New targeted therapies for non-small cell lung cancer

Lung cancer is representative of a high frequency and high mortality disease and ranks at the top in incidence and mortality in Korea, when excluding thyroid cancer. In this manuscript, we focused on current targeted therapies for lung cancer used widely in the medical field.Current Concepts: The majority of patients with lung cancer cannot be treated with surgery only and require chemotherapeutics or radiation therapy. Currently, classical chemotherapeutic agents, targeted agents, and immune checkpoint inhibitors are the most widely used. Recently, the Research and Development of antibody-drug conjugates is gaining attention, and this may become a more widely prescribed treatment in the future. Among the available treatment options, targeted therapy is becoming increasingly feasible and widespread for treating inoperable lung cancers, where driver mutations have been identified, and for adjuvant or neoadjuvant therapies. Next-generation sequencing (NGS) improves the ability to identify driver mutations that were previously difficult to detect and can also be performed on blood samples where no cancer tissue is available for testing. This makes it possible to identify therapeutic targets for targeted therapy more rapidly.Discussion and Conclusion: The most common type of lung cancer in Korea is adenocarcinoma, for which a driver mutation has been identified. Newly developed drugs target previously problematic mutations or cancer cell lines that have acquired resistance induced during the treatment process. The survival rate of patients with lung cancer is expected to improve with the development of tailored treatments for targets identified from the NGS data of the patient. This paper will help clinicians understand the current state of targeted therapies for lung cancer treatment.

Predictive Role of Lung Injury Prediction Score in the Development of Acute Respiratory Distress Syndrome in Korea

Purpose@#Early recognition and therapeutic intervention are important in patients at high risk of acute respiratory distress syndrome (ARDS). The lung injury prediction score (LIPS) has been used to predict ARDS development; however, it was developed based on the previous definition of ARDS. We investigated the predictive role of LIPS in ARDS development according to its Berlin definition in the Korean population. @*Materials and Methods@#This was a retrospective study that enrolled adult patients admitted to the intensive care unit (ICU) at a single university-affiliated hospital in Korea from September 1, 2018, to August 31, 2019. LIPS at the time of ICU admission and the development of ARDS were evaluated. @*Results@#Of the 548 enrolled patients, 33 (6.0%) fulfilled the Berlin ARDS definition. The LIPS for non-ARDS and ARDS groups were 4.96±3.05 and 8.53±2.45, respectively (p6 predicted the development of ARDS with a sensitivity of 84.8% and a specificity of 67.2% [area under the curve (AUC)=0.82]. A modified LIPS model adjusted for age and severity at ICU admission predicted ICU mortality in patients with ARDS (AUC=0.80), but not in those without ARDS (AUC=0.54). @*Conclusion@#LIPS predicted the development of ARDS as diagnosed by the Berlin definition in the Korean population. LIPS provides useful information for managing patients with ARDS.

Revised Korean Cough Guidelines, 2020: Recommendations and Summary Statements / 결핵및호흡기질환

Cough is the most common respiratory symptom that can have various causes. It is a major clinical problem that can reduce a patient’s quality of life. Thus, clinical guidelines for the treatment of cough were established in 2014 by the cough guideline committee under the Korean Academy of Tuberculosis and Respiratory Diseases. From October 2018 to July 2020, cough guidelines were revised by members of the committee based on the first guidelines. The purpose of these guidelines is to help clinicians efficiently diagnose and treat patients with cough. This article highlights the recommendations and summary of the revised Korean cough guidelines. It includes a revised algorithm for the evaluation of acute, subacute, and chronic cough. For a chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered in differential diagnoses. If UACS is suspected, first-generation antihistamines and nasal decongestants can be used empirically. In cases with CVA, inhaled corticosteroids are recommended to improve cough. In patients with suspected chronic cough due to symptomatic GERD, proton pump inhibitors are recommended. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, intake of angiotensin-converting enzyme inhibitor, intake of dipeptidyl peptidase-4 inhibitor, habitual cough, psychogenic cough, interstitial lung disease, environmental and occupational factors, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and unexplained cough can also be considered as causes of a chronic cough. Chronic cough due to laryngeal dysfunction syndrome has been newly added to the guidelines.

