Serial change in serum biomarkers during treatment of Non-HIV Pneumocystis pneumonia.

BACKGROUND: For patients with non-human immunodeficiency virus (HIV) Pneumocystis pneumonia (PCP), data are limited on serial changes in serum biomarkers and the correlations with clinical outcomes. OBJECTIVE: This study evaluated serial change in serum biomarkers and clinical outcomes of non-HIV PCP. METHODS: We retrospectively reviewed data from 63 patients treated for non-HIV PCP at Toho University Omori Medical Center. The patients were classified as survivors and nonsurvivors on the basis of 60-day PCP mortality. The groups were compared for clinical course and levels of serum biomarkers (ß-D glucan, Krebs von den Lungen-6 antigen [KL-6], and surfactant protein-D [SP-D]), which were measured at baseline, and 7 days and 14 days after starting treatment. In addition, serial changes in serum biomarkers were analyzed in survivors and nonsurvivors. RESULTS: There were 14 PCP nonsurvivors and 49 survivors. Biomarker values were not different between groups at baseline. At 7 and 14 days after starting treatment, the proportions of patients with elevated ß-D glucan and KL-6 did not significantly differ between groups; however, the proportion of patients with elevated SP-D was significantly lower among survivors than among nonsurvivors (57.1% vs. 100%, p = 0.009; 30% vs. 100%, p < 0.001; respectively). SP-D on day 14 was significantly lower than that at baseline among survivors (99.6 [61.0-190.3] vs. 156 [100.8-283.5]; p = 0.045) but significantly higher among nonsurvivors (974 [744.5-1565] vs. 317 [211-448]; p = 0.03). CONCLUSION: Serum SP-D value continues to increase after failure of treatment for non-HIV PCP and may thus be associated with outcomes for non-HIV PCP patients.

Characteristics of patients with bronchoscopy-diagnosed pulmonary Mycobacterium avium complex infection.

BACKGROUND: We occasionally treat patients with clinically suspected pulmonary Mycobacterium avium complex (MAC) infection and negative MAC culture on bronchoscopy. OBJECTIVE: This study aimed to investigate the usefulness of bronchoscopy in patients with suspected MAC lung disease with nodular bronchiectasis on chest computed tomography (CT) and to clarify the clinical characteristics of these patients. METHODS: We reviewed the records of 71 patients with clinically suspected pulmonary MAC infection on chest CT who underwent bronchoscopy. The patients were classified on the basis of MAC culture result, and their clinical characteristics were compared. RESULTS: MAC was detected in 33 of the 71 (46.5%) patients (positive group), and 35 (49.3%) were culture-negative for nontuberculous mycobacteria (NTM) (negative group). NTM other than MAC were detected in 3 of 71 (4.2%) patients. MAC was not detected in 14 of 38 (36.8%) patients positive for GPL core IgA antibody. Patients in the positive group had a higher body mass index (20.1 ± 3.4 vs 18.5 ± 2.9 kg/m2; p = 0.047) and positive rate for GPL core IgA antibody (72.7% vs 40%; p = 0.006) and a lower chronic obstructive pulmonary disease assessment test score (6.6 ± 6.6 vs 11.7 ± 8.5; p = 0.016) and rate of positive culture for Pseudomonas aeruginosa or Haemophilus influenzae (12.1% vs 45.7%; p = 0.003), as compared with the negative group. CONCLUSION: Bronchoscopy is useful for diagnosis of MAC in patients who cannot be diagnosed by sputum examination. In addition, patients with pulmonary MAC disease had less severe subjective symptoms and weight loss than did those with a negative MAC culture on bronchoscopy.

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and ß-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis.

We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a ß-d-glucan (ßDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and ßDG testing of BALF, respectively. The sensitivity and specificity of the GM test, ßDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and ßDG tests had the highest diagnostic odds ratio. The combination of the GM and ßDG tests on BALF was more useful than any single test for diagnosing CPA.

Effectiveness of combined therapy with pirfenidone and inhaled N-acetylcysteine for advanced idiopathic pulmonary fibrosis: a case-control study.

