Search

The involvement of patients and the public with researchers is essential in clinical research on cancer treatment. In recent years, patient and public involvement(PPI)has been required in all medical research processes. This paper summarizes practical considerations and examples of the PPI process referred to in the"Patient and Public Involvement(PPI)Guidebook"of the Japan Agency for Medical Research and Development(AMED). The process consists of the introduction of PPI, recruitment of PPI participants, conflict of interest management and rewards for PPI participants, the confidentiality of PPI participants, and reporting results and feedback. It is difficult to provide a standardized procedure because PPI activities vary among the research projects. It is recommended to implement PPI activities into your research project by utilizing the actual cases or existing information sources.

In clinical research, the term "conflict of interest" appears quiet frequently. Conflict of interest does not always result in research misconduct, nor is it always an issue. Conflict of interest rules differ depending on the type and stage of research, and researchers are expected to choose and follow them appropriately. In this paper, we review the fundamental concept of conflict of interest management in clinical research and the importance of conflict of interest management, and then organize the various rules based on the type and stage of research. Furthermore, the key points for effective conflict of interest management that researchers should be aware of are summarized.

We present 2 cases of carcinoma en cuirasse, an uncommon clinical manifestation of metastatic cutaneous breast cancer. Case 1, a 70-year-old woman, presented with diffuse erythematous, indurated skin lesions that covered her entire anterior chest wall. Skin biopsy revealed tumor cells in the dermis which were ER and PgR positive and HER2 negative. CT showed pleural and pericardial effusion which led to a final diagnosis of cutaneous metastasis from breast cancer. Fulvestrant monotherapy was initiated and maintained a good clinical effect for 40 months. She died of multiple liver metastasis after 53 months from her first visit. Case 2 was a 71-year-old woman, with a 24 month history of a left breast tumor that gradually accompanied erythematous skin indurations and erosion, which spread to her entire left chest wall and contralateral breast. Following skin biopsy and CT, she was diagnosed to have triple negative breast cancer with multiple lymph node and cutaneous metastasis. After 4 cycles of EC, capecitabine was administrated and her skin lesions improved rapidly, including the lymph nodes. She is currently alive after 12 months since her first visit and under chemotherapy against new cutaneous metastasis.

Improving public understanding and acceptance are critical for promoting coronavirus (COVID-19) vaccination. However, how to promote COVID-19 vaccine programs remains controversial due to various ethical issues. This study, thus, aimed to survey the acceptance of COVID-19 vaccines among Japanese citizens and discuss relevant ethical issues. A cross-sectional survey was conducted via an online platform. An anonymous, quantitative, self-administered online questionnaire was sent to 6965 registered Japanese residents (20-79 years of age), which included questions regarding the respondent's general knowledge, experience, and opinions of vaccines, vaccine development, COVID-19, and COVID-19 vaccines. Of the 1569 respondents, 730 (46.5%) and 839 (53.5%) were categorized into the younger and older groups, respectively. Most of the respondents possessed general knowledge of COVID-19 vaccines and their features. Of the respondents, 57.8% definitely agreed (10.5%) or somewhat agreed (47.3%) to receive COVID-19 vaccines. The older group showed significantly greater willingness to receive vaccines and higher literacy regarding vaccines in general. Possible reasons for the older group's greater willingness to receive COVID-19 vaccines are a high risk of severe COVID-19 infection and their past accumulated experience of receiving various vaccinations. Although active public intervention could increase vaccination rates, most of the respondents did not agree with mandatory vaccination. Furthermore, a gap between the participants in the COVID-19 vaccine trials and the prioritized population in real-world vaccination should be adjusted in future vaccine development.The online version contains supplementary material available at 10.1007/s41649-022-00207-4.

It is important to identify ethical and professional challenges associated with genetic counseling services and systems to improve these services. In previous studies, specific challenges in genetic counseling were categorized into 16 domains. However, these studies were limited to a few countries, and genetic counseling differs according to national cultures or systems. Thus, additional efforts should be made to collect and analyze challenges in genetic counseling to address these issues. We interviewed 48 genetic counseling professionals in Japan (including 29 clinical geneticists, 17 genetic counselors, and 2 other professionals) about anecdotes that included ethical professional challenges. Thematic analysis was used to code the interview data, and anecdotes were categorized according to the ethical and professional challenges. The anecdotes (n = 333) were classified into the 16 previously identified domains and three unique subcategories: 'lack of understanding about genetic professionals or departments of genetic counseling by other professionals and patients', 'insufficient communication skills to carry out counseling on the part of the genetic counseling professionals', and 'lack of a system for self-improvement'. Many of the anecdotes also noted the emotional responses domain. The challenges experienced by Japanese genetic counseling professionals described herein will improve the quality of the service these professionals provide. Furthermore, the results can assist development of high-quality genetic counseling systems in countries developing these systems.