Predictive Role of Lung Injury Prediction Score in the Development of Acute Respiratory Distress Syndrome in Korea

Purpose@#Early recognition and therapeutic intervention are important in patients at high risk of acute respiratory distress syndrome (ARDS). The lung injury prediction score (LIPS) has been used to predict ARDS development; however, it was developed based on the previous definition of ARDS. We investigated the predictive role of LIPS in ARDS development according to its Berlin definition in the Korean population. @*Materials and Methods@#This was a retrospective study that enrolled adult patients admitted to the intensive care unit (ICU) at a single university-affiliated hospital in Korea from September 1, 2018, to August 31, 2019. LIPS at the time of ICU admission and the development of ARDS were evaluated. @*Results@#Of the 548 enrolled patients, 33 (6.0%) fulfilled the Berlin ARDS definition. The LIPS for non-ARDS and ARDS groups were 4.96±3.05 and 8.53±2.45, respectively (p6 predicted the development of ARDS with a sensitivity of 84.8% and a specificity of 67.2% [area under the curve (AUC)=0.82]. A modified LIPS model adjusted for age and severity at ICU admission predicted ICU mortality in patients with ARDS (AUC=0.80), but not in those without ARDS (AUC=0.54). @*Conclusion@#LIPS predicted the development of ARDS as diagnosed by the Berlin definition in the Korean population. LIPS provides useful information for managing patients with ARDS.

Revised Korean Cough Guidelines, 2020: Recommendations and Summary Statements / 결핵및호흡기질환

Cough is the most common respiratory symptom that can have various causes. It is a major clinical problem that can reduce a patient’s quality of life. Thus, clinical guidelines for the treatment of cough were established in 2014 by the cough guideline committee under the Korean Academy of Tuberculosis and Respiratory Diseases. From October 2018 to July 2020, cough guidelines were revised by members of the committee based on the first guidelines. The purpose of these guidelines is to help clinicians efficiently diagnose and treat patients with cough. This article highlights the recommendations and summary of the revised Korean cough guidelines. It includes a revised algorithm for the evaluation of acute, subacute, and chronic cough. For a chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered in differential diagnoses. If UACS is suspected, first-generation antihistamines and nasal decongestants can be used empirically. In cases with CVA, inhaled corticosteroids are recommended to improve cough. In patients with suspected chronic cough due to symptomatic GERD, proton pump inhibitors are recommended. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, intake of angiotensin-converting enzyme inhibitor, intake of dipeptidyl peptidase-4 inhibitor, habitual cough, psychogenic cough, interstitial lung disease, environmental and occupational factors, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and unexplained cough can also be considered as causes of a chronic cough. Chronic cough due to laryngeal dysfunction syndrome has been newly added to the guidelines.

Age- and sex-related characteristics of the increasing trend of nontuberculous mycobacteria pulmonary disease in a tertiary hospital in South Korea from 2006 to 2016

