Incidence In Japan Research Articles

Descriptive Epidemiology of Fabry Disease Among Beneficiaries of the Specified Disease Treatment Research Program in Japan

BackgroundFabry disease (FD) is a rare X-linked lysosomal storage disorder and is included in the Specified Disease Treatment Research Program in Japan, which subsidizes medical care for beneficiaries with rare and other, designated diseases. However, no report on the epidemiologic features of Fabry disease has been published in Japan.MethodsWe used clinical research data reports submitted to the program between 2003 and 2008 to assess the epidemiologic features of 315 beneficiaries with FD.ResultsOf the 315 program beneficiaries, 198 were men (mean age, 37.4 years) and 117 were women (mean age, 51.2 years). The overall incidence in Japan was 0.25 cases per 100 000 individuals, and prevalence among men was 1.78 times that among women. More than 80% of beneficiaries were capable of working, going to school, or doing housework; however, 46 beneficiaries (14.6%) required home care, and 9 (2.9%) were living in hospitals or other medical facilities. As compared with the previous year, the clinical course of FD at beneficiary registration was unchanged for 178 of 290 beneficiaries (61.4%), worse for 81 (27.9%), and improved or cured for 31 (10.7%). The distribution of beneficiary-related characteristics was similar between men and women, and no significant difference was observed.ConclusionsThe high percentage (>80%) of individuals with FD who were able to work, attend school, and perform tasks such as housework could reflect an improvement in the clinical course of FD after enzyme replacement therapy. We must continue data collection and conduct further studies to improve our understanding of the descriptive epidemiology of FD.

IgG4-Related Disease and Malignancy

Mikulicz’s disease (MD) has been included within the diagnosis of primary Sjogren’s syndrome (SS), but it represents a unique condition involving the enlargement of the lacrimal and salivary glands and characterized by few autoimmune reaction (1). Glucocorticoid treatment is effective for the clinical improvement of this disease (2). Now it is considered that MD is quite a different disease from primary SS (1), and a type of IgG4-related disease (IgG4-RD) (3). IgG4-RD is characterized by a swelling of the affected organs along with elevated levels of serum IgG4, and abundant infiltration of IgG4-bearing plasma cells and fibrosis. IgG4-RD is a new concept of systemic and chronic inflammation (3), and usually includes MD, autoimmune pancreatitis (AIP) (4), and IgG4-related tubulointerstitial nephritis (5). IgG4-RD is an important disease for clinical physicians to discriminate from cancers and other rheumatic diseases. On the other hand, recent focus has been on the relationship between IgG4-RD and malignancies. IgG4-RD with pancreatic cancer has often been reported in cases of AIP (6, 7). It is known that positron emission tomography (PET) is very useful for systemic evaluation in IgG4RD (8, 9). Whenever we make a diagnosis of IgG4-RD, we consult PET images. In some instances, we are presented with cases involving abnormal accumulation at the lesion sites outside of the involved organs; this is known as organic dysfunction of IgG4-RD. Upon further examination, we often find that the lesion is cancer. In such instances, PET is very useful for detecting cancer. Our previous study (SMART database: Sapporo Medical University and Related institutes database for investigation and best treatments of IgG4-related disease) demonstrated that malignancies occurred in 10.4% of IgG4-RD cases. Using the database of national cancer registries in the monitoring of cancer incidence in Japan (2005) (10), the standardized incident ratio (SIR) for cancers in male patients with IgG4-RD was 331.1, and in female patients with IgG4-RD, 471.6. The total was 383.0. It was approximately 3.5 times higher than the incidence of cancer in the general population (11). Malignancies as complications of IgG4-RD are divided into lymphoma and non-lymphoid tumors. Lymphoma includes mucosa-associated lymphoid tissue (MALT) lymphoma and non-Hodgkin lymphoma. Lymphoma can present as a background of chronic inflammation. In SS, antigenic activation of B cells, together with oncogenic events, including p53 inactivation and bcl-2 activation, may play important roles in B cell monoclonal proliferation and malignant transformation (12). It is reported that the SIR for lymphoma in patients with SS was higher, 8.7 to 48.1 (13-15). It is suggested that this rate for lymphoma in MD is also high as well as in SS. In this issue of Internal Medicine, Uehara et al (16) report a 66-year-old man, who suffered from IgG4-RD, and performed autopsy. The patient had been followed as MD and IgG4-related pseudo-inflammatory tumor in the pelvis, but autopsy disclosed the coexistence of diffuse large B cell lymphoma. It could not be considered that lymphoma was complicated at the diagnosis of IgG4-RD. It is suggested that an activated B cell caused malignant transformation in the background of chronic inflammation. Therefore, it is critical to recognize the risk of lymphoma in MD as well as SS.

