Suicide risk among patients with cancer by sex in Japan: A population-based study.

BACKGROUND: In Japan, few studies have examined suicide risk for five-year relative survival rates for cancer sites. Since five-year relative survival rates differ by sex, we aim to examine suicide risk for patients with cancer separately for men and women. METHODS: We estimated the risk of suicide among patients with cancer by sex in Japan compared to the general population, using standardized mortality ratios (SMRs). Patients with cancer diagnosed between January 1, 1985-December 31, 2013 and registered in the Osaka Cancer Registry were followed-up with for up to 10 years. The outcome was suicide death. In addition, cancer sites were classified into three prognosis groups based on five-year relative survival rates: good (> 70%), moderate (40-70%), poor (< 40%). RESULTS: Among 623 995 patients with cancer observed for 2 349 432 person-years, 1210 patients died by suicide (867 men and 343 women). The SMRs were almost equal for men (1.66, 95% CI, 1.55-1.77) and women (1.65, 95% CI, 1.48-1.83). SMRs for cancer prognosis groups were 1.01 (95% CI, 0.84-1.22) for men and 1.47 (95% CI, 1.24-1.73) for women in the good group, 1.53 (95% CI, 1.39-1.68) for men and 1.74 (95% CI, 1.47-2.05) for women in the moderate group, and 2.54 (95% CI, 2.27-2.85) for men and 1.87 (95% CI, 1.43-2.46) for women in the poor group. CONCLUSIONS: In this population, both sexes had higher suicide risk with poor prognosis, but the difference in SMRs between the good and poor groups was smaller for women than men.

Prognostic impact of the presence or absence of prior cancer in patients with cancer using cure models: A population-based study.

Developing a subsequent cancer is one of the major concerns for cancer survivors; however, whether prior cancer could affect their prognosis is unknown. We therefore aimed to analyze how prognosis varies depending on prior cancer in patients with newly developed cancer, focusing on cancer that had been "cured." We used the record-linked database of the Osaka Cancer Registry and Vital Statistics to select 186,798 patients with stomach, colorectal, or lung cancer aged ≥40 years from 1995 to 2009 in Osaka, Japan. These cancers were defined as index cancers. We classified the patients into two groups according to whether they had a prior cancer diagnosis within 10 years before the index cancer diagnosis. The cured proportion was defined as the proportion of cancer patients with the same mortality as the general population and was estimated using the parametric mixture cure model. The cured proportion of patients with prior cancer by sex and age group was not significantly lower than those without prior cancer, except for patients with stomach cancer aged ≥65 years. According to the index cancer stage in the localized stomach or colorectal cancer, the cured proportion in patients with prior cancer was lower than in those without prior cancer. However, at any stage of lung cancer, the proportion of patients with prior cancer who had been cured was similar to patients without prior cancer, therefore prior cancer had a prognostic impact only in some patient groups based on the characteristics of their index cancer.

Short-term association of air pollution with lung cancer mortality in Osaka, Japan.

Long-term air pollution exposure has been linked to increased lung cancer mortality. However, little is known about whether day-to-day fluctuations in air pollution levels are in relation to lung cancer mortality, particularly in low-exposure settings. This study aimed to evaluate the short-term associations between air pollution and lung cancer mortality. Daily data on lung cancer mortality, fine particulate matter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and weather conditions were collected from Osaka Prefecture, Japan, from 2010 to 2014. Generalized linear models were combined with quasi-Poisson regression were applied to evaluate the associations between each air pollutant and lung cancer mortality after adjusting for potential confounders. Mean (standard deviation) concentrations of PM2.5, NO2, SO2, and CO were 16.7 (8.6) µg/m3, 36.8 (14.2) µg/m3, 11.1 (4.0) µg/m3, and 0.51 (0.16) mg/m3, respectively. Interquartile range increases in concentrations of PM2.5, NO2, SO2, and CO (2-d moving average) were associated with 2.65% (95% confidence intervals [CIs]: 0.96%-4.37%), 4.28% (95% CIs: 2.24%-6.36%), 3.35% (95% CIs: 1.03%-5.73%), and 4.60% (95% CIs: 2.19%-7.05%) increased risk of lung cancer mortality, respectively. Stratified analyses showed that the associations were strongest in the older population and men. Exposure‒response curves showed a continuously increasing mortality risk from lung cancer with elevation of air pollution levels, without discernible thresholds. In summary, we found evidence of increased lung cancer mortality in relation to short-term elevations in ambient air pollution. These findings may merit further research to better understand this issue.

