Yoshisada Shibata

Cancer consequences of the Chernobyl accident: 20 years on

26 April 2006 marks the 20th anniversary of the Chernobyl accident. On this occasion, the World Health Organization (WHO), within the UN Chernobyl Forum initiative, convened an Expert Group to evaluate the health impacts of Chernobyl. This paper summarises the findings relating to cancer. A dramatic increase in the incidence of thyroid cancer has been observed among those exposed to radioactive iodines in childhood and adolescence in the most contaminated territories. Iodine deficiency may have increased the risk of developing thyroid cancer following exposure to radioactive iodines, while prolonged stable iodine supplementation in the years after exposure may reduce this risk. Although increases in rates of other cancers have been reported, much of these increases appear to be due to other factors, including improvements in registration, reporting and diagnosis. Studies are few, however, and have methodological limitations. Further, because most radiation-related solid cancers continue to occur decades after exposure and because only 20 years have passed since the accident, it is too early to evaluate the full radiological impact of the accident. Apart from the large increase in thyroid cancer incidence in young people, there are at present no clearly demonstrated radiation-related increases in cancer risk. This should not, however, be interpreted to mean that no increase has in fact occurred: based on the experience of other populations exposed to ionising radiation, a small increase in the relative risk of cancer is expected, even at the low to moderate doses received. Although it is expected that epidemiological studies will have difficulty identifying such a risk, it may nevertheless translate into a substantial number of radiation-related cancer cases in the future, given the very large number of individuals exposed.

15 years after Chernobyl: new evidence of thyroid cancer

The Chernobyl nuclear power plant accident happened on April 26, 1986. We investigated the cause of the striking increase in frequency of thyroid cancer in children who lived within a 150 km radius of Chernobyl and who were born before and after the accident. No thyroid cancer was seen in 9472 children born in 1987-89, whereas one and 31 thyroid cancers were recorded in 2409 children born April 27, 1986, to Dec 31, 1986, and 9720 born Jan 1, 1983, to April 26, 1986, respectively. Short-lived radioactive fallout caused by the Chernobyl accident probably induced thyroid cancer in children living near Chernobyl.

Malaria-Specific and Nonspecific Activation of CD8+ T Cells during Blood Stage of Plasmodium berghei Infection

Cerebral malaria is one of the severe complications of Plasmodium falciparum infection. Studies using a rodent model of Plasmodium berghei ANKA infection established that CD8+ T cells are involved in the pathogenesis of cerebral malaria. However, it is unclear whether and how Plasmodium-specific CD8+ T cells can be activated during the erythrocyte stage of malaria infection. We generated recombinant Plasmodium berghei ANKA expressing OVA (OVA-PbA) to investigate the parasite-specific T cell responses during malaria infection. Using this model system, we demonstrate two types of CD8+ T cell activations during the infection with malaria parasite. Ag (OVA)-specific CD8+ T cells were activated by TAP-dependent cross-presentation during infection with OVA-PbA leading to their expression of an activation phenotype and granzyme B and the development to functional CTL. These highly activated CD8+ T cells were preferentially sequestered in the brain, although it was unclear whether these cells were involved in the pathogenesis of cerebral malaria. Activation of OVA-specific CD8+ T cells in RAG2 knockout TCR-transgenic mice during infection with OVA-PbA did not have a protective role but rather was pathogenic to the host as shown by their higher parasitemia and earlier death when compared with RAG2 knockout mice. The OVA-specific CD8+ T cells, however, were also activated during infection with wild-type parasites in an Ag-nonspecific manner, although the levels of activation were much lower. This nonspecific activation occurred in a TAP-independent manner, appeared to require NK cells, and was not by itself pathogenic to the host.

Lower-extremity muscle forces measured by a hand-held dynamometer and the risk of falls among day-care users in Japan: using multinomial logistic regression analysis.

Purpose : To assess the relationship between the lower extremity muscle forces and risk of falls among the elderly who were using day-care services in the long-term care insurance system. Method : The study population comprised 96 women aged 69 v - v 91 years. At baseline, we assessed ADL, functional capacity, isometric muscle forces of knee extension and ankle dorsiflexion obtained with a hand-held dynamometer. After 1 year, we asked subjects about falls during the follow up period. Results : In univariate analysis, only the knee extensor strength ( p v = v 0.003) and ankle dorsiflexor strength ( p v = v 0.02) differed significantly according to the fall status. After adjustment for age using multinomial logistic regression analysis, the weak quadriceps group was 7.50 times more likely than the strong group to fall once ( p v = v 0.02), and 5.00 times more likely to fall twice or more ( p v = v 0.02). The weakest ankle dorsiflexor group was 5.09 times more likely than the strongest group to fall twice or more ( p v = v 0.05). Conclusions : Our results indicated that the forces of knee extensor and ankle dorsiflexor were strongly associated with falls among day-care users. Physiotherapy should focus on the lower-extremity muscle strength to prevent falls and deterioration of physical ability among elderly persons who are partially dependent and need support.