Investigational treatments are those that have been approved for testing in humans but are not yet available as an approved treatment option. For many patients with a terminal illness who have no approved treatment option and are not eligible for a clinical trial, investigational treatments are the last resort. However, not much is known about the dissemination of information by patient advocacy organizations (PAOs). We evaluated the quantity and quality of information on preapproval access to investigational therapies provided by Japanese PAO websites between January 24 and March 29, 2019. A total of 49 PAOs were identified. Of these, 16 (33%) provided no relevant information. The most frequent information provided was the PAO's own clinical trial finder or list of clinical trials (n = 15, 31%); of the 10 cancer‐related PAOs, 5 (50%) provided this information. Nine (18%) PAOs had developed patient registries or provided a link to relevant registries. Only 1 PAO (2%) provided a link about the Ministry of Health, Labour, and Welfare trials that described the process and regulations of clinical trials. Our results indicate that PAOs do not disseminate adequate information on preapproval pathways. We suggest that the government involve PAOs in disseminating this information to both patients and physicians.

Oncoplastic breast conserving surgery had been challenged to achieve both of local control and the cosmetic appearance of preserved breast. We developed the lateral thoracoaxillar dermal-fat flap (LTDF) as an oncoplastic procedure to fill the defect of breast-conserving surgery in 1999. A total of 2338 breast cancer patients underwent surgery from January, 2000 to December, 2017. Mastectomy was performed in 706 patients (30%), and breast conservative surgery (BCS) was performed in 1634 patients (70%). The LTDF was adopted in 487/1634 (30%) of BCS cases to fill the large defect left by partial resection. we divided all patients into 3 groups: breast total mastectomy (BT group), the breast partial resection (BP) with LTDF (LTDF group), and Bp without LTDF (BP group) and compared the clinical characteristics, and recurrence rate. The Indications for LTDF increased up to 40% in 2010, while they decreased to 20%–30% in the most recent period, in accordance with the frequency of breast reconstruction increased. Patients who underwent BP + LTDF (LTDF group) included significantly higher proportions of stage II diseases and cases treated by neoadjuvant chemotherapy than those in BP or BT groups.. We found no marked difference of local recurrence and distant metastases between the LTDF and Bp groups. However, the rate of distant metastasis was significantly higher in BT group than in the Bp or LTDF group. Concerning the complications of LTDF, we experienced a few complications of Grade 3–4 requiring surgical management, namely one case of dislocation of the LTDF, three cases of bleeding, and five cases each of skin necrosis and fat necrosis. We reported satisfying long-term outcomes of 487 cases treated by LTDF. LTDF is a suitable oncoplastic technique for BCS.

The U.S. and Japan have preapproval access systems for patients who have exhausted approved treatment options. We compare the systems of both countries and discuss some ethical concerns surrounding non-trial access to investigational drugs. Notable points of comparison of the two countries' systems include cost of non-trial access to investigational drugs and purpose of the non-trial access system. All stakeholders and the public must understand the ethical issues associated with non-trial preapproval access systems. The current non-trial access programs in both countries depends on pharmaceutical companies' voluntary decisions about whether patients get access to investigational products. Moreover, the potential for inequity of access raises ethical concerns. Non-trial preapproval access is an exceptional way to practice medicine with various ethical and safety concerns, so we suggest that the scope and eligibility for using these pathways should thus be limited.

Background In comparison with foreign countries, living-organ transplantations (LOT) have been performed more frequently than dead organ transplants, including brain-dead organ transplantation (BOT) in Japan. This situation has given rise to organ transplantation tourism. Therefore, we clarify laypersons' preferences regarding organ transplantation that are producing the current situation in Japan, to suggest a possible framework for further efforts. Methods Voluntary completion of a quantitative and anonymous survey was promoted online (a sample size of 1030). The questionnaire had two types of variables concerning demographic characteristics and organ transplantation–related issues. Results LOT was favored over BOT. However, for willingness to donate to family members, the participants showed a significantly more positive attitude toward brain-dead organ donors (BODs) than living organ donors (LODs). In the evaluation of each transplantation technology, BOT and LOT were positioned in the middle, between transplantation that does not depend on others and the utilization of animal organs. Conclusions Although LOT was favored over BOT, for participants hypothesized to be in a position to donate and receive organs, BODs received a conversely better reputation than LODs. Our survey and discussion suggest that the present conditions of organ transplantation in Japan might be because there is a lack of deliberation on transplantation tourism and LOT. Therefore, more surveys concerning LOT cases and the implications of avoidance of organs from brain-dead bodies, coupled with more discussions based on these surveys, are necessary to formulate a Japanese transplantation policy for the future.

