Yuko Kodama

Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan

We have little information on chronic graft-versus-host disease (GVHD) after cord blood transplantation (CBT). We investigated its clinical features in 1072 Japanese patients with hematologic malignancies who received a transplant through the Japan Cord Blood Bank Network. The primary end point was to investigate the incidence of any chronic GVHD. Median age of the patients was 33 years (range, 0-79 years). The cumulative incidence of chronic GVHD 2 years after transplantation was 28%. Chronic GVHD was fatal in 29 patients. Multivariate analysis demonstrated that development of chronic GVHD was favorably associated with both overall survival and event-free survival. Multivariate analysis identified risk factors of chronic GVHD: higher patient body weight, higher number of mismatched antigens for GVHD direction, myeloablative preparative regimen, use of mycophenolate mofetil in GVHD prophylaxis, and development of grades II to IV acute GVHD. Although chronic GVHD is a significant problem after CBT, it is associated with improved survival, perhaps due to graft-versus-malignancy effects.

Safety of workers at the Fukushima Daiichi nuclear power plant

The 9·0 magnitude earthquake and following tsunami on March 11, 2011, destroyed many coastal cities in the northeastern part of Japan. It swamped emergency generators at the Fukushima Daiichi nuclear power plant operated by the Tokyo Electric Power Company in Fukushima prefecture, disabling the cooling systems. Since these catastrophic events, hundreds of nuclear workers have been trying to remove the radioactive water from the tsunamiravaged nuclear compound and restart the regular cooling systems for the overheated nuclear fuel. On March 15, the Japanese Government announced that the permissible cumulative radiation exposure for nuclear workers was increased to 250 mSv per year from 100 mSv per year. The purpose of this increase seems to be merely to extend the time nuclear workers could legally spend in a radioactive area. On April 12, the Nuclear and Industrial Safety Agency of Japan decided to raise the severity level of the crisis to 7—the highest level and equal to the 1986 disaster at Chernobyl in the former Soviet Union. We emphasise the need to predict potential scenarios in Fukushima and to prepare medical care providers for how to respond in cases of accidental high radiation exposure, since this operation is estimated to take months to years. Generally, rapidly dividing cells, such as intestinal-tract and haemopoietic cells, are most vulnerable to radiation. Radiation accidents can result in localised or whole-body exposure and in internal or external deposition of radioactive materials. On March 24, three workers at the Fukushima nuclear power plant were exposed accidentally to high localised radiation while standing in contaminated water. Fortunately, this accident did not cause major injuries, but the danger of a future accidental radiation exposure is not passed, since there has been a series of serious aftershocks even this April. A clinically signifi cant haemopoietic syndrome can occur after wholebody doses of 2 Gy or higher as a result of bone-marrow depression. If the haemopoietic cells are not completely damaged, a recovery phase can be enhanced through use of haemo poietic growth factors. In cases of radiation exposure of more than 5 Gy, haemopoietic stemcell rescue is essential. Indeed, in the Chernobyl disaster in 1986, nine patients who were exposed to high levels of radiation underwent intraosseous injections of allogeneic bone-marrow cells. In the radiation accident at a nuclear fuel processing plant in Tokaimura, Japan, in 1999, two victims received allogeneic stem-cell transplantation. However, allogeneic stem-cell transplantation has major limitations, such as timeconsuming donor searching, graft failure, graft-versus-host disease (GVHD), or profound immune suppression after transplantation, despite the reduced mortality associated with recent techniques. On March 25, we proposed the collection and storage of autologous peripheral-blood stem cells (PBSCs) for the nuclear workers in Fukushima in case of accidental major radiation exposure. This scheme has several advantages. First, autologous PBSC transplantation does not cause GVHD, which further exacerbates gut injury mediated by radiation exposure. Second, it does not require immuno suppressants, which make radiation victims more susceptible to severe infections. Third, PBSCs can induce more rapid haemopoietic recovery than can haemopoietic growth-factor support alone or bonemarrow cells. Fourth, they are easy to store by cryopreservation. Fifth, the short-term and long-term safety of this PBSC-collecting procedure has been confi rmed in a large number of healthy donors for patients with haematological cancers. Finally, long-term autologous PBSC banking might also have a therapeutic role for possible leukaemia in future, because radiation is a well known carcinogen in the long term. Several important limitations of this scheme should also be noted. Autologous PBSC transplantation is not a perfect strategy to treat radiation victims; it can rescue injury of bone marrow only, but not other tissues, such as gastrointestinal tract, skin, or lung. Additionally, there are adverse events for healthy individuals by administration of mobilising agents and apheresis procedures. Another concern must be medical costs, but several pharmaceutical companies off er donations for this scheme and the fi nancial burden is alleviated. On March 29, the Japan Society for Haematopoietic Cell Transplantation released a statement that “107 transplant teams are standing by to collect and store haemopoietic stem cells from the peripheral blood for workers who are striving to restrain the radiation.” The European Group for Blood and Marrow Transplantation also announced that this plan makes sense and more than 50 hospitals in Europe have agreed to help the workers if required. On the other hand, several experts have stated their objections to this scheme. The Nuclear Safety Commission of Japan, an advisory panel made up of non-government experts, reportedly stated that there is no need to collect and store autologous PBSCs. The reasons given are the physical and psychological burden for nuclear workers, no consensus among international authoritative bodies, and no suffi cient agreement among the Japanese public. The nuclear power industry of Japan is facing its worst-ever crisis. Not only Published Online April 15, 2011 DOI:10.1016/S01406736(11)60519-9

