Cost-effectiveness of preventive aspirin use and intensive downstaging polypectomy in patients with familial adenomatous polyposis: A microsimulation modeling study.

OBJECTIVE: Although there is increasing evidence to suggest the cost-effectiveness of aspirin use to prevent colorectal cancer (CRC) in the general population, no study has assessed cost-effectiveness in patients with familial adenomatous polyposis (FAP), who are at high risk of developing CRC. We examined the cost-effectiveness of preventive use of low-dose aspirin in FAP patients who had undergone polypectomy in comparison with current treatment practice. DESIGN: We developed a microsimulation model that simulates a hypothetical cohort of the Japanese population with FAP for 40 years. Three scenarios were created based on three intervention strategies for comparison with no intervention, namely intensive downstaging polypectomy (IDP) of colorectal polyps at least 5.0 mm in diameter, IDP combined with low-dose aspirin, and total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Cost-effective strategies were identified using a willingness-to-pay threshold of USD 50,000 per QALY gained. RESULTS: Compared with no intervention, all strategies resulted in extended QALYs (21.01-21.43 QALYs per individual) and showed considerably reduced colorectal cancer mortality (23.35-53.62 CRC deaths per 1000 individuals). Based on the willingness-to-pay threshold, IDP with low-dose aspirin was more cost-effective than the other strategies, with an incremental cost-effectiveness ratio of $57 compared with no preventive intervention. These findings were confirmed in both one-way sensitivity analyses and probabilistic sensitivity analyses. CONCLUSION: This study suggests that the strategy of low-dose aspirin with IDP may be cost-effective compared with IDP-only or IPAA under the national fee schedule of Japan.

Impact of cancer and other causes of death on mortality of cancer patients: A study based on Japanese population-based registry data.

Cancer registry data provide a very important source of information for improving our understanding of the epidemiology of various cancers. In this work, we estimated the 5-year crude probabilities of death from cancer and from other causes for five common cancers, namely stomach, lung, colon-rectum, prostate and breast, in Japan, using population-based registry data. Based on data on 344 676 patients diagnosed with one of these cancers between 2006 and 2008 in 21 prefectures participating in the Monitoring of Cancer Incidence in Japan (MCIJ) and followed-up for at least 5 years, we used a flexible excess hazard model to compute the crude probabilities of death for different combinations of sex, age and stage at diagnosis. For tumours diagnosed at the distant stage, as well as for regional lung tumours, the vast majority of deaths at 5 years in cancer patients were attributable to the disease itself (although this proportion was only around 60% in older prostate cancer patients). For localised and most regional tumours, the impact of other causes of death on the total mortality increased with age at diagnosis, especially for localised breast, colorectal and gastric cancer. By allowing the partition of the mortality experience of cancer patients into a cancer- and an other-cause-specific component, crude probability of death estimates provide insight into how the impact of cancer on mortality might differ among populations with different background mortality risks. This might be useful for informing discussions between clinicians and patients about treatment options.

Local recurrence after endoscopic resection of sessile serrated lesions: A multicenter prospective study by the Osaka Gut Forum.

BACKGROUND AND AIM: Sessile serrated lesions (SSLs) act as precursors to colorectal cancer, sometimes harbor carcinomas, and are sometimes incompletely resected. We aimed to evaluate local recurrence after endoscopic resection of SSL ≥10 mm. METHODS: This prospective, single-arm, observational study was performed at eight Japanese tertiary institutions. Colorectal lesions ≥10 mm were resected endoscopically, and the pathological diagnosis was either an SSL or hyperplastic polyp (HP). Follow-up colonoscopy was performed 1 year later, and the local recurrence was evaluated by biopsy. RESULTS: From October 2018 to September 2021, 104 cases with 123 lesions were registered. Among the pathologically diagnosed 105 SSLs and 18 HPs, 95 and 7 lesions were diagnosed as SSLs and HPs, respectively, by central pathological review. Among the 104 endoscopically diagnosed SSLs, 86 were diagnosed as SSLs, whereas among the 11 endoscopically diagnosed HPs, two were diagnosed as HPs by central pathological review (the rest were SSLs). Among the 95 patients with 113 lesions who underwent follow-up colonoscopy, resection scars were identified in 95 (84%) lesions. Three (3.1%; 95% confidence interval 0.6-8.7%) local recurrences were diagnosed pathologically among 98 pathologically diagnosed SSLs. Two (6%) local recurrences were diagnosed in patients with SSLs ≥20 mm. CONCLUSIONS: The local recurrence rate after endoscopic resection of SSLs ≥10 mm was 3.1%. Careful follow-up is recommended after endoscopic resection of large SSLs. Endoscopically diagnosed HPs ≥10 mm were sometimes pathologically diagnosed as SSL and should be considered for resection.

