Travel burdens to access care among children with cancer between 2016 and 2019: Analysis of a national population-based cancer registry in Japan.

BACKGROUND: Centralization of cancer care increases survival but increases the travel burden (i.e., travel durations, distances, and expenditures) in visiting hospitals. This study investigated the travel burdens to access cancer care for children aged 18 years and younger in Japan. METHODS: The study population comprised 10,709 patients diagnosed between 2016 and 2019 obtained from a national population-based cancer registry in Japan. Their residences were classified as urban or rural. We counted the number of patients treated at specialized hospitals and investigated the treatment centralization across diagnostic groups by Pareto plot. Travel burdens to access care were estimated using a route-planner web service and summarized using median values. A multivariable logistic model was performed to investigate factors associated with the events of car travel duration exceeding 1 h. RESULTS: Of the patients, 76.7% lived in urban areas, and 82.5% received treatment in designated hospitals for childhood cancer. The Pareto plot suggested that the top five hospitals treated 63.5% of patients with retinoblastoma. The estimated travel burdens for all patients were 0.62 h (0.57 h in urban areas and 1.00 h in rural areas), 16.9 km, and 0.0 dollars of toll charges. Regarding travel duration, 21.7% of patients had travel exceeding 1 h, and rural areas, retinoblastoma, malignant bone tumors, and childhood cancer-hub hospitals were associated with travel duration exceeding 1 h (adjusted odds ratios of 6.93, 3.59, 1.94, and 1.91, respectively). CONCLUSIONS: Most patients were treated in specialized hospitals and the treatments for specific diseases were centralized. However, most patients were estimated to travel less than 1 h, and the travel burden tended to increase for patients in rural areas, those with specific diseases, and those going to specialized hospitals. Cancer control measures in Japan have steadily improved centralized treatment while keeping the travel burden relatively manageable.

Proportions and characteristics of interval cancer in annual fecal immunochemical test screening and postcolonoscopy colorectal cancer: Results from a Japanese multicenter prospective study using questionnaires, the C-DETECT study.

OBJECTIVES: There are several types of colorectal cancer (CRC) according to the detection methods and intervals, including interval CRC (iCRC) and postcolonoscopy CRC (PCCRC). We aimed to examine their proportions and characteristics. METHODS: We conducted a multicenter prospective study using questionnaires in Japan ("C-DETECT study"), in which differences in CRC characteristics according to detection methods and intervals were examined from consecutive adult patients. Because the annual fecal immunochemical test (FIT) was used in population-based screening, the annual FIT-iCRC was assessed. RESULTS: In total, 1241 CRC patients (1064 with invasive CRC) were included. Annual FIT-iCRC (a), 3-year PCCRC (b), and CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy (c) accounted for 4.5%, 7.0%, and 3.9% of all CRCs, respectively, and for 3.9%, 5.4%, and 4.3% of invasive CRCs, respectively. The comparison among these (a, b, c) and other CRCs (d) demonstrated differences in the proportions of ≥T2 invasion ([a] 58.9%, [b] 44.8%, [c] 87.5%, [d] 73.0%), metastasis ([a] 33.9%, [b] 21.8%, [c] 54.2%, [d] 43.9%), right-sided CRC ([a] 42.9%, [b] 40.2%, [c] 18.8%, [d] 28.6%), and female sex ([a] 53.6%, [b] 49.4%, [c] 27.1%, [d] 41.6%). In metastatic CRC, (a) and (b) showed a higher proportions of BRAF mutations ([a] [b] 12.0%, [c] [d] 3.1%). CONCLUSIONS: Annual FIT-iCRC and 3-year PCCRC existed in nonnegligible proportions. They were characterized by higher proportions of right-sided tumors, female sex, and BRAF mutations. These findings suggest that annual FIT-iCRC and 3-year PCCRC may have biological features different from those of other CRCs.

Endoscopic Removal of Premalignant Lesions Reduces Long-Term Colorectal Cancer Risk: Results From the Japan Polyp Study.

BACKGROUND & AIMS: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. METHODS: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). RESULTS: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. CONCLUSIONS: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.

Short-term and long-term outcomes of submucosal dissection for residual or recurrent colorectal tumors after endoscopic resection: Analysis of a multicenter prospective study.

