Cancer and venous thromboembolism: a multidisciplinary approach

In this paper, we briefly review the relation between cancer and venous thromboembolism (VTE), an association that has been recognized for more than a century. In particular we focus on VTE as predictor and prognostic factor for cancer and the antineoplastic potential of antithrombotic treatment. Cancer may cause disturbances in the haemostatic system by numerous mechanisms that can lead to an increased risk of VTE. Patients with known cancer are at increased risk of VTE; however, VTE may also be a predictor of subsequent cancer in the years afterwards. Furthermore, cancer patients with VTE are more likely to have advanced disease and a worse prognosis than cancer patients without a VTE episode. These findings may have implications for the clinical care of patients with VTE in terms of screening for cancer. However, extensive cancer screening programs are not recommended in general for patients with VTE. A wide range of antithrombotic drugs including heparin, oral anticoagulants, and platelet inhibitors have been examined in order to study the effect on the prevention and treatment of various cancers. These efforts have resulted in a considerable amount of useful data from animal models and a number of promising reports from retrospective analyses and small-scale trials linking antithrombotic treatment with an increased survival in cancer patients and even a lower risk of primary cancer. However, the clinical implications of these findings must await properly designed and conducted randomized clinical trials.     

Optimising adjuvant endocrine treatment of breast cancer with aromatase inhibitors

There is mounting evidence that aromatase inhibitors (AIs) are superior to tamoxifen as adjuvant treatment for postmenopausal women with oestrogen receptor positive breast cancer. Nevertheless, tamoxifen still remains a useful and relatively nontoxic treatment, and further work is necessary to determine which patients need an AI. In terms of cost-effectiveness, letrozole has been estimated to be superior to tamoxifen. Anastrozole, letrozole and exemestane have not been compared directly in an adjuvant setting but letrozole proved superior to anastrozole in patients with advanced breast cancer. Although tumour receptor phenotype may be useful in selection for tamoxifen or AI, the evidence is mixed. Optimal sequencing and duration of treatment have yet to be determined. If nationally funded and organised trials could be instigated, these would give timely and reliable data, so that adjuvant endocrine treatment of breast cancer could be tailored to needs of the individual patient.     

Metastatic breast cancer manifested as refractory anemia and gastric polyps

Gastric metastasis from breast cancer is uncommon and typically occurs in patients with disseminated disease. The vast majority of patients with gastric lesions have a known preexisting diagnosis of breast cancer. In contrast, we describe a case in which a minimal breast cancer was found to be the primary tumor during the workup of a patient first diagnosed with carcinoma of unknown primary and subsequently presumed to have metastatic gastric cancer. Our case illustrates that a diagnosis of breast cancer metastatic to the stomach may require a high index of suspicion, as well as a meticulous breast workup. It also emphasizes that even tiny breast cancers have a small but real risk of metastatic spread. Determination of the correct primary source in these cases may not be only an academic exercise, since the treatment and prognosis of metastatic breast cancer (especially receptor positive) and metastatic gastric cancer are different.     

Symptom management issues in oncology nursing

Symptoms experienced by patients with cancer can occur as a direct effect of the disease process and be related to side effects of treatment. Many patients with cancer also are older in age and have comorbidities, such as diabetes and heart disease. Comorbid conditions also produce disease and treatment-related symptoms that may have an independent or compounding effect on cancer-related symptoms.     

Advances in oncology care: targeted therapies

The start of the 21st century has produced advances in cancer care that have improved both survival rates and quality of life for many persons diagnosed with cancer. Targeted therapy has given new hope for controlling cancer as a chronic illness. Alone, or in combination with traditional therapies such as surgery, radiation, and/or chemotherapy, this new form of therapy targets malignant cells, halting tumor growth and the potential metastatic spread of disease. Toxicities are limited, but some are serious and may require intensive care. It is imperative for the experienced critical care nurse to have an understanding of these new treatment options and those on the horizon, as these therapies are the future of cancer care. Whereas in previous decades, patients with cancer may not have survived an intensive care admission for treatment complications or advanced disease, many patients now are recovering from life-threatening events, continuing treatment for their disease, and going on to live meaningful, good-quality lives.     

