Hae-Seong Nam

Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases

OBJECTIVES Chronic necrotizing pulmonary aspergillosis (CNPA) is uncommon, and the optimal therapeutic regimen has not been established. In a retrospective cohort study, we investigated the clinical characteristics and treatment outcomes of patients with CNPA. METHODS We reviewed the medical records of all patients who had been diagnosed with CNPA at our institution over the last 10 years. RESULTS Forty-three patients were identified. Their median age was 60 years (interquartile range (IQR) 45-65 years), and 34 (79%) of the patients were men. The most common underlying lung disease was pulmonary tuberculosis (n=40, 93%). After CNPA was diagnosed, all patients were treated with antifungal drugs, including oral itraconazole (n=39, 91%) or intravenous amphotericin B (n=4, 9%). Seventeen (40%) patients discontinued therapy early (<3 months), 14 patients due to death and three to loss of follow-up. Twenty-six (60%) patients received oral itraconazole at a daily dose of 200-400mg for more than 3 months. The median treatment duration was 6 months (IQR 6-12 months). In these 26 patients, clinical improvement was observed in 15 (58%) and radiological improvement was observed in 11 (42%). Ten (38%) patients showed no improvement. Twenty-two (51%) patients died, including 18 (42%) CNPA-related deaths, during a median follow-up of 15 months (IQR 2.5-32 months). The median survival time was 62 months. CONCLUSIONS CNPA is difficult to treat and often has a poor outcome. Further studies with more patients are needed to identify the optimal therapy for patients with CNPA.

Prognostic Impact of Minimal Pleural Effusion in Non–Small-Cell Lung Cancer

PURPOSE Minimal (< 10 mm thick) pleural effusion (PE) may represent an early phase of malignant PE, but its clinical relevance has rarely been studied. Therefore, we examined the proportion of minimal PE in patients with non-small-cell lung cancer (NSCLC) and its impact on survival. We also considered possible accumulation mechanisms in our data set. PATIENTS AND METHODS On the basis of PE status from chest computed tomography scans at diagnosis, 2,061 patients were classified into three groups: no PE, minimal PE, and malignant PE. Twenty-one variables associated with four factors-patient, stage migration, tumor, and treatment-were investigated for correlation with survival. RESULTS Minimal PE presented in 272 patients (13.2%). Of 2,061 patients, the proportion of each stage was the following: 5.2% stage I, 10.9% stage II, 13.2% stage IIIA, 23.8% stage IIIB, and 13.9% stage IV. Minimal PE correlated significantly with shorter survival time than did no PE (median survival time, 7.7 v 17.7 months; log-rank P < .001), even after full adjustment with all variables (adjusted hazard ratio, 1.40; 95% CI, 1.21 to 1.62). Prognostic impact of minimal PE was higher in early versus advanced stages (Pinteraction = .001). In 237 patients (87.8%) with minimal PE, pleural invasion or attachment as a direct mechanism was observed, and it was an independent factor predicting worse survival (P = .03). CONCLUSION Minimal PE is a commonly encountered clinical concern in staging NSCLCs. Its presence is an important prognostic factor of worse survival, especially in early-stage disease.

Differential Effect of Polymorphisms of CMPK1 and RRM1 on Survival in Advanced Non-small Cell Lung Cancer Patients Treated with Gemcitabine or Taxane/Cisplatinum

Introduction: To determine whether genetic variations in CMPK1 or RRM1, which impact the pharmacodynamics of gemcitabine, differentially affect the outcomes of non-small cell lung cancer (NSCLC) patients treated with gemcitabine or taxane/cisplatinum. Methods: We conducted retrospective study evaluating the associations between overall survival in 298 NSCLC patients at stages IIIA/IIIB (140) and IV (158), treated with gemcitabine (139) or taxane (159)/cisplatinum and 14 tagging single-nucleotide polymorphisms (tSNPs): 4 in CMPK1 and 10 in RRM1. Results: The wild-type genotypes of CMPK1 IVS1+1057 and IVS1−928 were associated with shorter overall survival in patients treated with the gemcitabine/cisplatinum (adjusted hazards ratio = 1.97 and 1.89; Cox pBonferroni = 0.008 and 0.020), whereas this effect was not observed in patients treated with taxane/cisplatinum. No associations were observed for the other 2 CMPK1 or 10 RRM1 tSNPs. Analysis of the interaction between the CMPK1 and RRM1 genes showed that the survival of patients with CMPK1 IVS1+1057 CC and RRM1 IVS1−2374 TT, IVS7+25 AA, IVS7−425 AA, or IVS8+287 TT was significantly shorter when they were treated with the gemcitabine/cisplatinum (adjusted hazards ratio = 3.00, 2.89, 3.14, and 3.00; Cox pBonferroni = 0.007, 0.012, 0.006, and 0.007). However, these effects were not observed in patients treated with taxane/cisplatinum. Conclusions: These findings suggest that polymorphisms of CMPK1 and their combination with those of RRM1 are helpful in identifying patients who will benefit less from a gemcitabine/cisplatinum as the first-line regimen.

Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients

BACKGROUND Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.BACKGROUND Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.

Overexpression of a novel regulator of p120 catenin, NLBP, promotes lung adenocarcinoma proliferation

NLBP (novel LZAP-binding protein) was recently shown to function as a tumor suppressor capable of inhibiting the NFκB signaling pathway. NLBP is also known as a negative regulator of cell invasion, and its expression is reduced in several cancer cell lines that have little invasive activity. Although these phenomena suggest that NLBP may be a potential tumor suppressor, its role as a tumor suppressor in human lung cancer is not well established. In contrast to our expectation, NLBP was highly expressed in the early stage of lung adenocarcinoma tissues, and overexpression of NLBP promoted proliferation of H1299 lung adenocarcinoma cells. We also found that p120 catenin (p120ctn) was a novel binding partner of NLBP, and that NLBP binds to the regulatory domain of p120ctn, and p120ctn associates with N-terminal region of NLBP, respectively. This binding leads to p120ctn stability to inhibit proteasomal degradation of p120ctn by inhibiting its ubiqutination. In addition, we also found that overexpression of NLBP and p120ctn in human lung cancer are closely related with adenocarcinoma compared with squamous cell carcinoma. Taken together, our findings reveal that NLBP is highly overexpressed in human lung adenocarcinoma, and that overexpression of NLBP promotes the cell proliferation of lung adenocarcinoma through interacting with p120ctn and suggest that NLBP may function as an oncogene in early stage carcinogenesis of lung adenocarcinoma.

Catamenial hemoptysis: a nationwide analysis in Korea.

Background: Hemoptysis is a potentially serious clinical problem. However, there is no consensus on the clinical characteristics, treatment and patient outcome of catamenial hemoptysis. Objective: Clinical characteristics, treatments and outcome in patients of catamenial hemoptysis were evaluated. Methods: We conducted a retrospective nationwide observational analysis of Korean patients with catamenial hemoptysis. Results: Nineteen patients with catamenial hemoptysis were evaluated from 13 tertiary-care hospitals in Korea. The median age of the patients was 25 years; 8 (42%) were ever-smokers. Eight patients were pathologically diagnosed; 11 were diagnosed by clinical criteria. Sixteen (84%) patients had a history of obstetric or gynecological procedures before developing hemoptysis. The mean amount of hemoptysis (mean ± SD) was 58.3 ± 71.3 for surgery, 46.4 ± 33.2 for hormonal and 29.1 ± 26.3 for conservative treatment groups. Hemoptysis did not recur in 8 (89%) of 9 patients after surgery. None of the patients in the hormonal or conservative treatment groups had persistent hemoptysis. There was an excellent outcome (complete remission and partial responses) in all patients with conservative treatment, suggesting that endometrial cells implanted into the lung may have a benign course. Conclusion: Patients without massive hemoptysis can be treated conservatively or with hormonal agents.

