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Biomedical subjects

Joungho Han

Publications and source records attributed to Joungho Han.

At least 37 records · Page 2Linked to original sources

Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging.

PURPOSE: To evaluate prospectively the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) with use of fluorodeoxyglucose (FDG), compared with that of stand-alone CT, for the preoperative staging of non-small cell lung cancer, with surgical and histologic findings used as the reference standard. MATERIALS AND METHODS: Institutional review board approval and patient informed consent were obtained. From November 2003 to February 2004, 106 patients (78 men, 28 women; mean age, 56 years) with non-small cell lung cancer underwent curative surgical resection (tumor resection and lymph node dissection) after stand-alone CT followed by integrated FDG PET/CT. Tumor stages were determined by using the TNM and American Joint Committee on Cancer staging systems. Histopathologic results served as the reference standard. Statistically significant differences in tumor staging between integrated PET/CT and stand-alone CT were determined with P < .05 obtained by using the McNemar test or with a generalized estimating equation. RESULTS: The primary tumor was correctly staged in 84 patients (79%) at stand-alone CT and in 91 patients (86%) at integrated FDG PET/CT (P = .25). For the depiction of malignant nodes, the sensitivity, specificity, and accuracy of CT were 70% (23 of 33 nodal groups), 69% (248 of 360), and 69% (271 of 393), respectively, whereas those of PET/CT were 85% (28 of 33), 84% (302 of 360), and 84% (330 of 393) (P = .25, P < .001, and P < .001, respectively). There were 112 false-positive interpretations at CT for 54 hilar, 16 subcarinal, 29 paratracheal, 10 subaortic, and two pulmonary ligament nodal groups and one upper paratracheal group, compared with only 58 false-positive interpretations at PET/CT for 32 hilar, seven subcarinal, 13 lower paratracheal, and six subaortic nodal groups. There were 10 false-negative interpretations at CT for four hilar, two lower paratracheal, and two subcarinal nodal groups, one prevascular and retrotracheal group, and one inferior pulmonary group, but only five false-negative interpretations at PET/CT (one each for paratracheal, subaortic, subcarinal, inferior pulmonary, and hilar nodal groups). CONCLUSION: Integrated FDG PET/CT is significantly better than stand-alone CT for lung cancer staging and provides enhanced accuracy and specificity in nodal staging.

Carcinoma, Non-Small-Cell Lung↗

Disseminated dendriform pulmonary ossification associated with usual interstitial pneumonia: incidence and thin-section CT-pathologic correlation.

The aim of this work was to assess the incidence of disseminated pulmonary dendriform ossification in usual interstitial pneumonia and nonspecific interstitial pneumonia, and to correlate thin-section computed tomography (CT) and histopathologic findings. We retrospectively reviewed thin-section CT and pathologic specimens of biopsy-proven usual interstitial pneumonia (75 patients, 57 men and 18 women, mean age 60 years, range 29-83 years) and nonspecific interstitial pneumonia (44 patients, 9 men and 35 women, mean age 55 years, range 20-73 years). On review of CT and histopathologic specimens, diffuse dendriform ossification was identified in five (four men and one woman, age range 41-68 years, mean 58 years) of 75 patients (6.7%) with usual interstitial pneumonia. It was not seen in any of 44 patients with nonspecific interstitial pneumonia. With thin-section CT (osteoporosis window; window width 818, level 273), disseminated dendriform pulmonary ossification was detected as multiple tiny calcifications in bibasilar subpleural lungs (100% sensitive and 100% specific when compared with histopathologic findings as the gold standard). The thin-section CT finding of multiple tiny calcifications in bibasilar subpleural lungs might be of some help in the differential diagnosis between usual interstitial pneumonia and nonspecific interstitial pneumonia, considering they were not seen in any patients with nonspecific interstitial pneumonia (0%, 0/44) in our series.

Biopsy↗

Metabolic lung disease: imaging and histopathologic findings.