Inflammation as an exacerbation marker and target for prophylaxis against Coronavirus Disease 2019-related thrombosis.

Objectives: There are currently no appropriate markers and target for prophylaxis against COVID-19-related thrombosis, especially in the not-severe cases. We tested the hypothesis that inflammation is a suitable marker and target for prophylaxis against COVID-19-related thrombosis. Methods: Data of all 32 COVID-19 patients admitted to Saitama Medical Center between January 1 and March 30, 2021, were analyzed. Patients were divided into severe (requiring oxygen, n=12) and non-severe (no requirement for oxygen, n=20), and also those with high C-reactive protein (CRP) level (cutoff value: 30 mg/L, n=21) and low-CRP (n=11). We also compared the clinical and laboratory data of a 46-year-old post-liver transplant male patient, who was treated with a combination of immunosuppressants (methylprednisolone, fludrocortisone, cyclosporine, and everolimus) with those of other COVID-19 patients, using the Smirnoff-Grubbs and Box plots tests. Results: The levels of CRP, ferritin, lactate dehydrogenase, aspartate aminotransferase, and thrombin-antithrombin complex (TAT) were significantly higher in the high-severity group than the low-severity group; while other coagulation parameters were comparable. The time between onset of illness and blood levels of lactate dehydrogenase, fibrinogen, D-dimer, TAT, and plasmin alpha2-plasmin inhibitor complex (PIC) were significantly higher whereas lymphocyte count was significantly lower in the high-CRP group. Extremely low levels of TAT, PIC, and plasminogen activator inhibitor-1 (PAI-1) were recorded in the liver transplant patient treated with immunosuppressants. The TAT, PIC, and PAI-1 levels were deemed outliers. Conclusions: Inflammation is a potentially suitable marker and target for prophylaxis against COVID-19-related thrombosis.

Impact of the Great East Japan Earthquake on spontaneous abortion and induced abortion: A population-based cross-sectional and longitudinal study in the Fukushima Prefecture based on the census survey of the Fukushima maternity care facility and vital statistics.

AIM: The 2011 Great East Japan Earthquake (GEJE) was a disaster leading to radiation exposure and psychological distress, particularly among pregnant women. However, it is not known how this affected the seasonal changes of pregnancy and childbirth. Therefore, this study investigated the impact of the GEJE in the Fukushima Prefecture on spontaneous and induced abortions with regard to seasonal variability. METHODS: We used the data of vital statistics of live birth and stillbirth registry and the census survey of the Fukushima Maternity Care Facility. We calculated the spontaneous and induced abortion rate for 2011-2016 using two different methods (cross-sectional and longitudinal). We calculated the quartiles and outliers to determine the impact and duration of the GEJE. Periodicity was investigated using spectral density analysis. The data were analyzed for the entire Fukushima Prefecture and by region. RESULTS: The spontaneous abortion rate did not show specific changes after the GEJE. Contrarily, the monthly analysis in the cross-sectional method, revealed specific increases in induced abortion rate during the year after the GEJE; in the longitudinal method, induced abortions increased among women who became pregnant within 1 year after the GEJE. Spontaneous abortion showed no specific periodicity, while induced abortion showed cycles of 6 and 12 months, with a particular increase in May each year. CONCLUSIONS: The spontaneous abortion rate was not affected by the GEJE. The changes in the induced abortion rate after the disaster may have overlapped with the timing of the increased periodicity, and cannot be attributed solely to the GEJE.

The number of erupted teeth as a risk factor for dental caries in eighteen-month-old children: a cross­sectional study.

