The management with clinical path for esophagectomy for esophageal cancer

We have introduced a clinical path for esophagectomy of esophageal cancer from January, 2001 and got good results. It is important of the adaptation and the evaluation of variances for the critical path. Patients and co-medicals understood deeply the disease and the treatment of esophageal cancer. We could improvement the process of treatments by changing the critical path easily. We concluded that a critical path was adapted for esophagectomy of esophageal cancer, and it will be getting important.     

Consensus guidelines for radiation therapy of benign diseases: a multicenter approach in Germany

PURPOSE: To overcome the lack of written guidelines for radiation therapy (RT) of benign diseases, the German Working Group on Radiotherapy of Benign Diseases initiated a consensus process in 1999 to warrant continuous quality assurance and outcome research in this field. METHODS: An expert panel was convened to define key issues and develop written guidelines for RT of benign diseases. Pertinent information and data from published literature were reviewed, and data of most importance were identified. In addition, a patterns of care study was conducted to obtain a nationwide survey on the current status and treatment standards. RESULTS: From the data gathered, the expert panel prepared a first consensus statement that was open to propositions and comments from all participating institutions. After completion of the multicenter discussion, a final written consensus statement was compiled, discussed, and finally agreed on during a national conference of radiation therapists. For each individual nonmalignant disease, the accepted RT concepts were documented. Finally, specific evaluation tools and recommendations for follow-up examinations were defined. CONCLUSIONS: For the first time, written consensus guidelines for RT of nonmalignant diseases have been developed by the interaction of all institutions involved. These guidelines may serve as a starting point for quality assessment, prospective clinical trials, and outcome research.     

Operational aspect of participation in the multi-national clinical trials from the foreign pharmaceutical company's standpoint

As a means to reduce the delay with the West, the enhanced use of multi-national clinical trials is expected. It is necessary to improve the presence of Japan as a development base by making the best use of the quality of the clinical trials and becoming more competitive in terms of the speed and the cost as compared with other Asian countries. The development team in Japan has to play an active role in the planning stage of the trial and support improvements in the IT environment of the medical institution for introducing clinical trial management systems such as EDC. I expect the medical institutions to simplify the procedures required for conducting clinical trials, to accept English documents, to secure doctor's time for the clinical trials and to increase the number of CRCs, etc. The elimination of the difference between the domestic and international regulations is expected of the regulator. Finally, the revision of medical institutions by the government would contribute improvements in the current situation where staff are too busy to conduct clinical trials.     

Research misconduct in clinical research--the American experience and response

Research misconduct in the United States has occurred sporadically since 1961 in the laboratories of some of our most distinguished scientists. In view of the enormous number of research grants funded, cases of this kind are relatively uncommon, but have none the less attracted governmental supervision and calls for reform. The scientific community, universities and government have addressed the issue in various ways and changes have been proposed and some actually instituted. In view of human nature, no one seriously believes that dishonesty in research can be prevented to any greater extent than in any other human activity. However, some practices may discourage and mitigate such occurrences. These include: education in sound laboratory research practices, a fair distribution of authorship assignment, and adequate supervision of research personnel including appropriate reviewing of primary data. Other measures which might be considered include: an adequate check of the credentials of all new personnel, audits for clinical research, especially for those involving significant numbers of patients and multiple institutions, and the introduction of quality control concepts into research procedures. The hope is that the senior individual scientist responsible for the quality and integrity of the research will institute such measures as needed, and that institutional and government supervision will not interfere with the creative process.     

