Views on Precision Medicine among Health Professionals in Korea: A Mixed Methods Study

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Re-biopsy in Previously Treated Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used for the diagnosis and staging of lung cancer. However, evidence of its usefulness for re-biopsy in treated lung cancer, especially according to the previous treatment, is limited. We evaluated the role of EBUS-TBNA for re-biopsy and its diagnostic values in patients with different treatment histories. MATERIALS AND METHODS: We reviewed the medical records of patients who underwent EBUS-TBNA for re-biopsy of suspicious recurrent or progressive lesions between January 2006 and December 2016 at the National Cancer Center in South Korea. Patients were categorized into three groups based on the previous treatment modalities: surgery, radiation, and palliation. RESULTS: Among the 367 patients (surgery, n=192; radiation, n=40; palliation, n=135) who underwent EBUS-TBNA for re-biopsy, the overall sensitivity, negative predictive value (NPV), and diagnostic accuracy of EBUS-TBNA in detecting malignancy were 95.6%, 82.7%, and 96.3%, respectively. The sensitivity was lower in the radiation group (83.3%) when compared with the surgery (95.7%, p=0.042) and palliation (97.7%, p=0.012) groups. The NPV was lower in the palliation group (50.0%) than in the surgery group (88.5%, p=0.042). The sample adequacy of EBUS-TBNA specimens was lower in the radiation group (80.3%) than in the surgery (95.4%, p < 0.001) or palliation (97.8%, p < 0.001) groups. EGFR mutation analysis was feasible in 94.6% of the 92 cases, in which mutation analysis was requested. There were no major complications. Minor complications were reported in 12 patients (3.3%). CONCLUSION: EBUS-TBNA showed high diagnostic values and high suitability for EGFR mutation analysis with regard to re-biopsy in patients with previously treated lung cancer. The sensitivity was lower in the radiation group and NPV was lower in the palliation group. The complication rate was low.

Lung Cancer Screening with Low-Dose CT in Female Never Smokers: Retrospective Cohort Study with Long-term National Data Follow-up / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Because of growing concerns about lung cancer in female never smokers, chest low-dose computed tomography (LDCT) screening is often performed although it has never shown clinical benefits. We examinewhether or not female never smokers really need annual LDCT screening when the initial LDCT showed negative findings. MATERIALS AND METHODS: This retrospective cohort study included 4,365 female never smokers aged 40 to 79 years who performed initial LDCT from Aug 2002 to Dec 2007. Lung cancer diagnosis was identified from the Korea Central Cancer Registry Database registered until December 31, 2013. We calculated the incidence, cumulative probability, and standardized incidence ratio (SIR) of lung cancer by Lung Imaging Reporting and Data System (Lung-RADS) categories showed on initial LDCT. RESULTS: After median follow-up of 9.69 years, 22 (0.5%) had lung cancer. Lung cancer incidence for Lung-RADS category 4 was 1,848.4 (95% confidence interval [CI], 1,132.4 to 3,017.2) per 100,000 person-years and 16.4 (95% CI, 7.4 to 36.4) for categories 1, 2, and 3 combined. The cumulative probability of lung cancer for category 4 was 10.6% at 5 years and 14.8% at 10 years while they were 0.07% and 0.17% when categories 1, 2, and 3 were combined. The SIR for subjects with category 4 was 43.80 (95% CI, 25.03 to 71.14), which was much higher than 0.47 (95% CI, 0.17 to 1.02) for categories 1, 2, and 3 combined. CONCLUSION: Considering the low risk of lung cancer development in female never smokers, it seems unnecessary to repeat annual LDCT screening for at least 5 years or even longer unless the initial LDCT showed Lung-RADS category 4 findings.