Cancer Incidence and Incidence Rates in Japan in 2006: Based on Data from 15 Population-based Cancer Registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project

The Japan Cancer Surveillance Research Group estimated the cancer incidence in 2006 as part of the Monitoring of Cancer Incidence in Japan (MCIJ) project, on the basis of data collected from 15 of 32 population-based cancer registries. The total number of incidences in Japan for 2006 was estimated as 664 398 (C00-C96). The leading cancer site was stomach for men and breast for women. Age-standardized incidence rates remained at almost the same level as for the previous 3 years.

Trend analysis of cancer incidence in Japan using data from selected population‐based cancer registries

Population-based cancer registries are operated by over 80% of prefectures in Japan. However, only a limited proportion of the registries can provide long-term incidence data. Here, we aimed to establish a method for monitoring cancer incidence trends in Japan using data from selected prefectures. Based on the availability of long-term (≥ 20 years) high-quality data, we collected incidence data from five prefectures (Miyagi, Yamagata, Fukui, Osaka, and Nagasaki), which included an annual average of 54,539 primary cancer cases diagnosed between 1985 and 2004. Cancer mortality data for 1995-2004 were obtained from the vital statistics. Representativeness and homogeneity of the trends were examined by funnel plot analysis of log-linear regression coefficients calculated for the most recent 10 years of data (1995-2004) of age-standardized rates (ASR). The ASR of incidence for five prefectures in total (5-pref total) showed a significant decrease, with an annual percent change (APC) of -1.0 (95% confidence interval [CI] -1.4: -0.6) for males and -0.4 (95% CI -0.8: -0.1) for females. Excluding data from Osaka (4-pref total) reversed the decreasing trend; the corresponding APC was +0.4 (95% CI -0.2: +1.0) for males and +0.7 (95% CI +0.5: +0.9) for females. The APCs for the ASR of mortality for the 4-pref total (males, -1.5; females, -1.3) were more representative of nationwide data (males, -1.4 [95% CI -1.7: -1.2]; females, -1.1 [95% CI -1.4: -0.9]) than those for the 5-pref total (males, -1.7; females, -1.4). We conclude that using data from Miyagi, Yamagata, Fukui, and Nagasaki prefectures, with continuous monitoring of the representativeness of the data, is a provisionally relevant way to evaluate cancer incidence trends in Japan.

Trends in local therapy application for early breast cancer patients in the Japanese Breast Cancer Society Breast Cancer Registry during 2004–2009

