Jong Sun Park

Who should be admitted to the intensive care unit? The outcome of intensive care unit admission in stage IIIB-IV lung cancer patients.

Critical care for advanced lung cancer patients is still controversial, and the appropriate method for the selection of patients who may benefit from intensive care unit (ICU) care is not clearly defined. We retrospectively reviewed the medical records of stage IIIB–IV lung cancer patients admitted to the medical ICU of a university hospital in Korea between 2003 and 2011. Of 95 patients, 64 (67xa0%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, and 79 (84xa0%) had non-small-cell lung cancer. In total, 28 patients (30xa0%) were newly diagnosed or were receiving first-line treatment, and 22 (23xa0%) were refractory or bedridden. Mechanical ventilation was required in 85 patients (90xa0%), and ICU mortality and hospital mortality were 57 and 78xa0%, respectively. According to a multivariate analysis, a PaO2/FiO2 ratio <150 [odds ratio (OR)xa0=xa05.51, 95xa0% confidence interval (CI) 2.10–14.48, pxa0=xa00.001] was independently associated with ICU mortality, and an ECOG PS ≥2 (ORxa0=xa09.53, 95xa0% CI 2.03–44.85, pxa0=xa00.004) and a need for vasoactive agents (ORxa0=xa06.94, 95xa0% CI 1.61–29.84, pxa0=xa00.009) were independently associated with hospital mortality. Refractory or bedridden patients (nxa0=xa022) showed significantly poorer overall survival (11.0 vs. 29.0xa0days, pxa0=xa00.005). Among 21 patients who were discharged from the hospital, 11 (52xa0%) received further chemotherapy. Certain advanced lung cancer patients may benefit from ICU management. However, refractory patients and patients with a poor PS do not seem to benefit from ICU care. Oncologists should try to discuss palliative care and end-of-life issues in advance to avoid futile care.

Prognostic factors of Pneumocystis jirovecii pneumonia in patients without HIV infection

OBJECTIVESnThe incidence of Pneumocystis jirovecii pneumonia (PCP) in patients without HIV infection (non-HIV PCP) has been increasing along with the increased use of chemotherapeutic agents and immunosuppressants, but the prognostic factors of non-HIV PCP remain unclear. This study aimed to identify the prognostic factors of non-HIV PCP.nnnMETHODSnImmunocompromised patients without HIV infection who were diagnosed and treated for PCP were included. The PCP diagnosis was based on positive direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) results and compatible clinical symptoms and radiological findings.nnnRESULTSnIn total, 372 non-HIV patients with positive PCP DFA or PCR findings were screened and 173 were included. Univariate analysis indicated that age, smoking, chronic lung disease or hematologic malignancy, chemotherapeutic agents, high alveolar-arterial oxygen gradient (D[A-a]O2), C-reactive protein, albumin, blood urea nitrogen (BUN), CMV antigenemia, combined bacteremia, high percentage of neutrophils and rate of co-infection in BAL fluid, and mechanical ventilator care were related to the prognosis of non-HIV PCP. Multivariate analysis revealed that high D(A-a)O2, combined bacteremia, increased BUN and preexisting lung disease were indicators of a poor prognosis.nnnCONCLUSIONSnHigh D(A-a)O2, combined bacteremia, increased BUN and preexisting lung disease were independent factors of poor prognosis in non-HIV PCP patients.

Comparison of clinical characteristics between patients with ALK-positive and EGFR-positive lung adenocarcinoma.