The Korean guideline for lung cancer screening

Lung cancer is the leading cause of cancer death in many countries, including Korea. The majority of patients are inoperable at the time of diagnosis because symptoms are typically manifested at an advanced stage. A recent large clinical trial demonstrated significant reduction in lung cancer mortality by using low dose computed tomography (LDCT) screening. A Korean multisociety collaborative committee systematically reviewed the evidences regarding the benefits and harms of lung cancer screening, and developed an evidence-based clinical guideline. There is high-level evidence that annual screening with LDCT can reduce lung cancer mortality and all-cause mortality of high-risk individuals. The benefits of LDCT screening are modestly higher than the harms. Annual LDCT screening should be recommended to current smokers and ex-smokers (if less than 15 years have elapsed after smoking cessation) who are aged 55 to 74 years with 30 pack-years or more of smoking-history. LDCT can discover non-calcified lung nodules in 20 to 53% of the screened population, depending on the nodule positivity criteria. Individuals may undergo regular LDCT follow-up or invasive diagnostic procedures that lead to complications. Radiation-associated malignancies associated with repetitive LDCT, as well as overdiagnosis, should be considered the harms of screening. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Education and actions to stop smoking must be offered to current smokers. Chest radiograph, sputum cytology at regular intervals, and serum tumor markers should not be used as screening methods. These guidelines may be amended based on several large ongoing clinical trial results.

Technical Aspects of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration / 결핵및호흡기질환

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is becoming a standard method for invasive mediastinal staging and for the diagnosis of paratracheal and peribronchial lesions. It is essential to understand the technical aspects of EBUS-TBNA to ensure safe and efficient procedures. In this review, we discuss the practical aspects to be considered during EBUS-TBNA, including anesthesia, manipulation of equipment, understanding mediastinal ultrasound images, target selection, number of aspirations needed per target, sample handling, and complications.

A Case of Capecitabine-Induced Sarcoidosis / 결핵및호흡기질환

Sarcoidosis is an inflammatory disease involving multiple-organs with an unknown cause. The new onset of sarcoidosis associated with therapeutic agents has been observed in 3 clinical settings; tumor necrosis factor antagonists in autoimmune rheumatologic diseases, interferon alpha with or without ribavirin in patients with chronic hepatitis C or melanoma, and antineoplastic agent-associated sarcoidosis in patients with hematologic malignancies. Here, we report a female patient who developed sarcoidosis after capecitabine treatment as an adjuvant chemotherapy for sigmoid colon cancer. To our knowledge, this is the first report of a capecitabine-induced sarcoidosis.

Respiratory Review of 2012: Bronchoscopic Innovations and Advances / 결핵및호흡기질환

Recent advances in bronchoscopy have led to changes in clinical diagnostics and therapeutics in pulmonary medicine. In diagnostic bronchoscopy, there have also been new developments in endobronchial ultrasound technology which may be incorporated into clinical practice in the near future. Functional bronchoscopy, which evaluates information such as airway pressure, airflow, or gas exchange, suggests promising clinical advances in the near future. In therapeutic bronchoscopy, bronchoscopic volume reduction is a novel approach for the treatment of severe emphysema. In this review, seven recently published articles representing current advances in bronchoscopy are summarized and discussed.

First Isolation of Segniliparus rugosus from a Patient with Radiologic Features Similar to Non-Tuberculous Mycobacteriosis / 결핵및호흡기질환

In 2005, a group of mycolic acid-containing bacteria was characterized as belonging to a novel genus, Segniliparus with species Segniliparus rugosus and S. rotundus. We report a case of the S. rugosus isolated from a 54-year-old woman with radiologic features mimicking that of non-tuberculous mycobacteriosis (NTM). When the patient first visited our hospital, an acid-fast bacteria (AFB) smear tested positive and Mycobacterium tuberculosis polymerase chain reaction (TB PCR) was negative in the bronchoalveolar lavage sample. After 2 months, the growing colonies were reported as NTM, but could not be identified because they had died. One year after the initial visit, induced sputum samples showed the same results, positive AFB smear and negative TB PCR. At this point, the growing colonies were identified as S. rugosus. Therefore, we should consider Segniliparus genus as a differential diagnosis for AFB in respiratory specimens in addition to the genus Mycobacterium.

