Cancer vaccines in old age

The incidence of cancer has increased over the last decade, mainly due to an increase in the elderly population. Vaccine therapy for cancer is less toxic than chemotherapy or radiation and could be, therefore, especially effective in older, more frail cancer patients. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to T cell unresponsiveness, a phenomenon also observed in cancer patients per se. This review summarizes the current knowledge of T cell unresponsiveness in cancer patients and elderly, the results of cancer vaccination in preclinical models and in clinical trials, and recent data of cancer vaccination at young and old age in preclinical models. Finally, experimental approaches will be proposed how to make cancer vaccines more effective at older age.     

进展期胃癌的新辅助化疗

胃癌是我国最常见的恶性肿瘤之一。对于进展期胃癌,传统手术和术后化疗的临床疗效并不理想。近年来,人们主张对进展期胃癌进行以手术为主的综合治疗。术前新辅助化疗为胃癌综合治疗方法之一．其作用日益受到肯定。新辅助化疗可减低肿瘤负荷,降低临床分期,提高手术切除率。本文对进展期胃癌新辅助化疗的基本理论、临床应用和化疗药物的选择作一综述。     

Anemia in malignancies: Pathogenetic and diagnostic considerations

Abstract

Objectives

The aim of this paper is to review the pathogenesis and diagnostic approaches to anemia in cancer patients.

Methods

PubMed was queried for various combinations of anemia and cancer-related terms using appropriate filters for articles and practice guidelines published in the last 5 years. Specific searches were conducted for individual pathogenetic mechanisms and malignancies of specific anatomic sites.

Results

Anemia is the commonest hematological manifestation of cancer, afflicting 40–64% of patients treated for malignancies. Pathophysiologically, cancer-related anemia can be classified into four broad but overlapping categories: hypoproliferative anemia including the common anemia of inflammation/chronic disease, hemolytic anemia, miscellaneous etiologies, and uncertain etiologies. Anemia incidence increases with the administration of chemotherapy/radiotherapy. It reduces the quality of life and shortens survival in cancer patients. A positive correlation is observed between anemia and tumor hypoxia. Experimentally, hypoxemia enhances tumor growth and resistance to therapy by stimulating angiogenesis, acquisition of genomic mutations, and increasing resistance to apoptosis as well as to the killing effects of chemo/radiotherapy-generated free radicals.

Discussion

Diagnostic approaches to the anemic cancer patient begin with a detailed clinical history and physical examination. Peripheral blood morphology and reticulocyte count are also helpful. Patients with unexplained anemia are evaluated by standard approaches also used in patients of similar age without malignancy. Serum iron profile and bone marrow examination are often required in difficult cases. This review focuses on major aspects of the pathogenesis of the individual entities. Diagnostic approaches and uncommon causes including hemophagocytic lymphohistiocytosis, acquired hemoglobinopathies, and myelodysplasia are also discussed.     

Gastric cancer

Gastric cancer is one of the most common cancers and one of the most frequent causes of cancer-related deaths. The incidence, diagnostic studies, and therapeutic options have undergone important changes in the last decades, but the prognosis for gastric cancer patients remains poor, especially in more advanced stages. Surgery is the mainstay of treatment of this disease. At least D1 resection combined to removal of a minimum of 15 lymph nodes should be recommended. In recent years, important advances have been achieved in the adjuvant setting, where survival benefits were demonstrated by perioperative chemotherapy and postoperative chemoradiotherapy. In advanced disease, patient prognosis remains very poor with median survival times rarely approaching 1 year. In this setting, palliation of symptoms, rather than cure, is the primary goal of patient management. No standard regimens have yet been established worldwide. Recent clinical trials have demonstrated major improvements, which include the development of orally administered fluoropyrimidines (capecitabine, S-1), and the addition of new drugs such as docetaxel, irinotecan, oxaliplatin. This review summarizes the most important recommendations for the management of patients with gastric cancer.     

Ethical dilemmas in elderly cancer patients: a perspective from the ethics of care

In this article the authors have introduced specific characteristics of the increasingly large group of elderly cancer patients. They have argued that in order to provide good care we should extend our ethical awareness from issues of decision-making to a broader perspective focusing on the care relationship as developed by ethics of care principles. Cases like Mr. Michelson’s and Mrs Johnson’s show to what extent contemporary medicine is inclined to pursue its own goals of trying to do well, however taking the care receiver’s perspective into account too little. An ethics of care approach may help to be more attentive and responsive to the patient’s perspective. In the case of elderly cancer patients, being attentive and responsive to the patient’s perspective seems to be a major precondition for delivering good quality care attuned to the need, perspective, and vulnerable position of patients.     