BACKGROUNDnThe discovery of the chromosomal fusion product of anaplastic lymphoma kinase (ALK) with echinoderm microtubule-associated protein-like 4 (EML4) (EML4-ALK) has changed the treatment paradigm of lung cancer. In this study, we analysed the clinical characteristics, including bronchoscopic findings, of patients with EML4-ALK-positive adenocarcinoma and compared them with those of EGFR mutation-positive patients.nnnMATERIALS AND METHODSnIn this retrospective cohort study, the clinical characteristics and bronchoscopic findings of patients with ALK fusion-positive lung cancers were compared to patients with EGFR-mutant lung cancers.nnnRESULTSnAmong the 440 patients with adenocarcinoma of lung screened for this study, 46 (10.4%) harboured the EML4-ALK fusion, 90 (20.4%) harboured an activating EGFR mutation, and all had adenocarcinoma. In univariate analysis, ALK-positive patients were significantly younger than EGFR-positive patients (pxa0=xa00.004) and were more commonly male (pxa0=xa00.021). An initial status of stage IV metastatic cancer was more frequently noted in EML4-ALK-positive patients (pxa0=xa00.012), with initial brain metastasis frequently observed (pxa0=xa00.007). Compared with EGFR-positive patients, EML4-ALK-positive patients were significantly more likely to have positive bronchoscopic findings, which suggested a more centralized origin (pxa0=xa00.001). EML4-ALK patients also had significantly more positive bronchoscopic findings and were more commonly male in multivariate analysis.nnnCONCLUSIONSnThe EML4-ALK fusion defines a new molecular subset of NSCLC that has distinct clinical and bronchoscopic findings suggesting more proximal origin when compared to tumours harbouring EGFR mutations.

Adverse pulmonary reactions associated with the use of monoclonal antibodies in cancer patients.

BACKGROUNDnThe incidence and clinical characteristics of adverse pulmonary reactions resulting from anticancer monoclonal antibody (mAbs) therapy have not been well described. We determined the incidence and clinical characteristics of adverse pulmonary reactions in patients treated with anticancer chemotherapy including mAbs.nnnMETHODSnA retrospective cohort study was performed including patients who were treated with a chemotherapeutic regimen that included rituximab, trastuzumab, cetuximab, or bevacizumab at Seoul National University Hospital between January 1, 2004 and December 31, 2008. Rates of adverse pulmonary reactions classified as non-infectious and infectious complications were compared with those among patients treated with comparable regimens without mAbs.nnnRESULTSnIn total, 1078 patients were included (418 for rituximab, 329 for trastuzumab, 122 for cetuximab, 209 for bevacizumab). Adverse pulmonary reactions were identified in 36 patients (3.5%) and the incidence differed among agents: cetuximab (9%), rituximab (5.3%), trastuzumab (0.6%), bevacizumab (0.5%). Infectious pulmonary complications occurred in 28 patients, and eight patients experienced non-infectious pulmonary complications, most commonly interstitial lung disease (6 patients). In a multivariate analysis, low serum albumin level was associated with the development of pulmonary complications. The incidence of overall adverse pulmonary reactions did not differ between the mAbs users and the 1012 patients treated with comparable regimens other than mAbs (3.5% vs. 2.8%, P=0.53).nnnCONCLUSIONSnInfectious and non-infectious adverse pulmonary reactions occur in patients with cancer who are administered a regimen including mAbs. Clinicians should be alert for the possibility of pulmonary adverse reactions, particularly among patients with low serum albumin levels.

Lack of Association between Matrix Metalloproteinase 8 Promoter Polymorphism and Bronchiectasis in Koreans

The observation that human matrix metalloproteinase (MMP)-8 is over-expressed in ectatic bronchi in patients with bronchiectasis suggests that polymorphisms altering the expression of MMP-8 may contribute to the susceptibility to development of bronchiectasis. We evaluated the association between the presence of bronchiectasis in a Korean population and two single nucleotide polymorphisms (SNPs) (-799C/T and -381A/G) on the promoter region of the MMP-8 gene that are reported to alter the promoter activity and thereby the gene expression. Genotyping through polymerase chain reaction (PCR) and subsequent automatic sequencing was done in 167 patients with bronchiectasis and their age-, sex-matched healthy controls to reveal that only -799C/T is polymorphic among Koreans. In the patient group with bronchiectasis, the frequency of -799C/C, C/T, and T/T genotypes were 41.9%, 49.7%, and 8.4%, respectively. A similar distribution was observed in the control group: C/C (49.7%), C/T (43.1%), and T/T (7.2%) (p=0.36). In subgroup analysis, no significant difference was observed among the patients according to; the extent of disease (p=0.76), colonization of microorganisms (p=0.56), or association of mycobacteria (p=0.17). From these results, we conclude that -799C/T on the promoter region of MMP-8 lacks association with development of bronchiectasis in Koreans.

