Possible Serological Markers to Predict Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

Background and objectives: Idiopathic pulmonary fibrosis (IPF) has a particularly poor prognosis, and most IPF-related deaths are due to acute exacerbation (AE) of this condition. Few reports about biomarkers to predict prognosis of AE-IPF have been published since the release of the new AE-IPF criteria in 2016. The present study investigated relationships between serological markers and in-hospital mortality after the onset of AE-IPF. Methods: Demographic, serological, and imaging data from patients hospitalized at the Maebashi Red Cross Hospital (Gunma, Japan) between 1 January 2013, and 31 December 2017, were retrospectively reviewed. Subjects fulfilling the diagnostic criteria for AE-IPF were divided into those who survived or died; statistical analysis of risk factors was performed using data from these two groups. Results: Diagnostic criteria for AE-IPF were fulfilled by 84 patients (59 males (70.2%)), with a median age of 78 years (range, 56-95 years). IPF was diagnosed before hospitalization in 50 (59.5%) patients and 38 (45.2%) died in hospital. Among the serological markers at hospitalization in the deceased group, C-reactive protein (CRP) was significantly higher than in the survivor group (p = 0.002), while total serum protein (p = 0.031), albumin (p = 0.047) and total cholesterol (p = 0.039) were significantly lower. Cox hazard analysis of factors predicting mortality, corrected for age, sex and BMI, revealed the following: CRP (hazard ratio (HR) 1.080 (95% confidence interval (CI) 1.022-1.141); p = 0.006), LDH (HR 1.003 (95% CI 1.000-1.006); p = 0.037), and total cholesterol (HR 0.985 (95% CI 0.972-0.997); p = 0.018). Conclusions: Our data suggest that CRP, LDH, and total cholesterol may be biomarkers predicting mortality in patients with AE-IPF. However, only prospective controlled studies can confirm or not our observation as a generalizable one.

[Pulmonary nocardiosis with elevation of serum beta-D-glucan in a patient with polymyositis].

A 73-year-old woman with polymyositis, who had received corticosteroids and immune-suppressive agents, was admitted to our hospital because of general fatigue and severe cough. Chest X-ray film and CT scan showed a large tumor shadow in the left upper lobe and several ground-glass opacities (GGOs) scattered in both lungs. As the white blood cell and C-reactive protein levels were elevated, pnueumonia was suspected and antibiotics were administered. Subsequently, Nocardia spp. was cultured from the sputum and pulmonary nocardiosis was established. She gradually recovered after sulfamethoxazole-trimethoprim (ST) administration. The pretreatment serum beta-D-glucan level was highly elevated and decreased in parallel with clinical feature. In general, ST should be administered for 6 months to treat pulmonary nocardiosis in a compromised host. It is possible that P3-D-glucan may be a useful marker to treat pulmonary nocardiosis in patients with polymyositis.

Liver Cirrhosis and Hepatocellular Carcinoma Diagnosed from Chylothorax: A Case Report.

A 71-year-old man visited our hospital with dyspnea and left pleural effusion. Left pleural effusion was diagnosed as chylothorax by thoracentesis. He had no history of trauma or surgery, and there were no findings of malignant lymphoma or thrombosis. Furthermore, he was diagnosed with liver cirrhosis and hepatocellular carcinoma by computed tomography and hematological examinations, and the chylothorax was considered to be caused by liver cirrhosis. We report a review of the literature with this case since it is relatively rare for cirrhosis and hepatocellular carcinoma diagnosed from chylothorax.

Prognostic nutritional index as a predictor of mortality in nontuberculous mycobacterial lung disease.