树突状细胞肿瘤疫苗：全球临床试验巡礼

自2011年度的诺贝尔生理学或医学奖获得者Ralph M.Steinman发现树突状细胞(dendritic cell,DC)及其在获得性免疫应答中的关键作用以来,全球范围的DC肿瘤疫苗研究持续进行了数十年,一系列临床试验正在进行或已经完成,目前已经有3种DC肿瘤疫苗获得了上市批准:Sipuleucel-T、CreaVax RCC和Hybricell,但基于DC的免疫治疗方法尚未成为肿瘤治疗的一种标准方法。为了让国内同行深入了解全球范围内开展DC肿瘤疫苗临床试验的现状,本文基于国际医学期刊编辑委员会认可的临床试验注册网站和PubMed网站数据库对全球DC肿瘤疫苗临床试验概况(地区和国家分布、涉及的肿瘤类型、开展年份和试验分期)作了介绍,重点对43项已经有论文发表的临床试验情况(受试者选择、DC培养方法、疫苗接种方案、疗效评估方法和试验结果)进行了总结,着重分析了当前DC肿瘤疫苗临床研究的发展趋势和存在问题,提出了加强DC肿瘤疫苗临床试验工作的若干建议:健全我国DC肿瘤疫苗临床试验相关的监管政策;密切关注国际"体内DC靶向"策略的新动向;抓紧建立DC培养方法、疫苗接种方案和疗效评估的标准;加强对DC肿瘤疫苗的质量监控;重视DC肿瘤疫苗的基础研究和临床试验注册;提高临床试验方案的质量;慎重选择受试患者和疗效评估时间点;治疗时应同步开展免疫监测等。抛砖引玉,以期引起国内同行的重视和讨论,并尽可能在将来的工作中加以研究和得到解决。     

Cancer Control and the Communication Innovation in South Korea: Implications for Cancer Disparities

Over the last 10 years, the number of cancer survivors in South Korea has reached nearly one million with asurvival rate of 49.4%. However, integrated supportive care for cancer survivors is lagging. One area in which thecurrent cancer control policy needs updating is in the utilization of information and communication technology(ICT). The remarkable progress in the field of ICT over the past 10 years presents exciting new opportunitiesfor health promotion. Recent communication innovations are conducive to the exchange of meta-information,giving rise to a new service area and transforming patients into active medical consumers. Consequently, suchinnovations encourage active participation in the mutual utilization and sharing of high-quality information.However, these benefits from new ICTs will almost certainly not be equally available to all, leading to so-calledcommunication inequalities where cancer survivors from lower socioeconomic classes will likely have morelimited access to the best means of making use of the health information. Therefore, most essentially, emphasismust be placed on helping cancer survivors and their caregivers utilize such advances in ICT to create a moreefficient flow of health information, thereby reducing communication inequalities and expanding social support.Once we enhance access to health information and better manage the quality of information, as a matter of fact,we can expect an alleviation of the health inequalities faced by cancer survivors.     

Microsatellite instability in colorectal cancer: from molecular oncogenic mechanisms to clinical implications

Background

Microsatellite instability (MSI) constitutes an important oncogenic molecular pathway in colorectal cancer (CRC), representing approximately 15% of all colorectal malignant tumours. In roughly one third of the cases, the underlying DNA mismatch repair (MMR) defect is inherited through the transmission of a mutation in one of the genes involved in MMR, predominantly MSH2 and MLH1, or less frequently, MSH6 or PMS2. In the overwhelming number of sporadic cases, MSI results from epigenetic MLH1 silencing through hypermethylation of its promoter. MMR deficiency promotes colorectal oncogenesis through the accumulation of numerous mutations in crucial target genes harbouring mononucleotide repeats, notably in those involved in the control of cell proliferation and differentiation, as well as DNA damage signalling and repair.

Design

In this review, we describe the molecular aspects of the MMR system and the biological consequences of its defect on the oncogenic process, and we discuss the various experimental systems used to evaluate the efficacy of cytotoxic drugs on MSI colorectal cells lines. There is increasing evidence showing that MSI CRCs differ from all CRCs in terms of prognosis and response to the treatment. We report the clinical studies that have evaluated the prognostic and predictive value of MSI status on clinical outcome in patients treated with various chemotherapy regimens used in the adjuvant setting or for advanced CRCs.

Conclusion

In view of this, the opportunity of a systematic MSI phenotyping in the clinical management of patients with CRC is further discussed.     

Distinct clinical phenotype and genetic testing strategy for Lynch syndrome in China based on a large colorectal cancer cohort

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) predisposition syndrome. We performed a large-scale study to assess a screening strategy for identifying LS in Chinese CRC patients in routine clinical testing. A total of 4,195 eligible CRCs were universally screened. Then, 8.7% of CRCs were detected with dMMR. The incidence of LS was 2.7% (115 of 4,195) in this cohort; among patients over 70 years of age, only 0.3% (2 of 678) were diagnosed as LS. Then, 17.4% of LS cases showed large genomic deletions/duplications. LS probands developed CRCs predominantly at proximal colon location. The frequency of BRAF V600E mutation among Chinese CRCs was significantly lower than that among Western populations, and MLH1 promoter methylation significantly improved the efficiency of genetic screening for LS among MLH1-deficient patients. A comprehensive molecular testing strategy that includes detection of large genomic rearrangements is imperative for the diagnosis of LS. Among CRC patients aged 70 years or younger, a selective strategy for LS screening might be considered for routine clinical testing.     