OBJECTIVES: We previously demonstrated that a favorable long-term prognosis indicated that endoscopic submucosal dissection (ESD) could be the standard treatment for large colorectal epithelial neoplasms, but the usefulness of ESD for local residual or recurrent tumors with submucosal fibrosis has not been fully demonstrated. The aim of the present study was to assess the usefulness of ESD for local residual or recurrent colorectal tumors. METHODS: We conducted a nationwide multicenter prospective study to evaluate the outcomes of ESD for colorectal tumors. In this post hoc analysis, a total of 54 local residual or recurrent colorectal tumors in 54 patients were included, and we analyzed the short-term and long-term outcomes of ESD for these lesions. RESULTS: The median size of the lesions was 16.0 (interquartile range [IQR] 11-25) mm. ESD was completed in 53 cases (98.1%) with a median procedure time of 65.0 min, but it was discontinued in one case because of submucosal cancer invasion. En bloc resection was achieved in 52 cases (96.3%), whereas R0 resection was achieved in 45 cases (83.3%). Intraoperative perforation was observed in four cases (7.4%) and delayed perforation in one (1.9%), but all cases could be managed conservatively. Delayed bleeding was not observed. There were no significant differences in short-term outcomes between the rectal and colonic lesions. There was no recurrence of the tumor during the median follow-up period of 60 (IQR 50-64) months. CONCLUSION: An analysis of our multicenter prospective study suggests that ESD is an effective salvage management for local residual or recurrent colorectal lesions.

Identification of Early Biochemical Recurrence Predictors in High-Risk Prostate Cancer Patients Treated with Carbon-Ion Radiotherapy and Androgen Deprivation Therapy.

The aim of this retrospective study was to identify clinical predictors of early biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). A total of 670 high-risk PCa patients treated with CIRT and ADT were included in the study. Early BCR was defined as recurrence occurring during adjuvant ADT after CIRT or within 2 years after completion of ADT. Univariate and multivariate analyses were performed to identify clinical predictors of early BCR. Patients were also classified according to the Systemic Therapy in Advancing or Metastatic Prostate cancer (STAMPEDE) PCa classification. Early BCR was observed in 5.4% of the patients. Multivariate analysis identified clinical T3b stage and ≥75% positive biopsy cores as clinical predictors of early BCR after CIRT and ADT. The STAMPEDE PCa classification was also significantly associated with early BCR based on univariate analysis. These predictors can help clinicians identify patients who are at risk of early BCR. In the future, combination therapy of ADT with abiraterone may be an option for high-risk PCa patients who are at risk of early BCR, based on the results of the STAMPEDE study.

First report from the International Evaluation of Endoscopic classification Japan NBI Expert Team: International multicenter web trial.

OBJECTIVES: Narrow-band imaging (NBI) contributes to real-time optical diagnosis and classification of colorectal lesions. The Japan NBI Expert Team (JNET) was introduced in 2011. The aim of this study was to explore the diagnostic accuracy of JNET when applied by European and Japanese endoscopists not familiar with this classification. METHODS: This study was conducted by 36 European Society of Gastrointestinal Endoscopy (ESGE) and 49 Japan Gastroenterological Endoscopy Society (JGES) non-JNET endoscopists using still images of 150 lesions. For each lesion, nonmagnified white-light, nonmagnified NBI, and magnified NBI images were presented. In the magnified NBI, the evaluation area was designated by region of interest (ROI). The endoscopists scored histological prediction for each lesion. RESULTS: In ESGE members, the sensitivity, specificity, and accuracy were respectively 73.3%, 94.7%, and 93.0% for JNET Type 1; 53.0%, 64.9%, and 62.1% for Type 2A; 43.9%, 67.7%, and 55.1% for Type 2B; and 38.1%, 93.7%, and 85.1% for Type 3. When Type 2B and 3 were considered as one category of cancer, the sensitivity, specificity, and accuracy for differentiating high-grade dysplasia and cancer from the others were 59.9%, 72.5%, and 63.8%, respectively. These trends were the same for JGES endoscopists. CONCLUSION: The diagnostic accuracy of the JNET classification was similar between ESGE and JGES and considered to be sufficient for JNET Type 1. On the other hand, the accuracy for Types 2 and 3 is not sufficient; however, JNET 2B lesions should be resected en bloc due to the risk of cancers and JNET 3 can be treated by surgery due to its high specificity.