Cancer pain and depression: management of the dual-diagnosed patient

Depressive disorders and pain syndromes are very common in the experience of cancer patients and may be experienced simultaneously. There is an intuitive association between cancer pain and cancer depression, both of which are multidimensional entities. Research has suggested, but not conclusively proven a cause-effect relationship. Suicidal ideation is a common concern in cancer patients with severe depression or pain. Antidepressant therapy is a mainstay of management of depression. That some antidepressants have use in the management of cancer pain may influence choice of drug selection in depressed patients. Antidepressant side effects and the patient’s drug history are relevant variables. Because antidepressants that are effective as coanalgesics may not be tolerated at doses effective for depression, the clinician must be familiar with newer classes of antidepressants and psychostimulants. Combination drug therapy may be required. Psychotherapy also is common to the treatment of cancer pain and depression. With or without the intervention of pain and mental health specialists, ongoing supportive therapy from the primary clinician is essential.     

Prevention and treatment of osteoporosis in women with breast cancer

Women who have had breast cancer may be at higher risk for osteoporosis than other women. First, they are more likely to undergo early menopause, due to chemotherapy-induced ovarian failure or oopherectomy. In addition, chemotherapy may have a direct adverse effect on bone mineral density (BMD), and osteoclastic activity may increase from the breast cancer itself. While estrogen therapy is considered standard for the prevention and treatment of osteoporosis, use of estrogen in women with a history of breast cancer is usually contraindicated. The approach to osteoporosis in women with breast cancer is also affected by the use of tamoxifen in many, as this drug appears to have opposite effects on BMD in premenopausal and postmenopausal women. We have reviewed therapeutic alternatives for the prevention and treatment of osteoporosis, focusing on patients with a history of breast cancer. Alendronate and raloxifene are currently approved in the United States for the prevention of osteoporosis; alendronate, raloxifene, and calcitonin are approved for treatment. Alendronate has the greatest positive effect on BMD and reduces the incidence of vertebral and nonvertebral fractures. Raloxifene and calcitonin appear to reduce the incidence of vertebral fractures; their effects on the incidence of nonvertebral fractures are not yet proven. Although no published studies specifically address the use of these approved agents for osteoporosis in women with breast cancer, understanding their relative effects on BMD in postmenopausal women in general will facilitate therapy selection in this population. Postmenopausal women with a history of breast cancer should undergo bone mineral analysis. Normal results and absence of other risk factors ensure that calcium and vitamin D intake are adequate. If osteopenia or other risk factors are present, preventive therapy with alendronate or raloxifene should be considered. For osteoporosis, treatment with alendronate should be strongly considered. Raloxifene and calcitonin are alternatives when alendronate is contraindicated. Further studies are needed to evaluate the optimal timing of initial bone mineral analysis in premenopausal women after breast cancer diagnosis and to determine the value of preventive treatment in women scheduled to undergo chemotherapy.     

Gene therapy for cancer treatment: past, present and future

The broad field of gene therapy promises a number of innovative treatments that are likely to become important in preventing deaths from cancer. In this review, we discuss the history, highlights and future of three different gene therapy treatment approaches: immunotherapy, oncolytic virotherapy and gene transfer. Immunotherapy uses genetically modified cells and viral particles to stimulate the immune system to destroy cancer cells. Recent clinical trials of second and third generation vaccines have shown encouraging results with a wide range of cancers, including lung cancer, pancreatic cancer, prostate cancer and malignant melanoma. Oncolytic virotherapy, which uses viral particles that replicate within the cancer cell to cause cell death, is an emerging treatment modality that shows great promise, particularly with metastatic cancers. Initial phase I trials for several vectors have generated excitement over the potential power of this technique. Gene transfer is a new treatment modality that introduces new genes into a cancerous cell or the surrounding tissue to cause cell death or slow the growth of the cancer. This treatment technique is very flexible, and a wide range of genes and vectors are being used in clinical trials with successful outcomes. As these therapies mature, they may be used alone or in combination with current treatments to help make cancer a manageable disease.     