The Japanese Breast Cancer Society (JBCS) has been accumulating breast cancer patient data since 1975, reaching a total of 188,265 cases over 29 years. However, the recent increase of breast cancer incidence in Japan made it impossible for us to maintain the same data pool system for further analysis of trends in the disease. Therefore, the JBCS launched a new patient registration system in 2004, including 147,192 cases during the period 2004–2009. Herein, recent trends in local surgery, lymph node clearance, and radiation application are summarized. As shown in Table 1, annual numbers of registered patients have increased year on year. This is partly due to the increasing trend of breast cancer incidence in Japan, but mainly due to the increasing number of institutions/hospitals cooperating with the JBCS Breast Cancer Registry. The number of patients registered in the year 2004 was 15,675, compared with more than twice as many (34,987 patients) in 2009. Figure 1 shows the proportional trend in surgical procedures from 2004 to 2009. Our previous report showed that the number of cases with breast-conserving surgery (BCS) overtook those with modified or total mastectomy in 2003, and BCS cases continued to increase thereafter [1]. In our dataset, an increase of the BCS proportion could be noted until 2007. However, this increasing trend reached a plateau after 2007. In the standard procedure of BCS, radiation therapy after surgery should be mandatory. In some cases, such as older patients or patients with minimum tumor, there might be a relative indication for BCS without radiation therapy. In the JBCS registry data, an increase of standard BCS with radiation therapy was observed from 2004 to 2008 (Fig. 2). Furthermore, for patients with mastectomy and 4 or more positive nodes, radiation therapy of chest wall and local lymph node area should be considered. Figure 3 shows the increasing trend of radiation therapy from 2004 to 2008/2009. Since it is unlikely that the number of patients with multiple nodal involvement has increased in recent years, the main reason for this trend may be awareness of standard application of radiation therapy in such patients across all Japanese institutions/hospitals. Sentinel lymph node biopsy (SLNB) is the standard approach for the patient with clinical node-negative disease. Figure 4 indicates a continuous increase of patients who had only SLNB without further axillary lymph node dissection (ALND). Almost half of patients could avoid ALND in 2009, although over 80% of patients had to undergo this intensive surgery in 2004. This should be due to increased application of SLNB in a substantial fraction of Japanese institutions/hospitals. Also, as indicated by recent results of the American College of Surgeons S. Saji Department of Target Therapy Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Kawasaki Disease: A Review

Kawasaki disease, which was first described in Japan in 1967 by Dr. Tomisaku Kawasaki, is now the leading cause of acquired heart disease in children in developed nations. Kawasaki disease is an acute, self-limited vasculitis that primarily involves the coronary arteries (Newburger et al., 2004). Although it is more prevalent in Japan and in children of Japanese ancestry than among other people, the disease occurs in communitywide epidemics in children of all races. More than 4000 cases are diagnosed in the United States each year, with a 10-fold greater incidence in Japan. In 2000, 4248 hospitalizations were associated with the disease in the United States (Fimbres & Shulman, 2008; Holman, Curns, Belay, Steiner, & Schonberger, 2003). As expected, children of Japanese ancestry predominated, with an annual incidence of 112 per 100,000 children younger than 5 years. An annual incidence of 32.5 per 100,000 children younger than 5 years was reported for Americans of Asian and Pacific Island descent, compared with 16.9 for non-Hispanic African Americans, 11.1 for Hispanic children, and 9.1 for whites (Fimbres & Shulman, 2008; Holman et al., 2003). In the United States, 76% of children who present with Kawasaki disease are younger than 5 years, with the median age of onset being about 2 years (Chang, 2003; Holman et al., 2003). The disease occurs more commonly during the winter and early spring, and it affects more boys than girls by a ratio of 1.5 to 1.7:1 (Holman et al., 2003).

Risk of malignancies in IgG4-related disease

IgG4-related disease (IgG4-RD) is considered a systemic, chronic, and inflammatory disorder that is characterized by the enlargement of involved organs, elevated levels of IgG4, and abundant infiltration of plasmacytes with IgG4 and fibrosis in involved organs. It is necessary to differentiate IgG4-RD from malignant tumors. Recently we have looked at case reports of IgG4-RD with malignancy that was discovered at systemic screening. In this study, we analyzed the relationship between IgG4-RD and malignancies. The study subjects were 106 patients with IgG4-RD who had been referred to our hospital since April 1997. We analyzed the clinical characteristics of IgG4-RD patients who had cancer that was observed upon the initial diagnosis of IgG4-RD or that occurred during an average follow-up period of 3.1 years. Using data from national cancer registries that monitor cancer incidence in Japan, we evaluated the standardized incidence ratio (SIR) for malignancies in IgG4-RD. Malignancies were observed in 11 of the IgG4-RD patients (10.4%). The malignancies were all different and included lung cancer, colon cancer, and lymphoma. With the exception of the age at which the IgG4-RD diagnosis was made, there were no common features in patients with cancer and those without. The SIR for these malignancies in IgG4-RD was 383.0, which was higher than that for the general population. We should be cognizant of the possible existence of malignancies in patients with IgG4-RD at the time of diagnosis and during follow-up care.

Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines

Mesothelioma, a highly aggressive cancer with poor prognosis and refractory to currently available therapies show increasing trends of its incidence in Japan and other developing countries. Although surgery is a gold standard for patients with early mesothelioma, most patients with advanced disease are not suitable for surgical resection and have option of palliative chemotherapy alone. One of the new treatment strategies for mesothelioma, the humanized anti-CD26 monoclonal antibody therapy is under development. CD26, a 110-kDa transmembrane glycoprotein with known dipeptidyl peptidase IV activity, plays a role in tumor development and its expression was reported in various human malignancies. This study determined the preliminary selection criteria for humanized monoclonal anti-CD26 antibody therapy. Eighty-one epithelioid (49 differentiated and 32 less differentiated), 34 sarcomatoid, 19 biphasic mesothelioma and 8 mesothelioma cell lines were immunohistochemically examined using 8 different commercially available anti-CD26 antibodies for membranous and cytoplasmic expression. The cytoplasmic expression of CD26 was observed in all histological types of mesothelioma, while the membranous expression of CD26 was found in 88% of differentiated and 69% of less differentiated epithelioid mesothelioma, and none of sarcomatoid mesothelioma with anti-CD26 antibodies with rabbit polyclonal anti-DPP4 antibody and similar results were also obtained with goat polyclonal anti-DPP4/CD26 antibody. These antibodies absorbed with soluble human CD26 proteins do not show CD26 expression in mesothelioma tissue, suggesting these two antibodies localize true CD26 protein. Seven mesothelioma cell lines, including sarcomatoid types, also showed membranous expression of CD26 in cellblock preparation. CD26 vector transfection to CD26-negative MSTO-211H cells showed membranous expression of CD26 by flow cytometry, but not in tumor developed in NOD/SCID mice with inoculation of CD26 vector transfected MSTO-211H cells. We found that both rabbit and goat polyclonal antibodies are suitable for immunohistochemical evaluation of membranous expression of CD26 in mesothelioma.

Seasonal Variation of Stroke Incidence in Japan for 35631 Stroke Patients in the Japanese Standard Stroke Registry, 1998-2007

Seasonal variation of stroke incidence has been reported in many countries. The present study was designed to elucidate seasonal and monthly variations in the incidence of subtypes of acute ischemic stroke and hypertensive hemorrhagic stroke using the Japanese Standard Stroke Registry Study (JSSRS) database, which is currently the world's largest hospital-based stroke database, accumulating records from 163 Japanese institutions. Among 47,782 patients with acute stroke registered with JSSRS between 1998 and 2007, we selected 35,631 for analysis (patients with ischemic or hemorrhagic stroke of unknown etiology were excluded). A simple moving average was used to examine monthly variation of stroke incidence. We also examined seasonal variation of ischemic stroke subtypes. Monthly variation in incidence of all ischemic stroke was significant (P < .001). Noncardioembolic ischemic stroke was more frequent in summer than in winter (P < .001). Lacunar stroke showed higher incidence in summer than in winter (P < .001), although the increase did not reach significance for atherothrombotic stroke (P = .057). In contrast, cardioembolic stroke (P < .001) and hemorrhagic stroke (P < .001) occurred more frequently in winter than in summer. Hemorrhagic stroke showed a regional difference of incidence between northern and southern Japan. There is a temporal variation of stroke incidence in Japan, with different patterns of variation depending on stroke subtype. These findings may help in developing strategies for preventing stroke.