Impact of renal and hepatic function on first opioid prescriptions in cancer patients: an acute care hospital database study linked to medical claims data and laboratory data.

BACKGROUND: Cancer patients often have impaired renal and hepatic function. Opioids are essential to relieve painful symptoms in cancer patients. However, it is unknown which opioids are first prescribed for cancer patients with renal and hepatic impairment. The objective is to investigate the association between the type of first prescribed opioids and the renal/hepatic function of cancer patients. METHODS: We used a multicenter database from 2010 to 2019. The number of days from the first opioid prescription to the death was defined as the prognostic period. This period was divided into six categories. The prevalence of opioid prescriptions was calculated for each assessment of renal and hepatic function, divided into prognostic periods. Multinomial logistic regression analysis was used to explore the influence of renal and hepatic function on the first opioid choice. RESULTS: The study included 11 945 patients who died of cancer. In all prognostic period categories, the patients with worse renal function received fewer morphine prescriptions. No trend was observed in hepatic function. The odds ratio of oxycodone to morphine with reference to estimated glomerular filtration rate (eGFR) ≥90 was 1.707 (95% confidence interval: 1.433-2.034) for estimated glomerular filtration rate <30. The odds ratio of fentanyl to morphine with reference to estimated glomerular filtration rate ≥90 was 1.785 (95% confidence interval: 1.492-2.134) for estimated glomerular filtration rate <30. No association was identified between hepatic function and the choice of prescribed opioids. CONCLUSION: Cancer patients with renal impairment tended to avoid morphine prescriptions, and no specific trend was observed in cancer patients with hepatic impairment.

Association between Living Conditions and the Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults.

Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m2, current smoking, heavy alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia. Furthermore, in the solitary group, the proportions of men, unmarried individuals, and current smokers were significantly higher than in the cohabiting group. In addition, poor outcomes (modified Rankin Scale ≥4) of IS were more common in the solitary group than in the cohabiting group. Conclusion Our study showed that not only conventional vascular risk factors but also living conditions, especially living alone while unmarried, were independent risk factors for IS in young adults.

A Multicenter Prospective Validation Study on Selective Endoscopic Resection of Sessile Serrated Lesions Using Magnifying Colonoscopy in Clinical Practice.

INTRODUCTION: Sessile serrated lesions (SSLs) have malignant potential for colorectal cancer in the serrated pathway. Selective endoscopic resection of SSLs would reduce medical costs and procedure-related accidents, but the accurate endoscopic differentiation of SSLs from hyperplastic polyps (HPs) is challenging. To explore the differential diagnostic performance of magnifying colonoscopy in distinguishing SSLs from HPs, we conducted a multicenter prospective validation study in clinical practice. METHODS: Considering the rarity of diminutive SSLs, all lesions ≥6 mm that were detected during colonoscopy and diagnosed as type 1 based on the Japan narrow-band imaging expert team (JNET) classification were included in this study. Twenty expert endoscopists were asked to differentiate between SSLs and HPs with high or low confidence level after conventional and magnifying NBI observation. To examine the validity of selective endoscopic resection of SSLs using magnifying colonoscopy in clinical practice, we calculated the sensitivity of endoscopic diagnosis of SSLs with histopathological findings as comparable reference. RESULTS: A total of 217 JNET type 1 lesions from 162 patients were analyzed, and 114 lesions were diagnosed with high confidence. The sensitivity of magnifying colonoscopy in detecting SSLs was 79.8% (95% confidence interval [CI]: 74.7-84.4%) overall, and 82.4% (95% CI: 76.1-87.7%) in the high-confidence group. These results showed that the sensitivity of this study was not high enough, even limited in the high-confidence group. CONCLUSIONS: Accurate differential diagnosis of SSLs and HPs using magnifying colonoscopy was challenging even for experts. JNET type 1 lesions ≥6 mm are recommended to be resected because selective endoscopic resection has a disadvantage of leaving approximately 20% of SSLs on site.

Trends in strong opioid prescription for cancer patients in Japan from 2010 to 2019: an analysis with large medical claims data.