Metabolic lung disease includes pulmonary alveolar proteinosis (PAP), pulmonary amyloidosis, metastatic pulmonary calcification, dendritic pulmonary ossification, pulmonary alveolar microlithiasis, and storage diseases. In pulmonary alveolar proteinosis, CT demonstrates air-space consolidation with thickened interlobular septa, producing the so-called "crazy paving" appearance. Pulmonary amyloidosis can appear as parenchymal nodules (nodular parenchymal form), diffuse interstitial deposit (diffuse interstitial form), or submucosal deposits in the airways (tracheobronchial form). Metastatic pulmonary calcification may appear on high-resolution CT as numerous 3- to 10-mm diameter calcified nodules or, more commonly as fluffy and poorly defined nodular opacities. In pulmonary microlithiasis, high-resolution CT demonstrates diffuse punctuate micronodules showing slight perilobular predominance resulting in apparent calcification of interlobular septa. Niemann-Pick disease appears as ground-glass attenuation in the upper lung zone and thickening of the interlobular septa in the lower lung zone. Radiologic study including high-resolution CT will be helpful for the diagnosis and follow-up of these diseases.

Adult↗

Recruitment maneuvers attenuate repeated derecruitment-associated lung injury.

OBJECTIVE: Repeated derecruitments of previously recruited lungs can exacerbate lung injuries during mechanical ventilation. The aim of this study was to assess lung injury associated with repeated derecruitments and to assess whether this type of injury could be attenuated by recruitment maneuvers. DESIGN: Prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: Twenty-one rabbits were ventilated in pressure-controlled mode with constant tidal volume (10 mL/kg). After lung injury was induced by repeated saline lavage, positive end-expiratory pressure (PEEP) at a lower inflection point was applied for 3 hrs. The control group (n = 7) received ventilation with the same PEEP for 3 hrs without derecruitments. In the derecruitment group (n = 7), derecruitment was repeatedly induced by intentional disconnection of the ventilatory circuit for 1 min every 10 mins for 3 hrs. In the recruitment maneuver group (n = 7), continuous positive airway pressure of 30 cm H2O was applied for 30 secs after each derecruitment. MEASUREMENTS AND MAIN RESULTS: After PEEP levels were increased to lower the inflection point value, Pao2 increased to >500 mm Hg in all groups. Increased Pao2 persisted at >450 mm Hg in the control and recruitment maneuver groups, whereas progressive declines in arterial oxygen levels were observed in the derecruitment group (median, 381.1 mm Hg [interquartile range, 350.1-466.7 mm Hg] at 2 hrs and 318.2 mm Hg [214.3-414.9 mm Hg] at 3 hrs, p < .05 compared with other groups). Histologically, there was significantly increased hyaline membrane formation in alveolar ducts in the derecruitment group compared with the control group (p = .005). Also, significantly more membranous and respiratory bronchiolar injuries were observed in the derecruitment group compared with the control and recruitment maneuver group (p < .005). CONCLUSIONS: These findings suggest that repeated derecruitments could induce lung injuries during mechanical ventilation, and recruitment maneuvers may attenuate derecruitment-associated lung injuries.

Animals↗

Clinical features of recently diagnosed pulmonary paragonimiasis in Korea.

STUDY OBJECTIVE: Paragonimiasis is a typical food-borne parasitic disease that is common in Southeast Asia, the Far East, Latin American, and Africa. Recently, however, this disease has been seen in many parts of the world, largely due to increases in the numbers of immigrants and overseas travelers. The purpose of this study was to evaluate the clinical and radiologic features of recently diagnosed pulmonary paragonimiasis. PATIENTS: We retrospectively analyzed the clinical and radiologic characteristics of 36 patients (21 men and 15 women; median age 48 years; range, 19 to 75) with pulmonary paragonimiasis whose conditions were diagnosed between October 1994 and September 2004. RESULTS: Thirty-four patients (94%) presented with respiratory symptoms, including hemoptysis (n = 20, 56%) and cough (n = 17, 47%). However, chest pain (n = 5, 14%) and fever (n = 5, 14%) were less frequently reported. Chest radiography revealed intrapulmonary parenchymal lesions (n = 26, 72%), such as nodules (n = 14, 39%), linear opacity (n = 6, 17%), and airspace consolidations (n = 4, 11%), which occurred more commonly than did pleural lesions (n = 10, 28%). Most cases were initially suspected to be lung cancer or tuberculosis. In 13 patients with intrapulmonary parenchymal lesions who underwent bronchoscopy, bronchial luminal narrowing, coupled with congested or edematous mucosal changes, was seen in 7 patients (54%). Bronchial mucosal biopsy specimens exhibited chronic inflammation with eosinophilic infiltrations in three of these seven patients (43%). CONCLUSIONS: Our findings indicate that patients with pulmonary paragonimiasis presented with a variety of clinical and radiologic findings that were different from the classic presentations reported earlier, frequently mimicking those of lung cancer or tuberculosis.