Pressure-induced evolution in the durability of nickel-metal hydride batteries under high-current charge.

We found that an AAA-type battery (min. 750 mAh) pressurized with Ar or N2 at pressures of up to 5 MPa exhibited a significant durability enhancement even under high-current conditions. As an example of a charge-discharge cycle test at 3 amperes, the residual ratio of capacity at atmospheric pressure decreased to approximately 90% of the standard capacity before 50 cycles. However, at a pressure of 3 MPa of N2, the capacity remained at more than 90% until 180 cycles. With an increase in the pressure, the residual ratio of capacity was further improved. It has been considered that, at the positive electrode of the Ni-MH battery, the chemical reaction from nickel(II) hydroxide (Ni(OH)2) crystals to nickel oxide hydroxide (NiOOH) crystals occurs during the charging process. However, X-ray diffraction (XRD) results in the present study do not support this solid-solid reaction between these two types of crystal. To address this contradiction, we propose a different reaction mechanism by introducing the concept of non-crystalline fine particles of compounds, which are undetected by XRD. This mechanism clearly explains how the pressure affects the durability improvement. Pressurized batteries, which are capable of fast charge-discharge operation under high-current conditions, can provide a new route for application fields of unconventional energy storage.

How much can screening reduce colorectal cancer mortality in Japan? Scenario-based estimation by microsimulation.

BACKGROUND: Screening is one of the effective interventions for the reduction of colorectal cancer mortality. Though the Japanese government recommends faecal occult blood test and colonoscopy as a follow-up examination following a diagnosis, both participation rates have not been so high and the national mortality rate has not shown a clear decreasing trend. METHODS: Microsimulation models simulate the life histories of a large population of individuals under various scenarios. In this study, we applied a microsimulation model to estimate the reduction of colorectal cancer mortality based on screening scenarios. RESULTS: The effect of reducing the age-standardized mortality rate for colorectal cancer was estimated at 9.4% for men and 6.0% for women under the scenario which calls for 50% participation in faecal occult blood test and 90% participation of follow-up examination. This scenario corresponds to the goal setting for screening in the third-term of the Basic Plan to Promote Cancer Control Programs in Japan. CONCLUSIONS: Our microsimulation model was found to be useful in estimating the mortality reduction effect of cancer control policy. Such modelling techniques can be utilized to develop effective and optimal cancer control programs.

[A Systematic Review of Clinical and Epidemiological Studies Using Record Linkage Data between Hospital Based Cancer Registries and Biospecimen Data].

INTRODUCTION: Recently, registry-based cancer research linking biobanks with clinical information has become practical. In fact, hospital-based cancer registries(HBCR)are considered appropriate for basic medical information provision to link with biospecimen data since they can capture accurate information about cancer incidence and prognosis. The aim of this systematic review was to examine HBCR and biospecimen data uses in clinical and epidemiological studies. METHODS: We searched PubMed and Google Scholar for articles regarding HBCR and biospecimen data uses published before November 2019. Selected articles were summarized by study design into HBCR usage, biospecimen data usage, exposure, outcome, informed consent, and participant numbers. RESULT: Of the 2,767 identified articles, 148 studies were included in this review. In cohort studies, most HBCR usage was noted for patient selection, and most biospecimen data usage was factors affecting prognosis. Meanwhile, in case-control studies, most HBCR usage was noted for cancer incidence identification, and most biospecimen data usage was factors affecting cancer incidence. CONCLUSION: HBCR and biospecimen data usage in clinical and epidemiological studies were found to be different based on study design. Linkage of HBCR and biospecimen data will enable researchers to conduct clinical and epidemiological studies that correspond to varying research question types.

Sites of blood collection and topical antiseptics associated with contaminated cultures: prospective observational study.