BACKGROUND: Consumption of opioids, essential drugs for pain relief, has seen rapid growth worldwide. In Japan, where total opioid consumption still remains low among developed countries, little is known about trends in the clinical patterns of opioids in terminally ill cancer patients. METHODS: Patients who died of cancer from 2010 to 2019 were included in this study. Morphine, oxycodone, fentanyl, tapentadol, methadone and hydromorphone were examined as opioids for cancer pain. We calculated the prevalence of prescribed opioids prior to death by year and age group and the average opioid dose 30 days before death. RESULTS: The total number of patients was 221 598. We found that the prescription prevalence of opioids increased from 60.8 to 65.9% (5.1%). Morphine was most prescribed in 2010 but had decreased prevalence (-9.0%) during the 10-year period. Oxycodone had the highest increase in prescription prevalence (13.7%), and fentanyl prevalence decreased (-4.9%). In the subgroup comparison, the prescription prevalence of opioids in the elderly was lower than that in the younger group; however, the increasing trend in the elderly was greater than that in the younger group. The percentage of patients prescribed low-dose opioids (<60 mg/day) during the 30 days before death increased by 4.9% and was the highest throughout the study period. CONCLUSION: The prevalence of opioid prescriptions for terminally ill cancer patients has increased from 2010 to 2019 in Japan. The opioid-specific trends were similar to the global trend but differed by palliative care specialty.

Multifocal locules including the anterior mediastinum side as a surgical indicator in pleural infection.

Background: The indication for and the timing of surgery in patients with pleural infection remains unclear. Determining the need for surgery in patients with pleural infection may help in the early consultation of surgeons. Methods: Data of 167 consecutive patients with pleural infection were retrospectively reviewed. To detect a surgical indicator, the variables of patients who required surgery were compared with those of patients who were cured by non-surgical therapy (n=94) and patients resistant to the non-surgical therapy (n=73; 62 underwent surgery, and 11 showed recurrence or disease-related death after non-surgical treatment). Prognosis and timing of surgery were analyzed by comparing three groups: patients who underwent surgery within 7 days of admission (n=33), patients who underwent surgery after 7 days of admission (n=29), and patients who underwent non-surgical therapy (n=105). Results: The presence of multifocal locules, including a locule on the anterior mediastinum side (LAMS) was a significant indicator of resistance to initial non-surgical therapy, as compared to the absence of locules (P<0.0001), a single locule (P<0.0001), or multifocal locules without a LAMS (P=0.0041). Recurrence and mortality were not observed in the patients who underwent surgery within 7 days of admission, and the hospitalization period (P=0.0071) and duration of C-reactive protein (CRP) improvement (P<0.0001) were significantly shorter in these patients compared with those who that underwent surgery after 7 days. Conclusions: In patients with pleural infection, the presence of multifocal locules, including a LAMS, was associated with resistance to non-surgical therapy. Early surgery should be considered for these patients to shorten the hospitalization period and improve the prognosis.

Long-term Outcomes After Endoscopic Submucosal Dissection for Large Colorectal Epithelial Neoplasms: A Prospective, Multicenter, Cohort Trial From Japan.

BACKGROUND & AIMS: To determine the long-term outcomes after colorectal endoscopic submucosal dissection (ESD), we conducted a large, multicenter, prospective cohort trial with a 5-year observation period. METHODS: Between February 2013 and January 2015, we consecutively enrolled 1740 patients with 1814 colorectal epithelial neoplasms ≥20 mm who underwent ESD. Patients with noncurative resection (non-CR) lesions underwent additional radical surgery, as needed. After the initial treatment, intensive 5-year follow-up with planned multiple colonoscopies was conducted to identify metastatic and/or local recurrences. Primary outcomes were overall survival, disease-specific survival, and intestinal preservation rates. The rates of local recurrence and metachronous invasive cancer were evaluated as the secondary outcomes. RESULTS: The 5-year overall survival, disease-specific survival, and intestinal preservation rates were 93.6%, 99.6%, and 88.6%, respectively. Patients with CR lesions had no metastatic occurrence, and patients with non-CR lesions had 4 metastatic occurrences. Kaplan-Meier curves revealed that overall survival and disease-specific survival rates were significantly higher in patients with CR lesions than in those with non-CR lesions (P > .001 and P = .009, respectively). Local recurrence occurred in only 8 lesions (0.5%), which were successfully resected by subsequent endoscopic treatment. Multiple logistic regression analyses revealed that piecemeal resection (hazard ratio, 8.19; 95% CI, 1.47-45.7; P = .02) and margin-positive resection (hazard ratio, 8.06; 95% CI, 1.76-37.0; P = .007) were significant independent predictors of local recurrence after colorectal ESD. Fifteen metachronous invasive cancers (1.0%) were identified during surveillance colonoscopy, most of which required surgical resection. CONCLUSIONS: A favorable long-term prognosis indicates that ESD can be the standard treatment for large colorectal epithelial neoplasms. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000010136.