Adult↗

Optimal duration of IV and oral antibiotics in the treatment of thoracic actinomycosis.

STUDY OBJECTIVE: IV antibiotic therapy for 2 to 6 weeks followed by 6 to 12 months of oral antibiotic therapy is usually recommended for the treatment of thoracic actinomycosis. The objective of this study was to evaluate the duration of IV and oral antibiotic therapy for thoracic actinomycosis. METHODS: We present a retrospective case series of 28 patients with thoracic actinomycosis as confirmed by histopathology from October 1994 through December 2003. RESULTS: After diagnosis of actinomycosis, 54% (15 of 28 patients) received antibiotic therapy alone. The duration of IV antibiotic therapy ranged from 0 to 18 days (median, 2 days; interquartile range [IQR], 0 to 3 days), and the duration of oral antibiotic treatment ranged from 76 to 412 days (median, 167 days; IQR, 142 to 214 days) in patients who received antibiotics alone. Combination surgical and antibiotic therapy occurred in 46% (13 of 28 patients). The duration of IV antibiotic therapy ranged from 3 to 17 days (median, 8 days; IQR, 5 to 13 days), and the duration of oral antibiotic therapy ranged from 0 to 534 days (median, 150 days; IQR, 3.5 to 289 days) in these patients. Clinical cures were achieved in 96% (27 of 28 patients). There was no clinical evidence of recurrence during follow-up period at our hospital (median, 23 months; IQR, 9 to 44 months) in 21 patients, excluding 7 patients who were transferred to referring hospitals after completion of antibiotic therapy (n = 6) or during antibiotic therapy (n = 1). CONCLUSIONS: Thoracic actinomycosis is best treated with individualized therapeutic modalities, depending on factors such as the initial burden of disease, the performance of resectional surgery, and the clinical and radiologic responses to therapy. The traditional recommendation of IV antibiotic therapy for 2 to 6 weeks followed by oral antibiotic therapy for 6 to 12 months is not always necessary for all thoracic actinomycosis patients.

Actinomycosis↗

Giant cell interstitial pneumonia: high-resolution CT and pathologic findings in four adult patients.

OBJECTIVE: The purpose of our study was to describe the high-resolution CT and pathologic findings of giant cell interstitial pneumonia (GIP) in four adult patients. CONCLUSION: GIP appears on high-resolution CT as ground-glass and irregular linear opacities in both lungs. These CT findings correspond histopathologically to areas of interstitial thickening caused by fibrosis and inflammatory cell infiltration and to areas of intraalveolar accumulation of macrophages and multinucleated giant cells.

Adult↗

Hypothesis on the evolution of cavitary lesions in nontuberculous mycobacterial pulmonary infection: thin-section CT and histopathologic correlation.

