Association between the detection rate of thyroid cancer and the external radiation dose-rate after the nuclear power plant accidents in Fukushima, Japan.

A thyroid cancer ultrasonography screening for all residents 18 years old or younger living in the Fukushima prefecture started in October 2011 to investigate the possible effect of the radiological contamination after the Fukushima Daiichi Nuclear Power Plant accidents as of March 12 to 15, 2011. Thyroid cancer in 184 cases was reported by February 2017. The question arises to which extent those cancer cases are a biological consequence of the radiation exposure or an artefactual result of the intense screening of a large population.Experiences with the Chernobyl accident suggest that the external dose may be considered a valid surrogate for the internal dose of the thyroid gland. We, therefore, calculated the average external effective dose-rate (µSv/h) for the 59 municipalities of the Fukushima prefecture based on published data of air and soil radiation. We further determined the municipality-specific absolute numbers of thyroid cancers found by each of the two screening rounds in the corresponding municipality-specific exposed person-time observed. A possible association between the radiation exposure and the thyroid cancer detection rate was analyzed with Poisson regression assuming Poisson distributed thyroid cancer cases in the exposed person-time observed per municipality.The target populations consisted of 367,674 and 381,286 children and adolescents for the 1st and the 2nd screening rounds, respectively. In the 1st screening, 300,476 persons participated and 270,489 in the 2nd round. From October 2011 to March 2016, a total of 184 cancer cases were found in 1,079,786 person-years counted from the onset of the exposure to the corresponding examination periods in the municipalities. A significant association between the external effective dose-rate and the thyroid cancer detection rate exists: detection rate ratio (DRR) per µSv/h 1.065 (1.013, 1.119). Restricting the analysis to the 53 municipalities that received less than 2 µSv/h, and which represent 176 of the total 184 cancer cases, the association appears to be considerably stronger: DRR per µSv/h 1.555 (1.096, 2.206).The average radiation dose-rates in the 59 municipalities of the Fukushima prefecture in June 2011 and the corresponding thyroid cancer detection rates in the period October 2011 to March 2016 show statistically significant relationships.

Screening for hereditary angioedema (HAE) at 13 emergency centers in Osaka, Japan: A prospective observational study.

Hereditary angioedema (HAE) with deficiency of C1 inhibitor (C1-INH) is an autosomal-dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The objective is to study the incidence of HAE among patients who visit the emergency department.This was a 3-year prospective observational screening study involving 13 urban tertiary emergency centers in Osaka prefecture, Japan. Patients were included if they met the following criteria: unexplained edema of the body, upper airway obstruction accompanied by edema, anaphylaxis, acute abdomen with intestinal edema (including ileus and acute pancreatitis), or asthma attack. C1-INH activity and C4 level were measured at the time of emergency department admission during the period between July 2011 and June 2014.This study comprised 66 patients with a median age of 54.0 (IQR: 37.5-68.3) years. Three patients were newly diagnosed as having HAE, and 1 patient had already been diagnosed as having HAE. C1-INH activity levels of the patients with HAE were below the detection limit (<25%), whereas those of non-HAE patients (n = 62) were 106% (IQR: 85.5%-127.0%) (normal range, 70%-130%). The median level of C4 was significantly lower in the patients with HAE compared with those without HAE (1.2 [IQR: 1-3] mg/dL vs 22 [IQR: 16.5-29.5] mg/dL, P < 0.01) (normal range, 17-45 mg/dL).Three patients with undiagnosed HAE were diagnosed as having HAE in the emergency department during the 3-year period. If patients have signs and symptoms suspicious of HAE, the levels of C1-INH activity and C4 should be measured.

Comparison of chest computed tomography features in the acute phase of cardiogenic pulmonary edema and acute respiratory distress syndrome on arrival at the emergency department.