Pseudomyxoma peritonei (PMP) is an unusual condition in which massive amounts of mucinous ascites in conjunction with mucinous peritoneal and omental implants occur. We herein report a case of PMP due to low-grade appendiceal neoplasm (LAMN) and a literature review to clarify the clinical features of PMP. A 68-year-old female suffered from anorexia and abdominal distension and was referred to the emergency department of our hospital. Right-side inguinal hernia and uterine prolapse were revealed by a physical examination. Abdominal computed tomography at admission indicated massive ascites and a ruptured cystic mass in the lower-right abdomen. We diagnosed the patient with a ruptured appendiceal mucinous adenoma and PMP and scheduled a laparotomy. We performed an appendectomy containing the cystic mass, bilateral oophorectomy, and a biopsy for the peritoneum. We irrigated the abdominal cavity using 3000 ml of dextran solution. The macroscopic findings showed a ruptured cystic mass measuring 5 × 4 cm arising from the middle of the appendix. The bilateral ovaries and peritoneum were also covered with yellow mucin. The pathologic findings revealed the presence of low-grade atypical cells inside the capsule. However, no tumor cells were found on the surface of the ovary or peritoneum. A literature review revealed that the prognosis of PMP due to LAMN is relatively good, with a 5-year survival rate of 80%, and hernia is occasionally caused by PMP. According to this literature review, we knew this case might be a typical case. However, PMP is very rare; we need further follow-up data to select an optimal treatment for preventing the relapse of PMP.

Objective:The objective of this study is to assess public attitudes toward pharmaceutical companies’ secondary uses of patient records and public preferences regarding consent approaches.Method:3000 responses to an online survey were collected from adults in Japan. The questionnaire included 32 items related to (1) awareness of “clinical trials”; (2) awareness of the processes of drug development, such as cost, time, and the number of candidate substances in a new drug; (3) knowledge of the laws and regulations for use of patient records in Japan; (4) assessment of the public benefit of the secondary use of patient records; (5) preferences for consent for the secondary use of patient records; and (6) basic characteristics of the respondents.Results:The public benefit from secondary use of records by academic institutions for scientific research was rated highest. All of the activities by pharmaceutical companies were rated higher than those by governmental institutions and other for-profit companies. Regarding consent approaches, 37.9% preferred an “opt-in” approach for new drug development by pharmaceutical companies, 79.7% of whom would change their preference to an “opt-out” approach under specific conditions, such as ensuring intended uses only.Conclusion:Our respondents consider the “public benefit” as dependent on the relative distance from “promoting public health” when assessing the secondary purpose of patient record use. Pharmaceutical companies should include the beneficial purposes when using patient records with “opt-out” approach. Policy makers should pay more attention to the purposes of use when developing personal information protection policies.

Patient: Female, 45 Final Diagnosis: Breast cancer Symptoms: Breast tumor Medication: — Clinical Procedure: Analysis of circulating tumor DNA Specialty: Oncology Objective: Unusual setting of medical care Background: The analysis of circulating tumor DNA (ctDNA) is expected to be a modality to determine the status of cancer in real time. This case indicated utilities and issues in measuring the ctDNA in cancer patients. Case Report: A 45-year-old woman with metastatic breast cancer was treated with bevacizumab and paclitaxel. The lung metastases were decreased but the meningitis carcinoma developed rapidly and she died. During the treatment with bevacizumab and paclitaxel, blood samples were taken serially and ctDNA was analyzed using a next-generation sequencer. TP53 frameshift mutation (TP53; p.Arg158fs with 7 nucleotides deletion) was identified in the tumor, and dynamic change in this mutation in ctDNA was observed in serially sampled plasma in this patient. We observed a rapid decrease of TP53 mutation at the beginning of treatment, then it increased as a sign of relapse. However, the high allelic fraction value of TP53 mutation was not consistent during the progression of cancer, suggesting that several factors affected the value of ctDNA. Conclusions: Although this is a single-case experience, it strongly suggests ctDNA could be a modality to determine the cancer status in real time. However, we found that several factors affected the value of ctDNA. Further investigations are needed to reveal the significance of these very high-sensitivity changes.