BACKGROUND: Dental caries is one of the most common chronic diseases worldwide, affecting lifelong as well as children. Therefore, it is important to clarify factors related to early childhood caries (ECC) in a younger population in terms of caries prevention. However, the prevalence of ECC is low in developed countries in the twenty-first century and a large-scale survey is needed to clarify the risk factors. Furthermore, earlier tooth eruption is not taken into consideration in most studies of ECC, even though it may be a factor of ECC. The present study investigated the prevalence and risk factors of dental caries in children aged 18 months in a core city of Japan. METHODS: Findings from a total of 7351 children aged 18 months were analyzed. Anthropometric measurements of height and weight, as well as an oral examination and a microbiological caries-risk test, were performed. Additionally, a structured interview sheet was provided to the parents or guardians. Findings of dental caries at 18 months of age were evaluated using a logistic regression model. RESULTS: Of the enrolled children, 1.2% had experienced dental caries. Multivariable logistic regression analysis results indicated a significant association with dental caries at 18 months of age for the following factors: second child (OR = 1.78; 95% CI:1.08-2.93, P < 0.05), third and later child (OR = 2.08; 95% CI:1.12-3.89, P < 0.05), 12 or fewer erupted teeth (OR = 0.47; 95% CI:0.24-0.96, P < 0.05), 17 or more erupted teeth (OR = 4.37; 95% CI:1.63-11.7, P < 0.01), Cariostat score (+ + +) (OR = 3.99; 95% CI:1.29-12.31, P < 0.05), daily eating before bed (OR = 2.62; 95% CI: 1.55-4.45, P < 0.001), three or more snacks per day (OR = 2.03; 95% CI:1.15-3.58, P < 0.05), and breastfeeding (OR = 3.30; 95% CI:2.00-5.44, P < 0.001). CONCLUSIONS: These results suggest that the number of erupted teeth, as well as birth order, eating habits, and breastfeeding, are significant factors in dental caries occurrence at 18 months of age.

Effects of non-pharmacologic prevention on delirium in critically ill patients: A network meta-analysis.

BACKGROUND: Delirium is a common complication among patients in the intensive care unit (ICU). It is important to prevent the occurrence of delirium in critically ill patients. AIM: This review aimed to evaluate the efficacy of non-pharmacological interventions and determine what combination of these is effective in preventing delirium among Intensive Care Unit patients. STUDY DESIGN: A systematic review and meta-analysis. This review follows the guidelines of the Preferred Reporting Items for Systematic reviews and Meta Analysis statements for Network Meta-Analysis (PRISMA-NMA). Data sources included the Cumulative Index to Nursing & Allied Health Literature., MEDLINE, and Cochrane library databases. The integrated data were investigated with odds ratio (OR) and 95% confidence interval (95% CI), using the random-effects Mantel-Haenszel model. Data were considered significant when p < 0.05. Furthermore, to reveal what combination of care is effective, we performed a network meta-analysis estimated OR, 95% CI. RESULTS: We identified three randomized controlled trials and eight controlled before-after trials (11 in total, with 2549 participants). The pooled data from 11 trials of multicomponent intervention had a significant effect on delirium prevention (OR 0.58, 95% CI 0.44-0.76, p < 0.001). As a result of network meta-analysis, two bundles were effective compared to the control group in reducing the incidence of delirium: a) the combination of sleep promotion (SP), cognitive stimulation (CS), early mobilization (EM), pain control (PC), and assessment (AS) (OR 0.47, 95% CI 0.35-0.64, p < 0.002), and b) the combination of SP and CS (OR 0.46, 95% CI 0.28-0.75, p < 0.001). CONCLUSION: This study revealed that non-pharmacological interventions, particularly multicomponent interventions, helped to prevent delirium in critically ill patients. In the network meta-analysis, the most effective care combination for reducing incidence of delirium was found to be multicomponent intervention, which comprises SP-CS-EM-PC-AS, and SP-CS. RELEVANCE TO CLINICAL PRACTICE: These findings reveal an efficient combination of multicomponent interventions for preventing delirium, which may be a very important prerequisite in planning care programs in the future.

[Geographic information in National Cancer Registry data: Overseas examples and challenges in Japan].