PURPOSE: Discriminating cardiogenic pulmonary edema (CPE) from acute respiratory distress syndrome (ARDS) is a serious problem in emergency departments, and the ability of chest radiographs to differentiate between these 2 entities is limited. We compared the chest computed tomography (CT) findings in the acute phase of CPE with those of ARDS. MATERIALS AND METHODS: Outpatients with acute respiratory failure presenting to emergency departments with bilateral pulmonary opacities were enrolled. The patients included not only those who visited our hospital first but also those referred from other hospitals. Two intensivists who were blinded to the results of the chest imaging studies reviewed the patients' clinical records independently in order to determine a diagnosis of CPE or ARDS, and the chest CT findings were independently evaluated by 2 radiologists who were unaware of the patients' clinical information. The positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the statistically different findings were calculated using standard definitions. RESULTS: Forty-one patients with CPE and 20 patients with ARDS were assessed. Upper-lobe-predominant ground-glass attenuation, central-predominant ground-glass attenuation, and central airspace consolidation were associated with high PPVs (95.2%, 92.3%, and 92.0%, respectively) and moderate NPVs (47.5%, 51.4%, and 50.0%, respectively) to diagnose as CPE. Left-dominant pleural effusion and small ill-defined opacities revealed relatively high PPVs (71.4% and 58.3%, respectively) and NPVs (72.2% and 73.5%, respectively) to diagnose as ARDS. The overall accuracy of the diagnosis by chest CT was 88.5% (54/61). CONCLUSIONS: Chest CT may be a useful tool for differentiating CPE from ARDS in the emergency department setting.

Physicians' attitudes toward the definition of "death from age-related physical debility" in deceased elderly with aspiration pneumonia.

AIM: Deaths from aspiration pneumonia in elderly patients are occasionally considered to be "death from age-related physical debility", because most aspiration pneumonias are a result of aging and lead to death without any definitive therapy. The aim of the present study was to assess physicians' attitudes toward the diagnosis of and actual description of "death from age-related physical debility" on death certificates for deceased patients with aspiration pneumonia. METHODS: This study surveyed 62 Japanese physicians including 36 pulmonologists and 26 other physicians who treat patients with pneumonia. Their attitudes regarding consideration and actually recorded "death from age-related physical debility" for deceased patients with aspiration pneumonia were assessed by using anonymous questionnaires, which included the decision-making process and the necessity of detailed diagnostic criteria. RESULTS: A total of 32 (52%) respondents had considered deceased patients with aspiration pneumonia to be "death from age-related physical debility", and 10 (16%) have actually stated this on the death certificate. Advanced age, bedridden status, inability of oral intake and disturbance of consciousness including dementia were major factors in their decision-making. A total of 34 (55%) of the respondent physicians wanted detailed criteria to be established. CONCLUSIONS: Physicians' attitudes toward the definition of "death from age-related physical debility" vary a great deal depending on the respondent. The description in death certificates therefore might inaccurately reflect the results of current mortality statistics in Japan.

Relationship between CT findings and the plasma levels of brain natriuretic peptide in 29 patients with acute cardiogenic pulmonary edema.

RATIONALE AND OBJECTIVES: Brain natriuretic peptide (BNP) is a useful biomarker for the assessment of cardiogenic pulmonary edema. This study evaluated the relationship between computed tomography (CT) findings and plasma BNP levels in patients with cardiogenic pulmonary edema. MATERIALS AND METHODS: Twenty-nine consecutive outpatients with severe respiratory failure from cardiogenic edema presenting to emergency departments were enrolled. They underwent chest CT and plasma BNP levels were measured in the emergency room. CT findings were independently evaluated by two radiologists who were unaware of the patients' clinical information. RESULTS: The plasma BNP levels only correlated with the volume of pleural effusion in each side (right: r(s) = 0.519, P = .004; left: r(s) = 0.460, P = .012). No significant correlation was observed between the BNP levels and the findings of lung parenchyma or cardiovascular enlargement. CONCLUSION: Estimating the pleural effusion volume with CT may be a feasible method as well as measuring the plasma BNP level in the assessment of acute cardiogenic pulmonary edema.