We aimed to determine whether puncture sites for blood sampling and topical disinfectants are associated with rates of contaminated blood cultures in the emergency department (ED) of a single institution. This single-center, prospective observational study of 249 consecutive patients aged ≥ 20 years proceeded in the ED of a university hospital in Japan during 6 months. Pairs of blood samples were collected for aerobic and anaerobic culture from all patients in the ED. Physicians selected puncture sites and topical disinfectants according to their personal preference. We found 50 (20.1%) patients with potentially contaminated blood cultures. Fifty-six (22.5%) patients were true bacteremia and 143 (57.4%) patients were true negatives. Multivariate analysis associated more frequent contamination when puncture sites were disinfected with povidone-iodine than with alcohol/chlorhexidine (adjusted risk difference, 12.9%; 95% confidence interval [CI] 8.8-16.9; P < 0.001). Sites of blood collection were also associated with contamination. Femoral and central venous with other sites were associated with contamination more frequently than venous sites (adjusted risk difference), 13.1% (95% CI 8.2-17.9; P < 0.001]) vs. 17.3% (95% CI 3.6-31.0; P = 0.013). Rates of contaminated blood cultures were significantly higher when blood was collected from femoral sites and when povidone-iodine was the topical antiseptic.

CCL2 produced by CD68+/CD163+ macrophages as a promising clinical biomarker of microscopic polyangiitis-interstitial lung disease.

OBJECTIVES: Microscopic polyangiitis (MPA) is often complicated by interstitial lung disease (ILD); however, biomarkers that can be used to diagnose and predict the progression of MPA-ILD have not been identified. In this study, we evaluated various serum biomarkers in MPA-ILD to assess their diagnostic and predictive performance. METHODS: We enrolled 49 patients with anti-neutrophil cytoplasmic antibody (ANCA)+ MPA and 10 healthy controls, with 32 of the MPA patients also presenting ILD. The presence of ILD was assessed by high-resolution CT and evaluated by ground-glass opacity and fibrosis score. We compared 16 biomarker profiles among MPA-ILD patients, those without ILD, and healthy controls and extracted biomarkers with higher levels in MPA-ILD groups to determine correlations with disease activity and other biomarkers. Three lung biopsies were examined by haematoxylin-eosin staining and immunostaining. RESULTS: Initial serum C-C motif chemokine ligand 2 (CCL2) levels were significantly higher in the MPA-ILD group than those of the MPA group, and were significantly higher in MPA-ILD patients 1 year after immunosuppressive therapy than those before treatment. Initial serum CCL2 levels positively correlated with an increased fibrosis score during the year after treatment and with initial serum platelet-derived growth factor levels. Immunohistochemical staining showed intense CCL2 signals in CD68+/CD163+ macrophages and metaplastic epithelial cells in MPA-ILD lungs. CONCLUSION: CCL2 is associated with MPA-ILD pathogenesis and suggested its potential efficacy as a useful marker for diagnosing and predicting MPA-ILD progression. Therefore, targeting CCL2 in alveolar CD68+/CD163+ macrophages might represent a therapeutic intervention in ANCA+ MPA-ILD.

Determinant Factors on Differences in Survival for Gastric Cancer Between the United States and Japan Using Nationwide Databases.

BACKGROUND: Although the incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. An international study reported higher survival in Korea and Japan than other countries, including the United States. We examined the determinant factors of the high survival in Japan compared with the United States. METHODS: We analysed data on 78,648 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007 and compared them with 16,722 cases from the Surveillance, Epidemiology, and End Results Program (SEER), a United States population-based cancer registry data from 2004-2010. We estimated 5-year relative survival and applied a multivariate excess hazard model to compare the two countries, considering the effect of number of lymph nodes (LNs) examined. RESULTS: Five-year relative survival in Japan was 81.0%, compared with 45.0% in the United States. After controlling for confounding factors, we still observed significantly higher survival in Japan. Among N2 patients, a higher number of LNs examined showed better survival in both countries. Among N3 patients, the relationship between number of LNs examined and differences in survival between the two countries disappeared. CONCLUSION: Although the wide differences in GC survival between Japan and United States can be largely explained by differences in the stage at diagnosis, the number of LNs examined may also help to explain the gaps between two countries, which is related to stage migration.