Gastric Metastasis of Primary Lung Adenocarcinoma Mistaken for Primary Gastric Cancer / 결핵및호흡기질환

The stomach is a rare site for metastasis, with autopsy incidence rates of 0.2% to 1.7%. This low rate makes diagnosis of metastatic gastric cancer challenging for clinicians. The authors report a case of a 64-year-old man diagnosed with gastric metastasis of primary lung adenocarcinoma that was initially mistaken for primary gastric cancer, as well as a review of the medical literature.

Activation of NF-kappaB in Lung Cancer Cell Lines in Basal and TNF-alpha Stimulated States / 결핵

BACKGROUND: The NF-kappaB transcription factors control various biological processes including the immune response, acute phase reastion and cell cycle regulation. NF-kappaB complexes are retained in the cytoplasm in the basal state and various stimuli cause a translocation of the NF-kappaB complexes into the nucleus where they bind to the kappaB elements and regulate the transcription of the target genes. Recent reports also suggest that NF-kappaB proteins are involved in oncogenesis, tumor growth and metastasis. High expression of NF-kappaB expression was reported in many cancer cell lines and tissues. The constitutive activation of NF-kappaB was also reported in several cancer cell lines supporting its role in cancer development and survival. The anti-apoptotic action of NF-kappaB is important for cancer survival. NF-kappaB also controls the expression of several proteins that are important for cellular adhesion (ICAM-1, VCAM-1) suggesting a role in cancer metastasis. In lung cancer, high expression levels of the NF-kappaB subunit p50 and c-Rel were reported. In fact, high expression does not mean a high activity, and the activation pattern of NF-kappaB in lung cancer has not been reported. METHODS: In this study, the NF-kappaB nuclear binding activity in the basal and TNF-alpha stimulated states were examined in various lung cancer cell lines and compared with the normal bronchial epithelial cell line. Twleve lung cancer cell lines including the non-small cell and small cell lung cancer cell lines (A549, NCL-H358, NCI-H441, NCL-H522, NCL-H2009, NCI-H460, NCI-H1229, NCI-H1703, NCL-H157, NCL-H187, NCI-H417, NCI-H526) and BEAS-2B bronchial epithelial cell line were used. To evaluate the NF-kappaB expression amd DNA binding activity, western blot analysis and an electrophoretic mobility shift assay with the nuclear protein extracts. RESULTS: The basal expressions of the p50 subunits were observed in the BEAS-2B cell line and all lung cancer cell lines except for NCI-H358 and NCI-H460. The expression levels of p65 and p50 were increased 30 minutes after stimulation with TNF- alpha in BEAS-2B and in 10 lung cancer cell lines. In the NCI-H358 and NCI-H460 cell lines, p65 expression was not observed in the basal and stimulated states and the two p50 related protein levels were higher after stimulation with TNF-alpha. These new proteins were smaller than p50 and are thought to be variants of p50. In the basal state, NF-kappaB was nearly activated in the BEAS-2B and all lung cancer cell lines. The DNA binding activity of the NF-kappaB complexes was markedly higher after stimulation with TNF-alpha. In the BEAS-2B and all lung cancer cell lines except for NCI-H358 and NCI-H460, the activated NF-kappaB complex was a p65/p60 heterodimer. In the NCI-H358 and NCI-H460 lung cancer cell lines, the NF-kappaB complex was variant of a p50/p50 homodimer. CONCLUSION: The NF-kappaB activation pattern in the lung cancer cell lines and the normal bronchial epithelial cell lines was similar except for the activatio of a variant of the p50/p50 homodimer in some lung cancer cell lines.