Surgical resection of nodular ground-glass opacities without percutaneous needle aspiration or biopsy

BackgroundPercutaneous needle aspiration or biopsy (PCNA or PCNB) is an established diagnostic technique that has a high diagnostic yield. However, its role in the diagnosis of nodular ground-glass opacities (nGGOs) is controversial, and the necessity of preoperative histologic confirmation by PCNA or PCNB in nGGOs has not been well addressed.MethodsWe here evaluated the rates of malignancy and surgery-related complications, and the cost benefits of resecting nGGOs without prior tissue diagnosis when those nGGOs were highly suspected for malignancy based on their size, radiologic characteristics, and clinical courses. Patients who underwent surgical resection of nGGOs without preoperative tissue diagnosis from January 2009 to October 2013 were retrospectively analyzed.ResultsAmong 356 nGGOs of 324 patients, 330 (92.7%) nGGOs were resected without prior histologic confirmation. The rate of malignancy was 95.2% (314/330). In the multivariate analysis, larger size was found to be an independent predictor of malignancy (odds ratio, 1.086; 95% confidence interval, 1.001-1.178, p =0.047). A total of 324 (98.2%) nGGOs were resected by video-assisted thoracoscopic surgery (VATS), and the rate of surgery-related complications was 6.7% (22/330). All 16 nGGOs diagnosed as benign nodules were resected by VATS, and only one patient experienced postoperative complications (prolonged air leak). Direct surgical resection without tissue diagnosis significantly reduced the total costs, hospital stay, and waiting time to surgery.ConclusionsWith careful selection of nGGOs that are highly suspicious for malignancy, surgical resection of nGGOs without tissue diagnosis is recommended as it reduces costs and hospital stay.

Clinical Effects of Gemifloxacin on the Delay of Tuberculosis Treatment

Although gemifloxacin has low in vitro activity against Mycobacterium tuberculosis, the effect of gemifloxacin on the delay of tuberculosis (TB) treatment has not been validated in a clinical setting. The study group included patients with culture-confirmed pulmonary TB who initially received gemifloxacin for suspected community-acquired pneumonia (CAP). Two control groups contained patients treated with other fluoroquinolones or nonfluoroquinolone antibiotics. Sixteen cases were treated with gemifloxacin for suspected CAP before TB diagnosis. Sixteen and 32 patients were treated with other fluoroquinolones and nonfluoroquinolones, respectively. The median period from the initiation of antibiotics to the administration of anti-TB medication was nine days in the gemifloxacin group, which was significantly different from the other fluoroquinolones group (35 days). The median times for the nonfluoroquinolone group and the gemifloxacin group were not significantly different. There were no significant differences between the gemifloxacin and other fluoroquinolone group in terms of symptomatic and radiographic improvements. However, the frequency of radiographic improvement in the other fluoroquinolones group tended to be higher than in the gemifloxacin group. Gemifloxacin might be the preferred fluoroquinolone for treating CAP, to alleviate any concerns about delaying TB treatment.

Long-Term Follow-up of Small Pulmonary Ground-Glass Nodules Stable for 3 Years: Implications of the Proper Follow-up Period and Risk Factors for Subsequent Growth

