Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

Newspaper coverage before and after the HPV vaccination crisis began in Japan: a text mining analysis.

BACKGROUND: The human papillomavirus (HPV) vaccination coverage rate has fallen sharply in Japan since 2013, when newspapers began covering negative campaigns against the vaccination. We examined and compared contents from newspaper articles before and after the start of this HPV vaccination crisis. METHODS: We collected articles published between January 2005 and September 2017 in the four daily national Japanese newspapers with the highest domestic circulation. We then conducted text mining analysis to chronologically examine content distribution. RESULTS: From among the 1178 articles analyzed, 12 types of contents were identified. Contents related to cervical cancer prevention, such as on the risk of developing cervical cancer, causes of cervical cancer, and the effects of vaccination, were frequently conveyed until 2012. However, after March 2013, they were replaced with anti-vaccination contents, such as on adverse effects to vaccines, alleged victims, and related lawsuits. Meanwhile pro-vaccination contents, such as safety statements from the World Health Organization, scarcely received coverage. CONCLUSIONS: Newspaper contents changed profoundly before and after the start of the vaccination crisis. Those newspaper reports potentially had impact on readers' beliefs and actions. Journalists should strive for impartial coverage so readers can make more-informed decisions. Health professionals should be expected to work with journalists to help improve impartiality in newspaper coverage. The Ministry of Health, Labour and Welfare should discus benefits and risks of the HPV vaccination based on the scientific evidences, and consider to resume the proactive recommendation of HPV vaccination. Well-organized advocacy among medical societies, scientists and health professionals will also be needed to influence the government.

[Content analysis of newspaper reports on passive smoking regulations in Japan].

Objectives　Ever since Tokyo was awarded the privilege to host the 2020 Olympic Games, the Japanese Ministry of Health, Labour, and Welfare has worked toward implementing a ban on passive smoking. This study examined the present situation of passive smoking in Japan, and the coverage of passive smoking regulations in newspaper reports, based on a content analysis. This was followed by a comparison with the contents of the "White Paper on Tobacco," published by the Japanese Ministry of Health, Labour, and Welfare in August, 2016.Methods　In total, 182 articles published from September 7, 2013 to March 31, 2017 were collected from three major newspapers based in Tokyo (Asahi, Yomiuri, and Mainichi). The article search criteria included the presence of the following keywords in the title or main text: "passive smoking OR entire surface smoking cessation OR indoor smoking OR indoor smoking cessation OR smoking cessation in the site OR smoking cessation in the building." Online posts and articles that did not focus mainly on the regulation of passive smoking were excluded. The 37 coding categories that were developed were classified either as positive or negative (with respect to coverage of passive smoking regulations). The assessment of passive smoking in the White Paper on Tobacco informed the coding categories, to allow the evaluation of the extent to which the contents of the White Paper were reflected in newspaper reports.Results　Among the 182 articles examined, 107 addressed only the positive aspects of the regulations, while 7 addressed only the negative aspects. Further, 50 articles addressed both positive and negative aspects, while 18 addressed neither. Among those addressing both positive and negative aspects, 14 (28%) included counterarguments to the negative comments, which consistently reflected the contents of the White Paper on Tobacco.Conclusions　Majority of the articles reported only on the positive aspects of the regulations. Persuasive articles that presented both the positive and negative aspects of the issue, which included counterarguments to the negative opinions, were scarce. However, such articles were found to some degree in the editorials of newspapers. The influence of such editorials may increase if newspapers include the pros or cons of this issue, and present counterarguments. Additionally, some topics were not reported sufficiently. Thus, problems were observed in the newspaper reports regarding passive smoking regulations.

Amount of Narratives Used on Japanese Pro- and Anti-HPV Vaccination Websites: A Content Analysis

Background: HPV vaccination is an effective way in preventing cervical cancer. However, HPV vaccination coverage rate has fallen to only a few percent in Japan. Anti HPV-vaccination websites often use narratives of those who have experienced adverse reactions to HPV vaccine to enhance their persuasiveness. Scholars suggest using the same medium to promote HPV vaccination online; e.g., presenting narratives of those who have experienced cervical cancer. We examined the amount of narratives used on Japanese pro- and anti-HPV vaccination websites. Methods: We conducted online searches using two major search engines (Googl.jp and Yahoo!.jp). Identified websites were classified as "pro," "anti," or "neutral" depending on their claims. Two independent raters coded the pro and anti websites and counted the number of narratives of people who experienced side effects of HPV vaccine or cervical cancer. Results: A total 26% of anti websites posted narratives on side effects. No pro websites posted narratives about having cervical cancer. Conclusion: Pro-HPV vaccination websites is recommended to post narratives to enhance the persuasiveness of their arguments.

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps.

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP.

Persuasiveness of Statistics and Patients' and Mothers' Narratives in Human Papillomavirus Vaccine Recommendation Messages: A Randomized Controlled Study in Japan.