BACKGROUND: Although the association between nontuberculous mycobacterial lung disease (NTM-LD) and malnutrition is known, there are a few reports on the association between the nutritional score and death in patients with NTM-LD. This study investigated the association between the nutrition data at the time of NTM-LD diagnosis and death. METHODS: A retrospective study was conducted for patients with NTM-LD who visited the Maebashi Red Cross Hospital from January 2014 to December 2018. The patients were divided into the survival and death groups and analyzed statistically. RESULTS: The diagnostic criteria for NTM-LD were met by 150 patients. The median age was 70 years (range, 20-94 years). There were 51 (34.0%) men and 99 (66.0%) women. In the death group, the body mass index was significantly low, and there were significantly more patients with asthma. Further, computed tomography at the first visit revealed significantly fewer cases of the nodular bronchiectasis type. In the hematologic examination at the time of NTM-LD diagnosis, the white blood cell, neutrophil, and platelet counts and C-reactive protein and serum calcium levels were significantly higher in the death group, while the serum albumin level was significantly lower. In the death group, the prognostic nutritional index (PNI), calculated from the hematologic findings, was significantly lower, while the Glasgow Prognostic Score (GPS) was significantly higher. A logistic regression analysis was performed on items with significant differences, and the PNI and platelet count were independent factors predicting death. CONCLUSIONS: PNI might be effective as a prognostic factor for NTM-LD.

Evaluation of gefitinib efficacy according to body mass index, body surface area, and body weight in patients with EGFR-mutated advanced non-small cell lung cancer.

PURPOSE: In patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect gefitinib efficacy in such patients. METHODS: The medical charts of 138 consecutive patients with advanced NSCLC harboring sensitive EGFR mutations, who underwent gefitinib treatment, were reviewed. The median BSA and BW were used as cutoff values to evaluate their impact on gefitinib efficacy. BMI was categorized as underweight (<18.5 kg/m2), normal (18.5-25 kg/m2), and overweight (≥25 kg/m2). RESULTS: The median BSA and BW were 1.48 m2 and 53 kg, respectively. The overall response rate, progression-free survival (PFS), and overall survival (OS) were 65.2%, 12.2, and 24.2 months, respectively. There were no significant differences in clinical outcomes according to BSA, BW, or BMI alone. Subgroup analysis based on the mutation type and BSA revealed no significant differences in PFS between the groups; however, the median OS in those with exon 19 deletion combined with low BSA was significantly favorable compared with the other groups. CONCLUSIONS: Gefitinib efficacy in patients with NSCLC harboring sensitive EGFR mutations did not differ according to BSA, BW, and BMI. However, OS was superior in patients with both the exon 19 deletion and low BSA.

Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer.

PURPOSE: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples. RESULTS: EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022). CONCLUSIONS: These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.

Fulminant hepatic failure resulting from small-cell lung cancer and dramatic response of chemotherapy.

Prompt treatment in tumor-associated encephalopathy may prolong survival. We describe a 69-year-old male patient who was presented with fulminant hepatic failure, secondary to small-cell lung carcinoma with rapidly progressing encephalopathy. Both symptoms remitted following chemotherapy, suggesting swift diagnosis and administration of chemotherapy to be effective in treatment of fulminant hepatic failure and encephalopathy.

Intense accumulation of gallium-67 citrate in pancreatic endocrine tumor.

We report intense accumulation of gallium-67 (Ga-67) citrate in a pancreatic endocrine tumor. A 69-year-old woman was admitted because of cough, fever, and weight loss. An abdominal enhanced computed tomography (CT) scan revealed a large tumor located between the liver and pancreas as well as swollen paraaortic lymph nodes. Whole-body scintigraphy with Ga-67 revealed intense accumulation in the upper abdomen corresponding to the mass, as well as in the midabdomen and the mediastinal lesion. Percutaneous needle biopsy was performed, and the diagnosis was adenocarcinoma of the pancreas. The patient's condition deteriorated, and she died 2 months after admission. The pathological examination at autopsy revealed a pancreatic endocrine tumor. No report has described findings of Ga-67 citrate scintigraphy of pancreatic endocrine tumors. Pancreatic endocrine tumor should be included in a differential diagnosis when such scintigraphic findings are encountered.