Radiocesium in children residing in the western districts of the Bryansk Oblast from 1991-1996.

Measurements of 137Cs body burden were carried out in 1991-1996 for children residing in the western part of Bryansk Oblast (Russia) where area contamination with 137Cs following the Chernobyl accident varied from 0.03-3.7 MBq m(-2). The mean and median values of 137Cs specific activity (SA) in the bodies of children 5-15 y old for the whole period of surveillance averaged for 26,029 measurements was 85 Bq kg(-1) and 49 Bq kg(-1), respectively. Mean values in different places of residence varied from 30-342 Bq kg(-1) for the settlements where the number of examinees was not less than 50. There is a moderately strong relationship between mean SA in the settlement and the level of area contamination with 137Cs. A strong seasonal effect on 137Cs body burden was found. The ratio of average SA values is 1:1.75 for spring to autumn 1992-1995 in the settlement where the largest number of children was examined. This effect might be attributed to a seasonal change in diet. Based on questionnaire information on individual consumption of locally produced foods, the descending rank of contribution of food items to 137Cs intake by children was found to be: meat-mushrooms-milk-vegetables. Assuming that the dose distribution would follow the distribution of SA values, internal doses to the whole body from ingested 137Cs were assessed. The mean value of annual internal dose averaged for the whole set of measurements is 0.21 mSv, and the median of the individual dose distribution is 0.12 mSv y(-1) For 2% of the total sample the annual dose exceeded 1 mSv, with the highest individual dose being 9 mSv in 1994 for a 7-y-old girl.

Donepezil significantly improves abilities in daily lives of female Down syndrome patients with severe cognitive impairment: a 24-week randomized, double-blind, placebo-controlled trial.

Objective: Down syndrome (DS) patients share certain neuropathological features with Alzheimer disease patients. A randomized, double-blind, placebo-controlled study was performed to investigate the efficacy and safety of donepezil, an Alzheimer disease drug, for DS patients. Method: Twenty-one DS patients with severe cognitive impairment were assigned to take donepezil (3 mg daily) or a placebo for 24 weeks, and evaluated for activities in daily lives by concisely modified International Classification of Functioning, Disability and Health (ICF) scaling system. Results: ICF scores significantly increased without any adverse effects in the donepezil group in comparison to those in the placebo control. Among the individual functions tested, there was a dramatic improvement in the global mental functions and in specific mental functions. Conclusions: Donepezil may effectively and safely improve overall functioning of DS patients with severe cognitive impairment.

Assessment and follow-up of intercostal nerve damage after video-assisted thoracic surgery.

OBJECTIVE Chronic pain is a common complication after thoracic surgery. The most important factor appears to be intercostal nerve damage. The purpose of this prospective study was to objectively evaluate intercostal nerve damage associated with post-thoracotomy pain after three surgical procedures using current perception threshold testing. METHODS The 32 patients were classified into three groups: the video-assisted thoracic surgery group (n=7), the video-assisted minithoracotomy with metal retractors group (n=15), and the conventional thoracotomy group (n=10). Intercostal nerve function was assessed by a series of 2000-Hz (Aβ fiber), 250-Hz (Aδ fiber), and 5-Hz (C fiber) stimuli using current perception threshold testing (Neurometer CPT/C). The current perception threshold values were measured before and 1, 2, 4, 12, and 24 weeks after surgery. The intensities of ongoing pain were also assessed using a numeric rating scale (0-10). RESULTS The video-assisted thoracic surgery group showed no changes in any current perception threshold values and no residual pain more than 12 weeks after surgery. The video-assisted minithoracotomy with metal retractors group and the conventional thoracotomy group showed significantly higher current perception threshold values at 2000 Hz 1 week after surgery (p=0.0013, p=0.0012, respectively), with pain in approximately 70% of patients 12 weeks after surgery. The correlation between current perception threshold values at 2000 Hz and the intensities of ongoing pain 4 and 12 weeks after surgery was significant (p=0.03, p=0.04, respectively). CONCLUSIONS This is the first study that objectively evaluated pain after video-assisted thoracic surgery. The results suggest that the Aβ and Aδ fibers play a significant role in the development of intercostal nerve damage. The current perception threshold values clearly demonstrated that video-assisted thoracic surgery is a less-invasive procedure resulting in less post-thoracotomy pain and, they have some possibilities to objectively evaluate the ongoing pain after surgery.