BACKGROUND AND OBJECTIVE: Treatment with pirfenidone may slow the decline in vital capacity and increase progression-free survival (PFS) in idiopathic pulmonary fibrosis (IPF). The effects of combination therapy with inhaled N-acetylcysteine (NAC) and pirfenidone are unclear. We assessed the effects of this combination therapy in patients with advanced IPF. METHODS: Patients with a diagnosis of advanced IPF (Japanese Respiratory Society stage III/IV IPF) and a relative decline in forced vital capacity (FVC) of ≥ 10% within the previous 6 (± 2) months were enrolled. Outcomes were evaluated in a 12-month follow-up pulmonary function test. Treatment was considered ineffective if the decline in FVC was ≥ 10% and effective if the decline was <10%. We compared clinical characteristics, effectiveness and PFS between patients receiving inhaled NAC plus pirfenidone (n = 24) and those receiving pirfenidone alone (control; n = 10). RESULTS: Data from 34 IPF patients (age range, 59-82 years) were analysed. At the 12-month follow-up examination, treatment was deemed effective in 8 of 17 (47%) patients receiving NAC plus pirfenidone and in 2 of 10 (20%) receiving pirfenidone alone. The annual rate of change in FVC was -610 mL in the NAC plus pirfenidone group and -1320 mL in the pirfenidone group (P < 0.01). PFS was longer (304 days) in the NAC plus pirfenidone group than in the pirfenidone group (168 days; P = 0.016). CONCLUSIONS: Combination treatment with inhaled NAC and oral pirfenidone reduced the rate of annual FVC decline and improved PFS in patients with advanced IPF.

Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone.

BACKGROUND AND OBJECTIVE: The results of studies examining the outcome and the factors predicting prognosis in combined pulmonary fibrosis and emphysema (CPFE) have so far been contradictory. Our objective was to determine prognosis and the prognostic factors for CPFE. METHODS: Of 108 consecutive idiopathic pulmonary fibrosis (IPF) patients admitted to our hospital, 46 were diagnosed as having CPFE and 62 patients diagnosed as having IPF alone. We retrospectively compared the clinical features between these two groups. RESULTS: Annual increase in estimated systolic pulmonary arterial pressure (esPAP) was significantly greater in CPFE patients, and survival time was significantly lower. Moreover, the prognosis was unfavourable regardless of the presence of lung cancer. The multivariate Cox proportional hazard regression model showed that predictive factors were an increase in the modified Medical Research Council dyspnoea score and esPAP ≥ 30.4 mm Hg. We classified patients into the following four groups: CPFE with high esPAP (esPAP ≥ 30.4 mm Hg), CPFE with normal esPAP (esPAP < 30.4 mm Hg), IPF alone with high esPAP and IPF alone with normal esPAP. Survival in the CPFE with high esPAP group was significantly worse than that in the other three subgroups. Furthermore, CPFE with the paraseptal type of emphysema and high esPAP had the worst prognosis. CONCLUSIONS: This study demonstrated that the prognosis of CPFE is significantly worse than that of IPF alone. In particular, CPFE with paraseptal emphysema associated with high esPAP has an extremely poor prognosis.

Clinical evaluation of severe asthma attacks requiring tracheal intubation and mechanical ventilation.

BACKGROUND: Although the number of patients requiring hospitalization due to asthma attacks has decreased over the years, there are many who still require hospitalization for tracheal intubation and mechanical ventilation following a severe asthma attack. Therefore, we evaluated the characteristics of patients with asthma who required tracheal intubation and mechanical ventilation in our hospital. METHODS: We evaluated 20 patients who had severely exacerbated asthma, requiring tracheal intubation and mechanical ventilation. An evaluation was made based on their smoking history, the number of days from the onset of the asthma attack to admission, the level of asthma control, treatments before presenting to our hospital, the frequency of hospital visits, the reason for tracheal intubation and mechanical ventilation, and outcome. RESULTS: Of the 20 patients with asthma 13 were men and 7 women, with a mean age of 48.7 years. The characteristics of patients who required tracheal intubation and mechanical ventilation were as follows: (1) smokers, (2) not taking or irregularly taking medication, (3) using inhaled short-acting beta(2)agonist (SABA) alone as needed, and (4) not using inhaled corticosteroids (ICS). CONCLUSIONS: Our findings suggest that treatment mainly using ICS, in addition to increased awareness of the dangers of asthma among the patients themselves, are important in preventing severe asthma attacks requiring tracheal intubation and mechanical ventilation.