Clinical Features of Pulmonary Tuberculosis In The Elderly / 결핵

BACKGROUND: Pulmonary tuberculosis(TB) is still prevalent and remains a significant clinical problem for the elderly. However, the disease presents in many ways, and there are frequent adverse drug reactions that may prevent the early diagnosis and treatment of elderly TB patients compared to the young. The purpose of this study was to determine whether or not there are any differences in the clinical feature of pulmonary tuberculosis(TB) in both the diagnosis and treatment between the young (less than 64 years) and the elderly (65 years and more). METHODS: The medical records of 125 young and 70 elderly pulmonary TB patients, who were diagnosed with and treated for pulmonary TB at the Seoul Municipal Boramae Hospital from November 1991 to January 1997, were analyzed retrospectively. RESULTS: Anorexia(12% vs. 31.4%), general weakness (20.0% vs. 54.3%), dyspnea(21.6% vs. 37.1%) and an abnormal mentality (0.8% vs. 15.7%) were more frequent presenting symptoms in elderly TB patients, whereas hemoptysis (32.8% vs. 10.0%) and fever (BT>37℃ 58.4% vs. 35.7%) were more frequent in the young. The elderly had a higher number of cardiovascular and chronic obstructive pulmonary diseases as underlying illnesses. In chest PA, there were no differences in the location of the TB lesion, but the appearances were initially diagnosed more frequently as pneumonia or lung cancer (8.8% vs. 30.0%, p<0.05) in the elderly. There was no difference in the detection rate of acid fast bacilli(AFB) in the sputum between the two groups. There were no differences in the treatment response and follow-up loss. However, adverse drug reactions (13.6% vs. 45.7%, p<0.05), and changes in medication (4.9% vs. 25.7%, p<0.05) during treatment occurred more frequently in the elderly. One among the 125 young patients died from tuberculosis whereas 6 among the 70 elderly patients died from the disease. CONCLUSION: Because the clinical and radiological presentations were more atypical, a sputum AFB smear and culture should be done immediately in the elderly who are TB. The elderly experienced more frequent adverse drug reactions and mortality during treatment, but the response to treatment was good and rapid.

Pro-inflammatory cytokine expression through NF-kappaB/IkappaB pathway in lung epithelial cells / 결핵

BACKGROUND: The importance of pro-inflammatory cytokines, especially tumor necrosis factor α(TNF-α) and interleukin-1β(IL-1β), have been extensively documented in the generation of inflammatory lung disease. Lung epithelial cells are also actively involved in initiating and maintaining inflammation by producing pro-inflammatory mediators. Understanding the mechanism of pro-inflammatory cytokine expression in lung epithelial cells is crucial to the development of new therapeutic modalities for inflammatory lung disease. Transcription of most pro-inflammatory cytokines is dependent on the actiation of NF-κB. However, the relationship between pro-inflammatory cytokine expression and NF-κB/IκB pathway in lung epithelial cells is not clear. METHODS: BEAS-2B, A549, NCI-H719 cells were stimulated with IL-1β or TNF-α at various times, and then IL-8 and TNF-αmRNA expressions were assayed by Northern blot analysis. IL-1β or TNF-α-induced NF-κB activation was assessed by the nuclear translocation of p65 NF-κB subunit. The degradation of IκBα and IκBβ by IL-1βor TNF-α stimulation was assayed by Western blot analysis. The phosphorylation of IκBαwas evaluated by Western blot analysis after pre-treating cells with proteasome inhibitor followed by IL-1β or TNF-α stimulation. The basal level of IKKα expression was evaluated by Western blot analysis. RESULTS: IκBαand IκBβ was repidly degraded after 5 minutes of incubation with IL-1β or TNF-α in BEAS-2B, A549, and NCI-H157 cells. The activation of NF-κB and the induction of IL-8 and TNF-α mRNA expressions were observed by IL-1β or TNF-α stimulation in these cells. In contrast, neither the changes in NF-κB/IκB pathway nor IL-8 and TNF-α mRNA expression was induces by IL-1β or TNF-α stimulation in NCI-H719 cell. IL-1β and TNF-α-induced IκB phoshorylation was observed in BEAS-2B, A549, and NCI-H157 cells, but not in NCI-H719 cells. The basal level of IKKα expression was not different between cells. CONCLUSION: NF-κB/IκB pathway plays an important role in the ixpression of pro-inflammatory cytokine in most lung epithelial cells. The absence of the effect on NF-κB/IκB pathway in NCI-H719 cells seems to be due to the defect in the intracellular signal transduction pathway upstream to IKK.