Venous thromboembolism in patients with cancer. Part II. Current treatment strategies

Patients with cancer have an increased risk of thromboembolism. This complication is connected to a variety of different factors and is influenced by the conditions described in Virchow's triad: stasis, vascular endothelial damage, and hypercoagulability. Once thromboembolism is diagnosed, treatment in patients with cancer usually involves anticoagulation with unfractionated or low-molecular-weight heparin and progression to oral anticoagulant therapy. Duration of treatment is usually three to six months, with most patients receiving six months of anticoagulation. Patients with cancer may be at risk for recurrent thrombosis as well, despite optimal use of oral anticoagulant therapy, and some of these patients may require lifelong heparin therapy. This article describes the current treatment regimens to provide anticoagulation therapy to patients with cancer, including a discussion of the low-molecular-weight heparins and dosing parameters. Nursing interventions to help provide these treatments safely are discussed. Patients with cancer have a high rate of thromboembolism; oncology nurses should heighten their awareness of this important complication, treatment options, and appropriate nursing interventions.     

The older cancer patient

Providing effective and tolerable cancer treatment for the growing number of older adult patients who have cancer requires an understanding of the role of aging, comorbidity, functional status, and frailty on treatment outcomes. The incorporation of comprehensive geriatric assessment (CGA) into the care of older patients who have cancer ensures that the cognitive, physical, and psychosocial strengths and limitations of individual patients are considered in the development of treatment plans. CGA also may improve outcomes by identifying and optimally treating comorbid conditions and functional impairments. Optimal treatment of the older adult patient who has cancer starts with careful delineation of goals through conversation. The treatment plan should be comprehensive and address cancer-specific treatment, symptom-specific treatment, supportive treatment modalities, and end-of-life care.     

Methodological challenges of symptom management research in recurrent cancer

Completion of first-line treatment is an important milestone for adults newly diagnosed with cancer. However, for many adults, the cancer experience of the 21st century does not end with the completion of initial treatment. Decreased functional status, distressing symptoms, and residual effects of treatment impact the daily lives of cancer survivors. Cancer has evolved into a chronic illness, in which a disease-free period may be followed by recurrent cancer. Researchers face challenges in the design and analysis of symptom management studies in recurrent disease. Residual effects can preclude a true "baseline" measurement of the symptom(s) of interest to the researcher. In addition, as cancer survivors age, they are more likely to have comorbid conditions that increase the likelihood of developing toxicities and residual symptoms that are specific to cancer treatments. Research studies of cancer-related symptoms in adults with recurrent disease pose many methodological challenges. Selection of appropriate study design, sample inclusion and exclusion criteria, measures of comorbidity and symptoms, and advanced analysis techniques are among the strategies proposed to address these methodological challenges.     

Modulation of oral cancer and periodontitis using chemotherapeutic agents - A narrative review

Periodontitis, an inflammatory condition, is linked to a higher risk of developing oral cancer. Periodontitis may be a precipitating factor for tumorigenesis and the aggressiveness of specific cancer variants. Although genetics is considered the primary etiologic factor for the development of most cancers, many factors have come to be recognized in the initiation and progression of oral cancer. Consecutively, it is suggestive that periodontitis and oral cancer are distinct disease entities but share common pathogenic mechanisms. Oxidative stress and epigenetic mechanisms are among the most researched mechanisms responsible for initiating apoptotic mechanisms implicated in periodontitis and oral cancer. Current research aims to formulate therapeutic agents to intercede in these mechanisms via host modulation therapy and epigenetic therapy. These advances can revolutionize the treatment of periodontitis and oral cancer. This review aims to shed light on the common pathogenic mechanisms of these diseases and the various host modulation agents that could be beneficial in their treatment.     

Insulin analogues and cancer risk: cause for concern or cause célèbre?