The incidence of bile duct cancer developed in the patients with congenital choledochal cysts (CC) with a history of reparative surgery is not well known. We experienced a case developed choleductal cancer 45 years after reparative surgery. She underwent reparative surgery with cyst excision and hepatic bile duct duodenal anastomosis at 1 year of age. She developed the symptoms of jaundice, anorexia, and dull pain in the right upper part of the abdomen at 47 years of age. The carcinoma arose from the dilated proximal bile duct anastomosed with the duodenum. Cholestasis and regurgitation of duodenal fluids seemed to have influenced the development of cancer in this patient. We additionally reviewed seven cohort studies concerning the incidence of biliary carcinoma after surgery for congenital choledocal cysts. The incidence of biliary cancer developed after surgery was 2.2 ± 2.5 (ranged 0–6.5)%. We also reviewed 33 Japanese case reports cited in Japan MEDLINE from 1986 to 2015. Regarding the CC types according to the Totani’s classification, 12 were type I and 14 type IVa, 1 was type II and 6 were unknown type. The rate of coexistence of pancreaticobiliary maljunction (PBM) was 92%, (22/24; other 9 cases were not documented), and biliary cancer arose from the proximal stump of the reparative surgery in 68% (17/25) and from the distal stump in 32% (8/25) of cases. These findings suggested that the reflux of pancreatic juice due to PBM only partially explained the carcinogenesis of CCs. Intensive follow-up of such patients throughout their lives is necessary to avoid cancer death even after standard reparative surgery.

We herein experienced a case with pseudo-Meigs’ syndrome that developed both synchronous and metachronous metastases to the ovary from ascending colon cancer. A 57-year-old female visited a hospital for a 2-month history of abdominal distension and voiding difficulty. Massive pleural effusion on the right side and a small amount of left-sided pleural effusion were detected on CT. She underwent emergent laparotomy due to the severe symptom of abdominal distention. The tumor originated from the left ovary, and left-sided oophorectomy was performed. The histologic finding was moderately differentiated adenocarcinoma suggesting metastatic carcinoma from the colon. Left thoracic effusion disappeared at 3 days after the removal of the ovarian tumor. Subsequently, colon carcinoma of the cecum was detected by colonoscopy. The patient underwent second laparotomy of right colectomy and lymph node dissection. However, 6 months after the operation, pleural effusion on the right side re-developed again, and the serum levels of CEA and CA125 were elevated at 105 ng/ml and 125 U/ml, respectively. CT again revealed a large ovarian tumor. She subsequently underwent third laparotomy of right-sided oophorectomy and hysterectomy. Pleural effusion and ascites disappeared in a few days after the operation. The patient developed both synchronous and metachronous ovarian metastases and achieved a 7-year disease-free survival after the operation. The pathogenesis of pseudo-Meigs’ syndrome should be distinguished from carcinomatous peritonitis and/or pleuritis of malignant disease.

Highlights • The over-expression of P53 protein in gallbladder carcinoma is a biomarker correlating with a poor survival. However, the significance of P53 expression in peritumor tissues is unknown. We report a case of gallbladder carcinoma where the operative specimen showed over-expression of P53 on the peritumor epithelium, and early recurrence developed at the biliary tract. • The immunohistochemical staining of the GB wall or surgical stump for a surgical specimen of GBC may be crucial to predict the bile duct recurrence., Introduction The over-expression of P53 protein in gallbladder carcinoma is a biomarker correlating with a poor survival. However, the significance of P53 expression in peritumor tissues is unknown. We experienced a case of gallbladder carcinoma where the operative specimen showed over-expression of P53 on the peritumor epithelium, and early recurrence developed at the biliary tract. Presentation of case A 74-year-old female patient was referred to our hospital due to wall thickening of the gallbladder on ultrasonography. Radiographic examinations revealed wall thickening at the fundus of gallbladder and no abnormalities of the biliary tract or surrounding lymph nodes. We performed open cholecystectomy and lymph node dissection without extrahepatic bile duct resection, as a frozen section of the surgical stump of the cystic duct was cancer-free. However, a pathological examination revealed over-expression of P53 protein in the epithelium of the peritumor to the cystic duct, which were diagnosed as normal on hematoxylin eosin staining. The patient developed bile duct metastases, two and half years after the operation. She underwent endoscopic stenting for the obstruction of bile duct with no additional therapy, and died 6 months later. Discussion and conclusion The immunohistochemical staining of the GB wall or surgical stump for a surgical specimen of GBC may be crucial to predict the bile duct recurrence.