Early P2Y12 Inhibitor Single Antiplatelet Therapy for High-Bleeding Risk Patients After Stenting　- PENDULUM Mono 24-Month Analysis.

BACKGROUND: In PENDULUM mono, Japanese patients with high bleeding risk (HBR) received short-term dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with prasugrel after percutaneous coronary intervention (PCI). One-year data from PENDULUM mono showed better outcomes with prasugrel monotherapy after short-term DAPT compared with matched patients in the PENDULUM registry with longer DAPT durations according to guidelines at that time. This study presents 2-year results.Methods and Results: We compared 24-month data from PENDULUM mono (n=1,107; de-escalation strategy group) and the PENDULUM registry (n=2,273; conventional strategy group); both were multicenter, non-interventional, prospective registry studies, using the inverse probability of treatment weighting (IPTW) method. In the PENDULUM mono group, the cumulative incidence of clinically relevant bleeding (CRB) at 24 months post-PCI (primary endpoint) was 6.8%, and that of major adverse cardiac and cerebrovascular events (MACCE) was 8.9%. After IPTW adjustment, the cumulative incidence of CRB was 5.8% and 7.2% in PENDULUM mono and the PENDULUM registry, respectively (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.57-1.04; P=0.086), and that of MACCE was 8.0% and 9.5%, respectively (HR 0.77; 95% CI 0.59-1.01; P=0.061). CONCLUSIONS: Japanese PCI patients with HBR prescribed prasugrel SAPT after short-term DAPT had a lower ischemic event risk than those prescribed long-term DAPT, and this was particularly relevant for ischemic events after 1 year.

Combination of mean CT value and maximum CT value as a novel predictor of lepidic predominant lesions in small lung adenocarcinoma presenting as solid nodules.

Lung adenocarcinomas presenting as solid nodules are occasionally diagnosed as lepidic predominant lesions. The aim of this study was to clarify the histological structure and to identify factors predictive of lepidic predominant lesions. We retrospectively reviewed 38 patients that underwent lobectomy for small (≤ 2 cm) adenocarcinoma presenting as solid nodules. Resected tumor slides were reviewed and histological components were evaluated. Clinical and radiological data were analyzed to identify factors predictive of lepidic predominant lesions. Of 38 solid nodules, 9 (23.7%) nodules were lepidic predominant lesions. Five-year disease-free survival (DFS) rates were 100% for lepidic predominant lesions (n = 9) and 74.6% for non-lepidic predominant lesions (n = 29). Mean CT values (p = 0.039) and maximum CT values (p = 0.015) were significantly lower in lepidic predominant lesions compared with non-lepidic predominant lesions. For the prediction of lepidic predominant lesions, the sensitivity and specificity of mean CT value (cutoff, - 150 HU) were 77.8% and 82.8%, respectively, and those of maximum CT value (cutoff, 320 HU) were 77.8% and 72.4%, respectively. A combination of mean and maximum CT values (cutoffs of - 150 HU and 380 HU for mean CT value and maximum CT value, respectively) more accurately predicted lepidic predominant lesions, with a sensitivity and specificity of 77.8% and 86.2%, respectively. The prognosis of lepidic predominant lesions was excellent, even for solid nodules. The combined use of mean and maximum CT values was useful for predicting lepidic predominant lesions, and may help predict prognosis.

Efficacy of international web-based educational intervention in the detection of high-risk flat and depressed colorectal lesions higher (CATCH project) with a video: Randomized trial.

