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.

Long-term course of a case with a novel homozygous kyphoscoliosis peptidase variant.

We herein report a case with a novel homozygous variant in the kyphoscoliosis peptidase (KY) gene. A 58-year-old Japanese female was referred to our hospital with a gait disturbance that gradually worsened after the age of 50. She had bilateral equinus foot deformity since early childhood. Neurological examination revealed moderate weakness of the neck, trunk, femoral, and brachial muscles, mild respiratory failure, and areflexia. Whole-exome sequencing revealed a novel homozygous frameshift variant of the KY gene, NM_178554.6:c.824del p.(Glu275Glyfs*53). Our case demonstrated that KY-associated neuromuscular disease can present with extremely slow progressive muscle weakness and respiratory failure over a long natural course.

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.

A nationwide survey of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

BACKGROUND: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) seem to be increasing rapidly worldwide. However, nationwide studies have been limited to food-protein-induced enterocolitis (FPIES) and food-protein-induced allergic proctocolitis (FPIAP), with little attention to other non-IgE-GIFA subgroups. The aim of this study was to elucidate the clinical features of all patients with non-IgE-GIFAs, not just certain subgroups. METHODS: We conducted a nationwide cross-sectional survey of non-IgE-GIFAs in Japan from April 2015 through March 2016. A questionnaire was sent to hospitals and clinics throughout Japan. The questionnaire asked about the number of physician-diagnosed non-IgE-GIFA patients, the status of fulfillment of the diagnostic criteria, tentative classification into 4 clusters based on the initial symptoms, the day of onset after birth, complications, and the suspected offending food(s). RESULTS: The response rate to that questionnaire was 67.6% from hospitals and 47.4% from clinics. Analyses were conducted about "diagnosis-probable" patient cohort (n = 402) and the "diagnosis-confirmed" patients (n = 80). In half of the reported non-IgE-GIFA patients, onset occurred in the neonatal period. The patients were evenly distributed among 4 non-IgE-GIFA clusters. In Cluster 1, with symptoms of vomiting and bloody stool, the onset showed a median of 7 days after birth, which was the earliest among the clusters. Cow's milk was the most common causative food. CONCLUSIONS: In half of the patients, the onset of non-IgE-GIFAs was in the neonatal period. This highlights the importance of studying the pathogenesis in the fetal and neonatal periods.

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 psychological distress and disability-free life expectancy in the older Japanese adults.

BACKGROUND: Our study aimed to investigate the association between psychological distress and disability-free life expectancy (DFLE). METHODS: In 2006, a cohort study was conducted of 12,365 Japanese individuals aged ≥65 years, who were followed-up for 13 years. Psychological distress was measured using the Kessler 6-item psychological distress scale and was categorized into no (0-4), mild (5-9), moderate (10-12), and serious distress (13-24). The number of participants was 1277 (22.4 %) for mild distress, 330 (5.8 %) for moderate, and 208 (3.6 %) for serious in men, and was 1635 (24.6 %), 467 (7.0 %), and 384 (5.8 %) in women. Sex-specific DFLE was defined as the mean years a person could expect to live without disability and calculated by Interpolated Markov Chain (IMaCh) software. RESULTS: Compared to no distress, DFLE loss per person was 1.21, 2.61, and 4.43 years for mild, moderate, and serious distress respectively in men. At population level, DFEL loss (i.e., DFLE loss per person×number of participants) was 1545.17, 861.30, and 921.44 years for mild, moderate, and serious distress respectively in men. Accordingly, 46.4 % of the total DFLE loss was attributable to mild distress, 25.9 % to moderate, and 27.7 % to serious in men. Similarly, the results were 42.2 %, 25.4 %, and 32.4 % in women. LIMITATIONS: Psychological distress was measured only once at baseline, and 2409 participants were excluded from the analysis because of missing data on exposure. CONCLUSIONS: At population level, almost half of the total DFLE loss could be attributable to mild distress, underscoring the importance of population strategy for all levels of distress in promoting healthy aging.

NSUN3-mediated mitochondrial tRNA 5-formylcytidine modification is essential for embryonic development and respiratory complexes in mice.