People with diabetes, particularly those with type 2 diabetes, may be at an increased risk of cancer. Furthermore, their cancer risk may be modified by treatment choices. In this respect, metformin may be protective, whereas insulin and insulin analogues can function as growth factors and therefore have theoretical potential to promote tumour proliferation. Analogues causing inappropriate prolonged stimulation of the insulin receptor, or excess stimulation of the IGF‐1 receptor, are the most likely to show mitogenic properties in laboratory studies. Some recent epidemiological studies appear to be consistent with these experimental findings, suggesting that there could be different relative risks for cancer associated with different insulins, although these studies have attracted some methodological criticism. However, it is biologically plausible that hormonal factors that influence neoplasia could begin to manifest their effects in surprisingly short timescales (within 2 years) and hence these epidemiological studies justify further research. Even if future research were to document an increase in cancer risk among insulin users, this would be unlikely to significantly diminish the favourable benefit‐risk ratio for patients requiring insulin therapy. There is a need for further population studies and for the development of new laboratory models that are more sophisticated than previous experimental methods employed to assess potential tumour growth‐promoting properties of insulins.     

Pharmacological Treatment of Neuropathic Cancer Pain: A Comprehensive Review of the Current Literature

Abstract: Neuropathic cancer pain (NCP), commonly encountered in clinical practice, may be cancer‐related, namely resulting from nervous system tumor invasion, surgical nerve damage during tumor removal, radiation‐induced nerve damage and chemotherapy‐related neuropathy, or may be of benign origin, unrelated to cancer. A neuropathic component is evident in about 1/3 of cancer pain cases. Although from a pathophysiological perspective NCP may differ from chronic neuropathic pain (NP), such as noncancer‐related pain, clinical practice, and limited publications have shown that these two pain entities may share some treatment modalities. For example, co‐analgesics have been well integrated into cancer pain‐management strategies and are often used as First‐Line options for the treatment of NCP. These drugs, including antidepressants and anticonvulsants, are recommended by evidence‐based guidelines, whereas, others such as lidocaine patch 5%, are supported by randomized, controlled, clinical data and are included in guidelines for restricted conditions treatment. The vast majority of these drugs have already been proven useful in the management of benign NP syndromes. Treatment decisions for patients with NP can be difficult. The intrinsic difficulties in performing randomized controlled trials in cancer pain have traditionally justified the acceptance of drugs already known to be effective in benign NP for the management of malignant NP, despite the lack of relevant high quality data. Interest in NCP mechanisms and pharmacotherapy has increased, resulting in significant mechanism‐based treatment advances for the future. In this comprehensive review, we present the latest knowledge regarding NCP pharmacological management.     

Ways of understanding the encounter with head and neck cancer patients in the hospital dental team—a phenomenographic study

Introduction Head and neck cancer is the sixth most common malignancy in the world. Fifty percent of the patients can be cured by surgery, radiotherapy or a combination approach. Head and neck cancer is life-threatening, and treatment may leave the patient with visible facial disfigurements and impairment of functions such as speech and eating. This affects not only the patient, but may arouse difficult feelings in the treatment staff. Dental personnel are involved in all facets of treatment, yet they have no specific training in cancer care.Background The aim of this study was to describe the variation in ways dental personnel understand and experience the encounter with head and neck cancer patients, as the way of understanding a certain phenomenon is judged to be fundamental to the way we act and form our beliefs.Methods Twenty members of hospital dental teams were interviewed. The interviews focused on experiences of the encounter with head and neck cancer patients. A qualitative research approach, phenomenography, was used in analysing the interviews. The encounter was perceived in three qualitatively different ways: as an act of caring, as a serious and responsible task and as an overwhelming emotional situation. The results indicate that hospital dental personnel are not able to lean on education and professional training in finding ways of dealing with situations with strong emotional impact. This has implications for the treatment of patients with head and neck cancer, as well as education of dental personnel.     

Cancer Pain Emergencies: Is There a Role for Radiation Therapy?

Emergent cancer pain is a difficult entity to manage. Radiation therapy potentially may be used for its treatment. Several key issues must be addressed in patients with emergent cancer pain before initiating radiation. These issues include whether the necessary diagnostic information is available, whether the tumor will respond rapidly to radiation, and whether there are additional patient factors that will affect treatment. If these questions have been addressed, it is more likely that a successful outcome will be obtained if radiation therapy is used for the management of emergent cancer pain.     