Worldwide, research based on geographic information of official statistical data, including cancer registries, is utilized for cancer control and public health policies. The National Cancer Registry of Japan was launched in 2016, making it possible to use data on cancer incidence systematically. Given the nature of this comprehensive survey, the usefulness of the National Cancer Registry would be further enhanced when it is utilized at small-regional levels, such as in municipalities or even smaller geographical units. It is essential to maintain a balance between privacy protection and data usability. Currently, the national and prefectural councils determine the availability of the data from the National Cancer Registry at the small-regional level on an individual application basis. Under this framework, use of the data is often restricted or declined. This paper showcases three model countries where geographic information obtained from cancer registry data are widely utilized: the United States, Canada, and the United Kingdom. It further discusses measures to ensure that data are effectively used, without compromising data privacy. In the three countries, data-providing systems have been established to compile the necessary data from the cancer registry and other linked databases, in accordance with the purpose of use. The relationships between healthcare access and various outcomes are elaborately examined at the small-regional level. In Japan, similar utilization of data has not been fully implemented, and there remain many hurdles to the application of the data use. For the National Cancer Registry to promote research and further enhance cancer control, it is necessary to establish a system that enables effective and safe utilization of the data from the National Cancer Registry, including linkage with other data and on-site use.

Impact of endoscopic surveillance on mortality of metachronous esophageal and head and neck cancer after esophageal endoscopic resection.

BACKGROUND AND AIM: As more superficial esophageal cancer (EC) patients are being treated with endoscopic resection (ER), it is important to understand the outcomes, including survival data, of patients who develop metachronous EC and head and neck cancer (HNC). We aimed to evaluate the long-term surveillance and survival outcomes of metachronous EC and HNC after esophageal ER. METHODS: This study included 627 patients who underwent ER of superficial esophageal squamous cell carcinoma from 2008 to 2016 and were generally followed by annual or biannual esophagogastroduodenoscopy up to 2019 at Osaka International Cancer Institute. Data on metachronous cancer development and causes of death were collected from an integrated database of hospital-based cancer registry and Vital Statistics of Japan. RESULTS: During a median (range) follow-up period of 67.4 (3.8-142.7) months, 230 patients (36.7%) developed 500 metachronous ECs and 126 patients (20.1%) developed 239 metachronous HNCs, post-ER of index EC. The 3-year, 5-year, and 7-year cumulative incidences were 25.8%, 36.0%, and 43.6% for metachronous EC and 10.9%, 16.0%, and 26.9% for metachronous HNC, respectively. No patients died of metachronous EC, and only seven patients (1.1%) died of metachronous HNC. The 3-year, 5-year, and 7-year disease-specific survival rates were 99.8%, 99.6%, and 98.6%, respectively. CONCLUSIONS: The incidences of metachronous EC and HNC increase with time over 5 years after esophageal ER; therefore, surveillance endoscopy should be continued over 5 years. Endoscopic surveillance is useful for survivors after esophageal ER given the high incidence and extremely low mortality of metachronous EC and HNC.

Administration Method of Adjuvant Tegafur-Uracil and Leucovorin Calcium in Patients with Resected Colorectal Cancer: A Phase III Study.

LESSONS LEARNED: The 3-year disease-free survival rate of the twice-daily regimen was not inferior to that of the conventional three-times-daily regimen, and the twice-daily regimen did not lead to an increase in adverse events. The effectiveness of the twice-daily regimen highlights an increased number of treatment options for patients. This will facilitate personalized medicine, particularly for elderly or frail patients who may experience more severe side effects from the combination therapy. BACKGROUND: Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. METHODS: Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The primary endpoint was 3-year disease-free survival. RESULTS: In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). CONCLUSION: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase.

Hospital Surgical Volume and 3-Year Mortality in Severe Prognosis Cancers: A Population-Based Study Using Cancer Registry Data.