BACKGROUND: The human papillomavirus (HPV) vaccination percentage among age-eligible girls in Japan is only in the single digits. This signals the need for effective vaccine communication tactics. This study aimed to examine the influence of statistical data and narrative HPV vaccination recommendation massages on recipients' vaccination intentions. METHODS: This randomized controlled study covered 1,432 mothers who had daughters aged 12-16 years. It compared message persuasiveness among four conditions: statistical messages only; narrative messages of a patient who experienced cervical cancer, in addition to statistical messages; narrative messages of a mother whose daughter experienced cervical cancer, in addition to statistical messages; and a control. Vaccination intentions to have one's daughter(s) receive the HPV vaccine before and after reading intervention materials were assessed. Statistical analysis was conducted using analysis of variance with Tukey's test or Games-Howell post hoc test, and analysis of covariance with Bonferroni correction. RESULTS: Vaccination intentions after intervention in the three intervention conditions were higher than the control condition (p < 0.001). A mother's narrative messages in addition to statistical messages increased HPV vaccination intention the most of all tested intervention conditions. A significant difference in the estimated means of intention with the covariate adjustment for baseline value (i.e., intention before intervention) was found between a mother's narrative messages in addition to statistical messages and statistical messages only (p = 0.040). DISCUSSION: Mothers' narrative messages may be persuasive when targeting mothers for promoting HPV vaccination. This may be because mothers can easily relate to and identify with communications from other mothers. However, for effective HPV vaccine communication, further studies are needed to understand more about persuasive differences in terms of statistics, narratives, and narrators. Directions for future research are also suggested.

Soluble DNAM-1, as a Predictive Biomarker for Acute Graft-Versus-Host Disease.

Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because diagnosis of aGVHD is exclusively based on clinical symptoms and pathological findings, reliable and noninvasive laboratory tests for accurate diagnosis are required. An activating immunoreceptor, DNAM-1 (CD226), is expressed on T cells and natural killer cells and is involved in the development of aGVHD. Here, we identified a soluble form of DNAM-1 (sDNAM-1) in human sera. In retrospective univariate and multivariate analyses of allo-HSCT patients (n = 71) at a single center, cumulative incidences of all grade (grade I-IV) and sgrade II-IV aGVHD in patients with high maximal serum levels of sDNAM-1 (≥30 pM) in the 7 days before allo-HSCT were significantly higher than those in patients with low maximal serum levels of sDNAM-1 (<30 pM) in the same period. However, sDNAM-1 was not associated with other known allo-HSCT complications. Our data suggest that sDNAM-1 is potentially a unique candidate as a predictive biomarker for the development of aGVHD.

Nuclear grading of primary pulmonary adenocarcinomas: correlation between nuclear size and prognosis.

BACKGROUND: According to the World Health Organization Classification of Tumors, the prognostic value of morphometric cytologic atypia has not been assessed in pulmonary adenocarcinoma. METHODS: Primary tumors of 133 pulmonary adenocarcinomas

Bronchioloalveolar carcinoma (lepidic growth) component is a more useful prognostic factor than lymph node metastasis.

INTRODUCTION: Although many factors predictive of patient survival have been reported for lung cancer, no comparative studies have attempted to determine those that are most significant for practical medicine. METHODS: We conducted a retrospective review of 139 patients who underwent complete resection of adenocarcinomas less than 2 cm in diameter between 1993 and 2000 at the National Cancer Center Hospital (Tokyo, Japan). The MIB-1 labeling index (LI), immunohistochemical staining for carcinoembryonic antigen (CEA), p53, p27, epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), Cox-2, neuronatin, gammaH2AX, and thyroid transcription factor-1 (TTF-1), the prevalence of a micropapillary pattern, and the ratio of the bronchioloalveolar cell carcinoma (BAC) or lepidic growth (LG) component were determined, and their significance as prognostic factors for lung adenocarcinoma was compared. RESULTS: Univariate analysis showed that lymph node metastasis (p-N status), BAC/LG component, vascular invasion (p-V status), MIB-1 LI, pEGFR, and CEA were prognostically significant (p-N status: p < 0.0001, BAC/LG: p = 0.0005, p-V status: 0.002, MIB-1 LI: p = 0.005, pEGFR: p = 0.024, and CEA: p = 0.049). Multivariate analysis showed that only p-N status (p = 0.013) was of prognostic significance. However, BAC/LG component (p = 0.051) was a more reliable prognostic factor than p-N status in mixed adenocarcinoma with a BAC/LG component. CONCLUSION: In comparison with other immunohistochemical and histopathologic factors, BAC/LG component is independently and reliably prognostic for small adenocarcinoma of the lung, and, in particular, for the major histologic subtype (adenocarcinoma mixed subtype with BAC/LG), BAC/LG component is more reliably prognostic than lymph node metastasis.