OBJECTIVE: The objectives of our study were to evaluate the thin-section CT findings of the cavitary form of nontuberculous mycobacterial pulmonary infection and correlate these imaging findings with the histopathologic findings concerning the development of bronchiectasis and of centrilobular nodules and cavitary lesions. MATERIALS AND METHODS: We retrospectively reviewed thin-section CT scans (2.5-mm collimation, both axial and coronal reformation images) of 24 cases (male-female ratio, 13:11; mean age, 61 years; age range, 43-82 years) of the cavitary form of culture-proven Mycobacterium avium-intracellulare complex pulmonary infection including two cases with lobectomy specimens. Any changes in CT findings detected on the follow-up CT scans that were available for seven patients (follow-up interval, 6-24 months; mean, 12 months) were also assessed. RESULTS: Thin-section CT findings were bronchiectasis (24/24 patients, 100%), a patent bronchus running into a cavitary lesion (the "feeding bronchus" appearance) (18/24, 75%), nodules less than 10 mm (17/24, 71%), centrilobular nodules (17/24, 71%), nodules of 10-30 mm (13/24, 54%), peribronchial nodules (8/24, 33%), lobular consolidation (6/24, 25%), bronchial wall thickening (4/24, 17%), and consolidation (2/24, 8%). Two lobectomy specimens showed large cavitary consolidations with the feeding bronchus appearance on pathologic specimens. In two patients, small peribronchial nodules had changed into cavitary nodules with the feeding bronchus appearance on follow-up CT, which represented inflamed focal cystic bronchiectasis. CONCLUSION: In the cavitary form of M. avium-intracellulare complex pulmonary infection, the feeding bronchus appearance is another very frequent thin-section CT finding. This appearance may suggest that peribronchial nodules of M. avium-intracellulare complex infection evolve into inflamed focal cystic bronchiectasis manifesting as cavitary lesions.

Adult↗

CT findings of surgically resected pleomorphic carcinoma of the lung in 30 patients.

OBJECTIVE: The objective of our study was to assess the CT features of surgically resected pleomorphic carcinoma of the lung. CONCLUSION: The CT features of pleomorphic carcinoma of the lung appear to be dictated by the epithelial component of the tumor. Among the various subtypes of pleomorphic carcinoma, the large cell and giant cell subtype showed constant CT features including subpleural location, peritumoral areas of ground-glass attenuation, and extensive central low-attenuation areas.

Carcinoma, Non-Small-Cell Lung↗

Endobronchial actinomycosis associated with broncholithiasis: CT findings for nine patients.

OBJECTIVE: Our objective was to assess the CT findings for endobronchial actinomycosis associated with broncholithiasis. CONCLUSION: Endobronchial actinomycosis associated with broncholithiasis manifests as a proximal obstructive calcified endobronchial nodule associated with distal post-obstructive pneumonia of the involved lobe or segment on CT. The possibility of endobronchial actinomycosis should be entertained when broncholithiasis is seen on CT in tuberculosis-endemic areas.

Actinomycosis↗

Pleuropulmonary paragonimiasis: CT findings in 31 patients.

OBJECTIVE: The purpose of our study was to identify any specific CT features that may help in the diagnosis of pleuropulmonary paragonimiasis. CONCLUSION: Pleuropulmonary paragonimiasis usually manifests as a subpleural or subfissural nodule of about 2 cm in diameter that frequently contains a necrotic low-attenuation area. The constellation of focal pleural thickening and subpleural linear opacities leading to a necrotic peripheral pulmonary nodule is another frequent CT finding of paragonimiasis. Although minimal and easily overlooked, focal fibrotic pleural thickening adjacent to a pulmonary nodule can be an important clue in the diagnosis of pleuropulmonary paragonimiasis on CT.

Adult↗

Giant cystic chondroid hamartoma.

We report a case of huge pulmonary chondroid hamartoma with multilocular cysts in a 38-yr-old male patient. The lobectomy specimen of the left lower lobe showed a large multilocular cystic mass, 11.5 x 10 cm in size. The mass had thin-walled, variable-sized cysts and areas of solid cartilaginous small nodules in the interstitium, which occupied the superior segment and the upper portion of the basal segment. There was no connection with bronchus or vessel. Microscopically, the cysts and cleft-like spaces were lined by ciliated columnar epithelium and the solid components were composed of cartilage, myxohyalinized connective tissue, and adipose tissue. Also seen were foci of calcification within the sclerotic stroma.

Adult↗

Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin 19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas.