Long-term outcomes after endoscopic submucosal dissection for differentiated-type early gastric cancer that fulfilled expanded indication criteria: A prospective cohort study.

BACKGROUND AND AIM: Endoscopic resection for early gastric cancer (EGC) is widely performed. However, there is still a paucity of strong evidence regarding long-term outcomes after endoscopic submucosal dissection (ESD) for the expanded indication criteria of the Japanese guidelines (ver. 2010). METHODS: Endoscopic submucosal dissection was performed in patients with EGC that met the expanded indication criteria: (i) cT1a, differentiated-type EGC of 2 to 5 cm, ulcer negative or (ii) cT1a, differentiated-type EGC of ≤3 cm, ulcer positive. Patients whose pathological examination fulfilled the curative resection criteria were then enrolled in this cohort study: negative vertical margin, negative lymphovascular invasion, and (i) pT1a, differentiated-type, and ulcer negative; (ii) pT1a, differentiated-type, ≤3 cm, and ulcer positive; or (iii) pT1b1 (<500-µm submucosal invasion), differentiated-type, and ≤3 cm. Patients with only a positive horizontal margin as a noncurative factor were included for follow-up. RESULTS: From September 2003 to February 2012, a total of 356 patients underwent ESD, and 214 were enrolled in the survival analysis. One hundred twenty patients (56%) had >2 cm in diameter and ulcer-negative lesions, and 94 (44%) had ≤3 cm and ulcer-positive lesions. The vital status at 5 years after ESD was confirmed in all (100%) patients. No local or metastatic recurrence was detected; however, 26 metachronous gastric cancers developed, and 1 patient died of metachronous gastric cancer. The 5-year disease-specific and overall survival rates were 99.5% (95% confidence interval [CI], 97.2%-100%) and 93.9% (95% CI, 89.8%-96.4%), respectively. CONCLUSION: ESD for EGC that fulfills the expanded criteria is feasible and shows favorable long-term outcomes.

Long-term trends in sex difference in bladder cancer survival 1975-2009: A population-based study in Osaka, Japan.

In Japan, a study using population-based cancer registry data from six prefectures revealed a difference in bladder cancer survival between men and women. However, the period of the study was limited to 1993-2006. The recent introduction of immune checkpoint inhibitors, which have proved to be effective for the treatment for bladder cancer, has led to a rising demand for analysis of long-term trends in net survival in order to accurately assess the effect of the new treatment. The aim of the present study was to examine long-term trends in sex difference in bladder cancer net survival using large-scale population-based cancer registry data from Osaka, Japan (17,500 cases from 1975 to 2009). We also evaluated sex difference in bladder cancer survival after adjustment for stage, histologic type, and other prognostic factors. We showed the long-term trend of five-year net survival for each stage and found that women had poorer five-year net survival than men for the whole study period. The risk of death from bladder cancer was higher among men than women even after adjusting for period at diagnosis, histologic type, stage, age group, and treatment (Excess hazard ratios: 1.17; 95% Confidence interval: 1.10-1.25).

Rare cancers are not rare in Asia as well: The rare cancer burden in East Asia.

INTRODUCTION: Epidemiologic information on rare cancers is scarce outside of the Western countries. The project "surveillance of rare cancers in Asia" (RARECAREnet Asia) provides, for the first time, the burden of rare cancers in some Asian countries based on the latest list. OBJECTIVES: 1) to assess whether the European list of rare cancers fits the Asian setting and 2) to compare the incidences of rare cancers between Europe and Asian countries. MATERIAL AND METHODS: Population-based cancer registry data on patients diagnosed from 2011 to 2015 in Japan, Korea, and Taiwan and patients diagnosed from 2000 to 2007 in 94 European registries were analysed. The incidences for all cancers were calculated; they were then grouped into several tiers and families according to the rare cancer list, and whether cancers rare was examined. RESULTS: Rare cancer counts according to the list in the observed population were 196 in Japan, 203 in Korea, 198 in Taiwan, and 198 in the EU. The proportions of rare in overall incidence were 16.3% in Japan, 23.7% in Korea, 24.2% in Taiwan, and 22.2% in the EU. The numbers of newly diagnosed rare cancer cases in 2015 were 140,188 in Japan, 52,071 in Korea, and 24,147 in Taiwan. CONCLUSION: Most rare cancers in Europe were also rare in the Asian countries considered. The observed differences were due to well-known risk factors. The European definition and list of rare cancers appear to reflect well cancer incidence in East Asia.