Caregiver Perspectives on End-of-Life Experiences of PatientsWith Left Ventricular Assist Devices To the Editor In an article published in a recent issue of JAMA Internal Medicine, McIlvennan et al1 found that the bereaved caregivers of patients with left ventricular assist devices (LVADs) reported feelingsofconfusionandabandonment.How to support patients with LVADs and their caregivers in endof-life issues in an era of increasing destination therapy (DT) is a crucial issue. When considering end-of-life issues of LVAD-DT, McIlvennan et al1 should have mentioned the importance of the informed consent process. As the endpoint of LVAD-DT is patient death, patients, caregivers, and VAD teams must anticipate end-of-life issues at the beginning of therapy, including device discontinuation. Before introducing LVAD-DT, the VAD teamshouldprovide specific information regarding caregiver burden,2 in addition to information related to the procedure, risks, benefits, and alternative treatment options. As not all patients (and caregivers) who provide consent to the LVAD treatment fully understand it, even after implantation.3 Informed consent should not be a single event where patientsare informedandtheir consentobtainedbut ratheraprocess that continues for the duration of wearing a VAD. In a research participation context, a continuing consent process could address the factors relevant to an individual’s decisionmaking process; the nature of the research itself, participants’medical conditions, or participants’ preferences and interests may change unexpectedly after the initial informed consent.4 This would apply to the clinical situation of LVADDT.ThemedicalconditionandothercircumstancesofLVAD-DT patients and caregivers could change during the long treatmentperiod. Patientswhoconsent toLVAD-DTand their caregivers are facedwithday-to-daydecisions in the context of an extended period in which increasing symptoms adversely affect their daily lives. The IC process encompasses providing information via the IC form and signing the letter of consent. Patients and caregivers can reconsider both their daily liveswithanLVADandtheendpointof the therapybeforesigning; the VAD team can understand the concerns of patients and caregivers regarding therapy and partake in the treatment path, step-by-step, when providing information. Moreover, the processes via an IC form can record the decisionmakinghistory of bothpatients and caregivers. Continuing to progressively provide information will lead to better education asMcIlvennan et almentioned.1 The ethical and psychosocial needs of both patients and caregivers will change with thechronicprogressive illness trajectory.Thisgradual andcontinuous approach5 IC process could contribute to preparing patients and caregivers for the end of life with an LVAD.

Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial. We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor–node–metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC. We then selected the patients in the ER+ or PR+/HER2− subtype specifically and compared sites of recurrence, and the survival curve starting from the point of development of metastatic disease. The clinical stage was significantly higher in the ILC patients than in the IDC (p = 0.001). The mean (±SD) of DFS for the ILC and IDC patients was 2.6 ± 0.6 and 2.4 ± 0.3 years, respectively, with no significant difference (p = 0.18). However, the hormone receptor status was same between both groups; the rate of HER2 positivity was significantly lower in the ILC group (0%) than in the IDC group (16.2%) (p = 0.05). In ER+ or PR+/HER2− subtype, the mean DFS for the ILC and IDC was 2.9 ± 0.6 and 3.1 ± 0.3 years, and the median survival time after the recurrence for ILC and IDC patients was 4.2 ± 0.7 and 5.6 ± 0.7 years, respectively, with no significant difference (p = 0.77). The frequency of lung metastases was significantly lower in the ILC group (6.3%) than in the IDC group (53.7%) (p

Tumor heterogeneity has been suggested based on clinical and pathological findings. Several clinical findings can be explained by tumor evolution during progression and metastasis. We herein report a case of metastatic breast cancer indicated tumor heterogeneity by clinical findings and a genomic analysis. A 64-year-old woman with advanced breast cancer was treated with primary chemotherapy, to which primary tumor responded. After a 6 month treatment pause, lung, liver, and skin metastases developed and her serum tumor markers were elevated. None of those serum markers had been elevated before the treatment, despite the large tumor burden. Notably, there was discordance in the expression of human epidermal growth factor receptor 2 (HER2) between the primary tumor and metastatic skin lesions, with the former being negative and the latter positive. A genomic analysis was performed by in-house Breast Cancer Panel, which consisted of 53 pre-selected genes. Twenty-three somatic mutations were found in primary breast tumor and 7 in the skin metastasis. None of these 30 genes matched. However, the cell-free (cf) DNA in the plasma taken at the time of skin metastasis contained 10 mutations, 7 from the primary lesion and 3 from the metastasis. These data indicate that the clonal changes or tumor heterogeneity was shown in two solid tumors by clinical and the result of a genomic analysis. Of particular interest was that cell-free DNA could be a powerful tool to look into these dynamic changes.