Medical professionals' attitudes toward tube feeding for themselves or their families: a multicenter survey in Japan.

BACKGROUND: Many studies have shown a lack of advantages to tube feeding for elderly with advanced dementia, but tube feeding is still considered standard care in Japan. The aim of this study is to investigate what nutrition method health care professionals want for themselves or their families, if they fall into a bedridden state due to irreversible impaired cognition in old age. METHODS: In 2010 we surveyed 1321 Japanese health care professionals including 251 medical doctors and 1070 nurses. Their attitudes toward tube feeding were assessed by using an anonymous questionnaire, which included desired feeding methods for themselves or their families and propriety of card-based declaration of intent for end-of-life care. RESULTS: Rates of accepting tube feeding for themselves and their families were 14.4% and 43.4%, respectively. In multivariate analyses, working at a municipal hospital and high frequency of taking care of tube-fed elderly patients were predictors of refusing tube feeding for themselves. Working at a municipal hospital and being a medical doctor were predictors of refusing tube feeding for their families. The rate of welcoming card-based declaration of intent for end-of-life care including feeding methods was 65.2%. CONCLUSIONS: Many doctors and nurses, especially with more frequent contact with tubefed patients, rejected tube feeding for themselves on their own deathbed, but did not always refuse this option for their families.

Plasma C-reactive protein levels are associated with mortality in elderly with acute lung injury.

PURPOSE: The plasma C-reactive protein (CRP) level is considered to be a predictor of severity in both hospital- and community-acquired pneumonias, whereas recent reports have shown that higher CRP levels lead to better outcomes in patients with acute lung injury (ALI). To explain this discrepancy, we evaluated the relationship among plasma CRP levels, etiology, affectors of CRP production, and mortality in patients with ALI. MATERIALS AND METHODS: This was a case-control study of 76 consecutive patients with ALI. The plasma CRP levels had been measured in all of the patients within 1 hour of visiting an emergency department. The associations between the plasma CRP levels and 60-day mortality were analyzed after adjusting for the causes of ALI, disease severity, the patients' age, use of corticosteroids, and presence of hepatic failure. RESULTS: The CRP levels and patients' ages were strongly related to the mortality (adjusted hazard ratio, 1.005 [P = .007] and 1.059 [P = .011], respectively), whereas the etiology of ALI did not affect the mortality (adjusted hazard ratio, 0.789 [P = .530]) in the Cox proportional hazard models. CONCLUSIONS: The plasma CRP level may be a predictor of mortality in elderly patients with ALI.

Diagnostic utility of C-reactive protein combined with brain natriuretic peptide in acute pulmonary edema: a cross sectional study.

INTRODUCTION: Discriminating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary edema (CPE) using the plasma level of brain natriuretic peptide (BNP) alone remains controversial. The aim of this study was to determine the diagnostic utility of combination measurements of BNP and C-reactive protein (CRP) in critically ill patients with pulmonary edema. METHODS: This was a cross-sectional study. BNP and CRP data from 147 patients who presented to the emergency department due to acute respiratory failure with bilateral pulmonary infiltrates were analyzed. RESULTS: There were 53 patients with ALI/ARDS, 71 with CPE, and 23 with mixed edema. Median BNP and CRP levels were 202 (interquartile range 95-439) pg/mL and 119 (62-165) mg/L in ALI/ARDS, and 691 (416-1,194) pg/mL (p < 0.001) and 8 (2-42) mg/L (p < 0.001) in CPE. BNP or CRP alone offered good discriminatory performance (C-statistics 0.831 and 0.887), but the combination offered greater one [C-statistics 0.931 (p < 0.001 versus BNP) (p = 0.030 versus CRP)]. In multiple logistic-regression, BNP and CRP were independent predictors for the diagnosis after adjusting for other variables. CONCLUSIONS: Measurement of CRP is useful as well as that of BNP for distinguishing ALI/ARDS from CPE. Furthermore, a combination of BNP and CRP can provide higher accuracy for the diagnosis.