Sphincter preservation therapy for rectal cancer

Rectal cancer presents a unique challenge to oncologists and patients due to the location and anatomy of the rectum and the difficulties inherent in pre-operative staging. These issues are especially important with distal rectal tumors when patients may face the decision of tumor control without sphincter preservation or more limited surgical procedures that may potentially compromise tumor control and thus survival. Current options for sphincter preservation for low-lying rectal tumors are preoperative radiotherapy with or without chemotherapy for tumor downstaging, local excision with or without adjuvant chemoradiation and low anterior resection with coloanal anastomosis. Pretreatment evaluation, by radiologic studies and pathologic predictors of lymph node involvement, is an integral part of determining which patients are suitable candidates for treatment with local excision. Preoperative chemoradiotherapy is a treatment option for some patients who are not initially considered to be candidates for sphincter preservation. Many investigators have suggested that the rate of sphincter preservation in patients with rectal cancer may be improved following preoperative chemotherapy and radiation. For properly selected patients, local excision holds promise as a means of achieving sphincter preservation.     

Feasibility of exercise during treatment for multiple myeloma

Fatigue and insomnia are problems for patients with cancer. Research findings show that aerobic exercise decreases cancer-related fatigue. Because patients with cancer who have skeletal muscle wasting may not obtain maximum benefit from aerobic exercise training, exercise programs may need to include resistance training. Thus far, testing exercise as an intervention for fatigue has focused on patients with breast cancer and excluded patients with bone metastasis. There is a need to test the feasibility and effectiveness of exercise for patients with other types of cancer and with bone involvement. The effect of aerobic and strength resistance training on the sleep of patients with cancer has not been tested. A pilot/feasibility study with a randomized controlled design was conducted to investigate home-based exercise therapy for 24 patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation as treatment for multiple myeloma. None of the patients injured themselves. Because of the small sample size in the feasibility study, the effect of exercise on lean body weight was the only end point that obtained statistical significance. However, the results suggest that an individualized exercise program for patients receiving aggressive treatment for multiple myeloma is feasible and may be effective for decreasing fatigue and mood disturbance, and for improving sleep.     

NSAIDs and breast cancer: a possible prevention and treatment strategy

CONTEXT: Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and thereby reduce prostaglandin synthesis. Abnormally upregulated COX and prostaglandins are features of breast cancer so NSAIDs might have a role in treatment and prevention of the disease. OBJECTIVE: To review the available epidemiological data on the relation between NSAIDs and risk of breast cancer together with interventional studies in established disease. RESULTS: Both case-control and cohort studies indicate a moderate reduction in risk of breast cancer among women taking NSAID particularly aspirin. There may be a reduction in oestrogen receptor positive tumours in aspirin users but results are heterogeneous. It is not possible to estimate the dose-response effect for duration of use. In patients with breast cancer, aspirin increased levels of serum nitric oxide (NO) and maspin both of which inhibit growth of breast cancer cells in vitro. Furthermore, a reduced breast cancer and all-cause mortality has been reported in those taking NSAIDs after diagnosis. The cyclooxygenase 2 (COX-2) inhibitor celecoxib showed promising preliminary efficacy and acceptability in combination with exemestane in advanced breast cancer although cardiotoxicity led to discontinuation of celecoxib in a prevention trial for individuals with colonic polyps. CONCLUSIONS: NSAIDs may reduce breast cancer risk by 20% but the optimal type, dose and duration is still undetermined together with the feasibility of such an intervention in an at risk population. There may be a role for NSAIDs in combination with endocrine therapies as either an adjuvant or palliative treatment for women with established breast cancer.     

Anorexia: a taste of things to come?

Anorexia, the loss of the desire to eat, is common in patients with cancer. Studies report a prevalence of up to 66% and clinical practice suggests that it is an almost universal experience as the cancer progresses. It generally leads to a reduction in food intake that contributes to the development of malnutrition and cachexia, impairing quality of life and increasing morbidity and mortality. Successful curative or palliative treatment of the underlying cancer is an effective approach. When this is not possible, there are limited treatment options, which generally have not been shown to be practicable, tolerable, effective or safe in the long-term management of the cachexia-anorexia syndrome. Recent increases in the understanding of the physiology of energy intake and of the pathophysiology of anorexia are helping to guide the development of rational approaches. This journal club provides an outline of the pathophysiology of anorexia and highlights a paper that may provide an exciting glimpse of the future.