Safety and usefulness of emergency maternal transport using helicopter.

Aim:  Japan has a shortage of tertiary medical care facilities for maternal and fetal medicine. Establishment of efficient medical transport systems is needed for pregnant women and fetuses with severe complications. Maternal transport by helicopters is expected to shorten transportation time to advanced facilities, although its feasibility has not yet been evaluated. The aim of the present study was to investigate the status of maternal helicopter transport, and conditions of the pregnant patients and children transferred by helicopter to Kameda Medical Center (KMC).

Impact of natural disaster combined with nuclear power plant accidents on local medical services: a case study of Minamisoma Municipal General Hospital after the Great East Japan Earthquake.

OBJECTIVE To elucidate the impacts of nuclear plant accidents on neighboring medical centers, we investigated the operations of our hospital within the first 10 days of the Great East Japan Earthquake followed by the Fukushima Daiichi nuclear power plant accident. METHODS Data were extracted from medical records and hospital administrative records covering 11 to 20 March 2011. Factual information on the disaster was obtained from public access media. RESULTS A total of 622 outpatients and 241 inpatients were treated. Outpatients included 43 injured, 6 with cardiopulmonary arrest, and 573 with chronic diseases. Among the 241 inpatients, 5 died, 137 were discharged, and the other 99 were transferred to other hospitals. No communication methods or medical or food supplies were available for 4 days after the earthquake. Hospital directors allowed employees to leave the hospital on day 4. All 39 temporary workers were evacuated immediately, and 71 of 239 full-time employees remained. These employees handled extra tasks besides patient care and patient transfer to other hospitals. Committed effective doses indicating the magnitude of health risks due to an intake of radioactive cesium into the human body were found to be minimal according to internal radiation exposure screening carried out from July to August 2011. CONCLUSIONS After the disaster, hospitals located within the evacuation zone of a 30-km radius of the nuclear power plant were isolated. Maintenance of the health care system in such an event becomes difficult.