Challenges in the recruitment of adolescents and young adults to cancer clinical trials

The adolescent and young adult (AYA) oncology population has seen inferior progress in cancer survival compared with younger children and older adults over the past 25 years. Previously, AYAs had the best survival rates due to the prevalence of highly curable diseases including Hodgkin lymphoma and germ cell tumors, yet today AYAs have inferior survival rates to children and some adult cohorts. Survival rates are particularly poor for AYA-specific diseases such as sarcomas. Research involving children and adults diagnosed with common malignancies such as acute lymphoblastic leukemia has resulted in improved survival rates. However, AYAs have not directly benefited from such research due to low rates of access to and accrual on clinical trials. AYAs are less likely to have insurance or access to healthcare, are more likely to see providers who are not part of research institutions, and are less likely to be referred to or to join clinical trials, all of which may contribute to worse outcomes. Few clinical trials target AYA-specific diseases, leading to little information regarding how these diseases behave and what role the host plays. Tumor samples for this population are underrepresented in national tumor banks. Coupled with the need for more clinical trials that focus on AYA-specific cancers, better collaboration between adult and pediatric cooperative groups as well as increased education among community oncologists and primary care providers will be needed to enhance participation in clinical trials with the goal to increase survival and improve quality of that survival.     

Stakeholder research on biospecimen needs and reactions to the development of a national cancer human biobank by the National Cancer Institute

An initial survey conducted by the National Cancer Institute (NCI) in October 2008 with cancer researchers around the country revealed both a need and support for the development of a national cancer HUman Biobank (caHUB). NCI sought additional feedback from decision makers whose organizations are potential users of a caHUB and who would have a direct influence on whether or not their organizations would participate in a caHUB. NCI commissioned online discussion groups with executive-level decision makers at academic institutions with cancer research programs and pharmaceutical/biotechnology organizations. Across both groups, a clear need for a national caHUB was uniformly expressed. While having a broad range of biospecimens--especially those hard to obtain--in one location was important, stakeholders agreed that the level of standardization the caHUB could offer was the most important benefit. Stakeholders believed the development of standard operating procedures around collection, storage, and quality assessment of biospecimens would be the greatest contribution of the caHUB, allowing more collaboration and higher confidence in research results. Barriers to contribution and/or use of the caHUB focused on funding and resources required of participants, concerns over standard operating procedures, and impositions on their organizations' intellectual property. Findings from the qualitative research are consistent with previous research and point to an overwhelming need for a solution that will address growing concerns about access and availability of quality biospecimens to conduct cancer research and ultimately expedite future discoveries to treat and cure cancer.     

Present status and future perspectives of the regional referral clinical pathway of cancer in Kumamoto

Preparation of a system of community cooperation clinical pathway is called for by The Basic Act on Anti-Cancer Measures and The Basic Plans for National Cancer Strategy. Designated cancer care hospitals should play a very important role in constructing a local communication system among hospitals, clinics and nursing homes. In order to cooperate for seamless care of cancer, a notebook for patients with cancer has been made in Kumamoto by launching the Kumamoto Prefecture Regional Cooperation Conference of cancer management with the assistance of Kumamoto Prefectural government and the designated cancer care hospitals. This notebook consists of case information, treatment history, treatment goals, time schedule for cancer treatment, harmful phenomena due to cancer chemotherapy and counterplans for such side effects. This notebook will serve to improve comprehension and the attitude not only of patients, but also of co-medicals to cancer status and treatment. A physician approach and medical system are needed so that each patient can receive cooperative cancer treatment and care between hospitals and clinics.     