To examine the immunohistochemical alterations associated with the histological dedifferentiation of thyroid carcinomas, we performed staining for HBME-1, high molecular weight cytokeratin (HCK), CK 19, thyroid transcription factor-1 (TTF-1) and E-cadherin (E-CD) on 125 various types of thyroid carcinomas. The HBME-1 staining was strong and diffuse in follicular carcinoma (FC), papillary carcinoma (PC), and poorly differentiated carcinoma (PDC), while it was rare in undifferentiated carcinoma (UC) as well as in benign lesions. Strong, diffuse staining for CK19 and HCK was predominantly found in PC, and these markers were not much found in other carcinomas. TTF-1 uniformly stained the tumor cells of all cases of PC, FC and Hurthle cell carcinoma (HC) and 42% of the PDC, while there was only focal staining in one case of the UC. Compared to the strong, diffuse reactivity in the benign lesions, E-CD staining was noted in 67% of PC, 80% of FC, 83% of HC, 58% of PDC and none of the UC. These results suggest that HBME-1 may be a marker for well-differentiated carcinomas while CK19 and HCK are phenotypic markers for papillary carcinoma. The loss or reduced expression of TTF-1 and E-CD may be markers for dedifferentiation.

Biomarkers, Tumor↗

Synergistic effect of keratinocyte transplantation and epidermal growth factor delivery on epidermal regeneration.

Both keratinocyte transplantation and epidermal growth factor (EGF) delivery stimulate epidermal regeneration. In this study, we hypothesized that the combined therapy of keratinocyte transplantation and EGF delivery accelerates epidermal regeneration compared to the single therapy of either keratinocyte transplantation or EGF delivery. To test this hypothesis, we utilized fibrin matrix as a keratinocyte/EGF delivery vehicle for epidermal regeneration. Full-thickness wounds were created on the dorsum of athymic mice, and human keratinocytes and EGF in fibrin matrix were sprayed onto the wounds to regenerate epidermal layers (group 1). As controls, human keratinocytes in fibrin matrix (group 2), EGF in fibrin matrix (group 3), or fibrin matrix alone (group 4) was sprayed onto the wounds. Spraying keratinocytes suspended in fibrin matrix did not affect the keratinocyte viability, as the cell viabilities before and after spraying were not different. EGF was released from fibrin matrix for 3 days. The wounds were analyzed with histology and immunohistochemistry at 1 and 3 weeks after treatments. Compared with the control groups, initial wound closure rate was highest in group 1. Histological analyses indicated that group 1 exhibited faster and better epidermal regeneration than the other groups. Immunohistochemical analyses showed that regenerated epithelium in groups 1 and 2 stained positively for human involucrin at 3 weeks, whereas the tissue sections of the groups 3 and 4 stained negatively. Human laminin was detected at the dermal-epidermal junction of the regenerated tissues in groups 1 and 2 at 3 weeks and was not detected in groups 3 and 4. The epidermal thickness of the regenerated tissues in group 1 was significantly thicker than that of the other groups at all time points. These results suggest that the combined therapy of keratinocyte transplantation and EGF delivery is more efficacious for epidermal regeneration than each separate therapy alone.

Animals↗

Maspin expression is transactivated by p63 and is critical for the modulation of lung cancer progression.

Maspin inhibits metastasis of some cancer cells, and clinical studies have identified correlations between maspin loss and poor prognosis in several cancer types. Maspin was found to be significantly overexpressed in lung cancer samples as compared with matched normal lung tissues. However, the regulatory mechanism of maspin expression remains unclear. We show here that differential expression of maspin in carcinoma-derived lung cancer cells is regulated at the transcriptional level. We found that p63 is a critical factor for the transcription of maspin, which is lost in highly invasive cancer cells such as NCI-H157, NCI-322, and NCI-358. No correlation was found between maspin expression and the previously associated transcription factors, p53, Ets1, and Pdef. Instead, maspin expression was strictly dependent on the presence of p63 in lung cancer tissues (P < 0.001) and in the tested cell lines. Transient expression of p63 transactivated the maspin promoter with remarkable fold changes in cells expressing the TAp63, suggesting that TAp63 might be a novel stimulator of the maspin promoter in lung cancer. We have also demonstrated the binding of p63 protein to a previously identified p53-binding site on the maspin promoter by gel shift and chromatin immunoprecipitation assays. In tumor tissues, maspin expression was associated with lymph node involvement (P = 0.035) and tumor stage (P = 0.063) in all tested cases, except squamous carcinoma. In terms of function, ectopic expression of maspin inhibited cell invasion in squamous carcinoma as well as adenocarcinoma. Taken together, these results define maspin as a new molecular target of p63 that eventually inhibits the invasion of lung cancer.