We experienced a case with gallbladder carcinoma growing limited to the mucosa (T1a), which developed massive lymphatic vessel spread and lymph node metastases. A 72-year-old man was referred to our hospital for the swelling of his gallbladder during a routine ultrasound sonography checkup. We diagnosed the patient with gallbladder carcinoma with lymph node metastasis according to the radiographic findings and performed the open cholecystectomy and lymph node dissection. A histological examination showed poorly differentiated adenocarcinoma, solid type, and the tumor was limited to the mucosa. The number of lymphatic vessels was increased in the tumor and peritumor areas, and cancer cells were observed in the lymphatic vessels, which were detected via D2-40 immunohistochemistry. A careful histological examination and follow-up is required for T1a gallbladder carcinoma.

HPV vaccinations were recommended with the backing of a Japanese government subsidy program in 2010, and were included in the National Immunization Program in April 2013. However, the Ministry of Health, Labour, and Welfare withdrew the recommendation for the HPV vaccination in June 2013. We investigated HPV vaccine injury compensation programs for both the national and local governments. Approximately 3.38 million girls were vaccinated, and 2,584 complained of health problems. The majority of these received the vaccine shot as a non-routine vaccination. In total, 98 people developed health problems and applied for assistance from 2011 to 2014, but no cases have been processed since October 2014. Several local governments are providing their own compensation program for cases of vaccine adverse reactions, but the number is extremely low (16 of 1,741 municipalities and 1 of 47 prefectures). The local governments that are providing compensation are largely those where HPV vaccine victim support groups are prominent. The confusion regarding the national program for HPV vaccine injury was caused by the discrepancy between the compensation programs for those vaccinated under the immunization law and for those who received voluntary vaccinations. The establishment of a new compensation program might be key to finding a lasting resolution.

Everolimus levels were within the recommended range. An assessment of GM-CSF autoantibodies was not performed but might have been helpful to further elucidate the pathophysiology. Cessation of the drug resulted in an improvement in clinical symptoms and radiology, and neither whole-lung lavage nor GM-CSF was required. Drug-induced pulmonary alveolar proteinosis should be considered in the differential diagnosis of new pulmonary pathology in transplant patients receiving mammalian target of rapamycin inhibitor therapy. Onset may be insidious, and discontinuation of everolimus alone may be associated with resolution of pulmonary alveolar proteinosis.

Cancer patients can obtain information about their illness through a variety of media sources. Therefore, it is important to know how medical journalists treat cancer-related issues; to that end, we sent self-administered questionnaires to 364 journalists in 82 organisations who had reported on medical issues for the Japanese media, asking for their reasons for reporting on cancer-related issues and the difficulties they had faced. The most common reason for reporting on health-related issues was their personal interest in a particular issue (n = 36). They mainly covered conventional therapies (n = 33), healthcare policy (n = 30), new therapies (n = 25), and diagnosis (n = 25). All of the journalists that were surveyed experienced some difficulties in reporting health issues. Significant concerns included the quality of information (n = 36), social impact (n = 35), lack of technical knowledge (n = 35), and difficulty in understanding technical terms (n = 35). Journalists commonly used personal networks, including physicians, as information sources (n = 42), as well as social media (e.g., e-mail, Twitter and Facebook) (n = 32). Topic selection was biased, with 35 of 48 journalists having never reported on topics concerning hospices. Physicians were the most trusted source of information about cancer, and journalists attached high importance to interviewing them. As medical knowledge is advancing rapidly, journalists may have increasing difficulty covering cancer-related issues.

BackgroundA national agreement on human papillomavirus (HPV) vaccination was achieved relatively quickly in Japan as compared to the United States and India. ObjectiveThe objective was to identify the role of print and online media references, including references to celebrities or other informants, as factors potentially responsible for the relatively rapid national acceptance of HPV vaccination in Japan. MethodsA method of text mining was performed to select keywords, representing the context of the target documents, from articles relevant to the promotion of HPV vaccination appearing in major Japanese newspapers and Web pages between January 2009 and July 2010. The selected keywords were classified as positive, negative, or neutral, and the transition of the frequency of their appearance was analyzed. ResultsThe number of positive and neutral keywords appearing in newspaper articles increased sharply in early 2010 while the number of negative keywords remained low. The numbers of positive, neutral, and negative keywords appearing in Web pages increased gradually and did not significantly differ by category. Neutral keywords, such as “vaccine” and “prevention,” appeared more frequently in newspaper articles, whereas negative keywords, such as “infertility” and “side effect,” appeared more frequently in Web pages. The extraction of the positive keyword “signature campaign” suggests that vaccine beneficiaries cooperated with providers in promoting HPV vaccination. ConclusionsThe rapid development of a national agreement regarding HPV vaccination in Japan may be primarily attributed to the advocacy of vaccine beneficiaries, supported by advocacy by celebrities and positive reporting by print and online media.

