Assessment of SPECT-CT fusion images and semi-quantitative evaluation using SUV in 123I-IMP SPECT in patients with choroidal melanoma.

OBJECTIVES: The aim of this study was to assess the diagnostic ability of N-isopropyl-p-[I-123] iodoamphetamine (IMP) SPECT semi-quantitative evaluation based on the standardized uptake value (SUV) in patients with choroidal melanoma. The secondary aim was to investigate the 6-h IMP SPECT imaging in comparison with 24-h imaging. METHODS: Twenty-five patients (14 males and 11 females, mean age of 59.2-year-old) were analyzed in this retrospective study. Patients underwent 24-h IMP SPECT imaging with a gamma camera after intravenous injection of IMP. Twelve of 25 patients underwent 6-h SPECT imaging in addition to the 24-h imaging. All acquired SPECT images were fused with CT images using an image-analysis software. To assess the utility of semi-quantitative evaluation method, we introduced an image evaluation method using SUVmax comparing with conventional count-based uptake index (UI) evaluation of the lesion. Volumes-of-interest (VOIs) for SUVmax and regions-of-interest (ROIs) for UI were drawn referring to the SPECT-CT fusion image. Then the relationship between the 6- and 24-h images was examined both in SUV and UI evaluation. Furthermore, the relationship between the size category classification (SCC) by UICC/AJCC: 1-4 scales and each semi-quantitative value using SUVmax and UI was also assessed. RESULTS: SUVmax of the tumor was significantly higher than that of the normal side; 2.37 ± 0.88 and 1.77 ± 0.39 (P < 0.05) on 6-h image, 4.17 ± 1.73 and 2.04 ± 0.45 (P < 0.001) on 24-h image, respectively. UI of the tumor was also significantly higher than that of the normal side; 2.24 ± 0.67 and 1.53 ± 0.35 (P < 0.01) on 6-h image, 3.79 ± 1.24 and 1.67 ± 0.44 (P < 0.001) on 24-h image, respectively. There was a strong significant linear relationship in the evaluation with SUVmax between 6- and 24-h on the tumor side (R2 = 0.88, P < 0.0001), compared to that with Tumor-UI (R2 = 0.35, P < 0.05). In addition, SUVmax of the tumor clearly differentiated the SCC of the tumor category 4 from that of category 1, where SUVmax of the tumor for categories 1‒4 were 2.56 ± 0.59, 4.33 ± 1.92, 4.63 ± 1.45, and 5.73 ± 1.69, respectively (P < 0.05, for categories 1 and 4). CONCLUSIONS: The semi-quantitative evaluation by SUV of 123I-IMP SPECT images fused with CT images is useful for detecting choroidal melanoma. Moreover, 6-h imaging with SUV-based evaluation of 123I-IMP SPECT is promising compared to the conventional count-based UI evaluation method. Trial registration This study is registered in UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000038174.

Assessment of risk factors associated with development of oronasal fistula as a late complication after carbon-ion radiotherapy for head and neck cancer.

BACKGROUND: Oronasal fistulae (ONF) are one of the rare but serious complications of conventional photon radiotherapy. This study aimed to identify the risk factors for the development of ONF after carbon-ion radiotherapy (C-ion RT). MATERIALS AND METHODS: The data of 62 cases of sinonasal and oral cavity cancers treated with C-ion RT and followed-up in excess of 5 years were retrospectively reviewed. The correlation between the clinical and dosimetric parameters and the development of ONF was analysed. RESULTS: A total of 80.6% cases had sinonasal malignancies, and most tumours had advanced T stages (96.8%). Maxillary invasion was observed in 16 cases (25.8%), and malignant melanoma was the most common histology (46.8 %). All the cases received a dose of between 57.6 Gy (RBE) and 64 Gy (RBE) in 16 fractions over 4 weeks. At a median follow up of 88.8 months, 23 cases (37.1%) developed small localised ONF; however, none were of grade III severity. On separate multivariate analyses of clinical parameters in the entire cohort and in cases without maxillary invasion, the number of teeth irradiated with more than 50 Gy (RBE) was found to be the common significant independent risk factor for development of ONF. CONCLUSION: The number of teeth irradiated with more than 50 Gy (RBE) is a significant independent risk factor for the development of ONF, which is a late complication of C-ion RT delivered in 16 fractions.