Environmental radiation: Risk benchmarks or benchmarking risk assessment

In the wake of the compound March 2011 nuclear disaster at the Fukushima I nuclear power plant in Japan, international public dialogue has repeatedly turned to questions of the accuracy of current risk assessment processes to assess nuclear risks and the adequacy of existing regulatory risk thresholds to protect us from nuclear harm. We confront these issues with an emphasis on learning from the incident in Japan for future US policy discussions. Without delving into a broader philosophical discussion of the general social acceptance of the risk, the relative adequacy of existing US Nuclear Regulatory Commission (NRC) risk thresholds is assessed in comparison with the risk thresholds of federal agencies not currently under heightened public scrutiny. Existing NRC thresholds are found to be among the most conservative in the comparison, suggesting that the agency's current regulatory framework is consistent with larger societal ideals. In turning to risk assessment methodologies, the disaster in Japan does indicate room for growth. Emerging lessons seem to indicate an opportunity to enhance resilience through systemic levels of risk aggregation. Specifically, we believe bringing systemic reasoning to the risk management process requires a framework that (i) is able to represent risk-based knowledge and information about a panoply of threats; (ii) provides a systemic understanding (and representation) of the natural and built environments of interest and their dependencies; and (iii) allows for the rational and coherent valuation of a range of outcome variables of interest, both tangible and intangible. Rather than revisiting the thresholds themselves, we see the goal of future nuclear risk management in adopting and implementing risk assessment techniques that systemically evaluate large-scale socio-technical systems with a view toward enhancing resilience and minimizing the potential for surprise.

The burden of cancer in Japan, the United States, France, Germany, Italy, Spain, Sweden, and the United Kingdom.

1569 Background: Cancer causes a significant burden to society in terms of human suffering and costs. We analyzed the burden of cancer in Japan, the US, France, Germany, Italy, Spain, Sweden and the UK. Methods: We reviewed the incidence, mortality and costs in Japan and compared with other countries. We also conducted survey of the actual economic burden of cancer patients in Japan. Results: The overall incidence in Japan is lower than other countries. Only in stomach cancer is the incidence in Japan higher. The incidence in Japan has been increasing in the past decades for the major cancers, except stomach cancer. Similar trends are found in the US and the European countries, although some countries show declining long trends in male lung cancer (US, Germany, Italy, Sweden and UK), colorectal cancer (US and Germany), breast cancer (US) and in prostate cancer (US). The overall cancer mortality and that of all the five major cancer types are increasing in Japan, but declining in other countries. The direct cost of cancer treatment in Japan amounts to US$23 billion. Indirect costs of morbidity and mortality amount to $65 billion. The cost of cancer per capita in Japan is $691, which is lower than in the US ($784) but higher than in France ($582) and in Sweden ($504). The annual out-of-pocket expenses are $11,000 on average in Japan (n=6,604). 7.3% of all health care resources are spent on cancer treatment In Japan, which is higher than in other countries. The expenditure on cancer drugs in Japan is $57 per capita, which is lower than in the US ($64) and France ($69), but higher than in the remaining countries. Conclusions: The trend in cancer mortality in Japan is, in contrast to the US and Europe, increasing. A more systematic use of economic evaluations of new cancer treatments in Japan would also support the use of the most cost effective alternatives. It is important to discuss the cost with patients and to minimize the economic burden of patients in clinical settings and in policy making.

Steadily Increasing Control: The Professionalization of Mass Death

Recent mass death incidents in Japan and Haiti have again focused attention on the challenge of dealing with large numbers of dead. Focusing on mass death incidents involving large numbers of Canadian victims, including the Titanic, Halifax explosion, Air India bombing and the 2004 Tsunami, the paper researches incidents dating back to the beginning of the 20th Century. By examining each stage of the process including initial response, identification, funerals, communication, religious services and inquests, the paper identifies key changes in the way that mass death incidents are handled. For example, the research identifies greater professionalization and state control of mass death incidents, increased reliance on experts and technology and increased emphasis on accurate identification, through forensics, and causes, through inquests and inquiries.

The Incidence of Proximal Extension of Ulcerative Proctitis in Japan and Factors Related to Proximal Extension

The incidence of proximal extension in patients with ulcerative proctitis is reported to be 18%-46%, but recent data on the incidence in Japan is inadequate. The aim of this study was to investigate the incidence of proximal extension of ulcerative proctitis and factors associated with the extension in Japan. This is a retrospective observational study involving a cohort of 53 patients with an initial diagnosis of ulcerative proctitis. Following verification of the diagnoses, demographic and clinical data were compiled. The cumulative incidence of proximal extension was estimated as ‘person-years’ and cumulative probability was calculated by the Kaplan-Meyer method. Univariate and multivariate analyses were performed to identify association factors. During a mean follow-up of 6.8 years, proximal extension was observed in 14 patients (26.4%). The cumulative incidence of proximal extension was 4.22/100 person-years and the cumulative probability at 5 years was 20.1%, consistent with recent reports from Western countries and data obtained in Japan over 2 decades ago. Univariate analysis showed active smoking (P = 0.025) and corticosteroid therapy (P = 0.006) to be risk factors in proximal extension, however multivariate analysis revealed that corticosteroid therapy was the only significant factor (P = 0.005) separating patients with and without proximal extension. No patient underwent colectomy. The incidence of proximal extension in ulcerative proctitis in Japan is comparable to that in Western countries and has not changed significantly over the past two decades. Corticosteroid therapy was identified as the only significant factor in proximal extension.