Spindle cell carcinoma of the lung.

We report a rare case of spindle cell carcinoma in the lung. A 73-year-old woman was admitted because of a lung tumor, which was indicated during a group examination. Chest computed tomography revealed a tumor located in the right lung accompanied by spiculation. Right upper lobectomy with lymph nodal dissection was performed. Histological findings revealed only spindle-shaped tumor cells, and immunohistochemical stain showed that they were cytokeratin-positive. We diagnosed it as a pulmonary spindle cell carcinoma.

Unique extralobar sequestration with atypical location and aberrant vessels.

We report a unique extralobar pulmonary sequestration in the upper thoracic region with 3 aberrant vessels connecting to the right subclavian artery, right superior pulmonary vein, and right pulmonary artery in a 20-year-old man. The sequestered lung was completely excised using a video-assisted thoracoscopic approach.

Huge mediastinal cystic tumor penetrating the sternum.

We report a very rare case of a huge anterior mediastinal tumor penetrating the sternum that was diagnosed in a 59-year-old woman. The tumor was completely resected en bloc with the manubrium sterni, and the chest wall defect was closed with a pectoralis major muscle flap. Histologic examination of the cystic mass revealed the diagnosis of a benign mediastinal cystic tumor, most likely a benign cystic mature teratoma.

A phase II trial of gefitinib monotherapy in chemotherapy-naïve patients of 75 years or older with advanced non-small cell lung cancer.

BACKGROUND: Gefitinib has shown modest activity in patients with recurrent non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. However, the activity of gefitinib as first-line chemotherapy remains unclear, especially unknown in elderly patients. A multicenter phase II trial was conducted to evaluate the efficacy and tolerability of gefitinib for elderly patients with chemotherapy-naïve NSCLC. METHODS: Elderly chemotherapy-naïve patients with advanced NSCLC, ECOG PS of 0-2, and adequate organ functions received 250 mg/day of gefitinib. The primary objective of this study was to determine the objective response rate (RR). Secondary endpoints were tolerability, disease-related symptom using lung cancer subscale (LCS) in FACT-L, progression free survival (PFS) and overall survival (OS). We investigated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples. RESULTS: Fifty patients were enrolled, of whom 49 were eligible. Median age (range) was 80 (75-90) years. Thirty-two patients were female (65%) and 40 patients had adenocarcinoma (82%). The objective RR was 25% (CI 95%, 13-39). Median survival time was 10 months (CI 95%, 7-20) and 1-year survival rate was 50%. The most frequent adverse events were skin disorders (76%). Fifteen patients (30%) experienced toxicities >/=grade 3. There were four patients with possible interstitial lung disease including two treatment-related deaths. Symptom improvement rate using LCS was 49% at 4 weeks of gefitinib therapy. Tumor samples from 17 patients were analyzed for EGFR mutation status. EGFR mutations were detected in tumor tissues from 7 patients, of which 5 had partial responses (71%). CONCLUSIONS: Gefitinib monotherapy is effective and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Gefitinib has potential as a first-line therapeutic option in elderly patients with advanced NSCLC.

Prospective randomized trial of transnasal versus peroral endoscopy using an ultrathin videoendoscope in unsedated patients.