Mental health conditions among atomic bomb survivors in Nagasaki

To elucidate the effects of the bombing on the atomic bomb survivors’ mental health, a mental health survey was conducted using a 12‐item version of the General Health Questionnaire (GHQ‐12) and a mail survey on atomic bomb exposure conditions and lifestyle using a self‐administered questionnaire. A total of 3526 atomic bomb survivors in Nagasaki responded and a high GHQ‐12 score, as defined when the responses to four or more items were positive, was observed in 296 (8.4%) subjects. It was indicated that the risk of a high GHQ‐12 score will decrease 0.98‐fold with every 1‐year increase in age, and will increase 1.45‐fold and 1.70‐fold in those who lost family members due to the bombing and those who had acute symptoms, respectively, compared with those who did not. It was indicated that the atomic bomb exposure has affected survivors’ mental health and that the care of their mental health is important.

Radiation Exposure Does Not Significantly Contribute to the Risk of Recurrence of Chernobyl Thyroid Cancer

CONTEXT Papillary thyroid carcinoma (PTC) in patients exposed to environmental radioiodine after the Chernobyl accident is thought to have a relatively aggressive clinical course. Long-term results of treatment are not well known, especially in comparison with sporadic PTC. OBJECTIVE The determination of risk factors for PTC recurrence in a controlled for baseline factors group of patients with radiation-related and sporadic PTC. DESIGN Retrospective cohort study involving patients treated for PTC and followed-up in 1991-2008. Risk factors were assessed by stratified analysis using the proportional hazard model. SETTING Referral center-based. PATIENTS A total of 497 patients were enrolled. Patients exposed to radioiodine were 172 individuals with reconstructed individual radiation thyroid doses ranging 51-3170 mGy. Patients with sporadic PTC included 325 individuals matched to exposed patients for sex, age ± 5 yr and time to treatment ± 2 yr. MAIN OUTCOME MEASURE Cancer recurrence. RESULTS Nodal disease increased the recurrence rate (HR = 5.21; 95% CI = 1.63-16.7) while the presence of tumor capsule (HR = 0.17; 95% CI = 0.06-0.45) and, particularly, treatment according to the Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer significantly reduced it (HR = 0.16; 95% CI = 0.06-0.42). None of the tested variables interacted with radiation factor. CONCLUSIONS PTC developing after internal exposure to radioiodine does not display specific risk factors for recurrence different from those in sporadic PTC. Common treatment approaches for patients with PTC should be recommended regardless of a history of radiation exposure.

The usual ultrasonographic features of thyroid cancer are less frequent in small tumors that develop after a long latent period after the Chernobyl radiation release accident.

BACKGROUND The Chernobyl accident resulted in an unprecedented number of radiation-induced thyroid cancers in young individuals as detected by national and international screening programs. The vast majority of thyroid malignancies were papillary carcinomas that, despite being similar by histopathology, displayed large variability in clinical course. The correlations between ultrasound (US) and clinicopathological features in young patients with radiation-induced thyroid cancer, however, have not been well studied. Because of the importance of US for deciding which subjects should have fine-needle aspiration biopsy, we assessed the US features of papillary thyroid carcinoma in patients exposed to Chernobyl fallouts. DESIGN We performed a retrospective multivariate logistic regression analysis of US features, clinicopathological data, and the latency period between radiation exposure and the diagnosis of cancer in 94 patients who were 10.6-34.3 years old (16.5 +/- 6.2, mean +/- standard deviation) at the time of diagnosis and 0.1-18.0 years old (5.6 +/- 4.2) at the time of the Chernobyl accident. RESULTS Nodules greater than 10 mm were associated with the higher frequency of irregular margins (p = 0.001), longer period of latency (p = 0.016), and bilateral lymph node involvement (p = 0.025). Irregular tumor margins correlated with the shorter period of latency (p = 0.009) and unilateral nodal disease (p = 0.010). Hypoechoic nodules were observed more frequently in female patients (p = 0.012), in the absence of halo (p = 0.003) or calcifications (p = 0.005). Hypoechogenicity also correlated with the shorter latency (p = 0.015) and younger age of patients (p = 0.048). CONCLUSIONS Irregular nodule margins, a usual sign of malignancy, are less useful in detecting thyroid cancers in radiation-exposed patients with tumors less than 10 mm. Thyroid cancers that are detected after longer latent periods display less of the US features characteristic of a malignant process, while benign US features are observed more frequently. Therefore, we recommend fine-needle aspiration biopsy to ensure early diagnosis of thyroid cancer for patients with a history of radiation exposure, even if their nodules are less than 10 mm.