BACKGROUND: The impact of hospital surgical volume on long-term mortality has not been well assessed in Japan, especially for esophageal, biliary tract, and pancreatic cancer, although these three cancers need a high level of medical-technical skill. The purpose of this study was to examine associations between hospital surgical volume and 3-year mortality for these severe-prognosis cancer patients. METHODS: Patients who received curative surgery for esophageal, biliary tract, and pancreatic cancers were analyzed using the Osaka Cancer Registry data from 2006-2013. Hospital surgical volume was categorized into tertiles (high/middle/low) according to the average annual number of curative surgeries per hospital for each cancer. Three-year survivals were calculated using the Kaplan-Meier method. Hazard ratios (HRs) of 3-year mortality were calculated using Cox proportional hazard models, adjusting for patient characteristics. RESULTS: Three-year survival was higher with increased hospital surgical volume for all three cancers, but the relative importance of volume varied across sites. After adjustment for all confounding factors, HRs in middle- and low-volume hospitals were 1.34 (95% confidence interval [CI], 1.14-1.58) and 1.57 (95% CI, 1.33-1.86) for esophageal cancer; 1.39 (95% CI, 1.15-1.67) and 1.57 (95% CI, 1.30-1.89) for biliary tract cancer; 1.38 (95% CI, 1.16-1.63) and 1.90 (95% CI, 1.60-2.25) for pancreatic cancer, respectively. In particular for localized pancreatic cancer, the impact of hospital surgical volume on 3-year mortality was strong (HR 2.66; 95% CI, 1.61-4.38). CONCLUSION: We suggest that patients who require curative surgery for esophageal, biliary tract, and pancreatic cancer may benefit from referral to high-volume hospitals.

Clinicopathological Characteristics of Low-Grade Appendiceal Mucinous Neoplasm.

INTRODUCTION: Recently, "low-grade appendiceal mucinous neoplasms" (LAMNs) have been proposed as one subtype of appendiceal mucinous neoplasms, characterized by a villous or flat proliferation of mucinous epithelium with low-grade cytologic atypia. The aim of this study was to clarify the clinicopathological characteristics of LAMN. METHODS: In this multi-institutional cohort study, we retrospectively analyzed the clinicopathological characteristics in appendiceal neoplasms patients who underwent treatment from 2000 to 2017. RESULTS: In total, 922 patients were enrolled, with 279 (30.3%) cases of LAMN, and 93 (10.1%) cases of non-LAMN disease. In comparison with patients with non-LAMN disease, those with LAMN had significantly lower levels of CA19-9 (p = 0.045), a lower frequency of T4 tumors (p < 0.0001), a lower frequency of lymph node metastasis (p < 0.0001), and a lower frequency of distant metastasis (p < 0.0001). Survival analysis revealed that patients with LAMN had a significantly better prognosis than did those with non-LAMN disease (p < 0.001). Among the patients with distant metastasis, those with LAMN had a significantly better prognosis than did those with non-LAMN disease (p = 0.0020), but among the patients without distant metastasis, the difference between the 2 groups was not significant (p = 0.26). However, among patients who underwent complete resection, the difference in prognosis between the 2 groups was not significant (p = 0.10). CONCLUSIONS: A multicenter retrospective study revealed that the clinicopathological characteristics of LAMN was different from those of non-LAMN.

Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study.

BACKGROUND: For colorectal cancer (CRC) patients, the standard histological lymph node (LN) evaluation has low sensitivity. Our previously developed one-step nucleic acid amplification (OSNA™) assay measures cytokeratin 19 gene expression in whole LNs. We recently showed that 17.6% of pN0 stage II CRC patients were OSNA positive, suggesting a correlation between OSNA results and disease recurrence. This multicenter, prospective study investigateed the prognostic value of the OSNA assay for pStage II CRC patients. METHODS: We examined 204 CRC patients who were preoperatively diagnosed as cN0 and cN1 and surgically treated at 11 medical institutions across Japan. Nine patients were excluded, and 195 patients (Stage I: n = 50, Stage II: n = 70, Stage III: n = 75) were examined. All LNs, harvested from patients, were examined histopathologically using one-slice hematoxylin-eosin staining. Furthermore, half of the LNs was examined by the OSNA assay. Patients were classified according to the UICC staging criteria and OSNA results, and the 3-year, disease-free survival (DFS) of each cohort was analyzed. RESULTS: Average 21.2 LNs/patient were subject to pathological examination. Approximately half of all harvested LNs (average, 9.4 LNs/patient) were suitable for the OSNA assay. Significantly lower 3-year DFS rates were observed in pStage (pathological Stage) II OSNA-positive patients than in OSNA-negative patients (p = 0.005). Among all assessed clinical and pathological parameters, only the OSNA result significantly affected 3-year DFS rates in pStage II CRC patients (p = 0.027). CONCLUSIONS: This study shows that OSNA positivity is a risk factor for recurrence of the patients with pStage II CRC.

Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet.

BACKGROUND: Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor α modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. METHODS: Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated. RESULTS: After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone. CONCLUSIONS: Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression.

Analysis of Clinicopathological Characteristics of Appendiceal Tumors in Japan: A Multicenter Collaborative Retrospective Clinical Study- A Japanese Nationwide Survey.

BACKGROUND: Appendiceal tumor has recently been treated differently from colorectal cancer. However, obtaining knowledge of this disease is difficult because of its rareness. OBJECTIVE: This study aimed to investigate the clinicopathological characteristics of appendiceal tumors in a Japanese cohort. DESIGN: This was a nationwide multi-institution retrospective observational study. SETTING: This study was conducted at the participating tertiary referral hospitals. PATIENTS: Patients with appendiceal tumor who were diagnosed between 2000 and 2017 were included. MAIN OUTCOME MEASURES: The primary outcome measured was the total survivability. RESULTS: A total of 922 patients from the 43 facilities that participated were identified. Of these, 114 patients were diagnosed with cancer other than adenocarcinomas. The remaining 760 patients, with the exception of 48 patients with unknown survival data, were eligible for the final cohort analysis. Of these 760 patients, 515 (67.8%) had mucinous adenocarcinomas and 245 (32.2%) had nonmucinous adenocarcinomas. Within the mucinous adenocarcinoma group, 267 patients (35.1%) were diagnosed as having low-grade appendiceal mucinous neoplasm. The 5-year survival rate of mucinous adenocarcinoma (83.1%) was superior to that of nonmucinous adenocarcinoma (62.0%; p < 0.01). Regarding mucinous adenocarcinoma, multivariate analysis revealed that high differentiation grade (American Joint Committee on Cancer grade 2/3), distant metastases, and R2 operation were significantly associated with a higher 5-year mortality rate. The 5-year survival rate was significantly better for low-grade appendiceal mucinous neoplasms (93.3%) than for other mucinous adenocarcinomas (72.1%; p < 0.01). LIMITATIONS: This study was limited by its retrospective study design. CONCLUSIONS: We cumulatively investigated appendiceal tumors in a multicenter retrospective study; this is the first such report from Asia. Grouping the grades as per the American Joint Committee on Cancer was useful as a prognostic indicator of appendiceal mucinous adenocarcinomas, including low-grade appendiceal mucinous neoplasm. See Video Abstract at http://links.lww.com/DCR/B282. ANÁLISIS DE LAS CARACTERÍSTICAS CLINICOPATOLÓGICAS DE LOS TUMORES APENDICULARES EN JAPÓN: UN ESTUDIO CLÍNICO RETROSPECTIVO COLABORATIVO MULTICÉNTRICO: UNA ENCUESTA NACIONAL JAPONESA: El tumor apendicular recientemente se ha tratado de manera diferente al cáncer colorrectal. Sin embargo, obtener conocimiento de esta enfermedad es difícil debido a su rareza.Este estudio tuvo como objetivo investigar las características clinicopatológicas de los tumores apendiculares en una cohorte Japonesa.Este fue un estudio observacional retrospectivo de múltiples instituciones a nivel nacional.Este estudio se realizó en los hospitales de referencia terciarios participantes.se incluyeron pacientes con tumor apendicular que fueron diagnosticados entre el 2000 y 2017.El resultado primario medido fue la supervivencia total.Se identificaron un total de 922 pacientes de las 43 instalaciones que participaron. De estos, 114 pacientes fueron diagnosticados con cáncer distinto de adenocarcinomas. Los 760 pacientes restantes, excepto 48 pacientes con datos de supervivencia desconocidos, fueron elegibles para el análisis de cohorte final. De estos 760 pacientes, 515 (67,8%) tenían adenocarcinomas mucinosos y 245 (32,2%) tenían adenocarcinomas no mucinosos. Dentro del grupo de adenocarcinoma mucinoso, 267 pacientes (35,1%) fueron diagnosticados con neoplasia mucínica apendicular de bajo grado (LAMN). La tasa de supervivencia a 5 años del adenocarcinoma mucinoso (83.1%) fue superior a la del adenocarcinoma no mucinoso (62,0%) (p <0,01). Con respecto al adenocarcinoma mucinoso, el análisis multivariado reveló que el alto grado de diferenciación (Comité Estadounidense Conjunto sobre el Cáncer grado 2/3), las metástasis a distancia y la operación R2 se asociaron significativamente con una mayor tasa de mortalidad a 5 años. La tasa de supervivencia a 5 años fue significativamente mejor para las neoplasias mucinosas apendiculares de bajo grado (93.3%) que para otros adenocarcinomas mucinosos (72,1%) (p <0,01).Este estudio fue limitado por su diseño de estudio retrospectivo.Investigamos acumulativamente los tumores apendiculares en un estudio retrospectivo multicéntrico y este es el primer informe de este tipo de Asia. Agrupar los grados según el Comité Estadounidense Conjunto sobre el Cáncer fue útil como indicador pronóstico de los adenocarcinomas mucinosos apendiculares, incluida la neoplasia mucínica apendicular de bajo grado. Consulte Video Resumen en http://links.lww.com/DCR/B282. (Traducción-Dr. Yesenia Rojas-Khalil).

