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.

Have restrictions on human mobility impacted suicide rates during the COVID-19 pandemic in Japan?

During the COVID-19 pandemic in Japan, various measures have been implemented to prevent the spread of infection, including restrictions on human mobility. A dynamic fluctuation in the number of suicides has been observed during this period. The question is whether the increase/decrease in suicides during the pandemic is related to changes in human mobility. To answer the same, we estimated incidence rate ratios (IRR) of suicide for changes in human mobility using the relative number of suicides by month from March 2020 to September 2021, based on the same months in 2019 as reference. The IRR of suicide during the pandemic were significantly lower in the months when mobility decreased-in both the previous and current month-than in the months when mobility was stable; the IRR of suicide were statistically higher in the months with increased mobility compared with the stable months. The burden from a decrease in one's mobility, which might lead to an increase in suicide, may not occur immediately, as seen in the delayed effects of unemployment. It may be important to investigate people's mental health and stress levels after pandemic restrictions were relaxed. The findings may help practitioners and families consider the timing of intervention.

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.

Persistence of Mental Health Deterioration Among People Living Alone During the COVID-19 Pandemic: A Periodically-repeated Longitudinal Study.

BACKGROUND: This longitudinal study aimed to investigate how psychological distress levels changed from early to middle phases of the new coronavirus (COVID-19) pandemic depending on the living arrangements of individuals. METHODS: An internet-based, longitudinal survey of 2,400 Japanese people was conducted every 5-6 weeks between February 2020 and January 2021. The presence of severe psychological distress (SPD) was measured using the Kessler's psychological distress scale. Living arrangements were classified into two groups (ie, living alone or living with others). Mixed-effects logistic regression analysis was performed to assess whether changes in SPD status were different depending on living arrangements. RESULTS: Of 2,400 respondents, 446 (18.5%) lived alone. Although the proportion of SPD in both individuals living alone and those living with others increased to the same extent in the early phase of the pandemic, the distress levels decreased after the early phase of the pandemic in the group living with others, compared with the group living alone, for which SPD remained high. The odds ratio (OR) of developing SPD in interaction term with survey phases tended to be higher among those who lived alone than those who lived with others in Phase 6 (OR 1.89; 95% confidence interval [CI], 0.99-3.64) and Phase 7 (OR 1.88; 95% CI, 0.97-3.63). CONCLUSION: During the COVID-19 pandemic, those living alone are persistently at a higher risk of SPD compared to those living with others. Effective countermeasures targeting those living alone, such as enhancing online communication or providing psychological therapies, are essential.

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.

Geographical socioeconomic inequalities in healthy life expectancy in Japan, 2010-2014: An ecological study.

BACKGROUND: Area differences in life expectancy (LE) and healthy life expectancy (HLE) in large geographical units have been monitored around the world. Area characteristics may be based on culture, history, socioeconomic status and discrimination in smaller geographical units, so it is important to consider these when looking at health inequality. We aimed to evaluate LE, HLE, and non-healthy life expectancy (NHLE) in 1707 municipalities using Areal Deprivation Index (ADI) in Japan for the first time. METHODS: We calculated the observed LE, HLE, and NHLE using death, population, and Long-term care insurance data for 2010-2014 and applied the variance weighted least squares model to estimate LE, HLE, and NHLE by 100 percentiles using the standardized ADI. FINDINGS: The estimated LE, HLE, and NHLE became lower as the deprivation index worsened: the differences between the most and least deprived areas for HLE were 2·49 years for LE and 2·32 years for HLE in males; 1·22 years for LE and 0·93 years for HLE in females. The observed LE and HLE in the most deprived areas were much lower than other areas. INTERPRETATION: Using ADI has enabled us to see the disparity within municipalities precisely. LE and HLE outlier for the 100th percentile might be linked to historical areal deprivation and marginalization. Precise monitoring of socioeconomic status-based health inequalities could help manage these inequalities by identifying the groups most in need of intervention. FUNDING: The Ministry of Education, Science and Culture of Japan (a Grant-in-Aid for Scientific Research [A] No. 20H00040 and 18H04071).

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.

Evaluation of poor prognostic factors of respiratory related death in microscopic polyangiitis complicated by interstitial lung disease.

The prognosis of microscopic polyangiitis (MPA) with interstitial lung disease (ILD) is significantly worse than that of MPA without ILD. However, the clinical characteristics in MPA-ILD, especially poor prognostic factors, are not elucidated. We evaluated demographic, clinical, laboratory, and radiological findings, treatments, and outcomes of 80 patients with MPA, and investigated prognostic factors of respiratory-related death in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positive MPA-ILD. Ground-glass opacity and fibrosis were evaluated as scores on high-resolution computed tomography (HRCT). The presence of ILD was consistent with a high risk of respiratory-related death (hazard ratio, 4.8; P = 0.04). Multivariable logistic regression analyses using propensity scoring showed right or left lower lobe fibrosis score to be significantly associated with respiratory-related death (P = 0.0005 and 0.0045, respectively). A right or left lower lobe fibrosis score ≥ 2, indicating the presence of honeycombing at 1 cm above the diaphragm, was determined to be the best cut-off value indicating a poor prognosis. The 5-year survival rate was significantly lower in patients with right or left lower lobe fibrosis score ≥ 2 (survival rates: 37% and 19%, respectively) than those with a score < 2 (71% and 68%, respectively) (P = 0.002 and 0.0007, respectively). These findings suggest that the presence of honeycomb lesions in bilateral lower lobes on chest HRCT was associated with respiratory-related death in patients with MPO-ANCA positive MPA-ILD.