Gender Differences in Susceptibility to Smoking among Patients with Lung Cancer

Background/Aims To determine whether female smokers are more or less susceptible to the detrimental pulmonary-function effects of smoking when compared to male smokers among patients with lung cancer. Methods Pack-years and pulmonary function indices were compared between 1,594 men and women with lung cancer ifferences in individual susceptibility to smoking were estimated using a susceptibility index formula. Results Of the patients, 959 (92.8%) men and 74 (7.2%) women were current smokers. Common histological types of lung cancer were squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, among others. Women had a lower number of pack-years, forced expiratory volume in 1 second (FEV1, liters), forced vital capacity (FVC, liters), and total lung capacity (TLC, liters) compared to those of men (25.0 ± 19.2 vs. 42.9 ± 21.7 for pack-years; 1.4 ± 0.5 vs. 2.0 ± 0.6 for FEV1; 3.0 ± 0.7 vs. 2.0 ± 0.6 for FVC; 4.5 ± 0.8 vs. 5.7 ± 1.0 for TLC; all p < 0.001). The susceptibility index for women was significantly higher compared to that of men (1.1 ± 4.1 vs. 0.7 ± 1.1; p = 0.001). A significant inverse association was shown between the susceptibility index and TLC and FVC (r = -0.200 for TLC, -0.273 for FVC; all p < 0.001). Conclusions The results suggest that the detrimental effects of smoking on pulmonary function are greater in women, as compared to those in men, among patients with lung cancer.

Clinical Application of the Natural Y Stent in the Management of Benign Carinal Stenosis

BACKGROUND The Y-shaped structure of the carinal bifurcation causes difficulties in the treatment of carinal stenosis. We describe a new Y-shaped silicone stent, called the Natural Y stent. We investigated its clinical efficacy through a review of patients with benign carinal stenosis who undewent consecutive Natural Y stent placement. METHODS Between January 2004 and February 2008, 11 patients underwent ballooning, neodymium:yttrium-aluminum-garnet laser resection, or bougienation (by rigid bronchoscopy) to dilate the airway, followed by placement of the Natural Y stent. RESULTS The underlying etiologies of carinal stenosis included posttuberculosis stricture in 7 patients (64%), postintubation stenosis in 2 (18%), and postoperative malacia in 2 (18%). All patients reported subjective symptomatic relief immediately after stent placement. No procedurally related deaths or immediate major complications occurred. Stent-related late complications included granulation tissue formation (64%) and mucostasis (18%, defined as > or = 50% narrowing). The median duration of overall stent placement was 439 days (range, 119 to 1729 days). The stents were successfully removed in 4 patients (36%) after a median of 409 days. CONCLUSIONS The Natural Y stent provides an effective and feasible therapeutic modality in patients with benign carinal stenosis, with or without previous thoracic airway interventions.

Hepatic hydrothorax without ascites as the first sign of liver cirrhosis.

A 60‐year‐old woman without a history of liver diseases, but with a history of regular alcohol consumption, presented with a right‐sided transudative pleural effusion. Neither parenchymal lung lesion nor pleural thickening was seen on a chest computed tomography. On abdominal ultrasonography, the liver size and contour were normal, and ascites was not noted. Despite performing imaging and laboratory studies, we could not find a cause of the pleural effusion. Thus, due to her history of regular alcohol consumption, we decided to measure liver stiffness using a transient elastography (Fibroscan®, EchosensTM, Paris, France), which showed a value of 35.3 kPa suggestive of liver cirrhosis. An intraperitoneal injection of a radioisotope demonstrated the transdiaphragmatic flow of fluid from peritoneal cavity to pleural cavity. The diagnosis was confirmed as hepatic hydrothorax. Management consisting of restricted salt and water intake with diuretics resulted in resolution of the hepatic hydrothorax.

Lung Cancer Risk and Residential Exposure to Air Pollution: A Korean Population-Based Case-Control Study

Purpose To investigate the association between long-term exposure to ambient air pollution and lung cancer incidence in Koreans. Materials and Methods This was a population-based case-control study covering 908 lung cancer patients and 908 controls selected from a random sample of people within each Korean province and matched according to age, sex, and smoking status. We developed land-use regression models to estimate annual residential exposure to particulate matter (PM10) and nitrogen dioxide (NO2) over a 20-year exposure period. Logistic regression was used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CI). Results Increases in lung cancer incidence (expressed as adjusted OR) were 1.09 (95% CI: 0.96−1.23) with a ten-unit increase in PM10 (µg/m3) and 1.10 (95% CI: 1.00−1.22) with a ten-unit increase in NO2 (ppb). Tendencies for stronger associations between air pollution and lung cancer incidence were noted among never smokers, among those with low fruit consumption, and among those with a higher education level. Air pollution was more strongly associated with squamous cell and small cell carcinomas than with adenocarcinoma of the lung. Conclusion This study provides evidence that PM10 and NO2 contribute to lung cancer incidence in Korea.