[Clinical research and conflict of interest].

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.

[Patient and Public Involvement in Cancer Clinical Research].

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.

[Two Cases of Carcinoma en Cuirasse, as Cutaneous Metastasis of Breast Cancer].

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.

Ethical and professional challenges encountered by Japanese healthcare professionals who provide genetic counseling services.

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.

Development of a national agreement on human papillomavirus vaccination in Japan: an infodemiology study.

BACKGROUND: A national agreement on human papillomavirus (HPV) vaccination was achieved relatively quickly in Japan as compared to the United States and India. OBJECTIVE: The 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: The 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.

General public's understanding of rare diseases and their opinions on medical resource allocation in Japan: a cross-sectional study.

BACKGROUND: Rare diseases (RDs) may impose a considerable financial burden on patients and their families. Public acceptance is essential to ensure sustainable public systems supporting RDs, especially in countries with universal healthcare coverage, such as Japan. This study aimed to explore the public's understanding of RDs and identify crucial factors associated with the public acceptance of prioritizing financial support for RDs in Japan. METHODS: An online questionnaire was sent to 131,220 Japanese residents aged 20-69 years. The items included in the questionnaire were general interest in medical science and medical care, general knowledge regarding RDs and health care systems, opinions on the cost of medical care, opinions on the research and development of RDs and common diseases, and individual characteristics. RESULTS: The responses of 11,019 respondents were analyzed. Several respondents agreed to partially cover the medication cost of adult and pediatric RDs (59.5% and 66.8%, respectively) with public funding. The major reasons for agreeing were the huge financial burden imposed on patients and their families, limited available treatment options, effects of RDs on the life planning of patients, and difficulties caused by RDs in the patient's social life. Furthermore, the respondents ranked RDs (56.0%) higher than common diseases (44.0%) for government funding for research and development. The reasons for supporting government-funded research and development for RDs included the lack of treatment options for numerous RDs (34.9%) and difficulty of studying RDs owing to the small number of researchers (25.9%). The chief reasons for supporting government-funded research and development for common diseases were the large number of affected patients (59.7%) and the possibility of more treatment options becoming available through the promotion of research and development (22.1%). CONCLUSIONS: The general public considers burdens associated with daily living or finance more than the epidemiological characteristics of RD while making funding decisions, demonstrating that rarity was less prioritized. A gap appears to exist between the general public and RD experts regarding the understanding of the epidemiological characteristics of RD and its thresholds. This gap should be bridged to ensure that prioritization of financial support for RDs is accepted by the society.

Public Attitudes toward COVID-19 Vaccinations before Dawn in Japan: Ethics and Future Perspectives.

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. Supplementary Information: The online version contains supplementary material available at 10.1007/s41649-022-00207-4.

Comparative Assessment of Non-trial Access to Investigational Medical Products in the U.S. and Japan.

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.

The impact of H1N1 influenza A virus pandemic on the blood donations in Hyogo Prefecture, Japan.

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.

Public Attitudes Toward the Secondary Uses of Patient Records for Pharmaceutical Companies' Activities in Japan.

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.

Where Can Patients Obtain Information on the Preapproval Access Pathway to Investigational Treatment in Japan? A Survey of Patient Advocacy Organizations' Websites.

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.

"Tell me what you suggest, and let's do that, doctor": Patient deliberation time during informal decision-making in clinical trials.

Informed consent is an essential part of an ethical clinical trial; to this end, researchers have developed several interventions to promote participants' full understanding of trials and thereby improve the consent process. However, few empirical studies have examined how patients make the decision of whether to give consent. The objective of this study, therefore, is to analyze patients' decision-making process when participating in clinical trials. We conduct an internet survey (n = 2,045) and interview data analysis (n = 40) with patients and categorize respondents into three types of participants: active, passive, and non-participation. Our results show that patients often make informal and quick decisions before medical staff provide them with relevant information during the informed consent process. For example, 55.9% of patients received initial information on clinical trials from an online article or web advertising, and 54.5% consulted no one about whether to participate in the clinical trial before making a decision. Only 20.7% of respondents subjectively spent time making the decision whether to participate; 43.0% of patients who said that they "spent time" coming to a decision took four or more days to reach a decision, while 8.3% of people who "did not spend time" making a decision took this among of time. Based on these results, we were able to break patients' decision-making process into four steps: first contact, informal decision making, relevant information, and formal decision making. Our results show that patients are most likely to make a decision based on the first information they receive on the clinical trial, whatever the source. To this end, having a list of questions for potential participants to ask researchers would be useful in helping better collecting information of clinical trials. In addition, research teams should give patients more than four days to decide between providing them with relevant information and obtaining written consent, even if the patient seems to make a quick decision.

