In this retrospective study, we aimed to clarify the risk of developing a second primary cancer and to determine the periods of high risk of second primary cancers. Subjects were all patients who had ...been diagnosed with a first primary cancer and registered with the Nagasaki Prefecture Cancer Registry between 1985 and 2007. We calculated the standardized incidence ratio (SIR) of second primary cancer according to site and years after diagnosis of the first primary cancer. A second primary cancer developed in 14 167 of 174 477 subjects (8.1%) during a median follow‐up of 1.8 years. The SIR of all cancer was 1.10 (95% confidence interval, 1.08–1.11). Some specific relationships were observed between sites with risk factors in common, such as smoking, drinking, and hormone status. The SIRs were relatively high after approximately 10 years for all sites, and trends differ among cancer sites. We showed that cancer patients are at higher risk of a second primary cancer than the general population. In respect of the risk of a second primary cancer, physicians should be alert for cancers that have risk factors in common with the first primary cancer.
We examined the risk of developing a second primary cancer and the optimal duration of follow‐up for cancer patients in regard to multiple primary cancers. The results showed that medical scrutiny for second primary cancers that have risk factors in common with the first primary cancer is important, and follow‐up for 10 years for some sites is needed.
Aims: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a noninvasive biomarker for pericoronary inflammation and is associated with cardiac ...mortality. We aimed to investigate the association between PCAT attenuation and endothelial dysfunction assessed using flow-mediated dilation (FMD). Methods: A total of 119 outpatients who underwent both coronary CTA and FMD measurements were examined. PCAT attenuation values were assessed at the proximal 40-mm segments of all three major coronary arteries on coronary CTA. Endothelial function was assessed using FMD. Patients were then classified into two groups: those with endothelial dysfunction (FMD ＜4%, n=44) and those without endothelial dysfunction (FMD ≥ 4%, n=75). Results: In all three coronary arteries, PCAT attenuation was significantly higher in patients with endothelial dysfunction than in those without endothelial dysfunction. Multivariate logistic regression analysis revealed that PCAT attenuation in the right coronary artery (odds ratio OR=1.543; 95% confidence interval CI=1.004–2.369,p=0.048) and left anterior descending artery (OR=1.525, 95% CI=1.004–2.369, p=0.049) was an independent predictor of endothelial dysfunction. Subgroup analysis of patients with adverse CTA findings (significant stenosis and/or high-risk plaque) and those with coronary artery calcium score ＞100 showed that high PCAT attenuation in all three coronary arteries was a significant predictor of endothelial dysfunction. Conclusion: High PCAT attenuation was significantly associated with FMD-assessed endothelial dysfunction in patients with suspected coronary artery disease. Our results suggest that endothelial dysfunction is one of the pathophysiological mechanisms linking pericoronary inflammation to cardiac mortality.
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.
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.
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).
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Senescence mechanisms are vital to resistance to long-term olaparib maintenance treatment. Recently, peroxisome proliferator-activated receptor-γ agonists (e.g., rosiglitazone) have been ...reported to ameliorate the senescence-like phenotype by modulating inflammatory mediator production. This study examined synergistic effects on the anti-tumor activity of rosiglitazone combined with olaparib in ovarian cancer treatment.
Methods
A2780 and SKOV3 mouse subcutaneous xenograft models were established for observing anti-tumor effects in living organisms and were randomly split into combination (both olaparib and rosiglitazone), rosiglitazone (10 mg/kg), olaparib (10 mg/kg), control (solvent) groups that received treatment once every 2 or 3 days (
n
= 6 per group). Cell counting kit-8 (CCK-8) assays were used to test the influences of rosiglitazone and olaparib on cell proliferation. PI and Annexin-V-FITC staining was used with flow cytometry to assess the cell cycle distribution and cell apoptosis. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe cellular senescence. We performed quantitative real-time polymerase chain reaction assays to study the senescence-related secretory phenotype (SASP).
Results
Olaparib and rosiglitazone were observed to synergistically retard subcutaneous ovarian cancer growth in vivo, and synergistically suppress ovarian cancer cell proliferation in vitro. Compared with olaparib alone, the percentage of positive cells expressed SA-β-gal and SASP were significantly decreased in the treatment of combination of olaparib and rosiglitazone. Furthermore, olaparib plus rosiglitazone increased the percentage of apoptosis in ovarian cancer cell compared with olaparib alone. In A2780 cells, it showed lower expression of P53, phospho-p53 (Ser15), P21, and P18 protein in combination treatment compared with olaparib alone. While, in SKOV3 cells, it showed lower expression of phosphor-retinoblastoma protein (Rb) (Ser807/811), and higher expression of cyclin D1, P21, and P16 protein in combination treatment compared with olaparib alone.