miR-409-3p inhibits the proliferation and migration of human ovarian cancer cells by targeting Rab10.

Ovarian cancer is a leading cause of gynecological cancer-related mortality. It has been reported that miR-409-3p is involved in the proliferation and migration of cancer cells. However, the role of miR-409-3p in ovarian cancer has not been well studied. The present study aimed to investigate the functional role of miR-409-3p in the pathogenesis of ovarian cancer, and its potential mechanism. It was found that the expression levels of miR-409-3p in 6 ovarian cancer tissues were upregulated. Through proliferation, migration and colony formation assays, it was revealed that overexpression of miR-409-3p inhibited the proliferation and migration of ovarian cancer cells. It was predicted from bioinformatics assays that the complementary binding sites were within miR-409-3p and Rab10. It was also demonstrated that the downregulation of the expression of Rab10 reversed the miR-409-3p downregulation-induced abnormal proliferation of ovarian cancer cells. These results suggest that miR-409-3p expression can be used as a predictive marker for the prognosis of ovarian cancer. Thus, the miR-409-3p/Rab10 axis may be a novel therapeutic target for ovarian cancer.

Proposal of a Useful Surrogate Endpoint of the Overall Survival in Patients Undergoing Pulmonary Metastasectomy: The Time to Local Therapy Failure.

BACKGROUND: A recent study demonstrated remarkable discrepancy between the relapse-free survival (RFS) and overall survival (OS) after pulmonary metastasectomy (PM) in the current era. As the RFS may not be a suitable parameter after PM, a more suitable parameter is needed for PM as a surrogate marker for OS. METHODS: A total of 134 consecutive patients who underwent PM were retrospectively analyzed. In the present study, we introduced a new endpoint, time to local treatment failure (TLTF). This endpoint was defined as the time interval between the first PM and the first untreatable recurrence by local treatment with curative intent or death due to any cause. We analyzed the correlation between the RFS and OS and between the TLTF and OS to validate whether or not the TLTF is a better parameter than the RFS after PM. RESULTS: Thus far, 78 patients have experienced relapse. Of these, 37 patients (47%) underwent local therapy with curative intent, 29 of whom are alive without local treatment failure. The 5-year OS, RFS and TLTF were 70.9%, 36.5%, and 57.6%, respectively. The concordance proportions for the RFS and OS and for the TLTF and OS were 0.634 and 0.851 for all patients, respectively. The Spearman's rank correlation coefficient for the RFS and OS was 0.639, while that for the TLTF and OS was 0.875. CONCLUSIONS: The TLTF may be a good surrogate parameter for the OS after PM in the current era.

Brachial intima-media thickness is associated with coronary artery atherosclerosis in patients with diabetes mellitus.