OBJECTIVES: Three subcategories of high-risk flat and depressed lesions (FDLs), laterally spreading tumors non-granular type (LST-NG), depressed lesions, and large sessile serrated lesions (SSLs), are highly attributable to post-colonoscopy colorectal cancer (CRC). Efficient and organized educational programs on detecting high-risk FDLs are lacking. We aimed to explore whether a web-based educational intervention with training on FIND clues (fold deformation, intensive stool/mucus attachment, no vessel visibility, and demarcated reddish area) may improve the ability to detect high-risk FDLs. METHODS: This was an international web-based randomized control trial that enrolled non-expert endoscopists in 13 Asian countries. The participants were randomized into either education or non-education group. All participants took the pre-test and post-test to read 60 endoscopic images (40 high-risk FDLs, five polypoid, 15 no lesions) and answered whether there was a lesion. Only the education group received a self-education program (video and training questions and answers) between the tests. The primary outcome was a detection rate of high-risk FDLs. RESULTS: In total, 284 participants were randomized. After excluding non-responders, the final data analyses were based on 139 participants in the education group and 130 in the non-education group. The detection rate of high-risk FDLs in the education group significantly improved by 14.7% (66.6-81.3%) compared with -0.8% (70.8-70.0%) in the non-education group. Similarly, the detection rate of LST-NG, depressed lesions, and large SSLs significantly increased only in the education group by 12.7%, 12.0%, and 21.6%, respectively. CONCLUSION: Short self-education focusing on detecting high-risk FDLs was effective for Asian non-expert endoscopists. (UMIN000042348).

Optimal surveillance interval after piecemeal endoscopic mucosal resection for large colorectal neoplasia: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Colorectal neoplastic lesions (≥ 20 mm) are commonly treated via piecemeal endoscopic mucosal resection (p-EMR) but have a high rate of local recurrence. We aimed to clarify the optimal surveillance interval after p-EMR for these neoplasias. METHODS: In this multicenter (15 participating institutions) prospective, randomized trial, 180 patients recruited over a 4-year period and were classified based on tumor location, tumor diameter, histological diagnosis, institution, and number of resected specimens. The patients underwent curative p-EMR followed by scheduled surveillance colonoscopy at 3, 6, 12, and 24 months after p-EMR (group A; n = 90) or at 6, 12, and 24 months after p-EMR (group B; n = 90). The primary endpoint was cumulative local recurrence at 6 months after p-EMR. Secondary endpoints included local recurrence and the cumulative surgical resection rate of recurrent tumors during the 24-month follow-up period. RESULTS: The median tumor diameter was 25 mm (IQR 20-30). Six months after p-EMR, 12 and 6 local recurrences were noted in groups A and B, which corresponded to 13 and 8 recurrences, respectively, during the 24-month surveillance period. The primary and secondary endpoints of recurrence were not significantly different between the groups on either intention-to-treat or per-protocol analysis; no surgery case was observed in group B when a strict surveillance protocol of 6-, 12-, and 24-month follow-up post-EMR was followed. CONCLUSIONS: For patients who underwent p-EMR for neoplastic lesions, additional postprocedural 3-month surveillance did not show superior results in detecting recurrence compared with a 6-month surveillance interval. CLINICAL TRIAL REGISTRATION: UMIN000015740.

Association Between Social Participation and Disability-free Life Expectancy in Japanese Older People: The Ohsaki Cohort 2006 Study.

BACKGROUND: Although social participation has been reported to be associated with significantly lower risks of mortality and disability, to our knowledge, no study has estimated its impact on disability-free life expectancy (DFLE). Therefore, this study aimed to investigate the association between social participation and DFLE in community-dwelling older people. METHODS: We analyzed 11-year follow-up data from a cohort study of 11,982 Japanese older adults (age ≥65 years) in 2006. We collected information on the number of social participations using a questionnaire. Using this information, we categorized the participants into four groups. DFLE was defined as the average number of years a person could expect to live without disability. The multistate life table method using a Markov model was employed for calculating DFLE. RESULTS: The results revealed that DFLE according to the number of social participations was 17.8 years (95% confidence interval [CI], 17.3-18.2) for no activities, 20.9 (95% CI, 20.4-21.5) for one activity, 21.5 (95% CI, 20.9-22.0) for two activities, and 22.7 (95% CI, 22.1-23.2) for three activities in men, and 21.8 (95% CI, 21.5-22.2), 25.1 (95% CI, 24.6-25.6), 25.3 (95% CI, 24.7-25.9), and 26.7 years (95% CI, 26.1-27.4), respectively, in women. This difference in DFLE did not change after the participants were stratified for smoking, body mass index, physical activity, and depression. CONCLUSION: Social participation is associated with longer DFLE among Japanese older people; therefore, encouraging social participation at the population level could increase life-years lived in good health.