Cancer prevention and the contribution of cancer registries

“Because they know what they do” should be the contribution of cancer registration to prevention. The public should be informed about the successes and failures of prevention. In addition, each doctor and each hospital should know the long-term results for its patients despite the complex interdisciplinary health care provision. At the same time, the regional results should be available and contrasted with clinical studies and international standards. An important criterion is also the quality of life of the patients, whose cooperation is more than overdue. According to the possibilities of prevention, six important levels can be differentiated. On each level the outcome should be evaluated on the basis of slightly differing criteria. Primary prevention has the largest incidence-, and thus, mortality-reduction potential, essentially caused by the giving up of smoking. However, the primary prevention of the tumor depends upon what kind of tumor it is, as primary prevention is possible to different extents. Often, secondary prevention is the earliest intervention possible, that is, the early detection of cancer in prognostically favorable stages. However, early detection only offers a chance of cure, albeit a smaller one, for some kinds of tumor. The third prevention level comprises primary care according to the state-of-the-art standards, followed by posttreatment care (disease-free phase) even when the disease is running a fatal course (palliative phase). In the terminal phase, adequate tumor-pain therapy and symptom-oriented measures stand for the sixth prevention level. Even the quality of life of the dying can be optimized. At the beginning of treatment at the latest, the quality of life should also be added to the outcome criteria. In this paper, the individual levels of prevention and possible evaluation criteria for successful prevention, which a modern cancer registration should submit, are discussed and examples given. If the evaluation of the quality of treatment and its significance for health care provision becomes the central tasks of the cancer registers, they will need to be transformed into service centers for hospitals, doctors, and patients. Received: 18 October 2000 / Accepted: 7 November 2000     

Management of Anal Canal Cancer

PURPOSE Chemoradiotherapy has replaced radical surgery as the initial treatment of choice for anal canal cancer. The roles of these therapeutic modalities are discussed and recommendations on management of anal canal cancer are made based on currently available evidence. Areas for further studies also are identified.METHODS Literature on management of anal canal cancer from January 1970 to July 2003 obtained via MEDLINE was reviewed. Reports on anal margin cancers were excluded.RESULTS Randomized, prospective, Phase 3 trials in Europe and the United States showed that chemoradiotherapy with 5-fluorouracil and mitomycin C was superior in local control, colostomy-free rate, progression-free survival, and cancer-specific survival compared with radiation alone. In larger tumors, the addition of mitomycin C to radiotherapy and 5-fluorouracil improves local control, colostomy-free, and disease-free survival but is associated with more acute hematologic toxicity. Chemoradiotherapy, including Cisplatin and 5-fluorouracil, appeared to be equal or superior to surgery as salvage therapy in patients with residual disease six weeks after initial nonsurgical treatment.CONCLUSIONS To improve treatment outcomes and reduce treatment-related toxicities, further studies are required to elucidate the optimal drug combination and doses, optimal radiation field, total dose, and fraction sizes. Randomized, multicenter trials are needed to define the treatment protocol that provides the highest rate of sphincter preservation with acceptable toxicity. Few studies addressed the treatment of metastatic disease, which remains a major cause of mortality.     

慈丹胶囊在肝癌化疗放疗中的协同作用

目的;观察中成药慈丹胶囊在肝癌化疗、放疗中的作用。方法：将５４例经剖腹探查判定不可手术切除Ⅱ期的原发性肝癌分为两组,其中动脉化疗＋放疗＋慈 丹胶囊组２９例（治疗Ａ组）,仅动脉化疗＋放疗组２５例（对照Ｂ组）。结果：治疗组肝区疼痛减轻率、腹胀减轻率、近期有效率、１年生存率分别为９２％、８９．３％、７２．４％、９３．１％,分别高于对照组,Ｐ均〈０．０５。结论：慈丹胶囊与放疗、化疗并用,可望提高其疗效。     

Erythropoietin Response Is Inadequate in Cancer Patients Receiving Chemotherapy

The level of serum erythropoietin (EPO) is inappropriately decreased in cancer patients and has been advocated as the main cause of their anemia. In cancer patients, chemotherapy results in a cumulative anemia severe enough to require transfusion. We investigated the changes in serum EPO, hemoglobin, ceruloplasmin, and copper levels in cancer patients receiving chemotherapy. There was a weak but significant inverse relationship between hemoglobin and log[EPO] (r = -0.41; P < .001). Observed/expected serum EPO ratios decline with repeated chemotherapy indicating inadequate EPO response for the degree of anemia. There was no difference in the severity of anemia and in the degree of EPO response between platinum- and non-platinum-treated patients. Ceruloplasmin, copper, and ferritin levels did not change during chemotherapy. Our results suggest that the EPO response is inadequate for the degree of anemia and justifies the use of recombinant human EPO in cancer patients receiving chemotherapy.     