Conclusions
Rosiglitazone combined with olaparib can help manage ovarian cancer by ameliorating olaparib-induced senescence and improving anti-tumor effects.
The homothallic fission yeast Schizosaccharomyces pombe undergoes sexual differentiation when starved, but sam (skips the requirement of starvation for mating) mutants such as those carrying ...mutations in adenylate cyclase (cyr1) or protein kinase A (pka1) mate without starvation. Here, we identified sam3, a dominant negative allele of rad24, encoding one of two 14-3-3 proteins. Genetic mapping and whole-genome sequencing showed that the sam3 mutation comprises a change in nucleotide at position 959 from guanine to adenine, which switches the amino acid at position 185 from glutamic acid to lysine (E185K). We generated the rad24-E185K integrated mutant and its phenotype was similar to that of the sam3 mutant, including calcium sensitivity and UV non-sensitivity, but the phenotype is different from that of the DELTArad24 strain. While the UV-sensitive phenotype was observed in the DELTArad24 mutant, it was not observed in the sam3 and rad24-E185K mutants. The expression of the rad24-E185K gene in wild type cells induced spore formation in the nutrient rich medium, confirming rad24-E185K is dominant. This dominant effect of rad24-E185K was also observed in DELTAras1 and DELTAbyr2 diploid mutants, indicating that rad24-E185K generate stronger phenotype than rad24 null mutants. Ste11, the key transcription factor for sexual differentiation was expressed in sam3 mutants without starvation and it predominantly localized to the nucleus. The Rad24-E185K mutant protein retained its interaction with Check point kinase1 (Chk1), whereas it reduced interaction with Ste11, an RNA binding protein Mei2, and a MAPKKK Byr2, freeing these proteins from negative regulation by Rad24, that account for the sam phenotype and UV non-sensitive phenotype. Glucose depletion in rad24-E185K or DELTApka1 DELTArad24 double mutation induced haploid meiosis, leading to the formation of spores in haploid. The position of glutamic acid 185 is conserved in all major 14-3-3s; hence, our finding of a dominant negative allele of 14-3-3 is useful for understanding 14-3-3s in other organisms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hyperuricemia has been reported to be a risk factor for hypertension, but this association may be affected by alcohol consumption. This study aimed to investigate whether hyperuricemia remains a risk ...factor for hypertension after eliminating the effect of alcohol consumption. This study comprised 7848 participants (4247 men and 3601 women) aged 30-74 years without hypertension who had undergone a medical checkup between April 2008 and March 2009 at Saku Central Hospital, Nagano Prefecture, Japan. Hyperuricemia was defined as uric acid >7.0 mg/dl in men, ≥6.0 mg/dl in women, and/or receiving treatment for hyperuricemia or gout. The incidence of hypertension was defined as the first diagnoses of blood pressure ≥140/≥ 90 mmHg and/or initiations of antihypertensive drug treatment. Multivariable-adjusted hazard ratios (HRs) of hyperuricemia for the incidence of hypertension after adjustment for and classification by alcohol consumption were estimated using the Cox proportional hazard model. During a mean of 4.0 years of follow-up, 1679 individuals developed hypertension. After adjustment for alcohol consumption, the HRs (95% confidence interval) associated with hyperuricemia were 1.37 (1.19-1.58) in men and 1.54 (1.14-2.06) in women. Among nondrinkers, the HR was 1.29 (0.94-1.78) in men with hyperuricemia compared with men without, and the corresponding HR was 1.57 (1.11-2.22) in women. The corresponding HR was 1.88 (1.27-2.86) in all participants with baseline blood pressure <120/80 mmHg. The interactions between hyperuricemia and sex (P = 0.534) and between drinking and sex (P = 0.713) were not significant. In conclusion, hyperuricemia predicts the risk for developing hypertension independent of alcohol drinking status.