Background/Aims@#The incidence rate of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide. However, data regarding the age- and sex-specific epidemiology of NTM-PD are limited. This study aimed to investigate the long-term epidemiologic trends of NTM-PD within the recent 11- year period in a tertiary referral hospital in Korea. @*Methods@#We retrospectively reviewed the medical records of the patients diagnosed with NTM-PD between January 2006 and December 2016 at Severance Hospital, South Korea. @*Results@#There were 1,017 incident cases with NTM-PD during the study period. The mean age was 62.7 years, and 41.2% were men. Women were younger than men (59.9 years vs. 66.7 years, p < 0.001) and a higher proportion of women had bronchiectasis (88.6% vs. 77.1%, p < 0.001). The incidence rates of NTM-PD annually increased by 14% (95% confidence interval, 10% to 19%) from 1.2 in 2006 to 4.8 in 2016 (per 100,000 patients-year). The peak incidence rate was in the 50s for women and in the 70s for men, except for those aged ≥ 80 years. Mycobacterium avium complex was the most common causative species of NTM-PD (63.6%). @*Conclusions@#The incidence rate of NTM-PD in a tertiary referral hospital in South Korea continued to increase from 2006 to 2016. Furthermore, there were age- and sex-related differences in the clinical characteristics, which might contribute to understanding the nature of the disease and inherited and acquired host factors.

Experiences of Latent Tuberculosis Infection Treatment for the North Korean Refugees / 결핵

BACKGROUND: Tuberculosis (TB) is increasing in immigrants. We aimed to investigate the current status of latent tuberculosis infection (LTBI) treatment for North Korean Refugees (NKR) compared to South Koreans Contacts (SKC). METHODS: TB close contacts in a closed facility of SKC and NKR who underwent LTBI screening in a settlement support center for NKR were analyzed retrospectively. RESULTS: Among tuberculin skin test (TST) ≥10 mm (n=298) reactors, the males accounted for 72.2% in SKC (n=126) and 19.5% in NKR (n=172) (p<0.01). The mean age was higher in South Korea (42.8±9.9 years vs. 35.4±10.0 years, p<0.01). Additionally, the mean TST size was significantly bigger in NKR (17.39±3.9 mm vs. 16.57±4.2 mm, p=0.03). The LTBI treatments were initiated for all screened NKR, and LTBI completion rate was only 68.0%. However, in NKR, LTBI treatment completion rate was significantly increased by shorter 4R regimen (odds ratio [OR], 9.296; 95% confidence interval [CI], 4.159–20.774; p<0.01) and male (OR, 3.447; 95% CI, 1.191–9.974; p=0.02). CONCLUSION: LTBI treatment compliance must be improved in NKR with a shorter regimen. In addition, a larger study regarding a focus on LTBI with easy access to related data for NKR should be conducted.

Experiences of Latent Tuberculosis Infection Treatment for the North Korean Refugees / 결핵및호흡기질환

BACKGROUND@#Tuberculosis (TB) is increasing in immigrants. We aimed to investigate the current status of latent tuberculosis infection (LTBI) treatment for North Korean Refugees (NKR) compared to South Koreans Contacts (SKC).@*METHODS@#TB close contacts in a closed facility of SKC and NKR who underwent LTBI screening in a settlement support center for NKR were analyzed retrospectively.@*RESULTS@#Among tuberculin skin test (TST) ≥10 mm (n=298) reactors, the males accounted for 72.2% in SKC (n=126) and 19.5% in NKR (n=172) (p<0.01). The mean age was higher in South Korea (42.8±9.9 years vs. 35.4±10.0 years, p<0.01). Additionally, the mean TST size was significantly bigger in NKR (17.39±3.9 mm vs. 16.57±4.2 mm, p=0.03). The LTBI treatments were initiated for all screened NKR, and LTBI completion rate was only 68.0%. However, in NKR, LTBI treatment completion rate was significantly increased by shorter 4R regimen (odds ratio [OR], 9.296; 95% confidence interval [CI], 4.159–20.774; p<0.01) and male (OR, 3.447; 95% CI, 1.191–9.974; p=0.02).@*CONCLUSION@#LTBI treatment compliance must be improved in NKR with a shorter regimen. In addition, a larger study regarding a focus on LTBI with easy access to related data for NKR should be conducted.