Five-year quality of life assessment after carbon ion radiotherapy for prostate cancer.

The aim of this study was to prospectively assess 5-year health-related quality of life (HRQOL) of patients treated with carbon ion radiotherapy (C-ion RT) for clinically localized prostate cancer. A total of 417 patients received carbon ion radiotherapy at a total dose of 63-66 Gray-equivalents (GyE) in 20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation therapy (ADT) were administered for intermediate and high-risk patients. A HRQOL assessment was performed at five time points (immediately before the initiation of C-ion RT, immediately after, and at 12, 36 and 60 months after completion of C-ion RT) using Functional Assessment of Cancer Therapy (FACT) questionnaires. FACT-G and FACT-P scores were significantly decreased; however, the absolute change after 60 months was minimal. The transient decreases in the Trial Outcome Index (TOI) score returned to their baseline levels. Use of ADT, presence of adverse events, and biochemical failure were related to lower scores. Scores of subdomains of FACT instruments indicated characteristic changes. The pattern of HRQOL change after C-ion RT was similar to that of other modalities. Further controlled studies focusing on a HRQOL in patients with prostate cancer are warranted.

Respiration-gated fast-rescanning carbon-ion radiotherapy.

Phase-controlled rescanning of the carbon-ion beam offers fast and precise dose application with decreased irradiation of normal tissue. However, organ movement with respiration remains a unique challenge. Technological development has enabled the simultaneous application of beam-energy-modulated markerless phase-controlled rescanning with respiration gating, allowing scanning treatment of respiration-mobile tumors with carbon. A total of 10 patients with tumors in the liver or lung were treated in a feasibility study at our facility using this combination. At a median of 10.5 months, follow-up examination including computed tomography/magnetic resonance imaging revealed no grade 2+ acute adverse effects with this new therapy. Two patients with complex disease experienced local recurrence, which may be improved with increased dose delivery. One patient died of unrelated causes. All other patients are alive with good control at the time of writing. Though long-term observation is pending, these are promising initial results for use of the carbon-beam phase-controlled rescanning method in respiration-mobile disease.

Impact of individual components and their combinations within a family history of hypertension on the incidence of hypertension: Toranomon hospital health management center study 22.

Although a family history (FH) of hypertension is a risk factor for the development of hypertension, only a few studies have investigated in detail the impact of individual components of an FH on incident hypertension. We investigated the impact of individual components and their combinations on the presence or development of hypertension considering obesity, smoking habits, physical activity, and other metabolic parameters.Studied were 12,222 Japanese individuals without hypertension (n = 9,766) and with hypertension (n = 2,456) at the baseline examination. The presence or incidence of hypertension during 5 years after a baseline examination was assessed by the presence of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or a self-reported history of clinician-diagnosed hypertension. In this prospective study, the odds ratio for incident hypertension was 1.39 (95% confidence interval [CI], 1.22, 1.59) for individuals with any FH of hypertension compared with those without such an FH. Individuals with an FH of hypertension in both parents and one or more grandparents had an odds ratio of 3.05 (95% CI 1.74, 5.36) for hypertension compared with those without an FH of hypertension. FH was associated with incident hypertension independently of other modifiable risk factors such as obesity, smoking, physical inactivity, hyperglycemia, hyperuricemia, and hypertriglyceridemia.A parental history of hypertension was an essential component within an FH for incident hypertension. FH of hypertension over two generations with both parents affected was the most important risk factor for incident hypertension. Although an FH is not a modifiable risk factor, modifying other risk factors could contribute to reducing the risk of hypertension even among individuals with a family history of hypertension.

Dose prescription in carbon ion radiotherapy: How to compare two different RBE-weighted dose calculation systems.