[Human adjuvant disease which developed after silicone augumentation mammoplasty].

A 73-year-old woman was admitted to our hospital to evaluate mediastinal lymphadenopathy found on a chest CT scan. She had undergone mammoplasty with silicone augmentation 50 years previously and had the implants removed 5 years previously. Biopsied specimens of a mediastinal lymph node under video-assisted thoracic surgery (VATS) revealed multiple hyalinized non-caseating epithelioid cell granulomas and multinucleated giant cells and foamy macrophages containing some vacuoles. According to these clinicopathological findings, we diagnosed human adjuvant disease which developed after mammoplasty with silicone augmentation. In cases of mammoplasty, we should pay attention to the complication of chronic thoracic disorder as a human adjuvant disease.

[Case of pemetrexed-induced acute lung injury].

A 65-year-old man was admitted with dyspnea. Chest radiograph showed left pleural effusion and chest CT scan revealed multiple left pleural masses. The diagnosis of malignant pleural mesothelioma was made by CT-guided needle biopsy. He received the combination chemotherapy with pemetrexed and carboplatin. The day after initiating chemotherapy, he had fever and dyspnea. Chest CT scan showed diffuse ground glass opacities mainly in the right lung, suggestive of drug-induced interstitial pneumonia. Corticosteroid pulse therapy was started, but he died of respiratory failure 10 days after beginning chemotherapy. This is apparently the first reported case of pemetrexed-induced acute lung injury.

[Azithromycin-induced diffuse alveolar hemorrhage].

Azithromycin (AZM) is widely used for the treatment of respiratory infection. Macrolides are generally well tolerated and adverse reactions are extremely rare. A 78-year-old man was treated with AZM for upper respiratory infection in November 2007. He developed bloody sputum at 5 days after AZM administration. Chest X-ray and CT images revealed diffuse ground glass opacities in the bilateral lung fields. Bronchoalveolar lavage demonstrated bloody fluid. The clinical symptoms and CT image improved after the corticosteroid therapy. His past history revealed that he also developed similar clinical symptoms and radiological features after treatment with AZM for upper respiratory infection at another hospital in October 2006. At that time, his condition improved after the administration of corticosteroid under a diagnosis of interstitial lung disease of unknown etiology. Finally, we diagnosed recurrent alveolar hemorrhage caused by re-administration of AZM. This is apparently the first reported case of AZM-induced diffuse alveolar hemorrhage.

[An autopsied case of mucinous bronchioloalveolar carcinoma associated with multiple thin-walled cavities].

A 82-year-old man was found to have mucinous bronchioloalveolar carcinoma associated with a cavity 10-cm in size in the right lower lobe, and he underwent a surgical lobectomy in April 2005 (pT2N0M0). Seven months after the surgery, chest images showed multiple metastases with thick-walled cavities in bilateral lung fields. The serial HRCT showed that thick-walled cavity lesions transformed into thin-walled cystic cavities associated with decreasing serum CEA levels. The patient's condition was good with best supportive care for 24 months from the time of recurrence. Subsequent progression of the thick-walled cavities into thin-walled cavities, was acompanied by re-elevation of serum CEA levels, and he died of respiratory failure 5 months after re-exacerbation. Macroscopic findings at autopsy showed multiple cavities in both lungs. Microscopic findings of the right lung showed desquamative mucinous bronchioloalveolar carcinoma cells lining the thick-walled cavity surface, and a single layer of tumor cells proliferating in the thin-walled cavity surface. Tumor cells with excessive mucus and necrosis were observed in the thick-walled cavities. It is suggested that thick-walled cavities were formed as a result of avascular necrosis and destruction of the pulmonary alveoli by excessive mucus, and thin-walled cavities were formed as a result of a check-valve mechanism.

Clinical importance of Bcl-2-like 11 deletion polymorphism in idiopathic pulmonary fibrosis.