Increased financial burden among patients with chronic myelogenous leukaemia receiving imatinib in Japan: a retrospective survey

BackgroundThe financial burden of medical expenses has been increasing for cancer patients. We investigated the relationship between household income and financial burden among patients with chronic myelogenous leukaemia (CML) who have been treated with imatinib.MethodsA questionnaire was distributed to 1200 patients between May and August 2009. We retrospectively surveyed their household incomes, out-of-pocket medical expenses, final co-payments after refunds, and the perceived financial burden of their medical expenses in 2000, 2005 and 2008.ResultsA total of 577 patients completed the questionnaire. Their median age was 61 years (range, 15–94). A financial burden was felt by 41.2 % (28 of 68) of the patients treated with imatinib in 2000, 70.8 % (201 of 284) in 2005, and 75.8 % (400 of 528) in 2008. Overall, 182 patients (31.7 %) considered its discontinuation because of the financial burden and 15 (2.6 %) temporarily stopped their imatinib prescription. In 2000, 2005 and 2008, the patients’ median annual household incomes were 49,615 US Dollars (USD), 38,510 USD and 36,731 USD, respectively, with an average currency exchange rate of 104 Yen/USD in 2008. Their median annual out-of-pocket expenses were 11,548, 12,067 and 11,538 USD and their median final annual co-payments were 4,375, 4,327 and 3,558 USD, respectively. Older patients (OR = 0.96, 95 % CI: 0.95–0.98, p ≪ 0.0001 for 1-year increments), and patients with higher household incomes (OR = 0.92, 95 % CI: 0.85–0.99, p = 0.03 for 10,000 USD-increments) were less likely to have considered discontinuing their imatinib treatment. Conversely, patients with higher annual final co-payments (OR = 2.21, 95 % CI: 1.28–4.28, p = 0.004 for 10,000 USD-increments) were more likely to have considered discontinuing their imatinib treatment.ConclusionsThe proportion of CML patients who sensed a financial burden increased between 2000 and 2008. During this period, their annual incomes fell by 13,000 USD, although their medical expenses did not change. Financial support for patients being treated with expensive drugs remains a major problem in Japan.

Data mining of mental health issues of non-bone marrow donor siblings

BackgroundAllogenic hematopoietic stem cell transplantation is a curative treatment for patients with advanced hematologic malignancies. However, the long-term mental health issues of siblings who were not selected as donors (non-donor siblings, NDS) in the transplantation have not been well assessed. Data mining is useful in discovering new findings from a large, multidisciplinary data set and the Scenario Map analysis is a novel approach which allows extracting keywords linking different conditions/events from text data of interviews even when the keywords appeared infrequently. The aim of this study is to assess mental health issues on NDSs and to find helpful keywords for the clinical follow-up using a Scenario Map analysis.FindingsA 47-year-old woman whose younger sister had undergone allogenic hematopoietic stem cell transplantation 20 years earlier was interviewed as a NDS. The text data from the interview transcriptions was analyzed using Scenario Mapping. Four clusters of words and six keywords were identified. Upon review of the word clusters and keywords, both the subject and researchers noticed that the subject has had mental health issues since the disease onset to date with being a NDS. The issues have been alleviated by her family.ConclusionsThis single subject study suggested the advantages of data mining in clinical follow-up for mental health issues of patients and/or their families.

A study of cancer information for cancer patients on the internet

BackgroundThere have been few studies of the information provided for cancer patients on the internet.MethodsUsing the Japanese language, we searched for cancer-related web pages, using the Google search engine, and evaluated the characteristics of the 150 top-ranked search results. We collected information on the operators of the websites, number of links, existence of a search function, and advertisements on the site. According to their contents, the 150 websites were classified into seven categories, of which five (numbers 1, 2, 3, 4, and 6) each accounted for 20% of the websites. The categories were: (1) media-related websites (e.g., newspapers and publishers), and portal sites; (2) patient association websites, patients diaries, blogs by patients and/or their families (n = 33); (3) websites of medical institutions (e.g., hospitals; n = 27); (4) websites of research institutions (e.g., universities; n = 35); (5) websites of pharmaceutical companies; (6) other websites providing medical information (n = 32); and (7) other websites that did not belong to categories 1–6. Outgoing links were common in websites created by media-related organizations (median, 13) or patients and their families (median, 15), but such links were not common in the other types of websites (median, 0–4). Eight of the 13 cancer based hospitals in Japan, as well as the National Cancer Center were publishing general cancer information on their websites. Of the 13 cancer based hospitals, 12 included a link to the National Cancer Center. The National Cancer Center had the largest amount of information (736 575 words), exceeding the amount provided by the other cancer based hospitals (1 622–155 515 words). Two of the 7 websites of academic associations (included in category 6) had cancer information for patients, but the document sizes were small (3230–44 091 words).ConclusionThe website of the National Cancer Center is the most prominent source of general cancer information for patients, but it still has room for improvement in its usability.