In mammalian mitochondria, translation of the AUA codon is supported by 5-formylcytidine (f5C) modification in the mitochondrial methionine tRNA anticodon. The 5-formylation is initiated by NSUN3 methylase. Human NSUN3 mutations are associated with mitochondrial diseases. Here we show that Nsun3 is essential for embryonic development in mice with whole-body Nsun3 knockout embryos dying between E10.5 and E12.5. To determine the functions of NSUN3 in adult tissue, we generated heart-specific Nsun3 knockout (Nsun3HKO) mice. Nsun3HKO heart mitochondria were enlarged and contained fragmented cristae. Nsun3HKO resulted in enhanced heart contraction and age-associated mild heart enlargement. In the Nsun3HKO hearts, mitochondrial mRNAs that encode respiratory complex subunits were not down regulated, but the enzymatic activities of the respiratory complexes decreased, especially in older mice. Our study emphasizes that mitochondrial tRNA anticodon modification is essential for mammalian embryonic development and shows that tissue-specific loss of a single mitochondrial tRNA modification can induce tissue aberration that worsens in later adulthood.

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.

Association between the number of remaining teeth and disability-free life expectancy, and the impact of oral self-care in older Japanese adults: a prospective cohort study.

BACKGROUND: Tooth loss has been reportedly associated with shorter disability-free life expectancy (DFLE). However, no study has explored whether oral self-care offsets reduction in DFLE. The present study aimed to assess the association between oral self-care and DFLE in older individuals with tooth loss. METHODS: Data on the 13-year follow-up from a cohort study of 14,206 older Japanese adults aged ≥ 65 years in 2006 were analyzed. Information on the number of remaining teeth was collected using a questionnaire, and the participants were then categorized into three groups (0-9, 10-19, and ≥ 20 teeth). Additionally, "0-9" and "10-19" groups were divided into two subgroups based on whether they practiced oral self-care. DFLE was defined as the average number of years a person could expect to live without disability, and was calculated by the multistate life table method based on a Markov model. RESULTS: DFLE (95% confidence interval) was 19.0 years (18.7-19.4) for 0-9 teeth, 20.1 (19.7-20.5) for 10-19 teeth, and 21.6 (21.2-21.9) for ≥ 20 teeth for men. For women, DFLE was 22.6 (22.3-22.9), 23.5 (23.1-23.8), and 24.7 (24.3-25.1), respectively. Practicing oral self-care was associated with longer DFLE, by 1.6-1.9 years with brushing ≥ 2 times a day in people with 0-9 and 10-19 teeth, and by 3.0-3.1 years with the use of dentures in those with 0-9 teeth. CONCLUSIONS: Practicing oral self-care is associated with an increase in DFLE in older people with tooth loss.

Reliable Information from Health Professionals Encourages Urban Japanese Mothers' Continued Participation in Health Checkups.

We examined mothers' health information sources and their relationships with continued participation in health checkups among urban Japanese mothers. Participants were 152 mothers below 40 years old with one or more children under 12 years old. We collected data at a children's festival in Tokyo in 2019. A self-administered questionnaire was used to collect information regarding health checkups, trusted sources of information regarding mother's health, and anthropological variables. Continued participation in health checkups was defined as participating in health checkups almost every year during the past five years. Logistic regression analysis was used to adjust for health insurance, mothers' age, number of children, and current medical history. the sources of mothers' health information trusted by over 20% of mothers in the two groups were "family", "friends", "Web/SNS", and "healthcare professionals." However, continued participation in health checkups was significantly associated with only the source of health information from "healthcare professionals" (odds ratio: 2.8 [95% confidence interval: 1.26-6.31], p = 0.01). These findings suggest that reliable information from health professionals encourages urban Japanese mothers' continued participation in health checkups among Japanese mothers under 40 years old who have children under 12 years of age.

Changes in time spent walking and disability-free life expectancy in Japanese older people: The Ohsaki Cohort 2006 Study.

An increase in time spent walking is significantly associated with lower risks of mortality and disability. This study aimed to investigate the association between changes in time spent walking and disability-free life expectancy (DFLE) in community-dwelling older people. Thirteen-year follow-up data from a cohort study of 7105 Japanese older adults (age ≥ 65 years) in 2006 were analyzed. Information on time spent walking was collected using questionnaires at two time points (1994 and 2006). Based on this information, the participants were categorized into four groups according to changes in time spent walking: remained inactive, became inactive, became active, and remained active. 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 used to calculate DFLE. Of those who were inactive in 1994, DFLE of those who became active in 2006 (20.30 years in men; 24.06 years in women) was longer by about 2 years than of those who remained inactive (17.96 years in men; 21.87 years in women), and it was as long as those who remained active (20.34 years in men; 24.16 years in women). The 2-year difference in DFLE did not change after the participants were stratified by body mass index, motor function, cognitive function, and history of diseases. Increase in time spent walking is associated with longer DFLE in Japanese older people. Encouraging simple physical activity such as walking at the population level could increase life-years lived in good health.

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.