[Obstructive sleep apnea syndrome in a patient with superior vena cava syndrome caused by malignant lymphoma].

A 52-year-old man was given emergency admission because of progressive facial edema and dyspnea. Chest X-ray film on admission showed a large hemispherical mass in the right paratracheal region. Chest CT scan showed a large tumor in the mediastinum, narrowing of the trachea and superior vena cava. Severe snoring at night and excessive daytime sleepiness were noticed. Obstructive sleep apnea syndrome (OSAS) was diagnosed by polysomnogram (PSG). Although a histological diagnosis of the tumor was not established, chest irradiation was begun to reduce the size of tumor. After treatment, the mediastinal tumor almost completely disappeared, and the facial swelling and snoring were gradually relieved. PSG showed remarkable improvement of the apnea-hypopnea index (AHI). These findings suggested a significant correlation between SVCS and OSAS. After three months, right inguinal lymphadenectomy was done and it was diagnosed as malignant lymphoma (mantle cell lymphoma). OSAS may cause a deterioration of respiratory symptoms and the quality of life in a patient with SVCS. Therefore, in the case of SVCS, it is important to take account of the presence of OSAS and select an appropriate treatment.

[Thymic cancer effectively treated by combination chemotherapy of carboplatin and etoposide with concurrent radiotherapy].

A 63-year-old man was admitted to our hospital for acute heart failure. A chest CT scan revealed a large anterior mediastinal mass and pericardial effusion. Percutaneous needle biopsy showed that the mass was an advanced thymic cancer (squamous cell carcinoma). The patient was treated by combination chemotherapy of carboplatin and etoposide with concurrent radiotherapy (44 Gy). There was no severe toxicity except for grade 4 neutropenia. After 3 courses of chemotherapy, the mass showed an approximately 81% reduction in tumor size and disappearance of the pericardial effusion. Finally, the thymic cancer and small pulmonary metastatic lesions were all resected. This concurrent chemoradiotherapy can be effective against inoperable squamous cell carcinoma of the thymus.

First-line gefitinib treatment in elderly patients (aged ≥75 years) with non-small cell lung cancer harboring EGFR mutations.

PURPOSE: The efficacy of gefitinib [an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor] in elderly patients with non-small cell lung cancer (NSCLC) and EGFR mutation has not been elucidated. Therefore, the objective of this study was to investigate the efficacy and feasibility of gefitinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations. METHODS: We retrospectively evaluated the clinical effects of gefitinib as a first-line treatment for elderly (≥75 years) NSCLC patients with EGFR mutations (exon 19 deletion or exon 21 L858R mutation). All patients were initially treated with gefitinib (250 mg/day) at seven institutions. RESULTS: Between January 2006 and December 2012, 62 patients (17 men, 45 women) with a median age of 80 years (range, 75-89 years) were included in our analysis. The overall response and disease control rates were 61.2 and 83.8 %, respectively, and the median progression-free survival and overall survival were 13.2 and 19.0 months, respectively. Common adverse events included rash, diarrhea, and liver dysfunction. Major grade 3 or 4 toxicities included skin rash (3.2 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (21.0 %). Gefitinib treatment was discontinued owing to adverse events of liver dysfunction in 3 patients, drug-induced pneumonitis in 2, and diarrhea in 1. CONCLUSION: First-line gefitinib could be a preferable standard treatment in elderly patients with advanced NSCLC harboring sensitive EGFR mutations.

Roentgenological occult large-cell neuroendocrine carcinoma: Report of a long-term survivor.

A 64-year-old male patient complained of a one-month history of bloody sputum. A polypoid tumor was almost obstructing the orifice of the subsegmental bronchus (B8b) of the anterior basal segment of the right lower lobe on bronchoscopy. Biopsy specimens of the tumor surface yielded a diagnosis of undifferentiated carcinoma. Clinical staging was T1aN0M0, stage IA. Surgical resection that comprised a right upper lobectomy with systematic mediastinal and hilar lymph node dissection was performed. Histopathologically, the tumor specimen was compatible with large-cell neuroendocrine carcinoma (LCNEC) of the subsegmental bronchus. Pathological staging was T1aN0M0, stage IA. To our knowledge, few cases of central-type LCNEC have been reported in the English literature, and ours is the first report of roentgenological occult LCNEC.