Enhancing a Cancer Prevention and Control Curriculum Through Interactive Group Discussions

The Principles and Practice of Cancer Prevention and Control course (Principles course) is offered annually by the National Cancer Institute Cancer Prevention Fellowship Program. This 4-week postgraduate course covers the spectrum of cancer prevention and control research (e.g., epidemiology, laboratory, clinical, social, and behavioral sciences) and is open to attendees from medical, academic, government, and related institutions across the world. In this report, we describe a new addition to the Principles course syllabus, which was exclusively a lecture-based format for over 20?years. In 2011, cancer prevention fellows and staff designed and implemented small group discussion sessions as part of the curriculum. The goals of these sessions were to foster an interactive environment, discuss concepts presented during the Principles course, exchange ideas, and enhance networking among the course participants and provide a teaching and leadership opportunity to current cancer prevention fellows. Overall, both the participants and facilitators who returned the evaluation forms (n?=?61/87 and 8/10, respectively) reported a high satisfaction with the experience for providing both an opportunity to explore course concepts in a greater detail and to network with colleagues. Participants (93?%) and facilitators (100?%) stated that they would like to see this component remain a part of the Principles course curriculum, and both groups provided recommendations for the 2012 program. The design, implementation, and evaluation of this initial discussion group component of the Principles course are described herein. The findings in this report will not only inform future discussion group sessions in the Principles course but may also be useful to others planning to incorporate group learning into large primarily lecture-based courses.     

Predicting clinical end points: treatment nomograms in prostate cancer

Due to the generally indolent nature of prostate cancer, patients must decide among a wide range of treatments, which will significantly affect both quality of life and survival. Thus, there is a need for instruments to aid patients and their physicians in decision analysis. Nomograms are instruments that predict outcomes for the individual patient. Using algorithms that incorporate multiple variables, nomograms calculate the predicted probability that a patient will reach a clinical end point of interest. Nomograms tend to outperform both expert clinicians and predictive instruments based on risk grouping. We outline principles for nomogram construction, including considerations for choice of clinical end points and appropriate predictive variables, and methods for model validation. Currently, nomograms are available to predict progression-free probability after several primary treatments for localized prostate cancer. There is need for additional models that predict other clinical end points, especially survival adjusted for quality of life.     

The changing landscape of breast cancer clinical research

Clinical research for breast cancer is moving in three new directions following: 1) a critical analysis of three decades of randomized clinical trials for early disease; 2) increasing awareness of this lethal disease among women, generating women's associations which are pressing for improved breast cancer education, screening and treatment; 3) an exponential growth in our understanding of breast cancer molecular biology, leading to a number of innovative therapies with new targets in the cancer cell or its environment.It is the remarkable work of the Oxford Group which has finally vindicated the use of our three main weapons against breast cancer micro-metastases, namely tamoxifen, chemotherapy and ovarian ablation. There is now consensus that clinical research in the adjuvant setting may gain speed and efficiency through intergroup collaboration. Such an 'Intergroup' has been recently created in Europe and will collaborate with the American–Canadian Intergroup.Women's associations have only recently stepped forward to demand better care, and more effective therapies: they are becoming new partners in identifying critical issues in breast cancer research.Medical oncologists involved in breast cancer research are facing a new challenge: the optimal integration of traditional breast cancer therapies, namely endocrine treatments and chemotherapy, and entirely new strategies targeting signal transduction, apoptosis or angiogenesis.In view of the above, there is no doubt that we are entering a new and exciting era in breast cancer clinical research.     

Pour le patient et ses proches,pour le soignant,l’épreuve psychique de la mort à vivre

In a discussion around clinical case studies, authors touch on the delicate end of life support for patients who are suffering. Alongside monitoring, the slow work in institutions, where professionals share their points of view, their doubts and their questions, enables the gradual development of situations that affect them, and for the large part, go beyond them. This work would appear to be vital to the care of patients, but also for providing balance for the care provider, who seek “motivation” so as not to find themselves isolated, and at the brink of a professional burnout.     

Concepts for clinical testing of biological agents exemplified for vaccines

Biologics are a heterogeneous group of substances with unique characteristics that are clearly distinguishable from classical cytotoxic drugs. Current concepts for clinical oncology drug development are mostly based on experiences obtained with cytotoxic agents and therefore do not (or not properly) account for several aspects that are crucial when it comes to the use of new biologics. This can lead to extreme cases where new substances that clearly bear a potential of antitumor efficacy do not reach needed levels of significance in clinical trials or are never introduced to advanced stages of clinical testing at all. In order to increase the number of biologics that can be successfully led through all phases of clinical development the currently established standards will have to be reconsidered and modified in such a way that they meet the specific needs of the tested biologics. It is important to mention that such an agent-specific adjustment of clinical development paradigms does not mean that the currently demanded high standards of safety and quality will have to be lowered by any means. The most striking arguments for a new clinical development paradigm are exemplified for therapeutic tumor vaccines but also hold true for related biologics.     