BACKGROUND AND PURPOSE: In carbon ion radiotherapy (CIRT), the use of different relative biological effectiveness (RBE) models in the RBE-weighted dose (DRBE) calculation can lead to deviations in the physical dose (Dphy) delivered to the patient. Our aim is to reduce target Dphy deviations by converting prescription dose values. MATERIAL AND METHODS: Planning data of patients treated at the National Institute of Radiological Sciences (NIRS) were collected, with prescribed doses per fraction ranging from 3.6Gy (RBE) to 4.6Gy (RBE), according to the Japanese semi-empirical model. The Dphy was Monte Carlo (MC) re-calculated simulating the NIRS beamline. The local effect model (LEM)_I was then applied to estimate DRBE. Target median DRBE ratios between MC+LEM_I and NIRS plans determined correction factors for the conversion of prescription doses. Plans were re-optimized in a LEM_I-based commercial system, prescribing the NIRS uncorrected and corrected DRBE. RESULTS: The MC+LEM_I target median DRBE was respectively 15% and 5% higher than the NIRS reference, for the lowest and highest dose levels. Uncorrected DRBE prescription resulted in significantly lower target Dphy in re-optimized plans, with respect to NIRS plans. CONCLUSIONS: Prescription dose conversion factors could minimize target physical dose variations due to the use of different radiobiological models in the calculation of CIRT RBE-weighted dose.

Assessment of kidney dysfunction with cystatin C- and creatinine-based estimated glomerular filtration rate and predicting type 2 diabetes: Toranomon Hospital Health Management Center Study 21.

OBJECTIVE: Whether early stages of kidney dysfunction assessed by the estimated glomerular filtration rate from cystatin C measurements (eGFRCysC) rather than from creatinine measurements (eGFRCr) would more precisely reflect the risk of developing type 2 diabetes (T2D) has not been clarified. We compared the risk of developing T2D associated with renal dysfunction indicated by eGFRCysC or eGFRCr measurements. METHODS: Studied were 2131 Japanese individuals without diabetes. Hazard ratios (HRs) for the development of T2D over 3-5 y were calculated across categories of eGFRCysC and eGFRCr, respectively. RESULTS: Reduced levels of eGFRCysC were associated with a step-wise increase in the cumulative incidence rate of T2D (p=0.007). In comparison with the eGFRCysC >85th percentile group (≥ 117.4 ml/min/1.73 m(2)), the lowest group, which was the eGFRCysC <15th percentile group (<86.2 ml/min/1.73 m(2)), had an adjusted HR of 2.30 (95% CI 1.13, 4.68) for T2D. Compared with the eGFRCr >85th percentile group, the lowest eGFRCr group (<15th percentile) had an HR of 1.19 (0.63, 2.24) for T2D. However, individuals with eGFRCr <60 ml/min/1.73 m(2) had a significantly increased risk of T2D. Clustering of both low eGFRCysC and low eGFRCr further elevated the HR for T2D compared with the presence of either. CONCLUSIONS: Although eGFRCr in ranges indicating chronic kidney disease reflected an elevated risk of developing diabetes, earlier stages of kidney dysfunction indicated by reduced eGFRCysC, which could not be captured by reduced eGFRCr, would be a marker for an elevated risk of developing T2D.

Challenges and solutions in immigrant occupational health in the United States: a literature review and comparative analysis.

OBJECTIVES: Because of the declining birthrate in Japan, an increasing number of companies are hiring immigrants to fill the labor shortage. Although research on migrant occupational health has progressed in the United States, this topic has received little attention in Japan. The aim of this study was to elucidate the current situation, challenges, and solutions surrounding the occupational health of immigrant workers in the United States. METHODS: Data and selected studies were reviewed and analyzed. The results are discussed, and a few anecdotal experiences in the United States are introduced and compared. RESULTS: Possible causes of disparities in immigrant occupational health fell into the following seven categories. (Keywords for each category are shown in parentheses.) (1) Occupation (hazardous job, injury, missed workday, blue-collar worker, low birth weight); (2) Education (academic record, health literacy, training); (3) Culture (culture-specific, community-based); (4) Environment (poor hygiene, regional disparities, environmental change); (5) Access (language, statistics, workers' compensation, health insurance, voluntary restraint); (6) Infection (tuberculosis, human immunodeficiency virus/AIDS, follow-up); and (7) Discrimination (race, assault, harassment). Lack of data on immigrant workers was found to be a common problem. Some businesses and community groups achieved positive results by simultaneously dealing with multiple aforementioned categories. DISCUSSION: In the United States, the occupational health of immigrant workers has been studied mainly in terms of health disparities. Possible causes of disparities in immigrant occupational health fell into seven categories. Solutions centered on the keywords in each category were inferred. Some businesses and community groups achieved positive results by simultaneously dealing with multiple aforementioned categories. Occupational health professionals have to take each of seven categories into account to improve immigrant occupational health. Even the United States-a developed country facing many migrant occupational health problems-needs further research and better data. To address this issue in Japan, we too need more data and further research on immigrants, along with efforts by businesses and community groups.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan.