Does cold snare polypectomy completely resect the mucosal layer? A prospective single-center observational trial.

BACKGROUND AND AIM: The true incidence of incomplete muscularis mucosa resection with cold snare polypectomy (CSP) is unknown. We examined the incidence of incomplete muscularis mucosa resection both with and without cold snare defect protrusion (CSDP). METHODS: We prospectively enrolled patients undergoing polypectomy for 4 to 9mm nonpedunculated polyps. We evaluated the presence of CSDP immediately following CSP and biopsied the CSDP or the center of the mucosal defect without CSDP. The presence of the muscularis mucosa and any residual polyp in the biopsies was evaluated histologically. The primary outcome was the incidence of incomplete mucosal layer resection defined as the presence of muscularis mucosa or residual polyp in the biopsies. RESULTS: From August 2017 to October 2018, 188 patients were screened, and 357 polyps were included. CSDP was detected in 122/355 (34%) evaluated mucosal defects. Excluding five lesions requiring hemostasis immediately following CSP, 352 mucosal defects were biopsied. After excluding 102 biopsies containing normal mucosa, we evaluated 250 biopsies. The overall incidence of incomplete mucosal layer resection was 63% (159/250), 76% (68/90) with CSDP and 57% (91/159) without CSDP (P < 0.01). Both univariate and multivariate analyses showed that size (≥ 6 mm), resection time (≥ 5 s), and serrated lesions were risk factors for CSDP. CONCLUSIONS: Cold snare defect protrusion (CSDP), which was present with 36%, was a good indicator for incomplete mucosal layer resection. Even in nonCSDP polypectomies, 57% of the mucosal layer was not removed completely. Thus, CSP should be used for intra-epithelial lesions only, and careful pretreatment evaluation is recommended.

Exploration of pathomechanism using comprehensive analysis of serum cytokines in polymyositis/dermatomyositis-interstitial lung disease.

OBJECTIVES: To elucidate the serum cytokine profile and address the pathomechanism of interstitial lung disease (ILD) complicated with PM/DM. METHODS: Forty patients with PM/DM-ILD were enrolled, and principal components analysis and cluster analysis were performed to classify patients into subgroups. Additionally, we compared cytokine profiles between the survivors and dead patients and between anti-melanoma differentiation-associated gene 5 antibody- and anti-aminoacyl tRNA synthetase antibody-positive ILD patients. We also examined the association of various cytokines with disease activity indicators and prognosis of ILD. RESULTS: The principal components analysis data allowed classification of the cytokine profile into three groups: group 1, neutrophilic and M1-macrophage-driven cytokines; group 2, type 1 Th cell-driven and M2-macrophage-induced cytokines; and group 3, M2-macrophage-driven cytokines. Cluster analysis showed the presence of PM/DM-ILD patient groups with high or low levels of total cytokines. Ninety percent of patients who died of ILD were included in clusters with high cytokine levels. Serum cytokine levels of all groups were significantly higher in the anti-melanoma differentiation-associated gene 5 antibody-positive patients than in the anti-aminoacyl tRNA synthetase antibody-positive patients. Groups 1 and 2 significantly correlated with known factors for poor prognosis, such as serum ferritin levels and alveolar-arterial oxygen difference. Serum cytokine levels of patients in group 1 were significantly higher initially and at 2 and 4 weeks in those who died. CONCLUSION: These findings suggested that the activation of monocytes, macrophages and type 1 Th cells, and neutrophils play roles in the pathomechanism of PM/DM-ILD, and group 1 cytokines could be useful biomarkers for predicting prognosis of PM/DM-ILD.

Trends in incidence and long-term survival of Japanese women with vulvar cancer: a population-based analysis.