Introduction: How long persistent and stable ground‐glass nodules (GGNs) should be followed is uncertain, although a minimum of 3 years is suggested. Here, we evaluated a group of GGNs that had remained stable for an initial period of 3 years with the aim of determining the proportion of GGNs showing subsequent growth after the initial 3 years and identifying the clinical and radiologic factors associated with subsequent growth. Methods: We retrospectively analyzed patients who underwent further computed tomography (CT) after the initial 3‐year follow‐up period showing a persistent and stable GGN (at least 5 years of follow‐up from the initial CT). Results: Between May 2003 and June 2015, 453 GGNs (438 pure GGNs and 15 part‐solid GGNs) were found in 218 patients. Of the 218 patients, 14 had 15 GGNs showing subsequent growth after the initial 3 years during the median follow‐up period of 6.4 years. For the person‐based analysis, the frequency of subsequent growth of GGNs that had been stable during the initial 3 years was 6.7% (14 of 218). For the nodule‐based analysis, the frequency was 3.3% (15 of 453). In a multivariate analysis, age 65 years or older (OR = 5.51, p = 0.012), history of lung cancer (OR = 6.44, p = 0.006), initial size 8 mm or larger (OR = 5.74, p = 0.008), presence of a solid component (OR = 16.58, p = 0.009), and air bronchogram (OR = 5.83, p = 0.015) were independent risk factors for subsequent GGN growth. Conclusions: For the individuals with GGNs having the aforementioned risk factors, the longer follow‐up period is required to confirm subsequent GGN growth.

Diagnostic Yield of Bronchial Washing Fluid Analysis for Hemoptysis in Patients with Bronchiectasis

Purpose Bronchiectasis is the main cause of hemoptysis. When patients with bronchiectasis develop hemoptysis, clinicians often perform bronchoscopy and bronchial washing to obtain samples for microbiological and cytological examinations. Bronchial washing fluids were analyzed from patients with bronchiectasis who developed hemoptysis, and the clinical impacts of these analyses were examined. Materials and Methods A retrospective observational study of patients who underwent fiberoptic bronchoscopy for hemoptysis in Seoul National University Bundang Hospital, a university affiliated tertiary referral hospital, between January 2006 and December 2010 were reviewed. Among them, patients who had bronchiectasis confirmed by computed tomography and had no definite cause of hemoptysis other than bronchiectasis were reviewed. The demographic characteristics, bronchoscopy findings, microbiological data, pathology results and clinical courses of these patients were retrospectively reviewed. Results A total of 130 patients were reviewed. Bacteria, non-tuberculous mycobacteria (NTM), and Mycobacterium tuberculosis were isolated from bronchial washing fluids of 29.5%, 21.3%, and 0.8% patients, respectively. Suspected causal bacteria were isolated only from bronchial washing fluid in 19 patients, but this analysis led to antibiotics change in only one patient. Of the 27 patients in whom NTM were isolated from bronchial washing fluid, none of these patients took anti-NTM medication during the median follow-up period of 505 days. Malignant cells were not identified in none of the patients. Conclusion Bronchial washing is a useful method to identify microorganisms when patients with bronchiectasis develop hemoptysis. However, these results only minimally affect clinical decisions.

Significance of fractional exhaled nitric oxide in chronic eosinophilic pneumonia: a retrospective cohort study.

BackgroundChronic eosinophilic pneumonia (CEP) is characterized by chronic eosinophilic infiltration of the lung. It is dramatically responsive to corticosteroid treatment, but symptoms and radiopacities recur frequently after tapering or discontinuing the medication. Fractional exhaled nitric oxide (FeNO) is a well-known noninvasive marker of eosinophilic airway inflammation. The aim of this retrospective cohort study was to investigate the relationships of FeNO with peripheral eosinophilia and the clinical state of CEP and its validity for predicting exacerbation of CEP.MethodsStandard clinical and laboratory parameters, peripheral eosinophil percentage and count, and FeNO level were measured in 18 patients with CEP at several assessment points over 1xa0year.ResultsFeNO level was positively correlated with peripheral eosinophil count (ru2009=u20090.341, Pu2009=u20090.005) and percentage (ru2009=u20090.362, Pu2009=u20090.003). The median (IQR) FeNO levels were 79 (41–88) and 35 (26–49) ppb in uncontrolled (13/74 measurements) and controlled (61/74 measurements) CEP, respectively (Pu2009=u20090.010). The FeNO level of 66.0xa0ppb showed the largest area under the curve (0.835) for predicting exacerbation of CEP (sensitivityu2009=u20090.80, specificityu2009=u20090.84).ConclusionFeNO may be useful for monitoring eosinophilic parenchymal inflammation and determining the appropriate corticosteroid dose in CEP.