BACKGROUND: The impact of the H1N1 influenza on blood donation is unknown. STUDY DESIGN AND METHODS: We examined number of blood donors presenting to blood donation centers or bloodmobiles using a blood donation database of Red Cross Hyogo Prefectural Blood Center between 4 weeks before and after May 16, 2009, respectively, when the first case of H1N1 influenza was confirmed in Kobe. The numbers of blood donors per donation site (i.e., blood donation centers and bloodmobiles) and per blood products (i.e., red blood cells [RBCs], platelet [PLT]-poor plasma, and PLTs) were also examined. RESULTS: The number of blood donors decreased by 21% and whole blood donations declined by 1329 units within 1 week of the first case of H1N1 influenza. While number of blood donors showed a rapid decrease, blood donations returned to the normal level within 1 week. This quick recovery was attributed to the diligent efforts made by Red Cross Centers, including the use of e-mail to encourage blood donation, on-the-street campaigns, and requesting new bloodmobile drives in workplaces and universities. RBCs that were donated in bloodmobiles was predominantly affected; the number of blood donors in bloodmobiles decreased by 39%. CONCLUSION: H1N1 influenza pandemic had a great but transient impact on blood donation.

Vaccination is a preventive measure against influenza that does not require placing restrictions on social activities. However, since the stockpile of vaccine that can be prepared before the arrival of an emerging pandemic strain is generally quite limited, one has to select priority target groups to which the first stockpile is distributed. In this paper, we study a simulation-based priority target selection method with the goal of enhancing the collective immunity of the whole population. To model the region in which the disease spreads, we consider an urban area composed of suburbs and central areas connected by a single commuter train line. Human activity is modelled following an agent-based approach. The degree to which collective immunity is enhanced is judged by the attack rate in unvaccinated people. The simulation results show that if students and office workers are given exclusive priority in the first three months, the attack rate can be reduced from [Formula: see text] in the baseline case down to 1-2%. In contrast, random vaccination only slightly reduces the attack rate. It should be noted that giving preference to active social groups does not mean sacrificing those at high risk, which corresponds to the elderly in our simulation model. Compared with the random administration of vaccine to all social groups, this design successfully reduces the attack rate across all age groups.

In order to understand the evolution of the 2009 influenza A (H1N1) pandemic within local regions of Japan, we studied the significance of regional migration between these regions. For this purpose, we have employed an extended SEIR model to describe the immigration of infected people and the stochastic variation of the infectious efficiency. We then applied a data assimilation technique in order to study how the agreement of the simulation results with the observed data depends on the presence/absence of immigration and the degree of variation of the infectious efficiency. Reproducibility is evaluated by log-likelihood values. The log-likelihood does not indicate the significance of immigration. Although there are multiple waves in the time course of the number of reported infected individuals, these waves could be explained by the stochastic nature of infectious events.

The impact of the H1N1 influenza on blood donation is unknown.We examined number of blood donors presenting to blood donation centers or bloodmobiles using a blood donation database of Red Cross Hyogo Prefectural Blood Center between 4 weeks before and after May 16, 2009, respectively, when the first case of H1N1 influenza was confirmed in Kobe. The numbers of blood donors per donation site (i.e., blood donation centers and bloodmobiles) and per blood products (i.e., red blood cells [RBCs], platelet [PLT]-poor plasma, and PLTs) were also examined.The number of blood donors decreased by 21% and whole blood donations declined by 1329 units within 1 week of the first case of H1N1 influenza. While number of blood donors showed a rapid decrease, blood donations returned to the normal level within 1 week. This quick recovery was attributed to the diligent efforts made by Red Cross Centers, including the use of e-mail to encourage blood donation, on-the-street campaigns, and requesting new bloodmobile drives in workplaces and universities. RBCs that were donated in bloodmobiles was predominantly affected; the number of blood donors in bloodmobiles decreased by 39%.H1N1 influenza pandemic had a great but transient impact on blood donation.