Public Attitudes Toward the Secondary Uses of Patient Records for Pharmaceutical Companies' Activities in Japan.

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.

Lateral thoracoaxillar dermal-fat flap for breast conserving surgery: the changes of the indication and long-term results.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: We reported satisfying long-term outcomes of 487 cases treated by LTDF. LTDF is a suitable oncoplastic technique for BCS.

Fat necrosis after breast-conserving oncoplastic surgery.

BACKGROUND: Fat necrosis is a subjective early as well as delayed complication, which sometimes mimics local recurrence and ruins the quality of life by pain and poor cosmetic result. While, the frequency and severity of fat necrosis are important issues that breast surgeons should explain to the patient, these data are not revealed well. METHODS: A total of 1476 patients who underwent breast surgery from January 2000 to December 2012 were enrolled in the present study. We assessed fat necrosis by mammographic and physical findings and created grading criteria: Grade (G) 0, no fat necrosis; G1, no symptomatic fat necrosis (mammographic dystrophic calcification); G2, mild symptomatic necrosis (mammographic dystrophic necrosis with tumor); G3, severe symptomatic necrosis (mammographic dystrophic necrosis with pain or skin change); and G4, symptomatic necrosis requiring surgical intervention. RESULTS: Of the 1476 patients enrolled, 393 (27%) underwent mastectomy, and 1083 (73%) underwent breast-conserving surgery. We achieved a high rate of breast-conserving surgery at a total rate of 73% over the study period and maximum rate of 88% in 2010, using oncoplastic procedures. We mainly adopted a pedicled fat flap (417/1083; 39%) and a free dermal fat flap (40/1083; 3.7%). Among the 626 patients who underwent partial resection with no replacement for the defect, G1-G2 fat necrosis was seen in 29/626 (4.6%). While, the incidence of fat necrosis with pedicled fat flap and free dermal fat graft was 68/417 (16%) and 40/40 (100%), respectively, showing a significant difference (p < 0.01). Furthermore, the incidence of G3-G4 fat necrosis was significantly higher with free dermal fat grafts (25%; 10/40) than with pedicled flap (2.9%; 12/417) (p < 0.01). Among pedicled flaps, the incidence of fat necrosis with inframammary adipofascial flaps was 56% (14/25) which was higher than that with lateral epidermal fat flaps (12%; 33/276) (p < 0.01), and rotation of surrounding breast tissues (8%; 21/116) (p < 0.01). The incidence of G3 fat necrosis was also high at 20% (5/25) in inframammary adipofascial flaps. CONCLUSIONS: Breast-conserving oncoplastic surgery carries a risk of fat necrosis as a delayed complication. The incidence rate and severity of fat necrosis with each procedure should be assessed. We should select fat grafts with a good blood supply to replace defects of breast-conserving therapy.

Rapid Changes in Circulating Tumor DNA in Serially Sampled Plasma During Treatment of Breast Cancer: A Case Report.

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.

A study of tumor heterogeneity in a case with breast cancer.

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.

Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.01), while the frequency of peritoneal metastases was significantly higher in the ILC group (68.8%) than in the IDC group (1%) (p = 0.00). Of note, the prognosis after the diagnosis of peritoneal metastases was poor, with a median survival time of 19 ± 9 months and resistance to hormone therapy. CONCLUSIONS: The extremely high rate (68.8%) of peritoneal metastases was observed in long-term follow-up for the metastatic breast cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.

Biliary cancer developed after the reparative surgery for congenital choledochal cyst: a case report and review of the literature.

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.