Coronary artery calcification (CAC) as measured by computed tomography is a strong predictor of coronary artery disease. The brachial intima-media thickness (IMT) was recently reported to be associated with cardiovascular risk factors. This study investigated the association of brachial IMT with CAC, which is a marker of coronary artery atherosclerosis, in patients with diabetes. We enrolled 292 patients with diabetes (mean age, 65 ± 12 years; 59% men) who underwent both endothelial function testing and computed tomography for risk assessment of coronary artery disease. Flow-mediated dilation (FMD) and IMT in the brachial artery were measured with a specialized machine. FMD was lower and brachial IMT was thicker in patients with than without CAC. The CAC score was significantly correlated with both brachial IMT and FMD, while the multivariate logistic analysis demonstrated that brachial IMT (> 0.32 mm) but not FMD (< 5.1%) was significantly associated with the presence of CAC (odds ratio, 2.03; 95% confidence interval, 1.10-3.77; p = 0.02). The receiver operating characteristic curve analysis showed that the area under the curve for discriminating patients with CAC was 0.67 for IMT (p < 0.001) and 0.62 for FMD (p < 0.001). When patients were classified into four groups based on brachial IMT and FMD, the CAC score was higher in patients with thicker brachial IMT and lower FMD than in patients of the other groups (p < 0.001). Measurement of brachial IMT could be useful for the risk assessment of patients with diabetes.

Inhibitory Effects of Tofogliflozin on Cardiac Hypertrophy in Dahl Salt-Sensitive and Salt-Resistant Rats Fed a High-Fat Diet.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs for diabetes and might prevent heart failure. In this study, we investigated the effects of tofogliflozin, an SGLT2 inhibitor, on cardiac hypertrophy and metabolism in hypertensive rats fed a high-fat diet. Dahl salt-sensitive (DS) rats, hypertensive model rats, and Dahl salt-resistant (DR) rats, non-hypertensive model rats, were fed a high-salt and high-fat diet containing tofogliflozin (0.005%) for 9 weeks to examine the effects of this drug on cardiac hypertrophy and metabolism. Tofogliflozin tended to suppress a rise of the systolic blood pressure, relative to the control, throughout the treatment period in both DR and DS rats, and significantly suppress a rise of the systolic blood pressure, relative to the control, at the 9th week in DS rats. Tofogliflozin reduced cardiac hypertrophy (heart weight/body weight) not only in DS rats but also in DR rats. Histological analysis showed that tofogliflozin significantly decreased cardiomyocyte hypertrophy and perivascular fibrosis in both DS and DR rats. Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-ß1 and collagen type IV), in DS rats. Recent studies have shown that hypertrophied and failing hearts shift to oxidizing ketone bodies as a significant fuel source. We also performed metabolome analysis for ventricular myocardial tissue. Tofogliflozin reduced 3-hydroxybutyrate, a ketone body, and significantly decreased the expression levels of ß-hydroxybutyrate dehydrogenase 1 and 3-oxoacid CoA-transferase, which are related to ketone oxidization. In conclusion, tofogliflozin ameliorated cardiac hypertrophy and fibrosis along with reduction of ketone usage in myocardial tissue.

Impact of fatty pancreas and lifestyle on the development of subclinical chronic pancreatitis in healthy people undergoing a medical checkup.

BACKGROUND: Although fat accumulation in human organs is associated with a variety of diseases, there is little evidence about the effect of a fatty pancreas on the development of subclinical chronic pancreatitis over the clinical course. METHODS: We conducted a prospective cohort study from 2008 to 2014 of patients who underwent a medical checkup consultation for fat accumulated in the pancreas. Patients included in the analysis were divided into a non-fatty pancreas group (n = 9710) and fatty pancreas group (n = 223). The primary end point was the odds ratio (OR) for chronic pancreatitis associated with fatty pancreas, which was diagnosed using ultrasonography. We used a multiple logistic regression model to estimate the OR and the corresponding 95% confidence interval (CI). RESULTS: Ninety-two people were diagnosed with chronic pancreatitis, including both presumptive and definitive diagnoses. Twelve people were diagnosed with chronic pancreatitis by ultrasonography among the 223 patients with fatty pancreas, and 80 patients among 9710 were diagnosed with non-fatty pancreas. The crude OR was 6.85 (95% CI 3.68, 12.75), and the multiple adjusted OR was 3.96 (95% CI 2.04, 7.66). CONCLUSIONS: Fat accumulation in the pancreas could be a risk factor for developing subclinical chronic pancreatitis.