We simulated the early phase of the 2009 influenza A(H1N1) pandemic and assessed the effectiveness of public health interventions in Japan. We show that the detection rate of border quarantine was low and the timing of the intervention was the most important factor involved in the control of the pandemic, with the maximum reduction in daily cases obtained after interventions started on day 6 or 11. Early interventions were not always effective.

when the MHLW’s prohibition against vaccinating people other than members of priority groups was unrealistic in clinics and hospitals. Under such pressures, clinicians and patients might have chosen to receive a shot instead of missing their chance and taking the risk of influenza A (H1N1) in addition to their underlying diseases. The MHLW made the vaccine that was dispatched on 29 January and thereafter available to all [10]. The circulation of vaccine available to all at the discretion of clinicians and vaccinees may partly explain the lack of deaths after March, together with the decreased number of vaccinees. The vaccine manufactured by Novartis and GlaxoSmithKline obtained regulatory approval on the basis of clinical trial data, but the vaccine made by Japanese manufacturers went through the routine process of strain change for the annual seasonal influenza vaccine, which did not require clinical data. The details of the approval process have not been revealed by the MHLW. The withdrawal of the MHLW’s interference in clinicians’ decisions regarding the administration of vaccines may save lives. We also recommend that a legal basis for a national vaccine program, including some type of regulatory approval process that can be implemented quickly in an emergency, be discussed in Japan. Acknowledgments

Yukiko Kishi1, Naoko Murashige2, Yuko Kodama1, Tamae Hamaki1, Kazuhiro Murata3, Haruka Nakada1, Tsunehiko Komatsu3, Hiroto Narimatsu1,4, Masahiro Kami1, Tomoko Matsumura11Division of Social Communication System for Advanced Clinical Research, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan; 2Ministry of Health, Labor and Welfare, Aide of the Minister, Health Sector Reform Office, Tokyo, Japan; 3Department of Hematology, Teikyo University Chiba Medical Center, Chiba, Japan, 4Advanced Molecular Epidemiology Research Institute, Faculty of Medicine, Yamagata University, Yamagata, JapanAbstract: Media reports of medically related events have a major effect on the healthcare ­community but there have been few detailed investigations conducted to investigate their content. The Nikkei Telecom 21 database was used to investigate the number of reports concerning medically related events between 1992 and 2007 in Japan’s 5 national newspapers. For this period, both the total number of articles and the number of articles containing medically-related keywords were determined. The number of reports relating to medically related occurrences increased sharply from 1999 to 2000 and displayed a decrease from 2003 before increasing again in 2008. As of 2008, such reports account for 0.17% of total newspaper articles. The use of the word ‘iryokago’ (medical professional negligence or error) drastically increased in 1999 but showed a consistent decrease from 2004. On the other hand the frequency of reports relating to ‘litigation’ and ‘punishment’ increased rapidly in 1999 before leveling off. Despite this, the number of articles relating to medically related occurrences that were caused by doctor shortages and system errors increased sharply between 2006 and the present. Results indicate that the manner in which newspapers report medically related events is undergoing major changes.Keywords: coverage, incident, doctor shortage, system error, litigation

Highlights • This article reports an extremely rare case of spontaneous mesenteric hematoma that ruptured into the jejunum. The etiology of this condition was not revealed by detailed pathological examinations., Introduction A spontaneous mesenteric hematoma is a rare condition. Furthermore, it is extremely rare that the mesenteric hematoma caused gastrointestinal bleeding with an unknown etiology. We experienced a case with a spontaneous mesenteric hematoma that ruptured into the jejunum. Presentation of case A 75-year-old man was referred to our hospital because of anal bleeding and anemia. Abdominal computed tomography (CT) showed a low density mass measuring 3.0 cm in diameter, including an enhanced spot. This finding suggested that a pseudo-aneurysm or mesenteric hematoma caused active bleeding into the jejunum. He underwent emergent laparotomy and partial resection of the jejunum and the mesentery including the tumor. A histological examination of the jejunum indicated no pathogenic findings causing active bleeding. And there were no findings suggesting the mesenteric aneurysm had developed. The patient had no history related to the development of a mesenteric hematoma, such as trauma, labor, surgery, or anticoagulant treatment. Therefore, we finally diagnosed that a spontaneous mesenteric hematoma had ruptured into the jejunum. Discussion and conclusion We reported extremely rare condition that the mesenteric hematoma was developed and ruptured into the jejunum without definitive etiology.