OBJECTIVE: The incidence and long-term survival analysis for vulvar cancer, due to its rarity, has not been fully described in Asian population. The objective of the study is to determine the trends in incidence and long-term survival for vulvar cancer in a Japanese population, using a population-based cancer registry data in Osaka, Japan. METHODS: The age-standardized incidence rate of 389 cases of vulvar squamous cell carcinoma (SCC) diagnosed between 1976 and 2010 was calculated, using the 1985 model population of Japan. The annual percentage change (APC) of the age-standardized incidence was estimated by the joinpoint regression models. The 5- and 10-year relative survival of 290 cases with vulvar SCC diagnosed between 1976 and 2008 were analyzed, using a cohort or period approach. Using the 10-year relative survival, the conditional 5-year survival for patients who lived for some years after diagnosis was also calculated. RESULTS: We have found that the age-standardized incidence rate for vulvar cancer trended downward during the period of 1979-1992 (APC - 6.3%; 95% confidence interval (CI) [- 11.3% to - 1.0%]), whereas it trended upward from 1993 to 2010 (APC 1.9%; 95% CI [- 0.7% to 4.6%]). There was no statistically significant difference for the 5- and 10-year relative survival between the two periods of 1976-2000 and 2001-2008. A statistically significant increase in the conditional 5-year survival at 2 years after diagnosis was observed (48.4%; 95% CI [41.1-55.3] versus 75.6%; 95% CI [64.0-83.9]). CONCLUSION: Despite an increasing trend in vulvar cancer incidence among Japanese population, the relative survival rate for vulvar cancer did not change over the 35 years of this study. We found that the conditional 5-year survival for vulvar cancer, as patients survived additional years, approached within reach of 100%. These data can provide valuable information for both patients and clinicians.

Statistical inference for estimating the incidence of cancer at the prefectural level in Japan.

Information of prefectural cancer incidence in Japan is an important resource to plan an effective regional cancer control program. In order to obtain accurate prefectural cancer incidence, we have to adjust for both of completeness of regional cancer registries and regional dispersion, simultaneously, Then, we developed a hierarchal Bayes model with a completeness adjustment by using the relation between MI ratio (mortality divided by incidence) and proportion of death certificate notified among incidence. Prefectural cancer incidence is estimated with the 95% credible interval, which suggests that the national MI ratio should be 0.386 if the registry were complete. Because cancer behavior has a variation depending on prefecture, such accurate incidence must contribute to plan and assess regional cancer control program.

Trends and projections of cancer mortality in Osaka, Japan from 1977 to 2032.

Projecting cancer mortality is fundamental to the process of planning cancer control. Although the prefecture is one of the main units for the implementation and evaluation of cancer control in Japan, a long-term detailed future projection of cancer mortality has not been conducted by prefecture. The main objective of this paper is to estimate the future number of cancer deaths in Osaka prefecture. Projections were made using the Nordpred model to estimate future trends in cancer mortality. The projected age-standardized mortality rate decreased by 24.5% in males and 16.8% in females from 2012-16 to 2032-36. However, the number of deaths showed a small decrease in males (1.3%) and an increase in females (13.1%). The largest contributor to the increasing number of cancer deaths is the aging population. In Japan, cancer control programmes are implemented by prefecture; our report can therefore be used for prefecture-level cancer control planning.

Epidemiologic and Clinical Analysis of Cervical Cancer Using Data from the Population-Based Osaka Cancer Registry.

Cervical cancer screening rate is extremely low and the governmental recommendation of HPV vaccine has been suspended for 5 years in Japan. Here, we utilized data from the Osaka Cancer Registry, collected between 1976 and 2012, to evaluate cervical cancer trends in Japan. Age-adjusted incidence, relative survival, and conditional survival rates were calculated using multiple imputation methods and period analyses in 25,826 cervical cancer cases. Association of survival rates and clinical factors, including patients' age, clinical stage, and treatment procedures, were also analyzed. A trend for significantly decreasing age-adjusted incidence of cervical cancer (per 100,000) began in 1976 but reversed after 2000, increasing significantly to date (annual percent change = 3.8, 95% confidence interval, 2.7-4.8; age-adjusted rate: 28.0 in 1976, 9.1 in 2000, 14.1 in 2012). The 10-year relative survival rate improved significantly after 2002, especially in cases of "localized" and "adjacent organs" disease; this was likely due to the introduction of concurrent chemotherapy and radiation. The conditional 5-year relative survival rate improved significantly yearly until the fourth survival year. In the surgery-based group, we observed no age-dependent differences in outcomes. Unexpectedly, however, prognosis for younger age groups was poorer in the radiation-based treatment group. These results indicate that although relative survival rates have recently increased, treatment for more advanced cases with distant metastasis requires further improvement. In addition, this study is the first to suggest that age might be an important predictor of radiotherapy resistance in cervical cancer.Significance: A large-cohort analysis of cervical cancer cases reveals that age-adjusted incidence in Japan has increased since 2000 and that age may negatively correlate with resistance to radiotherapy.