A review of latest clinical practice guidelines for the management of cancer-associated thrombosis

The management of cancer-associated thrombosis (CAT) poses unique challenges to healthcare professionals. While low‐molecular weight heparins (LMWHs) have long been the gold standard for both the primary and secondary prevention of CAT, results from large randomized controlled trials assessing the benefit of direct oral anticoagulants (DOACs) in both settings have resulted in some paradigm shifts. Herein, we review and compare recommendations from the latest authoritative clinical practice guidelines (CPGs) for the management of CAT and summarize the most recent evidence on available treatment options. A rigorous methodology was used to select high quality CPGs and compare the recommendations across CPGs. Only CPGs focusing on the management of CAT developed by a multidisciplinary international working group and issued or endorsed by national or international scientific societies, or government organizations were eligible for inclusion. The quality of selected CPGs was assessed using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) tool. Four CPGs met the inclusion criteria, including the International Initiative on Thrombosis and Cancer (ITAC), the American Society of Clinical Oncology (ASCO), the American Society of Hematology (ASH), and the National Comprehensive Cancer Network (NCCN).     

FAM方案经皮门静脉注射治疗晚期肝癌

在B超引导下经皮门静脉注射化疗药物(ADM、MMC、5FU)治疗晚期肝癌共4例,最长观察时间为11个月,无腹水及黄疸出现.推测该法对降低门静脉压力,控制门静脉癌栓形成有一定疗效.本文对经皮门静脉注射的方法、适应症及疗效机理进行了讨论.     

Brief intervention for female heavy drinkers in routine general practice: a 3-year randomized, controlled study

BACKGROUND: Today, heavy drinking is a common health hazard among women. The evidence in favor of providing some kind of brief intervention to reduce drinking is quite convincing. However, we do not know if intervention works in a natural environment of routine health care. The purpose of this study was to evaluate the effectiveness of long-lasting, brief alcohol intervention counseling for women in a routine general practice setting. METHODS: In five primary care outpatient clinics in a Finnish town, 118 female early-phase heavy drinkers who consulted their general practitioners for various reasons were given brief alcohol intervention counseling. Intervention groups A (n = 40) and B (n = 38) were offered seven and three brief intervention sessions, respectively, over a 3-yr period. The control group C (n = 40) was advised to reduce drinking at baseline. Main outcome measures were self-reported weekly alcohol consumption, carbohydrate-deficient transferrin, mean corpuscular volume (MCV), aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase. RESULTS: Depending on the outcome measure and the study group, clinically meaningful reduction of drinking was found in 27% to 75% of the heavy drinkers. Within all the groups, MCV significantly decreased. However, there were no statistically significant differences between study groups A, B, and C in the mean changes between the beginning and endpoint in the main outcome measures. CONCLUSIONS: The present study indicated that minimal advice, as offered to group C, was associated with reduced drinking as much as the brief intervention, as offered to groups A and B, given over a 3-yr period. Furthermore, in the routine setting of the general practice office, the effectiveness of the brief intervention may not be as good as in special research conditions. The factors possibly reducing the effectiveness in a routine setting are unknown. Thus, different methods of implementing brief intervention need to be evaluated to find better ways to support general practice personnel in their efforts to help heavy-drinking female patients to reduce their drinking.     

Attitudes and intentions of UK general practitioners to diabetes care at the time of implementation of their new contract.

Prior to the introduction of their new contract, the intentions of general practitioners in Leeds (UK) towards diabetes care were assessed. All general practices in one Health District (n = 74) were contacted. Assessment was made of 46 (62%), while 28 expressed lack of interest. Of the 46 assessed, 2 (4%) were single-handed, and 44 (96%) were group practices, and list size was 700-15,500. Practice nurses were employed in 44 (96%) practices. There were 35 (76%) practices which expressed an interest in starting a diabetic clinic, while 6 (13%) had established a clinic. Practice facilities necessary to establish and run a clinic were surveyed. Those available were: register of diabetic patients in 12 (26%) (six of which were incomplete); blood sampling facilities in 45 (98%); blood glucose reagent strips in 45 (98%); glucose meters in 21 (46%) (but five with inappropriate test strips). All practices could check urine, blood pressure, and fundi (dark room available in 40 (87%) practices). Access to dietetic and chiropody services on the premises was available in 19 (41%) and 17 (37%) practices, respectively. Some expertise in diabetes was claimed by only 10 (22%) doctors. Staff at all practices desired further training in diabetes. In conclusion, despite the interest of most practices in starting a diabetic clinic, access to dietetic and chiropody services was inadequate. Expertise was generally lacking, but enthusiasm and desire for training were strong.