A Case of Renal Oncocytomatosis with Chronic Renal Failure / 대한신장학회잡지

Renal oncocytomas account for approximately 5% of renal parenchymal tumors. Usually it has unilateral solitary oncocytic nodule, but bilateral multifocal renal oncocytomasis is rare. The term renal oncocytoma should be used to characterize a well-differentiated renal epithelial tumor with eosinophilic granular cytoplasm that has benign behavior and favourable progress. Also, multiple oncocytoma distributed diffusely in both kidneys is termed renal oncocytomatosis Because of the benign nature, multicentricity, possible bilaterality and absence of pathognomonic radiographic features, renal oncocytomas should be considered in differential diagnosis of solid masses, especially renal cell carcinoma. We report a patient with bilaleral multifocal renal oncocytomatosis, who had progressive renal failure. Renal oncocytomatosis was diagnosed pathologically after bilateral nephrectomy.

Histologic Accuracy of Diagnostic Methods in Lung Cancer / 결핵

BACKGROUND: Identification of the histologic cell type of lung cancer is important because it is related to the treatment modality and prognosis. Currently, many diagnostic methods are used to determine the cell type. We have studied to evaluate the histologic accuracy of each diagnostic methods in lung cancer. METHOD: 168 cases were analysed retrospectively, who underwent curative thoracotomy for lung cancer in Seoul National University Hospital from January, 1994 to Feburary, 1997. Sputum cytology, percutaneous needle aspiration(PCNA), percutaneous needle biopsy(PCNB), bronchial washing cytology and flexible bronchoscopic biopsy were evaluated respectively. The kappa coefficient was applied to evaluate the degree of concordance between the histologic diagnosis obtained by each methods and the one derived from thoracotomy. RESULTS: 1. The kappa value in sputum cytology was 0.86 In the 34 cases with squamous cell carcinoma(SQ), 32 cases were finally diagnosed as having such by thouacotomy. 7 of the 8 cases with adenocarcinoma(AD) turned out to have the same. 2. The kappa value in PCNA was 0.51. In the 31 cases with SQ, only 14 cases were finally diagnosed as having such. All of the 3 cases with small cell carcinoma(SC) turned out to have the same. 3. The kappa value in PCNB was 0.77. The diagnosis was correct in 13 of the 16 patients with SQ and in 30 of the 32 cases with AD. 4. The kappa value in bronchial washing cytology was 1.0. In all of the 29 cases with SQ and all of the 7 cases with AD, the diagnosis was correct. 5. The kappa value in flexible bronchoscopic biopsy was 0.77. The diagnosis was correct in 51 of the 52 cases with SQ and in 1 of the 2 cases with SC. CONCLUSION: The concordance rate with the final histologic diagnosis in sputum cytology, PCNB, bronchial washing cytology and flexible bronchoscopic biopsy were excellent (kappa >or=0.75), while that in PCNA was fair (kappa=0.53). Because PCNA showed lower concordance rate than other diagnostic methods, PCNA is recommended to perform with PCNB.