Factors Associated with Lung Function Recovery at the First Year after Lung Transplantation

PURPOSE: Post-operative pulmonary function is an important prognostic factor for lung transplantation. The purpose of this study was to identify factors affecting recovery of forced expiratory volume in 1 second (FEV1) at the first year after lung transplantation. MATERIALS AND METHODS: We retrospectively reviewed the medical records of lung transplantation patients between October 2012 and June 2016. Patients who survived for longer than one year and who underwent pulmonary function test at the first year of lung transplantation were enrolled. Patients were divided into two groups according to whether they recovered to a normal range of FEV1 (FEV1 ≥80% of predicted value vs. < 80%). We compared the two groups and analyzed factors associated with lung function recovery. RESULTS: Fifty-eight patients were enrolled in this study: 28 patients (48%) recovered to a FEV1 ≥80% of the predicted value, whereas 30 patients (52%) did not. Younger recipients [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.87–0.98; p=0.010], longer duration of mechanical ventilator use after surgery (OR, 1.14; 95% CI, 1.03–1.26; p=0.015), and high-grade primary graft dysfunction (OR, 8.08; 95% CI, 1.67–39.18; p=0.009) were identified as independent risk factors associated with a lack of full recovery of lung function at 1 year after lung transplantation. CONCLUSION: Immediate postoperative status may be associated with recovery of lung function after lung transplantation.

Lymphocytic interstitial pneumonia in a patient with Sjögren's syndrome / 영남의대학술지

Lymphocytic interstitial pneumonia (LIP) is a rare benign lymphoproliferative disorder characterized by diffuse infiltration of the pulmonary parenchymal interstitium by polyclonal lymphocytes and plasma cells. LIP has been associated with a variety of clinical conditions; such as connective tissue disorders and other immune system abnormalities. Treatment usually involves administration of corticosteroids and other immunosuppressants. We report on a 38-year-old female patient who complained of shortness of breath, dry mouth, and dry eyes for more than 1 month, and was positive for Raynaud's phenomenon. Based on surgical biopsy, she was diagnosed as having LIP accompanied by Sjögren's syndrome. The patient was treated with high-dose steroids followed by maintenance therapy for approximately 2 years, and her condition improved.

A late onset solitary mediastinal cystic lymphangioma in a 66-year-old woman who underwent kidney transplantation / 영남의대학술지

Lymphangioma is a congenital abnormality of the lymphatic system detected primarily in early childhood. There are rare reports of mediastinal lymphangioma in older adults. We hereby report on a 66-year-old female patient who underwent kidney transplantation 20 years previously and who developed pathologically confirmed solitary mediastinal lymphangioma 1 year ago. Chest radiography showed a mediastinal nodule, which was not observed 2 year previously, therefore she was referred to the pulmonary division. She had no symptoms, and chest computed tomography demonstrated a 25-mm, well-defined, low-density nodule located at the anterior mediastinum. The size of the nodule had increased from 25 mm to 34 mm 1 year later, and it was completely resected via video-assisted thoracic surgery. The histological diagnosis was cystic lymphangioma. Therefore, we recommend that clinicians consider cystic lymphangioma as a possible diagnosis even in older patients with a mediastinal cystic mass that shows progressive enlargement.

A Case of Allergic Bronchopulmonary Aspergillosis Forming Broncholith Misdiagnosed as an Uncontrolled Asthma with Broncholithiasis

A 55-year-old woman was referred to the division of pulmonology at Severance Hospital for the investigation of uncontrolled asthma with recurrent cough at night, blood-tinged sputum, malaise, and wheezing since 3 months. Chest computed tomography revealed bronchiectasis and broncholithiasis in the lateral segmental bronchus of the right middle lobe and the anterobasal segmental bronchus of the right lower lobe. Bronchoscopic broncholith removal was performed because of recurrent blood-tinged sputum and the outflow of purulent exudate behind the broncholith in the lateral segmental bronchus of the right middle lobe. The extracted material presenting amorphous eosinophilic necrotic materials with calcification was compatible with broncholithiasis. Following decalcification, histopathology revealed degenerated septate fungal hyphae and spores that were morphologically consistent with Aspergillus spp. A final diagnosis was allergic bronchopulmonary aspergillosis (ABPA) forming broncholith. The results from this case suggest that the early recognition of ABPA should be considered in patients with uncontrolled asthma accompanied by broncholithiasis.