Tobacco Price Increases and Population Interest in Smoking Cessation in Japan Between 2004 and 2016: A Google Trends Analysis.

INTRODUCTION: Tobacco price increases can generate increased public interest in smoking cessation, but it is not clear how long this interest lasts. Our objective was to evaluate the duration of the impact of cigarette price increase in Japan using Google search data. METHODS: Monthly or daily aggregated Google search volume for smoking cessation in Japan from 2004 to 2016 was collected in terms of relative search volume (RSV) ranging from 0 to 100. Using monthly RSV data, we evaluated possible relationships between the RSVs and tobacco control measures in Japan. Time periods within which the impact of search volume significantly increased were identified by cluster detection test, using daily RSV data. A spike in RSV preceding the enforcement of a cigarette price increase revealed an anticipation effect. RESULTS: Between 2004 and 2016, the three highest monthly RSV spikes were observed in July 2006 (RSV = 66), when cigarette prices increased by 11%, and in September (RSV = 90) and October 2010 (RSV = 100), when cigarette prices increased by 37%. Regarding daily RSV, the detected cluster size around the price increase in 2010 (52 days) was longer than that in 2006 (17 days). In 2010, a cluster period of 25 days before the date of the price increase was observed, suggesting an anticipation effect. After the onset of the price increase, a cluster of 27 days was detected. When the cigarette price increased due to consumption tax in April 2014, almost no anticipation effect was observed. CONCLUSIONS: The population impact of tobacco price increases on smoking cessation may be assessed using Google Trends data. The cluster indicates that a higher cigarette price increase had a higher and longer lasting effect on population interest in cessation, but the impact may continue for a relatively short time. IMPLICATIONS: To examine the duration of the impact of cigarette price increases on population interest in smoking cessation in Japan, Google search data for smoking cessation were analyzed. Between 2004 and 2016, the three highest spikes of monthly RSV were observed in October 2010, when cigarette prices increased by 37%. Analyzing daily RSV data, the detected cluster size around the price increase in 2010 was 52 days, and a cluster period of 25 days before the date of the price increase was observed, suggesting an anticipation effect. The cluster indicates that a higher cigarette price increase had a higher and longer lasting effect, but the population impact continues for a relatively short time. Further increases in the price of cigarettes are necessary.

Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers: a prospective randomized phase II study.

BACKGROUND: Vonoprazan, potassium-competitive acid blocker, is expected to reduce incidence of delayed bleeding after gastric endoscopic submucosal dissection (ESD); however, preliminary data to design a large-scale comparative study are lacking. This study aimed to assess the efficacy of vonoprazan in preventing delayed bleeding after gastric ESD. METHODS: In this single-center randomized phase II trial, a modified screened selection design was used with a threshold non-bleeding rate of 89% and an expected rate of 97%. In this design, Simon's optimal two-stage design was first applied for each parallel group, and efficacy was evaluated in comparison with the threshold rate using binomial testing. Patients were randomly assigned in a 1:1 ratio to receive either vonoprazan 20 mg (VPZ group) or lansoprazole 30 mg (PPI group) for 8 weeks from the day before gastric ESD. The primary endpoint was the incidence of delayed bleeding, defined as endoscopically confirmed bleeding accompanied by hematemesis, melena, or a decrease in hemoglobin of ≥ 2 g/dl. RESULTS: Delayed bleeding occurred in three of 69 patients (4.3%, 95% CI 0.9-12.2%, p = 0.047) in the VPZ group, and four of 70 (5.7%, 95% CI 1.6-14.0%, p = 0.104) in the PPI group. As only vonoprazan showed significant reduction in delayed bleeding compared with the threshold rate, it was determined to be efficacious treatment. CONCLUSIONS: Vonoprazan efficaciously reduced the delayed bleeding rate in patients with an ESD-induced gastric ulcer. A large-scale, randomized, phase III study is warranted to definitively test the effectiveness of vonoprazan compared with proton pump inhibitors.