Forecasting Japan's Physician Shortage in 2035 as the First Full-Fledged Aged Society

Introduction Japan is rapidly becoming a full-fledged aged society, and physician shortage is a significant concern. The Japanese government has increased the number of medical school enrollments since 2008, but some researchers warn that this increase could lead to physician surplus in the future. It is unknown how many physicians will be required to accommodate future healthcare needs. Materials and Methods We simulated changes in age/sex composition of the population, fatalities (the number of fatalities for the consecutive five years), and number of physicians from 2010 to 2035. Two indicators were defined: fatalities per physician and fatalities by physician working hour, based on the data of the working hours of physicians for each tuple of sex and age groups. We estimated the necessary number of physicians in 2035 and the number of new physicians to maintain the indicator levels in 2010. Results The number of physicians per 1,000 population is predicted to rise from 2·00 in 2010 to 3·14 in 2035. The number of physicians aged 60 years or older is expected to increase from 55,375 (20% of physicians) to 141,711 (36%). In 2010 and 2035, fatalities per physician were 23·1 and 24·0 for the total population, and 13·9 and 19·2 for 75 years or older, respectively. Fatalities per physician working hour are predicted to rise from 0·128 to 0·138. If working hours are limited to 48 hours per week in 2035, the number of fatalities per physician working hour is expected to be 0·196, and the number of new physicians must be increased by 53% over the current pace. Discussion The number of physicians per population continues to rise, but the estimated supply will not fulfill the demand for healthcare in the aging society. Strategies to increase the number of physicians and improve working conditions are urgently needed.

Trastuzumab after adjuvant chemotherapy in older patients.

We would like to comment on the Article by Ian Smith and colleagues (Jan 6, p 29) regarding the eff ects of the trastuzumab-containing regimen on older patients. Patients older than 65 years account for 42·6% of the breast cancer population in the USA, whereas only 16% of the patients were 60 years or older in Smith and colleagues’ study. These fi gures indicate that patients in this trial represented a younger population than the actual patients’ population. The benefi t of trastuzumab was marginal in patients older than 60 years (hazard ratio for events 0·91; 95% CI 0·59–1·41), and the eff ectiveness of trastuzumab-contain ing chemotherapy in older patients is frequently hampered by cardio toxicity. Considering that age was not incorporated into the eligibility criteria of this study, Smith and colleagues might have regarded elderly patients as candidates for the trastuzumabcontaining regimen. We would be grateful if they could provide information on the eff ectiveness and adverse events in elderly patients given trastuzumab. We declare that we have no confl ict of interest.

Macrophages in Hodgkin's lymphoma.

To the Editor: Steidl et al. (March 11 issue)1 report that an increased number of CD68+ cells was a significant prognostic factor in patients with classic Hodgkin’s disease, especially in those with limited disease. Age is a well-known prognostic factor in both limited2 and advanced3 Hodgkin’s disease. In the present study, univariate analysis showed that both age and CD68 were significant prognostic factors for disease-specific survival. However, multivariate analysis did not identify age as a significant prognostic factor, whereas CD68 positivity remained significant. These findings suggest the possible association between age and expression of CD68. We would be grateful for information on this association.