AIM: The aim of this study was to compare the acceptance and tolerance of transnasal and peroral esophagogastroduodenoscopy (EGD) using an ultrathin videoendoscope in unsedated patients. METHODS: A total of 124 patients referred for diagnostic endoscopy were assigned randomly to have an unsedated transnasal EGD (n = 64) or peroral EGD (n = 60) with local anesthesia. An ultrathin videoendoscope with a diameter of 5.9 mm was used in this study. A questionnaire for tolerance was completed by the patient (a validated 0-10 scale where '0' represents no discomfort/well tolerated and '10' represents severe discomfort/poorly tolerated). RESULTS: Of the 64 transnasal EGD patients, 60 patients (94%) had a complete examination. Four transnasal EGD examinations failed for anatomical reasons; all four patients were successfully examined when switched to the peroral EGD. All 60 peroral EGD patients had a complete examination. Between the transnasal and peroral groups, there was a statistically significant difference in scores for discomfort during local anesthesia (1.5 +/- 0.2 vs 2.6 +/- 0.3, P = 0.003), discomfort during insertion (2.3 +/- 0.3 vs 4.3 +/- 0.3, P = 0.001), and overall tolerance during procedure (1.6 +/- 0.2 vs 3.8 +/- 0.2, P = 0.001). In all, 95% of transnasal EGD patients and 75% of peroral EGD patients (P = 0.002) were willing to undergo the same procedure in the future. Four patients in the transnasal EGD group experienced mild epistaxis. CONCLUSION: For unsedated endoscopy using an ultrathin videoendoscope, transnasal EGD is well tolerated and considerably reduces patient discomfort compared with peroral EGD.

Phase II study of amrubicin in previously untreated patients with extensive-disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study.

PURPOSE: To evaluate the efficacy and safety of amrubicin, (+)-(7S, 9S)-9-acetyl-9-amino-7-[(2-deoxy-beta-D-erythro-pentopyranosyl )oxy]-7,8,9,10-tetrahydro-6,11-dihydroxy-5,12-naphthacenedione hydrochloride, in previously untreated patients with extensive-disease small cell lung cancer (SCLC). PATIENTS AND METHODS: A total of 35 previously untreated patients with extensive-disease SCLC were entered into the study. Amrubicin was given by daily intravenous infusion at 45 mg/m(2)/day for 3 consecutive days, every 3 weeks. Unless there was tumor regression of 25% or greater after the first cycle, or 50% or greater after the second cycle, treatment was switched to salvage chemotherapy in combination with etoposide (100 mg/m(2), days 1, 2, and 3) and cisplatin (80 mg/m(2), day 1). RESULTS: Of the 35 patients entered, 33 were eligible and assessable for efficacy and toxicity. Of the 33 patients, 3 (9.1%) had a complete response (95% confidence interval [CI], 1.9-24.3%) and 22 had a partial response, for an overall response rate of 75.8% (95% CI, 57.7-88.9%). Median survival time was 11.7 months (95% CI, 9.9-15.3 months), and 1-year and 2-year survival rates were 48.5% and 20.2%, respectively. The most common toxicity was hematologic. Non-hematologic toxicity of grade 3 or 4 was only seen in 3 patients with anorexia (9.1%) and 1 patient with alopecia (3.0%). Salvage chemotherapy was administered to only 6 patients. CONCLUSION: Amrubicin was active for extensive-disease SCLC with acceptable toxicity. Further studies in combination with other agents for SCLC are warranted.

Multicenter phase II study of amrubicin, 9-amino-anthracycline, in patients with advanced non-small-cell lung cancer (Study 1): West Japan Thoracic Oncology Group (WJTOG) trial.

PURPOSE: Amrubicin is a novel 9-aminoanthracycline. This multicenter phase II study was conducted to evaluate the efficacy and safety of amrubicin in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-one previously untreated patients with stage III or IV NSCLC were entered this study. The patients were required to have cytologically or histologically proven measurable NSCLC, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and adequate organ function. Amrubicin was administered by daily intravenous injection at 45 mg/m2/day for 3 consecutive days every 3 weeks. At least 3 cycles of treatment were administered to each patient. RESULTS: All 61 patients registered in this trial were eligible and assessable for efficacy and toxicity. Of them, 17 patients achieved objective responses, consisting of one complete response and 16 partial responses, and the overall response rate was 27.9% (95% confidence interval [CI], 17.1% to 40.8%). The median survival time was 9.8 months (95% CI, 7.7 months to 14.9 months). The major toxicity was myelosuppression. The incidences of grade 3 or 4 toxicity were 72.1% for neutropenia, 52.5% for leukopenia, 23.0% for anemia, and 14.8% for thrombocytopenia. As noticeable toxic events, grade 3 hypotention and alkaline phosphatase elevation were transiently observed in one patient each. In addition, three patients who had had asymptomatic interstitial pneumonitis, identified by diagnostic imaging before treatment, aggravated after amrubicin treatment; two of them died. Other non-hematologic toxicities were relatively mild. CONCLUSION: Amrubicin was an active, well-tolerated agent in the treatment of NSCLC.