Outcomes of endoscopic submucosal dissection for colorectal neoplasms: Prospective, multicenter, cohort trial.

OBJECTIVES: Endoscopic mucosal resection (EMR) is the gold standard for the treatment of noninvasive large colorectal lesions, despite challenges associated with nonlifting lesions and a high rate of local recurrence. Endoscopic submucosal dissection (ESD) offers the possibility of overcoming these EMR limitations. However, a higher risk of complications and longer procedure time prevented its dissemination. As ESD now provides more stable results because of standardized techniques compared with those used earlier, this study aimed to quantify the rates of en bloc and curative resections, as well as ESD complications, in the present situation. METHODS: A multicenter, large-scale, prospective cohort trial of ESD was conducted at 20 institutions in Japan. Consecutive patients scheduled for ESD were enrolled from February 2013 to January 2015. RESULTS: ESD was performed for 1883 patients (1965 lesions). The mean procedure time was 80.6 min; en bloc and curative resections were achieved in 1759 (97.0%) and 1640 (90.4%) lesions, respectively, in epithelial lesions ≥20 mm. Intra- and postprocedural perforations occurred in 51 (2.6%) and 12 (0.6%) lesions, respectively, and emergency surgery for adverse events was performed in nine patients (0.5%). CONCLUSIONS: This trial conducted after the standardization of the ESD technique throughout Japan revealed a higher curability, shorter procedure time, and lower risk of complications than those reported previously. Considering that the target lesions of ESD are more advanced than those of EMR, ESD can be a first-line treatment for large colorectal lesions with acceptable risk and procedure time. (Clinical Trial Registration: UMIN000010136).

Familial Hypercholesterolemia in Patients with Acute Coronary Syndrome: Genetic Insights from EXPLORE-J.

AIM: Genetic testing can provide a definitive diagnosis of familial hypercholesterolemia (FH). However, accessibility of genetic testing may be limited in certain countries where it is not considered "standard of care," including Japan. In addition, mutations responsible for FH cannot be identified in approximately 30% of patients. METHODS: EXPLORE-J is a multicenter, prospective, observational study of patients presenting with acute coronary syndrome (ACS). The genetic data were analyzed and adjudicated as pathogenic, indeterminate, or nondetectable pathogenic variant. RESULTS: Of 1,944 patients, 431 underwent genetic screening. Overall, most patients had nonpathogenic variants of LDLR, LDLRAP1, or PCSK9 (n=396, 91.9%). Of the 25 (5.8%) patients with pathogenic variants, variants of the LDLR gene and the PCSK9 gene were seen in 10 and 15 patients, respectively. Indeterminate variants were observed in 10 (2.3%) patients. Of the 431 patients, eight (1.9%) met the criteria for a diagnosis of FH using the Japanese Atherosclerosis Society (JAS) 2017 guidelines. When genetic data were incorporated, 33 (7.7%) patients met the JAS guidelines. No patients with FH pathogenic variants satisfied the JAS clinical criteria for a diagnosis of FH. CONCLUSIONS: The results revealed a higher prevalence of genetic mutations of FH among Japanese patients with ACS and a low sensitivity of the FH diagnostic criteria of the JAS 2017 guidelines. These findings highlight the difficulties of FH diagnosis in patients with ACS in the acute phase and suggest the importance of genetic testing and family history.

Prediction of Lifetime Risk of Cardiovascular Disease Deaths Stratified by Sex in the Japanese Population.

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person-years of follow-up were included. The lifetime risk at the index-age of 45 years for those with optimal risk factors (total cholesterol <4.65 mmol/L, systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, absence of diabetes, and absence of smoking habit) was lower compared with the highest risk profile of ≥2 risk factors (6.8% [95% CI, 0%-11.9%] versus 19.4% [16.7%-21.4%] for men and 6.9% [1.2%-11.5%] versus 15.4% [12.6%-18.1%] for women). Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short-term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.