The 2011 Great East Japan Earthquake (within Fukushima, Iwate, and Miyagi prefectures) was a complex disaster; it caused a tsunami and the Fukushima Daiichi Nuclear Power Plant accident, resulting in ...radiation exposure. This study investigated the earthquake’s effects on the migration patterns of pregnant women and their concerns regarding radiation exposure. We also considered the following large-scale earthquakes without radiation exposure: Great Hanshin-Awaji (Hyogo prefecture), Niigata-Chuetsu, and Kumamoto. Pregnant women were categorized as outflow and inflow pregnant women. Data on the annual number of births three years before and after the earthquake were used as a denominator to calculate the outflow and inflow rates per 100 births. The odds ratios of annual outflow and inflow rates after the earthquake, using three years before the earthquake as the baseline, were calculated. The odds-ratio for outflow significantly increased for Hyogo, Fukushima, Miyagi, and Kumamoto prefectures after the earthquake, particularly for Fukushima, showing a significant increase until three years post the Great East Japan Earthquake (disaster year: odds-ratio: 2.66 95% confidence interval: 2.44–2.90, 1 year post: 1.37 1.23–1.52, 2 years post: 1.13 1.00–1.26, 3 years post: 1.18 1.05–1.31), while the remaining three prefectures reported limited increases post one year. The inflow decreased after the earthquake, particularly in Fukushima, showing a significant decrease until 2 years post the Great East Japan Earthquake (disaster year: 0.58 0.53–0.63, 1 year post: 0.76 0.71–0.82, 2 years post: 0.83 0.77–0.89). Thus, pregnant women’s migration patterns changed after large-scale earthquakes, suggesting radiation exposure concerns possibly have a significant effects. These results suggested that plans for receiving assistance and support that considers the peculiarities of disaster related damage and pregnant women’s migration patterns are needed in both the affected and non-affected areas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To report aging-associated change rates in circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and macular ganglion cell-inner plexiform layer and complex thickness (MGCIPLT, MGCCT) ...in normal Japanese eyes and to compare the data in linear scaled visual field (VF) sensitivity of central 4 points of Humphrey Field Analyzer (HFA) 24-2 test (VF
4TestPoints
) to that in MGCIPLT in four 0.6-mm-diameter circles corresponding to the four central points of HFA 24-2 adjusted for retinal ganglion cell displacement (GCIPLT
4TestPoints
).
Study design
Prospective observational study
Methods
HFA 24-2 tests and spectral-domain optical coherence tomography (SD-OCT) measurements of cpRNFLT, MGCIPLT, MGCCT and GCIPLT
4TestPoints
were performed every 3 months for 3 years in 73 eyes of 37 healthy Japanese with mean age of 50.4 years. The time changes of SD-OCT-measured parameters and VF
4TestPoints
were analyzed using a linear mixed model.
Results
The aging-associated change rates were -0.064 μm/year for MGCIPLT and and -0.095 for MGCCT (P=0.020 and 0.017), but could not be detected for cpRNFLT. They accelerated with aging at -0.009μm/year/year of age for MGCIPLT (P<0.001), at 0.011 for MGCCT (P<0.001) and at 0.013 for cpRNFLT(0.031). The aging-associated decline of -82.1 1/Lambert/year of VF
4TestPoints
corresponded to -0.095 μm/year of GCIPLT
4TestPoints
.
Conclusion
We report that aging-associated change rates of cpRNFLT, MGCIPLT and MGCCT in normal Japanese eyes were found to be significantly accelerated along with aging. Relationship between VF sensitivity decline rates and SD-OCT measured GCIPLT decline rates during physiological aging in the corresponding parafoveal retinal areas are also documented.
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.
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.
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).
We suggest that patients who require curative surgery for esophageal, biliary tract, and pancreatic cancer may benefit from referral to high-volume hospitals.
Improvement in patient waiting time in dispensing pharmacies is an important element for patient and pharmacists. The One-Dose Package (ODP) of medicines was implemented in Japan to support medicine ...adherence among elderly patients; however, it also contributed to increase in patient waiting times. Given the projected increase in ODP patients in the near future owing to rapid population aging, development of improved strategies is a key imperative. We conducted a cross-sectional survey at a single dispensing pharmacy to clarify the impact of ODP on patient waiting time. Further, we propose an improvement strategy developed with use of a discrete event simulation (DES) model. A total of 673 patients received pharmacy services during the study period. A two-fold difference in mean waiting time was observed between ODP and non-ODP patients (22.6 and 11.2 min, respectively). The DES model was constructed with input parameters estimated from observed data. Introduction of fully automated ODP (A-ODP) system was projected to reduce the waiting time for ODP patient by 0.5 times (from 23.1 to 11.5 min). Furthermore, assuming that 40% of non-ODP patients would transfer to ODP, the waiting time was predicted to increase to 56.8 min; however, introduction of the A-ODP system decreased the waiting time to 20.4 min. Our findings indicate that ODP is one of the elements that increases the waiting time and that it might become longer in the future. Introduction of the A-ODP system may be an effective strategy to improve waiting time.
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