First report on 30-day and operative mortality in risk model of isolated coronary artery bypass grafting in Japan.

BACKGROUND: Risk models of coronary artery bypass grafting (CABG) using a large database are useful for improving surgical quality. To obtain accurate, high-quality assessments of the surgical outcomes, each country should maintain its own database. This study was conducted to collect Japanese data and prepare a risk stratification of isolated CABG procedures using the Japan Adult Cardiovascular Surgery Database (JACVSD). METHODS: We analyzed 7133 CABG-only records from 97 participating sites throughout Japan using a data entry form with 255 variables that was sent to the JACVSD office by our Web-based data collection system. The statistical model was constructed by multiple logistic regression. Model discrimination was tested using the area under the receiver operating characteristic curve (C index). Model calibration was tested by the Hosmer-Lemeshow test. RESULTS: Of 7133 operations, 47.2% had diabetes mellitus, 14.0% were urgent, and 15.6% involved peripheral vascular disease. The observed 30-day and operative mortality rates were 2.02% and 2.72%, respectively. Significant variables with high odds ratios included emergency or salvage status (3.71), preoperative creatinine value exceeding 3.0 mg/dL (3.59), aortic valve stenosis (3.01), and moderate to severe chronic lung disease (2.86). Hosmer-Lemeshow test and C-index values for 30-day mortality were satisfactory at 0.96 and 0.85, respectively. CONCLUSIONS: The results obtained in Japan were at least as good as those reported elsewhere. The performance of our risk model also matched those of the Society of Thoracic Surgeons National Adult Cardiac Database and the European Society Database.

Geographical distribution for malignant neoplasm of the pancreas in relation to selected climatic factors in Japan.

BACKGROUND: Malignant neoplasm of the pancreas has become one of the leading causes of death from malignant neoplasm in Japan (the 5th in 2003). Although smoking is believed to be a risk factor, other risk factors remain unclear. Mortality from malignant neoplasm of the pancreas tends to be higher in northern Japan and in northern European countries. A recent study reported that standardized mortality ratios (SMRs) for malignant neoplasm of the pancreas were negatively correlated to global solar radiation level. People residing in regions with lower solar radiation and lower temperatures may be at higher risk of development of malignant neoplasm of the pancreas. Therefore, this study aimed to examine the relationship between SMRs for malignant neoplasm of the pancreas and climatic factors, such as the amount of global solar radiation and the daily maximum temperature in Japan. RESULTS: The study used multiple linear regression models. Number of deaths and demographic data from 1998 to 2002 were used for the calculation of SMR. We employed mesh climatic data for Japan published in 2006 by the Japan Meteorological Agency. Regression coefficients for the amount of global solar radiation and the daily maximum temperature in males were -4.35 (p = 0.00034) and -2.81 (p < 0.0001) respectively, and those in females were -5.02 (p < 0.0001) and -1.87 (p < 0.0001) respectively. Increased amount of global solar radiation or daily maximum temperature was significantly related to the decreased SMRs for malignant neoplasm of the pancreas in both males and females. CONCLUSION: This study suggested that low solar radiation and low temperature might relate to the increasing risk of malignant neoplasm of the pancreas. Use of group data has a limitation in the case of evaluating environmental factors affecting health, since the impact of climatic factors on the human body varies according to individual lifestyles and occupations. Use of geographical mesh climatic data, however, proved useful as an index of risk or beneficial factors in a small study area. Further research using individual data is necessary to elucidate the relationship between climatic factors and the development of malignant neoplasm of the pancreas.

Geographical pattern of malignant neoplasm by cluster analysis using standardized mortality ratios (SMRs) in Ibaraki Prefecture, Japan.

We investigated the geographical patterns of mortality from eight (males)/ten (females) sites of malignant neoplasm, using cluster analysis with Standardized Mortality Ratios (SMRs), and examined the relationship between the mortality structure and urbanization. To explore the geographical tendencies is important for the prevention of cancers; such as noticing risk factors associated with regional variance. The death rates, by site, gender and age from 1990 to 1994 in Japan, were obtained from Vital Statistics. The deaths and population in municipalities were obtained from "Population of Ibaraki Prefecture". These were represented as averaged values in five-year periods. As an indicator of urbanization and mortality structure, the population density of municipalities and the overall rank scores of SMRs were used, respectively. Cluster analysis formed some distinctive structures. For males, Cluster 1 included four municipalities and three of these were located in the mountainous area in northwest Ibaraki, characterized by high SMRs from bone marrow. Cluster 5 consisted of the mid-south areas, characterized by high SMRs from stomach cancer. For females, the clusters seemed to be characterized by SMRs from esophagus cancer. An association between mortality structure and urbanization was found for females, 0.364 (p<0.01), but not for males, 0.162 (p=0.14).