High pulse pressure is associated with increased risk of stroke in Japanese: The JMS Cohort Study

Background. The relationship between pulse pressure (PP) and stroke has been described in populations outside Japan. Here, we investigated the relationship between PP and stroke incidence in Japan. Methods. Study subjects were 11,097 people (4315 men and 6782 women) in 12 rural areas of Japan enrolled in the Jichi Medical School Cohort Study, a population-based prospective study. The subjects were divided into quintiles of PP. Baseline data were obtained by questionnaire and health checkups between April 1992 and July 1995, and the incidence of all strokes and stroke subtypes was monitored. Results. A total of 412 strokes were observed during a mean follow-up period of 10.7 years. After adjusting for age, smoking status, drinking status, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, body mass index and diabetes mellitus, hazard ratios [HRs] in the second to fifth quintiles of PP for all strokes were 1.06 (95% confidence interval [CI] 0.69–1.64), 1.53 (CI 1.02–2.28), 2.02 (CI 1.38–2.96) and 2.22 (CI 1.53–3.20) compared with the first quintile using Cox's proportional hazard model, respectively. Conclusion. Our findings suggest high PP is at an increased risk of stroke.

Cancer Incidence and Incidence Rates in Japan in 2005: Based on Data from 12 Population-based Cancer Registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project

The Japan Cancer Surveillance Research Group estimated the cancer incidence in 2005 as part of the Monitoring of Cancer Incidence in Japan (MCIJ) project, on the basis of data collected from 12 of 30 population-based cancer registries. The total number of incidences in Japan for 2005 was estimated as 646,802 (C00-C96). The leading cancer site was the stomach for men and the breast for women. Age-standardized incidence rates remained almost the same level as the previous 2 years.

Cancer Incidence and Incidence Rates in Japan in 2004: Based on Data from 14 Population-based Cancer Registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project

The Japan Cancer Surveillance Research Group estimated the cancer incidence in 2004 as part of the Monitoring of Cancer Incidence in Japan (MCIJ) project, on the basis of data collected from 14 of 31 population-based cancer registries. The total number of incidences in Japan for 2004 was estimated as 623,275 (C00-C96). The leading cancer site according to the crude and age-standardized incidence rates was the stomach for men and breast for women. The apparent increase in age-standardized incidence rates in 2003 was calmed down in 2004.

Crohn’s disease and ruminant farming. Got lactase?

Crohn's disease (CD) is a well known chronic pathological condition whose aetiology has remained unrecognized for nearly a century. Complex immune mechanisms in a specific genetic background causing an abnormal local inflammatory response are thought to be directly responsible for the clinical picture, but no external factor triggering such host responses has been identified. Humans lose the capability of breaking down milk lactose early in life and, afterwards, ingestion of large amounts of lactose causes a transient digestive illness known as lactose intolerance. Some human populations developed mutations for lactase persistence in adulthood that allowed better exploiting a product, milk, from not food-competitive domesticated species. This adaptation to dairy farming could have had as a collateral effect the exposure of human populations to a ruminant parasite with the ability to cause chronic inflammation in the intestine. Humans with a genetic susceptibility might develop a similar inflammatory disease caused by a defect in a highly conserved innate immunity mechanism. Data from different published sources regarding by country CD and type I diabetes incidence, lactose intolerance, livestock population, food production, Gross National Income and human population were submitted to Pearson and Kendall correlation, multiple regression and principal components analyses. Multiple regressions were also applied to a published 20-year time series for CD incidence in Japan. These analyses showed a strong association between country incidence of CD and frequency of lactase persistence as well as other ruminant production and consumption variables that further supports the meaning of those observations. Association of these variables with higher per capita income suggests that IBD incidence would be a side-effect of an otherwise highly successful adaptation. The evolutionarily plausible framework provided by this association with the species suffering a similar inflammatory bowel disease (IBD), its coincidence with the expanse of a cattle breed that could act as a Trojan horse, in addition to recent microbiological, immunological and therapeutical observations consistent with a slow infection type of pathogenesis, supports a mycobacterial aetiology of human IBD. Further research challenging the hypothesis of a shared aetiology by Mycobacterium avium subsp. paratuberculosis of human and ruminant IBD by increasing research on the pathogenesis of the latter and focusing on effective specific antibiotic or immune aetiological therapies seems to be the obvious next step. Either confirmation or rejection of the hypothesis presented here should create new knowledge that will bring closer the eradication of a cause of human and animal suffering.