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy(-1) and ß = 0.0615 Gy(-2) as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ± 1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

Impact of introducing HbA1c into the diagnostic criteria on prevalence and cardiovascular risk profiles of individuals with newly diagnosed diabetes in Japan: the Toranomon Hospital Health Management Center Study 2 (TOPICS 2).

OBJECTIVE: To evaluate the impact of HbA1c for diagnosis of diabetes and investigate whether cardiovascular risks profiles differ among individuals with diabetes diagnosed by HbA1c or fasting plasma glucose (FPG). METHODS: This cross-sectional study involved 26,884 participants (30.6% women; aged 20-91 years) without known diabetes. Subjects were categorized into 4 groups according to the presence or absence of FPG ≥7.0 mmol/L and/or HbA1c ≥6.5%, which were American Diabetes Association criteria. Oral glucose tolerance test data were not available. RESULTS: Prevalence of undiagnosed diabetes was 3.6%. Of those individuals, 47.5% fulfilled both two criteria and 26.0% fulfilled only HbA1c criterion. Individuals with diabetes according to FPG ≥7.0 mmol/L alone were characterized as having poorly controlled hypertension while those with HbA1c ≥6.5% alone were characterized as older, female, and having lower blood pressure and γ-glutamyltransferase values. Persons with newly diagnosed diabetes by HbA1c had low HDL cholesterol and high LDL or non-HDL cholesterol levels. CONCLUSIONS: Introducing HbA1c into the diagnosis allowed detection of many previously undiagnosed cases of diabetes in Japanese individuals. Those diagnosed by FPG were characterized by hypertension and those diagnosed by HbA1c had unfavorable lipid profiles, reflecting an atherosclerotic trait.

Effects of sodium monofluoroacetate on glucose, amino-acid, and fatty-acid metabolism and risk assessment of glucose supplementation.

Sodium monofluoroacetate (SMFA; also known as compound 1080) is a highly toxic chemical; therefore, accidental exposure and intentional misuse are of great concern. SMFA intoxication is reportedly caused by the inhibition of aconitase. However, the pathogenesis underlying SMFA intoxication is not clear. This study was conducted to elucidate the acute effects of SMFA on glucose, amino-acid, and fatty-acid metabolism and to assess glucose supplementation as a possible alleviator or aggravator in SMFA intoxication. Rats were assigned to three groups: SMFA+saline, SMFA+glucose, and control (i.e., no SMFA), and blood samples were analyzed at 3 hours after SMFA or saline (control) administration. Additional rats were used for the monitoring of blood-glucose and lactate concentrations for 10 hour- and 14-day survival rates. SMFA increased the serum-citrate, serum-pyruvate, and blood-lactate concentrations. However, despite significant increases in these parameters when SMFA was administered with glucose, the effects on pH values were small and the survival rate was not changed. SMFA also increased the serum concentrations of free fatty acids, branched-chain amino acids, ammonia, urea, and calcium. The presence of glucose enhanced or suppressed these metabolic changes. Amphibolic intermediates in the tricarboxylic acid cycle might be supplied through the catabolism of proteins in SMFA intoxication. We conclude that other factors, in addition to the accumulation of lactate, citrate, and pyruvate, may affect survival rates, and that SMFA induces imbalances in glucose, amino-acid, and, fatty-acid metabolism. All these changes are inter-related and may contribute to SMFA intoxication.