Wedge tracheobronchoplasty technique for primary pulmonary carcinoma of the right upper bronchus.

We describe a novel tracheobronchoplasty procedure for advanced squamous cell carcinoma of the right upper lung. A 78-year-old male was referred for further investigation of an abnormal shadow on a chest x-ray. A conventional right upper sleeve lobectomy was not applicable because of the invasion of lateral wall of the lower trachea. So, we performed a modified tracheobronchoplasty. This report shows that our cutting design for the trachea and bronchus was reasonable and appropriate for a caliber mismatch, with adaptation and suturing of each edge of the wedge-shaped defect of the trachea.

Late-onset chylothorax after blunt chest trauma at an interval of 20 years: report of a case.

We herein report an extremely rare case of a patient chylothorax at an interval of 20 years after thoracic vertebrae fractures, who underwent a successful thoracoscopic thoracic duct ligation and pleurodesis. A 51-year-old man was referred to our hospital with shortness of breath on effort about 1 month after participating in archery. Twenty years previously, he was involved in a traffic accident. At that time, the patient sustained trauma to the spine and suffered a spinal injury, thus resulting in paralysis in the lower part of his body. A chest roentgenogram and computed tomogram revealed a large amount of bilateral pleural effusion. After thoracentesis was performed, a diagnosis of chylothorax was made and the patient was hospitalized. Conservative management by a low-fat diet proved to be unsuccessful. The patient did not request pleurodesis, because pleural adhesions might impair pulmonary function. As a result, we decided to perform surgery. On the right side, we performed video-assisted thoracoscopic surgery by clipping the thoracic duct and applying an absorbable sealing material. Thereafter, pleurodesis was performed and OK-432 was instilled. Thereafter, the pleural fluid flow was almost completely stopped. On the left side, pleurodesis was effective. The patient has since remained symptom free and has been followed up on an outpatient basis for 9 months after the 100th postoperative day. We assumed that the chylothorax in this case was related to the earlier traffic accident.

Impact of preexisting pulmonary fibrosis detected on chest radiograph and CT on the development of gefitinib-related interstitial lung disease.

OBJECTIVES: Although preexisting pulmonary fibrosis (PF) on chest radiograph is known to be a risk factor of gefitinib-related interstitial lung disease (ILD), the significance of PF detected by chest computed tomography (CT) on the development of gefitinib-related ILD has not been investigated sufficiently. METHODS: We reviewed 182 nonsmall cell lung cancer patients treated with gefitinib between July 2002 and March 2003. Chest radiographs and CT were taken in all patients periodically and reviewed by radiologists. PF was defined as ground-glass attenuation, consolidation, or reticular shadow without segmental distribution. Gefitinib-related ILD was defined as the acute respiratory failure developed during the course of gefitinib administration and lack of evidence for other cause of respiratory failure. Expected risk factors for gefitinib-related ILD were evaluated in multivariate analysis. RESULTS: There were 15 patients with PF. Nine PF were detected on both chest radiograph and chest CT, and 6 on only chest CT. Twelve patients (6.6%) developed ILD during the course of gefitinib monotherapy and 4 died of it. Univariate and multivariate analyses showed that PF detected on chest radiograph was found to be the only significant risk factor for developing ILD (32.2, P < 0.001). Preexisting fibrosis diagnosed on chest CT but not apparent on chest radiograph was not significantly correlated with ILD. CONCLUSION: Gefitinib should not be given to patients with PF apparent on chest radiograph. Patients with PF on chest CT but not detected on chest radiograph could be treated carefully with gefitinib, but a risk-benefit analysis should be considered.