Epigenetic biomarkers of colorectal cancer: Focus on DNA methylation

The original theory of the multi-step process of colorectal cancer (CRC), suggesting that the disease resulted from the accumulation of mutations in oncogenes and tumor suppressor genes in colonic mucosa cells, has been largely revised following the observation that epigenetic modifications of several genes occur in the average CRC genome. Therefore, the current opinion is that CRCs are the consequence of the accumulation of both mutations and epigenetic modifications of several genes. This mini-review article focuses on DNA methylation biomarkers in CRC. Recent large-scale DNA methylation studies suggest that CRCs can be divided into at least three-four subtypes according to the frequency of DNA methylation and those of mutations in key CRC genes. Despite hundreds of genes might be epigenetically modified in CRC cells, there is interest in the identification of DNA methylation biomarkers to be used for CRC diagnosis, progression, tendency to tissue invasion and metastasis, prognosis, and response to chemotherapeutic agents. Moreover, DNA methylation largely depends on one-carbon metabolism, the metabolic pathway required for the production of S-adenosylmethionine, the major intracellular methylating agent. Complex interactions are emerging among dietary one-carbon nutrients (folates, vitamin B6, vitamin B12, methionine, and others), their metabolic genes, CRC risk, and DNA methylation profiles in CRC. Moreover, active research is also focused on the possible contribution of folic acid dietary fortification during pregnancy and the possible methylation of CRC-related genes in the offspring.     

P27kip1在结直肠癌中的表达及临床意义

Objective To investigate the significance of p27 expression in colorectal carcinomas (CRCs). Methods The samples were obtained from 44 cases. P27 expression was detected by immunohistochemistry using the SABC staining method at the three sites: carcinoma tissue, pericarcinoma (1 cm away from CRC) and the incision margin (3 cm away from CRC). Results Expression of p27 was found in 56.82% (25/44) of CRCs, in 88.64% (39/44) of percarcinoma and and in 97.73% (43/44) of the mucosa at the incison margin. P27 expression in CRCs was correlated significantly with Dukes stage (P<0.05), histology grade (P<0.01) and local lymph node involvement (P<0.05), but not with age, gender, and site or size of the CRC. Conclusion The decrease of p27 expression may be involved in the malignant transformation of colorectal epithelial cells to CRC. Expression of p27 in CRC correlates with some clinicopathological characteristics and may be of prognostic significance.     

Issues in clinical trial design for tumor marker studies

Scientific inquiry into the discovery, development, and application of tumor markers is proceeding rapidly. Despite this explosion in research and interest, the design of studies to formally assess the value of tumor markers in clinical practice is inconsistent and immature. Indeed, few markers have been widely accepted into standard clinical practice. Many issues must be prospectively considered in a methodical, systematic, and scientific fashion if progress is to be made in the development of validated tests that will have value in the management of patients with cancer. The purpose of this report is to present a discussion of the issues involved in designing clinical studies of putative tumor markers which provide sufficient data to result in the incorporation of the marker into clinical practice. We will focus on the design of studies to demonstrate and validate the clinical utility of both prognostic and predictive markers. Topics to be covered include issues of patient and sample heterogeneity, the prevalence of the marker, the sample capture rate, and the choice of endpoints. This will be followed by explicit consideration of study design, specifically the trial randomization schema for both prognostic and predictive factor studies.     

Précarité psychosociale et impact sur le cancer: pour une approche différentielle des logiques subjectives

Current clinical practice in public hospitals presupposes that encountered patients are often not included in a social network, with a poor, weakened, or even completely compromised economic background. It is mainly the case of institutions that bear a historical identity of “refuge hospital” such as our University Hospital Centre St-Pierre, Brussels, Belgium. We find patients who are isolated and/or exiled; in addition, illegal situation, drug addiction, and general negligence are frequently found in their history. These clinical patterns have been thus wholly removed from the social services that have been intended to provide. From a psychopathological point of view, it is patently clear that we see clinical variations, including psychosis (acutely progressive or well-compensated psychosis), that were previously handled by psychiatry or with a smoldering evolution (via social services, and sometime by the individual himself) as a problematic limiting factor from social integration point of view. In a work context, within the service of hematooncology, our research puts clinical practice to the test with a differential approach (for psychosis and neurosis) to attempt to identify variables following diagnostic practices in cancer patients. We present our theoretical and clinical orientation, from psychoanalytical and differential perspectives, as well as our methodology focusing on schizophrenia through the presentation of case studies.