A Case of Extensive IgG4-Related Disease Presenting as Massive Pleural Effusion, Mediastinal Mass, and Mesenteric Lymphadenopathy in a 16-Year-Old Male / 결핵및호흡기질환

IgG4-related disease is an immune-mediated fibro-inflammatory disease, characterized by lymphoplasmacytic infiltration composed of IgG4-positive plasma cells of various organs with elevated circulating levels of IgG4. This disease is now reported with increasing frequency and usually affects middle-aged men. Massive pleural effusion in children is an uncommon feature in IgG4-related disease. Here, we report a case of a 16-year-old male patient with extensive IgG4-related disease presenting with massive pleural effusion, mediastinal mass, and mesenteric lymphadenopathy.

A Case of Duodenal Intramural Hematoma Caused by Acute Alcoholic Pancreatitis / 대한췌담도학회지

Intramural duodenal hematoma (IDH) is a rare disease which defined a hematoma formation localized within the wall of the duodenum. The most common cause of IDH is due to blunt abdominal trauma while most of other cases of IDH are more related to the use of anticoagulants or coagulation disorders such as haemophilia and Von Willebrand disease. We report a very rare case of a large IDH caused by acute alcoholic pancreatitis without any kind of anticoagulation therapies nor coagulopathies. The patient was recovered by only medical treatment and observation without surgical intervention.

The Comparison of Clinical Outcomes of Off-Pump versus On-Pump Coronary Artery Bypass Grafting in High Risk Patients / 대한흉부외과학회지

Background: Off-pump coronary artery bypass grafting (Off-Pump CABG) has been proven to have less morbidity and to facilitate early recovery. High-risk surgical patients may have benefitted by avoiding the adverse effects of the cardiopulmonary bypass. We compared the effectiveness of Off-Pump CABG with that of coronary artery bypass using cardiopulmonary bypass (On-Pump CABG) in high-risk patients. Material and Method: 682 patients (424 Off-Pump CABG and 258 On-Pump CABG) underwent isolated coronary artery bypass grafting between January 200l and June 2003. Patients who were considered high risk were selected High risk is defined as the presence of one or more of nine adverse prognostic factors. Data were collected from 192 patients in Off-Pump CABG and 100 in On-Pump CABG for risk factors, extent of coronary disease, and in-hospital outcomes. Result: Off-Pump CABG group and On-Pump CABG group did not show differences in their preoperative risk factors. We used more arterial grafts in Off-Pump CABG group (p<0.05). Postoperative results showed that operative mortality (0.5% in Off-Pump CABG versus 2.0% in On-Pump CABG), renal failure (2.6% in Off-Pump CABG versus 7.0% in On-Pump CABG), and perioperative myocardial infarction (l.5% in Off-Pump CABG versus l.0% in On-Pump CABG) did not differ significantly. However, Off-Pump CABG had shorter mean operation time (p<0.05), lower mean CK-MB level (p<0.05), lower rate of usage of inotropics (p<0.05), shorter mean ventilation time (p<0.05), lower perioperative stroke (0% versus 2.0%), and shorter length of stay (p<0.05) than On-Pump CABG. On-Pump CABG had more distal grafts (p<0.05) than Off-Pump CABG. Although Off-Pump CABG and On-Pump CABG did not show statistical differences in mortality and morbidity was more frequent in CABG. Conclusion: Off-Pump CABG reduces morbidity and favors hospital outcomes. Therefore, Off-Pump CABG is safe, reasonable and may be a preferable operative strategy for high-risk patients.

