, is a common symptom for which outpatient care is sought. The most common etiologies of chronic cough are postnasal drip, asthma, and gastroesophageal reflux. Methacholine challenge is a useful diagnostic study in the evaulation of chronic cough, particularly useful in chronic cough patients with asthmatic symptom. Patients with chronic cough may have dysfunction of bronchial and extrathoracic airways. To evaluate if dysfunction of the bronchial and extrathoracic airways causes chronic cough, we assessed bronchial (BHR) and extrathoracic airway (EAHR) responsiveness to inhaled methacholine in patients with chronic cough. Method : 111 patients with chronic cough were enrolled in our study. Enrolled patients had no recorded diagnosis of asthma, bronchopulmonary disease, hypertension, heart disease or systemic disease and no current treatment with bronchodilator or corticosteroid. Enrolled patients consisted of 46 patients with cough alone, 24 patients with wheeze, 22 patients with dyspnea, 19 patients with wheeze and dyspnea. The inhaled methacholine concentrations causing a 20% fall in forced expiratory volume in 1s($PC_{20}FEV_1$) and 25% fall in maximal mid-inspiratory flow ($PC_{25}MIF_{50}$) were used as bronchial and extra thoracic hyperresponsiveness. Results : There were four response patterns to methacholine challenge study : BHR in 27 patients, EAHR in 16 patients, combined BHR and EAHR in 8 patients, and no hyperresponsiveness in 60 patients. In patients with cough alone, there were BHR in 3 patients, EAHR in 9 patients, and combined BHR and EAHR in 2 patients. In patients with wheeze and/or dyspnea, there were BHR in 24 patients, EAHR in 7 patients, and BHR and EAHR in 6 patients. Compared with patients with wheeze and/or dyspnea, patients with cough alone had more common EAHR than BHR. In patients with wheeze and/or dyspnea, BHR was more common than EAHR. Conclusion : These results show that among patients with hyperresponsiveness to methacholine, those with dyspnea and/or wheezing had mainly bronchial hyperresponsiveness, whereas those with chronic cough alone had mainly extrathoracic airway hyperresponsiveness.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1094-1104
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• 1997

Background : Spontaneous pneumothoraces(SP) are divided into primary spontaneous pneumothoraces (PSP) which develop in healthy individuals without underlying pulmonary disorders and secondary spontaneous pneumothoraces(SSP) which occur in those who have underlying disorders such as tuberculosis or chronic obstructive lung diseases. Yet there is no established standard therapeutic approach to this disorder, i.e., from the spectrum of noninvasive treatment such as clinical observation with or without oxygen therapy, to aggressively invasive thoracoscopic bullectomy or open thoracotomy. Although chest tube thoracostomy has been most widely used, the patients should overcome pain in the initiation of tube insertion or during indwelling it potential infection and subcutaneous emphysema. Thus smaller-caliber tube has been challenged for the treatment of pneumothorax. Previously, we studied the therapeutic efficacy of 8 French catheter for spontaneous pneumothorax. But there has been few data for effectiveness of small-caliber catheterization in comparison with that of chest tube. In this study, we intended to observe the long-term effectiveness of 8 French catheter for the treatment of spontaneous pneumothoraces in comparison with that of chest tube thoracostomy. Method : From January, 1990 to January, 1996, sixty two patients with spontaneous pneumothoraces treated at Chung-Ang University Hospital were reviewed retrospectively. The patients were sub-divided into a group treated with 8 French catheter(n=23) and the other one with chest tube insertion(n=39). The clinical data were reviewed(age, sex, underlying pulmonary disorders, past history of pneumothorax, size of pneumothorax, follow-up period). And therapeutic effect of two groups was compared by treatment duration(duration of indwelling catheter or tube), treatment-associated complications and recurrence rate. Results : The follow-up period(median) of 8 French catheter group and chest tube group was 28 and 22 months, which had no statistical significance. Ther was no statistically significant difference of clinical characteristics between two groups with SP, PSP, SSP. The indwelling time of 8 French catheter group was $6.2{\pm}3.8$ days, which was significantly shorter than that of chest tube group in SP, $9.1{\pm}7.5$ days(p=0.047). In comparison of treatment-related complication in PSP, 8 French catheter group as 6.25% of complication showed lower tendency than the other group as 23.8% (p=0.041 ; one-tailed, p=0.053; two-tailed). The recurrence rate in each group of SP was 17.4%, 10.3%, which did not show any statistically significant difference. Conclusion : Treatment with 8 French catheter resulted in shorter indwelling time in sponteous pneumothorax, and lower incidence of treatment-related complication in primary spontaneous pneumothorax. And the recurrence rate in each of treatment group showed no statistically significant difference. So, we can recommend the 8 French small-caliber catheter for the initial therapy for spontaneous pneumothorax for the replacement of conventional chest tube thoracostomy. But further prospective study with more subjects of spontaneous pneumothorax will be needed for the evaluation of effectiveness of 8 French cateter.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.180-190
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• 2000

Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.465-484
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• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.