BACKGROUND: Reactive oxygen species (ROS) can play a role in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF) by contributing to epithelial damage. Bcl-2-like 11 (BIM) is involved in the generation of ROS via forkhead box O3 (FOXO3), and a BIM deletion polymorphism related to apoptosis has been reported to be specific to Asians. Here we examine the clinical features of IPF in patients with BIM deletion polymorphism. METHODS: In this single-center retrospective study, we reviewed the medical records of 63 patients with IPF who were treated at our hospital from January 2006 through April 2018. Patients with and without BIM deletion polymorphism were compared in relation to clinical characteristics, pulmonary function test results, frequency of acute exacerbation (AE)-IPF, and redox status [including oxidized glutathione (GSSG), reduced glutathione (GSH), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-isoprostane (8-iso)] at baseline and at 1 and 2 years after treatment. RESULTS: No fatal AE-IPF occurred in patients with BIM deletion polymorphism (0% vs. 36.4% of polymorphism-negative cases; P=0.038). Change in forced vital capacity from baseline (ΔFVC) at 2 years was significantly lower in patients with the BIM deletion polymorphism than in those without the polymorphism (‒0.42±0.50 vs. ‒0.88±0.83 L, respectively; P=0.045). Total blood glutathione (tGSH) was significantly higher in patients with the deletion polymorphism than in those without the polymorphism (988±48.3 vs. 858±25.8 µM, respectively; P=0.042). 8-iso was significantly lower in the former group (246.1±81.6 vs. 400.9±334.1 pg/mL, respectively; P=0.022). CONCLUSIONS: IPF patients with BIM deletion polymorphism had a good redox balance and may thus have a better clinical outcome than patients without this polymorphism.

Pathophysiological study of chronic necrotizing pulmonary aspergillosis.

The aim of the present study is to define the characteristics of the clinical and histopathological features of chronic necrotizing pulmonary aspergillosis (CNPA) cases with severe hemoptysis. We conducted a histological study of three patients clinically diagnosed as having CNPA who had hemoptysis for 5 years. A tuberculosis sequelae was found as the underlying disorder in all three cases. All patients had fever, general fatigue, and hemoptysis, and their chest computed tomographic images revealed fungus balls, cavity wall thickening, consolidation surrounding the cavity, and satellite foci. All had been treated with anti-fungal drugs and corticosteroids. However, all patients died from respiratory failure due to massive hemoptysis. Histopathological examination revealed that the cavity wall consisted of three layers comprised of necrotic, granulation, and fibrous tissue layers. Aspergilli were found in both the fungus ball and necrotic tissue comprising the inner layer of the cavity. In addition, most of the vessels were incompletely occluded with thrombosis and were necrotic, as well as showing local invasion of Aspergilli. Surgical intervention should be considered as a prior procedure for CNPA patients, because vessels at the cavity wall, whether occluded completely or incompletely, are usually necrotic and/or show local invasion of Aspergilli.

[A case of pulmonary alveolar hemorrhage caused by methylergometrine].

A 35-year-old woman underwent endometrial curettage for suspicion of miscarriage. A few minutes after intravenous injection of methylergometrin (0.2 mg) for inducing uterine contraction, blood gas analysis revealed severe hypoxemia. Chest CT showed diffuse ground-glass opacities in both lung fields and consolidation in the right lower lobe. Bronchoscopy revealed blood coagulation in the right bronchus intermedius. Bronchoalveolar lavage fluid showed fresh blood-like fluid containing hemosiderin-laden macrophages. We diagnosed pulmonary alveolar hemorrhage associated with pulmonary edema. Although we analyzed the possible causes of alveolar hemorrhage such as pulmonary thromboembolism, collagen disease, ANCA-related angitis and malignant disease, there were no underlying systemic diseases. It seems likely that contraction of the blood vessels caused by methylergometrin caused the increased pulmonary arterial and wedge pressure which led to pulmonary edema and alveolar hemorrhage. We believe this is the first reported case of pulmonary alveolar hemorrhage caused by methylergometrin, confirmed by bronchoscopy.

New risk scoring system for predicting acute exacerbation of interstitial pneumonia after chemotherapy for lung cancer associated with interstitial pneumonia.

