Kentaro Wakamatsu

Interleukin-8 participates in angiogenesis in non-small cell, but not small cell carcinoma of the lung

We examined interleukin-8 (IL-8) production in 17 lung cancer cell lines, IL-8 expression in tumor specimens and IL-8s contribution to tumor-induced angiogenesis in vivo. Eight of 13 non-small cell lung cancer cell lines constitutively produced high levels of IL-8. Four small cell lung cancer cell lines produced little or no IL-8. Immunohistochemical analysis of transbronchial biopsy specimens revealed IL-8 staining within adenocarcinomas (22/32), squamous cell carcinomas (12/21) and large cell carcinomas (2/3), but not within most small cell carcinomas (1/22). Anti-IL-8 antisera blocked tumor angiogenesis by two IL-8 producing cell lines in a mouse model.

Immunohistochemical expression of glutathione S-transferase-π can predict chemotherapy response in patients with nonsmall cell lung carcinoma

Resistance to chemotherapy agents is a major problem in the treatment of patients with nonsmall cell lung carcinoma (NSCLC). Recent studies have indicated that glutathione S‐transferase‐π (GST‐π) may play an important role in the resistance of cancer cells to alkylating agents, including cisplatin compounds.

Rapid decrease in forced vital capacity in patients with idiopathic pulmonary upper lobe fibrosis

BACKGROUND We are occasionally presented with patients with unclassifiable interstitial pneumonia of unknown etiology. Idiopathic pulmonary upper lobe fibrosis (IPUF) does not fit any of the currently defined subsets of idiopathic interstitial pneumonias (IIPs). This study was performed to examine clinical, functional, and pathological characteristics of IPUF. METHODS We present 9 cases of histologically confirmed IPUF. The clinical and histological characteristics of the 9 patients were evaluated. The baseline respiratory function of all patients was measured. There were 7 patients whose forced vital capacity (FVC) had been monitored for at least a year who were selected to quantify the yearly decline in FVC. RESULTS All patients were slender, with a body mass index of 16.0-19.8 kg/m(2). Seven patients had a history of pneumothorax. Six patients died 1.8 to 5.7 years after the onset of the first symptoms. Fundamental histological features were intraalveolar collagen deposition and densely packed elastic fibers in the subpleural areas. These findings are the same as those seen in pleuroparenchymal fibroelastosis. However, the visceral pleura was thickened with dense collagen in only 2 patients, and pleural thickening was localized, if present, in the remaining 7 patients. Ventilatory impairment was also a characteristic. The time course decline of FVC was rapid and almost linear. The median yearly decline in FVC was -20.3% (range, -7.7% to -26.5%), which was more rapid than that reported for chronic fibrosing interstitial pneumonias such as idiopathic pulmonary fibrosis. CONCLUSIONS IPUF is a unique pulmonary fibrosis that results in rapid deterioration of ventilatory function and poor prognosis.

The thoracic cage becomes flattened in the progression of pleuroparenchymal fibroelastosis

To the Editor: Pleuroparenchymal fibroelastosis (PPFE) was first reported by Frankel et al. [1]. PPFE can occur without any aetiology or underlying diseases (idiopathic PPFE), or with underlying diseases or conditions. Idiopathic PPFE has been listed as one of the rare idiopathic interstitial pneumonias (IIPs) in the revised international multidisciplinary consensus classification of IIPs [2]. The natural history of PPFE is variable, some are slowly progressive and others sometimes show rapid deterioration resulting in poor prognosis, like idiopathic pulmonary fibrosis (IPF). Idiopathic pulmonary upper lobe fibrosis (PULF), first proposed by Amitani et al. [3], is currently considered to be almost identical to idiopathic PPFE [1, 4, 5], which is now globally accepted as a representative nomenclature for this disorder. Therefore, we use the term PPFE to describe the same disease as PULF. Amitani et al. [3] recognised a characteristic constitution in patients with PPFE: they are slender and their thoracic cage is flattened, i.e. the ratio of the anteroposterior diameter of the thoracic cage (APDT) to the transverse diameter of the thoracic cage (TDT) is abnormally lower than in normal populations. Herein, we have provisionally named this deformity of the thoracic cage as “flat chest”. Other investigators have also noticed this deformity in idiopathic PPFE [6–8]. Flat chest may result from a congenital disposition or …