Excess Mortality From Suicide During the Early COVID-19 Pandemic Period in Japan: A Time-Series Modeling Before the Pandemic.

BACKGROUND: Suicide amidst the coronavirus disease (COVID-19) pandemic is an important issue. In Japan, the number of suicides in April 2020 decreased by nearly 20% from that in 2019. To assess the impact of an infectious disease pandemic, excess mortality is often discussed. Our main purpose was evaluating excess mortality from suicide in Japan during the early pandemic period. METHODS: We used data on suicides collected by the National Police Agency of Japan until June 2020. We estimated excess mortality during the early pandemic period (March-June 2020) using a time-series model of the number of suicides before the pandemic. A quasi-Poisson model was employed for the estimation. We evaluated excess mortalities by the categories of age and sex, and by prefecture. RESULTS: No significant excess mortality was observed throughout the early pandemic; instead, a downward trend in the number of suicides for both sexes was noted. For males, negative values of excess mortalities below the lower bound of the 95% prediction interval were observed in April and May. All numbers of females during the period were included in the interval, and the excess mortalities in June were positive and higher than those in April and May. In Tokyo, the number of suicides was below the lower bound throughout the period. CONCLUSION: Our results suggest that various changes, such as communication, and social conditions amid the early COVID-19 pandemic induced a decrease in suicides in Japan. However, continuous monitoring is needed to evaluate the long-term effects of the pandemic on suicides.

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.

Changes in Psychological Distress During the COVID-19 Pandemic in Japan: A Longitudinal Study.

BACKGROUND: This longitudinal study aimed to examine the changes in psychological distress of the general public from the early to community-transmission phases of the COVID-19 pandemic and to investigate the factors related to these changes. METHODS: An internet-based survey of 2,400 Japanese people was conducted in two phases: early phase (baseline survey: February 25-27, 2020) and community-transmission phase (follow-up survey: April 1-6, 2020). The presence of severe psychological distress (SPD) was measured using the Kessler's Six-scale Psychological Distress Scale. The difference of SPD percentages between the two phases was examined. Mixed-effects ordinal logistic regression analysis was performed to assess the factors associated with the change of SPD status between the two phases. RESULTS: Surveys for both phases had 2,078 valid respondents (49.3% men; average age, 50.3 years). In the two surveys, individuals with SPD were 9.3% and 11.3%, respectively, demonstrating a significant increase between the two phases (P = 0.005). Significantly higher likelihood to develop SPD were observed among those in lower (ie, 18,600-37,200 United States dollars [USD], odds ratio [OR] 1.95; 95% confidence interval [CI], 1.10-3.46) and the lowest income category (ie, <18,600 USD, OR 2.12; 95% CI, 1.16-3.86). Furthermore, those with respiratory diseases were more likely to develop SPD (OR 2.56; 95% CI, 1.51-4.34). CONCLUSIONS: From the early to community-transmission phases of COVID-19, psychological distress increased among the Japanese. Recommendations include implementing mental health measures together with protective measures against COVID-19 infection, prioritizing low-income people and those with underlying diseases.

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.

Effect of Shakuyaku-kanzo-to in patients with muscle cramps: A systematic literature review.

BACKGROUND: Previous clinical studies have reported that Shakuyaku-kanzo-to (SKT) has a therapeutic effect on muscle cramps, but few studies have clarified how SKT acts to treat muscle cramps. The aim of this study was to perform an updated systematic review of clinical trials for SKT in patients with muscle cramps. METHODS: The literature was systematically reviewed to assess the effects of SKT in patients with muscle cramps. PubMed, Web of Science, Cochrane Library, Google Scholar, and Ichushi-Web were searched using the terms "Shakuyaku-kanzo-to" ("shakuyakukanzoto", etc), "clinical trials" and "muscle cramps". Two quality assessments were conducted independently by three authors. Data were extracted using a standardized extraction tool, and a qualitative synthesis of evidence was performed. RESULTS: Three randomized controlled articles were identified and enrolled in this study. A systematic review, but not a meta-analysis, was performed because of the high heterogeneity and limited number of studies. In patients with liver cirrhosis, the odds ratio (OR) for improvement with SKT compared to placebo was 1.27 (95% confidence interval [CI], 0.445-2.086) and compared to Goshajinkigan was 0.81 (95%CI, -1.734-0.114). The OR for improvement with SKT compared with eperisone hydrochloride in patients with lumbar spinal stenosis was 2.86 (95%CI, 0.980-4.744). CONCLUSIONS: Current evidence appears insufficient to allow a meta-analysis of the effects of SKT, but SKT might show efficacy in treating muscle cramps in patients with cirrhosis or lumbar spinal stenosis.