BACKGROUND: Fatal acute exacerbation (AE) of interstitial pneumonia (IP) sometimes occurs after chemotherapy for lung cancer. We developed and evaluated a scoring system for assessing AE risk after chemotherapy in patients with lung cancer associated with IP. METHODS: A review of medical records identified 109 patients with primary lung cancer associated with IP who had received chemotherapy at our center during the period from June 2007 through September 2017. We developed a model to score AE risk after chemotherapy in this patient group, and logistic regression was used to evaluate the model. RESULTS: The anticancer agent score was determined by using AE rates reported in past studies. The risk score was calculated with the following formula: (1 × anticancer agent score) + (3 × smoking history [>70 pack-years]) + (4 × history of steroid use) + (3 × %diffusing capacity of lung carbon monoxide [<50%]). Patients were then classified into three groups. The AE incidence rate was 12% for a risk score of 0-5, 47% for a score of 6-10, and 66.7% for a score of ≥11. The sensitivity of the scoring system was 78.6% and specificity was 67.8%. CONCLUSIONS: The present scoring system was able to identify IP patients at high risk for AE after chemotherapy for lung cancer associated with IP.

PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma.

Molecular mechanisms of programmed death-ligand 1 (PD-L1) mRNA expression and roles of apoptosis and biomarkers are poorly understood in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients. Thirty-three patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 16, L858R in 15, G719C in 2 patients) treated with gefitinib were studied. PD-L1 mRNA expression of formalin-fixed paraffin-embedded paratumoral and intratumoral tissues was quantified by PCR. Correlations of PD-L1 mRNA expression with BIM, p53 upregulated modular of apoptosis (PUMA), human epidermal growth factor receptor 2 (HER2), mesenchymal-epithelial transition (MET), EGFR, and vascular endothelial growth factor A (VEGFA) were determined. Eleven of the 33 patients (33.3%) and 14/33 patients (42.4%) expressed intratumoral and paratumoral PD-L1 mRNA, respectively. Patients with intratumoral PD-L1 mRNA expression had significantly higher BIM and lower VEGFA expression compared with paratumoral PD-L1 mRNA patients (P=0.049, P=0.009). PD-L1 mRNA expression was not associated with the expression of PUMA, HER2, EGFR and MET but was positively correlated with BIM expression (r=0.41, P=0.017) and inversely correlated with VEGFA expression (r=-0.33, P=0.043). Patients with intratumoral PD-L1 mRNA expression had significantly shorter median progression-free survival (PFS) after gefitinib therapy compared with no PD-L1 expression (255 vs. 732 days, respectively; P=0.032). Thus, PD-L1 mRNA expression in EGFR-mutant lung adenocarcinoma was associated with BIM and VEGFA mRNA expression and with shorter PFS after gefitinib therapy.

[Clinicopathological study of invasive pulmonary aspergillosis complicated by leukemia].

OBJECTIVE: We assessed the clinicopathological features of invasive pulmonary aspergillosis. PATIENTS AND METHODS: We conducted chest radiograph-pathologic correlations in 8 cases with invasive pulmonary aspergillosis diagnosed at autopsy. RESULTS: Subjects were 4 men and 4 women with a mean age of 57.4 years and all having leukemia as an underlying hematological disorder. All had been treated with anticancerous drugs and corticosteroids. Histopathologically, coagulation necrosis with marginal hemorrhage and agranulocytosis were observed in 6 whose initial abnormal shadows in chest X-ray appeared during the neutropenic phase less than 500/microL. In contrast, numerous infiltration of neutrophils and colliquation necrosis at the center of lesions were observed in 2 whose initial abnormal shadows in chest X-ray appeared having more than 500/microL of neutrophils in the peripheral blood.

[An autopsy case of obliterative bronchiolitis associated with Stevens-Johnson syndrome].