Heterogeneous clinical features in patients with pulmonary fibrosis showing histology of pleuroparenchymal fibroelastosis

BACKGROUND The histological pattern of pleuroparenchymal fibroelastosis (PPFE) is well defined, but its clinical features remain unclear. METHODS We retrospectively examined the predominantly involved lung-fields (based on abnormal opacities on computed tomography [CT] images), and the initial value and annual decline of respiratory function in patients with pulmonary fibrosis presenting with histologically confirmed PPFE. RESULTS Thirteen female and nine male subjects were included. Eleven interpreters independently analyzed 231 CT image series. One-third of the CT series (78/231) was interpreted as demonstrating equal involvement of the upper and lower lung fields, i.e., six out of 21 patients had equal involvement of the upper and lower lung fields, based on a majority decision of the interpreters. The residual volume/total lung capacity (RV/TLC) was increased and correlated inversely with forced vital capacity (FVC) at the initial measurement. FVC followed two patterns of decline over time: a gradual decline over a follow-up period of more than 6 years (-55mL/year, R(2)=0.799), and a relatively rapid decline over a shorter period (-364mL/year, R(2)=0.855) as determined by mixed-effect linear regression. CONCLUSIONS The predominantly involved sites seen on CT images of PPFE were not limited to the upper lobes. In some cases, upper lung fields were predominantly involved, but in other cases, both upper and lower lung fields were equally involved. Two patterns of FVC decline exists: a rapid decline over a short period and a slow decline over a longer period, suggesting that the disease follows a heterogeneous clinical course.

Retrospective analysis of nursing and healthcare-associated pneumonia: Analysis of adverse prognostic factors and validity of the selection criteria

BACKGROUND Nursing and healthcare-associated pneumonia (NHCAP) is a relatively new condition that was recently defined by the Japanese Respiratory Society. Previous reports and guidelines have not thoroughly investigated the adverse prognostic factors and validity of the selection criteria for NHCAP. The purpose of this research was to clarify the adverse prognostic factors of NHCAP and investigate the validity of the selection criteria with respect to patient deaths. METHODS We retrospectively analyzed 418 patients with pneumonia who were admitted to our hospital between January 2009 and December 2011. RESULTS We analyzed 215 (51.4%) cases of community-acquired pneumonia (CAP) and 203 (48.6%) cases of NHCAP. NHCAP patients were generally older and had poorer performance status (PS), more complications, and higher levels of mortality than CAP patients. In both groups, the most common causative pathogen was Streptococcus pneumoniae. A multivariate analysis of NHCAP revealed that age ≥ 80 years, oxygen saturation (SpO2) ≤ 90%, and methicillin-resistant Staphylococcus aureus (MRSA) infection to be independent factors associated with mortality. Of the NHCAP selection criteria, a PS ≥ 3 and a hospitalization history within the past 90 days were adverse prognostic factors in the broad community-acquired pneumonia category (CAP+NHCAP), according to a multivariate analysis. Univariate analysis revealed that admission to an extended care facility or nursing home was associated with death. CONCLUSIONS Our results demonstrated that age ≥ 80 years, SpO2 ≤ 90%, and MRSA infection were adverse prognostic factors for NHCAP patients. Furthermore, we confirmed the validity of the NHCAP selection criteria.

Granulocyte-colony stimulating factor promotes invasion by human lung cancer cell lines in vitro

The effects of exogenous and endogenous granulocyte colony-stimulating factor (G-CSF) on invasion by cancer cells were studied, using lung cancer cell lines that produce G-CSF (NCI-H157) and lines that do not (PC-9 and NCI-H23). The invasive capacity of NCI-H157 cells was 26- to 27-fold higher than that of PC-9 and NCI-H23 cells. The invasiveness of PC-9 cells was stimulated by exogenous G-CSF, while that of NCI-H157 cells was not. Antibodies against G-CSF blocked the stimulation of PC-9 cell invasiveness by exogenous G-CSF. Anti G-CSF antibodies also inhibited invasion by NCI-H157 cells in the absence of exogenous G-CSF. These results suggest that endogenous and exogenous G-CSF both stimulate invasion by lung cancer cells.

Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias

BackgroundIt is difficult to predict survival in patients with idiopathic pulmonary fibrosis. Recently, several proteins, such as surfactant protein (SP) and KL-6, have been reported to be useful biologic markers for prediction of prognosis for interstitial pneumonias. It is not clear whether there is any relationship between expression of these proteins in regenerative/hyperplastic alveolar epithelial cells and prognosis of idiopathic interstitial pneumonias (IIPs).ObjectivesThis study aimed to elucidate the clinical significance of the expression of such lung secretory proteins as SP-A and KL-6 in lung tissues of patients with IIPs.MethodsWe retrospectively investigated the immunohistochemical expression of SP-A, KL-6, cytokeratin (CK), and epithelial membrane antigen (EMA) in alveolar epithelial cells in lung tissues obtained from surgical lung biopsy in 43 patients with IIPs, and analyzed the correlation between expression of these markers and the prognosis of each IIP patient. CK and EMA were used as general markers for epithelial cells.ResultsIn patients with usual interstitial pneumonia (UIP), the ratio of SP-A positive epithelial cells to all alveolar epithelial cells (SP-A positive ratio) in the collapsed and mural fibrosis areas varied, ranging from cases where almost all alveolar epithelial cells expressed SP-A to cases where only a few did. On the other hand, in many patients with nonspecific interstitial pneumonia (NSIP), many of the alveolar epithelial cells in the diseased areas expressed SP-A. The SP-A positive ratio was significantly lower in patients who died from progression of UIP than in patients with UIP who remained stable or deteriorated but did not die. In NSIP patients, a similar tendency was noted between the SP-A positive ratio and prognosis.ConclusionsThe results suggest that the paucity of immunohistochemical SP-A expression in alveolar epithelial cells in diseased areas (i.e. regenerative/hyperplastic alveolar epithelial cells) may predict a worse prognosis for patients with IIPs, especially patients with UIP. A prospective study is needed to confirm these results.

Recurrent Chest Opacities in a Patient with Thromboembolic Pulmonary Hypertension

We describe a 42-year-old man with chronic thromboembolic pulmonary hypertension associated with protein S deficiency. He presented with unusual roentgenographic findings of migratory pulmonary infiltrates.

Prognostic value of serial serum KL-6 measurements in patients with idiopathic pulmonary fibrosis

BACKGROUND The prognostic significance of serial measurements of serum KL-6 levels in patients with idiopathic pulmonary fibrosis (IPF) is unclear; hence, it was assessed in this study. METHODS Medical records of 66 patients with IPF, who were not treated with pirfenidone prior to enrollment, were retrospectively reviewed for information on clinical progress, forced vital capacity (FVC), survival, and serum KL-6 levels. We assessed initial serum levels of KL-6, serial changes in serum KL-6 levels, yearly decline in FVC (ΔFVC), and the rate of decline (%ΔFVC). RESULTS Patients with increased serum KL-6 levels during follow-up had a significantly steeper decline in ΔFVC than those with no KL-6 increase (-201 vs. -50.7ml/year; p=0.0001). Patients with both initial serum KL-6 ≥1000U/ml and serial increases in serum KL-6 had the steepest decline, while those with both initial serum KL-6 <1000ml and no serial increases in KL-6 had the least decline in ΔFVC and %ΔFVC. Relative to the non-increased KL-6 group, survival in the increased KL-6 group tended to be poorer (p=0.0530). Patients with both initial serum KL-6 values <1000U/ml and no serial increase in KL-6 had more favorable prognoses than those with serial increases in KL-6 or initial serum KL-6 values ≥1000U/ml (p<0.0044). Prognosis was significantly poorer in patients with serial KL-6 changes >51.8U/ml/year than in those with serial KL-6 changes <51.8U/ml/year (p=0.0009). CONCLUSION Thus, serial serum KL-6 measurements can be useful for assessing prognosis in patients with IPF.