Nodal Station as a Prognostic Factor in Resected Stage IIIA N2 Non-Small Cell Lung Cancer / 대한흉부외과학회지

BACKGROUND: To clarify the prognostic implication of the location and number of the metastatic mediastinal nodes in resected stage IIIA N2 non-small cell lung cancer. MATERIAL AND METHOD: One hundred and seventy-four patients with resected non-small cell lung cancer who eventually proved to have pathologic stage IIIA N2 disease were studied. Patients who received preoperative induction therapy, non-curative operation or defined as operative mortality were excluded from this study. RESULT: In upper lobe tumors, there was no difference in 5-year survival according to the involvement of lower mediastinal nodes (32.3% vs 25.6%, p=0.86). In lower lobe tumors, no differencee was found in 5-year survival according to the involvement of upper mediastinal nodes (25.1% vs 14.1%, p=0.33). There was no significant difference in 5-year survival between patients with or without metastatic subcarinal node (20.9% vs 25.6%, p=0.364). In terms of the number of metastatic mediastinal nodes, 5-year survival was better in single station group (26.3%) than multiple station group (18.3%) (p=0.048). In multiple station N2 group, the patients who received postoperative chemotherapy and radiation therapy had better 5-year survival (34.2%) (p=0.01). Cox's proportional hazards model revealed that the age > or =60 (O.R: 1.682, p=.006), multiple station N2 (O.R: 1.503. p=0.021), pneumonectomy (O.R: 1.562, p=0.018), postoperative chemotherapy and radiation therapy (O.R: 0.625, p=0.012) were the factors affecting the postoperative survival. CONCLUSION: Multiple station N2 disease was the important prognostic factor for postoperative survival in resected stage IIIA N2 non-small cell lung cancer. Postoperative chemotherapy and radiotherapy were thought to improve the survival in case of multiple station N2 disease.

The Comparison of Clinical Study of Off Pump and On Pump CABG / 대한흉부외과학회지

BACKGROUND: In an attempt to avoid the adverse effects of the cardiopulmonary bypass, off pump coronary artery bypass grafting(Off pump CABG) that has recently been rediscovered and refined. We compared the preoperative risk factors and in-hospital outcomes of patients done Off pump with those done On pump CABG. MATERIAL AND METHOD: One hundred seventy eight patients was underwent CABG between January 2001 and July 2001. 12 patients whom underwent associated valvular or left ventricular volume reduction surgery were excluded in this study. Data were collected for 52 Off pump CABG and 114 On pump CABG for patient and disease risk factors, extent of coronary disease, and in-hospital outcomes. RESULT: Off pump CABG and On pump CABG groups did not show any differences in their patient and disease risk factors, and extent of coronary disease. Off pump CABG group had significantly lower mean operation time(234 +/- 37 min vs 290 +/- 48 min, p < 0.001), lower mean CK-MB level(10.1 +/- 13.5 IU/L vs 33.1 +/- 18.2 IU/L, p < 0.001) and mean ventilation time(14.8 +/- 3.5 hours vs 16.2 +/- 4.9 hours, p=0.048) than On pump CABG groups. On pump CABG group had significantly more distal grafts(3.4 +/- 0.9 vs 2.6 +/- 0.8, p < 0.001) than Off pump CABG groups. There were no operative mortality in two groups. Off pump CABG and On pump CABG groups did not show any differences in their postoperative complications and outcomes including perioperative myocardial infarction, stroke, respiratory failure, renal failure, reoperation, the amount of bleeding, the need of intraaortic balloon pump, the need of inotropics, and the stay of intensive care unit and hospital. Two patients were converted to On pump CABG. CONCLUSION: This study showed that patients having Off pump CABG are not exposed to a greater risks of adverse outcomes and also provided evidence that patients having Off pump CABG have significantly lower operation time, CK-MB, ventilation time and less distal grafts. Although there may be potential benefits to Off pump CABG, further studies must be directed to determine those patients who would benefit from Off pump CABG.