Cell Line, Tumor↗

Solitary pulmonary nodules: dynamic enhanced multi-detector row CT study and comparison with vascular endothelial growth factor and microvessel density.

PURPOSE: To evaluate enhancement dynamics of solitary pulmonary nodules at multi-detector row computed tomography (CT) and to correlate results with extent of tumor angiogenesis in pathologic specimens. MATERIALS AND METHODS: One hundred thirty-one patients with solitary pulmonary nodules underwent unenhanced thin-section CT, followed by dynamic helical CT (throughout the nodule for 30 mm along the z-axis [13 images] and at 20-second intervals for 3 minutes [130 images total]) after intravenous injection of 120 mL of contrast medium. Diagnosis of malignancy or benignancy was assigned in 109 patients, and follow-up imaging suggested benignancy in the remaining 22. CT findings were analyzed for peak attenuation, net enhancement, and enhancement dynamics. In 54 patients with surgical diagnoses, Pearson correlation coefficient was used to correlate enhancement pattern with extent of microvessel density and vascular endothelial growth factor (VEGF) staining. RESULTS: With 30 HU or more of net enhancement as a cutoff value in differentiation of malignant and benign nodules, sensitivity for malignant nodules was 99% (69 of 70 malignant nodules), specificity was 54% (33 of 61 benign nodules), positive predictive value was 71% (69 of 97 malignant readings), negative predictive value was 97% (33 of 34 benign readings), and accuracy was 78% (102 of 131 nodules). Peak attenuation was correlated positively with extent of microvessel density (r = 0.369, P =.006) and VEGF staining (r = 0.277, P =.042). Malignant nodules showed significantly higher VEGF expression (P =.009) than that of benign nodules. CONCLUSION: Dynamic enhancement with multi-detector row CT shows high sensitivity and negative predictive values for diagnosis of malignant nodules but low specificity because of highly enhancing benign nodules. Extent of enhancement reflects underlying nodule angiogenesis.

Adult↗

Promoter methylation of retinoic acid receptor beta 2 and the development of second primary lung cancers in non-small-cell lung cancer.

PURPOSE: To investigate whether the promoter hypermethylation of retinoic acid receptor beta 2 (RARbeta2) is associated with the development of second primary lung cancers (SPLCs) differentially according to smoking status in primary non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively analyzed the relationship between RARbeta2 methylation and the SPLC development in a total of 342 NSCLCs. The methylation status of RARbeta2 was determined by using methylation-specific polymerase chain reaction. The difference in the time to SPLC development was analyzed by using the log-rank test and the Cox proportional hazards model. The median follow-up was 4.1 years. RESULTS: SPLCs developed in 19 (5.6%) of the 342 NSCLCs, and overall incidence rate of SPLC development was 1.54 per 100 patient-years. SPLCs did not occur in 39 patients who had not smoked. After controlling for possible confounding factors, the hazard of failure for former smokers with RARbeta2 hypermethylation was about 2.87 (95% CI, 0.92 to 13.64; P =.08) times higher compared to those without RARbeta2 methylation. However, for current smokers, hypermethylation of the RARbeta2 was found to have a protective effect against the SPLC development (hazard ratio = 0.23; 95% CI, 0.11 to 0.87; P =.03). CONCLUSION: Hypermethylation of RARbeta2 promoter had a differential effect on the development of SPLCs in NSCLC, and this was dependent on smoking status. Our study suggests that a combination of retinoids and/or a demethylating agent may be effective in the prevention of SPLCs in never-smokers and former smokers with NSCLC.

Adult↗