Double cancer in small cell lung cancer patients treated with intensive chemotherapy with or without radiation therapy

Development of double cancer was evaluated in 311 small cell lung cancer patients who had received intensive chemotherapy with or without radiotherapy. Of those, 10 patients (3.2%) developed a second malignancy:stomach cancer in four, non-small cell lung cancer in three, acute myelogenous leukemia in two, and liver cancer in one. The cumulative risk for the development of double cancer was 1.0% at 1-year, 17.0% at 3-years, and 100% at 8.1 years. The relative risk for the development of double cancer calculated by person-year method utilizing age and sex adjusted cancer incidence in Japan was 2.96-fold (p less than 0.01). The risk of non-small cell lung cancer (6.65-fold) and acute myelogenous leukemia (54.9-fold) was particularly high. Of 21 patients who survived disease-free for more than 2 years, 8 patients died; four patients (50%) died of second malignancy, two died of infectious disease, and only two patients died from recurrent small cell lung cancer. These results indicate that a cautious follow-up program for the detection of double cancer is indicated in patients surviving small cell lung cancer.

帯状疱疹とその予防に関する考察

The mean herpes zoster incidence in Japan was 4.15/1,000 person-years and was 5.23-7.84/1,000 person-years among those 50 years old and older. One in three persons experiences herpes zoster before age 80, indicating how common it is. The Oka varicella vaccine was developed to prevent varicella in healthy and immunocompromized children and is now used to prevent varicella in 20 million people worldwide. Contact with varicella patients and Oka varicella vaccine are reported to augment varicella-zoster virus immunity in adults and the elderly. Oxman et al. have shown that Oka varicella vaccine prevents herpes zoster and postherpetic neuralgia (PHN) in the elderly. Oka varicella vaccine is approved to prevent herpes zoster and PHN in the elderly in USA and Europe. We review the relationship between varicella/Oka varicella vaccine and herpes zoster, the study by Oxman et al., and the need to introduce this new application of Oka varicella vaccine in Japan.

Clinical aspects and adrenal functions in eleven Japanese children with X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a genetic disease associated with demyelination of the central nervous system, adrenocortical insufficiency and accumulation of very long chain fatty acids. It is a clinically heterogeneous disorder ranging from a severe childhood cerebral form to an asymptomatic form. The incidence in Japan is estimated to be between 1:30,000 and 1:50,000 boys as determined by a nationwide retrospective survey between 1990 and 1999, which found no cases with Addison's form. We reviewed the medical records of eleven Japanese boys with X-ALD from 1990 to 2010 in our institute. Eight patients were detected by neuropsychological abnormalities, whereas a higher prevalence of unrecognized adrenocortical insufficiency (5/11: 45%) was observed than previously recognized. While no neurological abnormalities were demonstrated in two brothers, the elder brother had moderate Addison's disease at diagnosis and the presymptomatic younger brother progressed to Addison's disease six months after the diagnosis of X-ALD. Early detection of impaired adrenal function as well as early identification of neurologically presymptomatic patients by genetic analysis is essential for better prognosis. Addison's form might be overlooked in Japan; therefore, X-ALD should be suspected in patients with adrenocortical insufficiency.