We reviewed an autopsied 27-year-old female with obliterative bronchiolitis associated with Stevens-Johnson syndrome. She had a history of Stevens-Johnson syndrome at age 10 years old and was treated with corticosteroids. Two months after the onset of dermatitis, the patient complained of dyspnea on exertion. The chest radiograph showed hyperinflation, and pulmonary function tests revealed obstructive impairment. The respiratory failure progressed due to respiratory tract infection and pneumothorax. She underwent thoracoscopic cyst surgery for right pneumothorax. Although the patient was clinically diagnosed as having obliterative bronchiolitis and received corticosteroids therapy and mechanical ventilation, she died of progressive respiratory failure 17 years after the onset of Stevens-Johnson syndrome. On autopsy, the macroscopic appearance of both lungs showed multiple white nodules in the centrilobular lesion corresponding to the obliteration of the small bronchioli. The microscopic appearance revealed constrictive bronchiolitis in the membranous bronchioli of both lungs associated with secondary bronchiectasis caused by superimposed infection.

Characterization and evaluation of a novel immunochromatographic assay for pharyngeal Mycoplasmapneumoniae ribosomal protein L7/L12 antigens.

Point-of-care testing for Mycoplasma pneumoniae infection may be ideal and useful because significant numbers of the cases will be seen as outpatients. Recently, a new immunochromatographic method (ICM) targeting M. pneumoniae ribosomal protein L7/L12 (RP-L7/L12) in pharyngeal swabs became available in Japan, although clinical data and basic information regarding efficacy and characterization of this ICM are limited. The present study examined the fate of M. pneumoniae RP-L7/L12 during in vitro growth and the correlation between M. pneumoniae concentration in clinical specimens and the sensitivity of the ICM test. The usefulness of the ICM was investigated in patients suspected of having M. pneumoniae pneumonia and upper respiratory tract infection (137 children and 39 adults). The limit of detection for the ICM test was 1.1×104 c.f.u. ml-1 of M. pneumoniae. Bacterial production of RP-L7/L12 correlated positively with the viable M. pneumoniae concentration in vitro; antigen was then degraded in culture broth, with an in vitro half-life of approximately 2 days. Five other Mycoplasma spp. and 14 representative respiratory pathogens were ICM assay negative at bacterial concentrations of 106 c.f.u. ml-1. The clinical sensitivity and specificity of the ICM assay were 57.1 % (20/35) and 92.2 % (130/141), respectively, in comparison with bacterial culture. Clinical specimens containing ≥106 c.f.u. ml-1 of M. pneumoniae burden were ICM positive in 13 of 18 cases (72.2 %). The ICM is a poorly sensitive but reasonably specific means for detecting M. pneumoniae infections.

Usefulness of nanofluidic digital PCR arrays to quantify T790M mutation in EGFR-mutant lung adenocarcinoma.

AIM: The present pilot study assessed the usefulness of nanofluidic digital polymerase chain reaction (PCR) arrays in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma after tyrosine kinase inhibitor (TKI) resistance. PATIENTS AND METHODS: We enrolled 12 patients with primary lung adenocarcinoma with sensitive EGFR mutation-confirmed T790M status by re-biopsy after TKI resistance. Nanofluidic digital PCR arrays were used to quantify T790M in genomic DNA from the pre-treatment primary site and in serum cell-free DNA (cfDNA). RESULTS: On digital PCR, quantified T790M at the pre-treatment primary site was higher in re-biopsy-positive T790M patients (n=4) than in re-biopsy-negative patients (n=8) (0.78%±0.36% vs. 0.07%±0.09%, p<0.01). T790M at the pre-treatment primary site correlated with progression-free survival (PFS) after gefitinib therapy (r=0.67, p=0.016). CONCLUSION: Use of digital PCR to quantify T790M at the primary site of EGFR-mutant lung adenocarcinoma predicted T790M emergence in re-biopsies after TKI resistance and PFS after gefitinib therapy.

An anomalous unilateral single pulmonary vein associated with a bone morphogenetic protein receptor II gene mutation.

Anomalous unilateral single pulmonary vein (AUSPV), a rare congenital anomaly, is associated with an aberrant course but normal drainage, and resembles arteriovenous malformation (AVM). We treated a 26-year-old man with AUSPV in the right lung and an anomalous segmental pulmonary vein in the left lung. CT revealed a tortuous vascular shadow with an enhancement pattern identical to that of the pulmonary vein, suggesting AUSPV. This was confirmed by pulmonary angiography. Although pulmonary AVMs were not detected on angiography, microvascular AVMs could not be excluded because delayed bubbles appeared on contrast echocardiography. A genetic examination revealed a missense mutation of BMPR2.