Cases of the Pulmonary Malignant Lymphoma of the Bronchus-Associated Lymphoid Tissue (BALT) / 결핵

The primary mucosa-associated lymphoid tissue(MALT) lymphoma of the lung is a rare low grade B cell lymphoma arising from bronchus-associated lymphoid tissue(BALT) which had been regarded as pseudolymphoma. It has the characteristic histologic with monoclonal B cells of centrocyte-like lymphoid cells and a lymphoepithelial lesion. Clinically it shows an indolent clinical course course and much more favorable prognosis than lymphoma of other site. We report 3 cases of the pulmonary malignant lymphoma of BALT, which was confirmed by lung biopsy, immunohistochemistry and PCR assay.

Clinical Characteristics of Pneumococcal Bacteremia in Adults: The Effect of Penicillin Resistance on the Mortality of Patients with Pneumococcal Bacteremia / 결핵

BACKGROUNDS: The advent of penicillin has led to the marked reduction in the mortality from pneumococcal bacteremia, however, the mortality is still relatively high in this post-antibiotic era. Actually the prevalence of infection due to penicillin-resistant penumococci is increasing worldwide, and it is especially high in Korea due to irrelevant use of antibiotics. So, the high mortality of pneumococcal sepsis might be related to the emergence of penicillin-resistant strains, however, many other antibiotics, which eradicate pneumococci effectively, are available in these days. This has led us to suspect the role of penicillin- resistance in the high mortality rate. In this study, we evaluated the effect of penicillin resistance on the mortality of patients with penumococcal bacteremia. METHODS: The study population consisted of 50 adult patients with penumococcal bacteremia who were admitted between Jan, 1990 and July, 1997. Medical records were analyzed retrospectively. RESULTS: Most of the patients (96%) had underlying diseases. The most common local disease associated with pneumococcal bacteremia was pneumonia (42%), which was followed by spontaneous bacterial peritonitis (14%), cholangitis (10%), meningitis (8%), liver abscess (4%), pharyngotonsillitis (4%), sinusitis (2%) and cellulitis (2%). While the overall case-fatality rate in this study was 24%, it was higher when peumococcal bacteremia was associated with pneumonia (42%) or meningitis (50%). The rate of penicillin resistance was 40%, which was increased rapidly from 1991. The rate of penicillin resistance was significantly higher in patients with the history of recent antibiotics use and hospitalization within 3 months respectively. The clinical manifestations, that is, age, severity of underlying diseases, nosocomial infection, associated local diseases, and the presence of shock or acute renal failure were not statistically different between the patients with penicillin- resistant and -sensitive pneumococcal bacteremia. The mortality of patients infected with penicillin-resistant pneumococci was not statistically different from those with penicillin-sensitive pneumococcal bacteremia. CONCLUSION: Penicillin resistance is not associated with high mortality in adult patients with pneumococcal bacteremia. As the overall mortality is high, active penumococcal vaccination is recommended in patients with high risk of infection.

A Case of Diffuse Nodular Pulmonary Ossification / 결핵

Diffuse pulmonary ossification is rare disease of unknown etiology. Since the first description by Luschka in 1856, about 140 cases have been reported worldwide, but no such case has been reported in Korea yet. We report 40-year-old woman who was diagnosed as diffuse nodular pulmonary ossification on open lung biopsy. She has no respiratory symptoms & physical findings and no previous disease history. She was incidentally found to have multiple pulmonary nodules on roentgenographic examination. Open lung biopsy was done for above lesion and S he was proven to have diffuse nodular pulmonary ossification. She was followed by roentgenographic examination and showed no progression.

A Case of Tracheal Hamartoma / 결핵

BACKGROUND: Tracheal hamartoma is a very rare cause of upper airway obstruction. Its clinical features can mimic medical conditions, such as bronchial asthma, chronic bronchitis, and so on. CASE: This report presents the case of a 65 year old man whose major symptom was dyspnea. We found a tumor in his distal tracheal lumen, and the tumor was removed with success using rigid bronchoscope. The tumor was histologically proven to be a hamartoma, and his symptoms were much improved. CONCLUSION: It is important to distinguish it from other conditions because medical management is often not helpful. surgical correction-with or without thoracotomy-is inevitable.