Uracil/tegafur plus cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer: a multi-institutional phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a novel combination treatment using concurrent radiotherapy with cisplatin plus UFT, which is comprised of uracil and tegafur, in locally advanced non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this Phase II trial, patients with unresectable stage III NSCLC were treated with the oral administration of UFT (400 mg/m(2)/d tegafur) on days 1-14 and days 29-42 whereas 80 mg/m(2) cisplatin was administered i.v. on days 8 and 36. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions from day 1. RESULTS: Seventy patients were enrolled and eligible, as follows: 57 males/13 females; mean age 61 ranging from 36 to 74; performance status 0/1:45/25; stage IIIA/IIIB, 14/56. A complete response was observed in two patients and a partial response in 54 patients, and the overall response rate was 81% (95% confidence interval; 70-89%). The median survival, the 1- and 2-year survival rates were 16.5 months, 67% and 33%, respectively. Grade 3/4 leukopenia occurred in 14%/1% of the patients. Grades 3 non-hematological toxicities were only reported in three patients with nausea, two with esophagitis and one with pneumonitis whereas no grade 4 non-hematological toxicity was observed. CONCLUSIONS: UFT plus cisplatin with concurrent radiotherapy is considered to be a feasible and effective treatment for locally advanced NSCLC patients. Additional study of this concurrent chemoradiotherapy is warranted.

Combination chemotherapy of gemcitabine and vinorelbine for patients in stage IIIB-IV non-small cell lung cancer: a phase II study of the West Japan Thoracic Oncology Group (WJTOG) 9908.

OBJECTIVES: Vinorelbine (V) and gemcitabine (G) are two active single agents used in the treatment of non-small cell lung cancer (NSCLC). A multicenter clinical trial (West Japan Thoracic Oncology Group (WJTOG) 9908) was conducted to evaluate the efficacy and toxicity of V and G in patients (pts) with advanced NSCLC. ELIGIBILITY CRITERIA: no previous chemotherapy; performance status (PS) 0 or 1; age <75 years old. V, 25mg/m2, was given as a 2-3 min IV infusion, followed by a 30 min IV infusion of G, 1000 mg/m2, on days 1 and 8 of each 21-day cycle. RESULTS: From April 2000 to September 2000, 52 pts were enrolled in the study. Two pts were ineligible. Baseline characteristics: median age 60, males 30 (60%), Eastern Cooperative Oncology Group (ECOG) PS 0/1=21/29 (58%), stage IIIB/IV=12/38 (76%), adenocarcinoma=35 (70%). The median number of cycles administered was 2. Fifty pts were evaluable for response. The response rate was 18% by the Response Evaluation Criteria in Solid Tumors (RECIST) (no complete response (CR), 9 partial response (PR), 25 stable disease, 12 progressive disease, 4 not evaluable). Grade III/IV toxicities were as follows: neutropenia grade III/IV=66%, anemia grade III/IV=16%, thrombocytopenia grade III/IV=2%, nausea grade III/IV=10%, vomiting grade III/IV=0%, documented infection grade III/IV=10%, skin rash grade III/IV=2%, and hepatic grade III/IV=8%. There were no treatment-related deaths. The median time to progression was 4.1 months. The overall median survival time (MST) was 13.9 months (range, 2.4 to >16.2 months) with a median follow-up time of 13.9 months. The MST for stage IIIB and stage IV was >14.5 and 12.7 months, respectively. The overall estimated 1-year survival rate was 55.4%. CONCLUSIONS: This regimen has modest activity and is very well tolerated, with an encouraging 1-year survival rate.