Showing papers in "Hematology-oncology Clinics of North America in 2000"

Aging and cancer in America. Demographic and epidemiologic perspectives.

Abstract: It has been stated in this article and elsewhere that cancer patients aged 65 years and older deserve special attention as a target group for research efforts across the cancer-control spectrum. The available data show that the vulnerability of older persons to cancer is unmistakable. Clinicians will be treating more older patients as the nation ages. The future needs of this segment of the population must be anticipated. In this context, the following generic treatment questions are pertinent. What are the peculiarities of the aged host of which clinicians must be aware in evaluating the older cancer patient? Do various forms of cancer present differently in the elderly? How can be complications caused by the multiple pathologies inherent in the older patient be anticipated? What are the potential hazards and limitations of surgery, radiotherapy, and chemotherapy for older persons with cancer? What is known regarding increased risk of adverse reactions to medications, drugs, and interaction of drugs in older patients? The surveillance data and population estimates and projections presented in this article illustrate the extent of the problems of cancer in the elderly at the macro level. For the individual patient, the special knowledge of aging individuals and their health status based on geriatric medicine and gerontology that has been accumulating for the past several decades needs to be incorporated into the oncology armamentarium that has developed during the same period. The information and expertise from both fields must converge, and new knowledge must be developed at the aging/cancer interface and applied for the optimal treatment of cancer in the elderly.

Treatment of Adult ALL according to protocols of the German Multicenter Study Group for Adult ALL (GMALL)

Abstract: Since 1978 more than 4500 adult ALL patients have been treated according to the protocols of the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL). GMALL protocols are administered in hospitals all over Germany and the number of participating centers in Germany increased from 25 in 1981 to 120 in the most recent trial. Up to now seven consecutive trials for adult de novo ALL have been conducted. The major aim of all trials was the improvement of remission duration and survival of adult ALL patients, detailed diagnostic characterization, the development of prognostic models and the evaluation of risk-adapted, individualized and targeted treatment strategies. The time-periods and further aims of these studies are briefly summarized in Table 13.1.

Cancer and aging. An evolving panorama.

Abstract: This article illustrates how the nosology of cancer evolves with the patient's age. If the current trends are maintained, 70% of all neoplasms will occur in persons aged 65 years and over by the year 2020, leading to increased cancer-related morbidity among older persons. Cancer control in the older person involves chemoprevention, early diagnosis, and timely and effective treatment that entails both antineoplastic therapy and symptom management. These interventions must be individualized based on a multidimensional assessment that can predict life expectancy and treatment complications and that may evaluate the quality of life of the older person. This article suggests a number of interventions that may improve cancer control in the aged. Public education is needed to illustrate the benefits of health maintenance and early detection of cancer even among older individuals, to create realistic expectations, and to heighten awareness of early symptoms and signs of cancer. Professional education is needed to train students and practitioners in the evaluation and management of the older person. Of special interest is the current initiative of the Hartford Foundation offering combined fellowships in oncology and geriatrics and incorporating principles of geriatric medicine in medical specialty training. Prudent pharmacologic principles must be followed in managing older persons with cytotoxic chemotherapy. These principles include adjusting the dose according to the patient's renal function, using epoietin to maintain hemoglobin levels of 12 g/dL or more, and using hemopoietic growth factors in persons aged 70 years and older receiving cytotoxic chemotherapy of moderate toxicity (e.g., CHOP). To assure uniformity of data, a cooperative oncology group should formulate a geriatric package outlining a common plan for evaluating function and comorbidity. This article also suggests several important areas of research items: Molecular interactions of age and cancer Host-tumor interactions in the older tumor host Chemoprevention of cancer and aging Laboratory evaluation of aging Development of shorter forms of geriatric assessment Management of the frail cancer patients Clinical trials of tumor-specific issues.

A BRIEF HISTORY OF THE RANDOMIZED CONTROLLED TRIAL: From Oranges and Lemons to the Gold Standard

Abstract: This article discusses the history and development of randomized clinical trial methodology, the reasons for its status and authority as a method of therapeutic evaluation, and the continuing role of clinical judgement in designing, interpreting, and applying the findings of trials.

Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation. A follow-up report of the French protocol LALA 87.

Abstract: The French protocol LALA 87 was designed to compare three different postinduction strategies in adult acute lymphocytic leukemia (ALL): chemotherapy, autologous transplantation, and allogeneic transplantation. This trial demonstrated a significant superiority of allogeneic bone marrow transplantation (BMT) in high-risk ALL patients. Similarly, there was a trend in favor of autologous BMT over chemotherapy in those same patients. Allogeneic BMT was not superior to autologous BMT or chemotherapy in less aggressive leukemia (standard-risk ALL). Further improvements are warranted in the treatment of adult ALL. The authors' current ongoing study is stratifying patients to allocate them to regimens with risk-adapted treatment intensity.

The family caregiver of the older cancer patient

Abstract: It is estimated that in 1999 about 1,221,800 new cases of invasive cancer will be diagnosed in the United States, and approximately 563,100 people are expected to die of cancer. 32 More than 60% of all cases of cancer occur in persons aged over 65 years, and the cancer mortality rate in those aged over 55 years has increased by 17%. 22 Families usually prefer to care for disabled relatives themselves, and older adults with chronic disease and disability usually want to remain in their homes, 15 where they can have a comfortable environment, maintain a normal life, and have access to family and friends. In recent years, shortened hospital stays and expanded outpatient care services for patients receiving adjuvant cancer treatment have further shifted the caregiving responsibility from health care professionals to the patients' families. 30 Limited community services and the financial pressure associated with hospital and nursing home care also lead family members, particularly spouses and adult daughters, to assume caregiver roles. Family caregiving for older adults with cancer is the result of both demographic and health care delivery changes. Cancer causes changes in the family's identity, roles, and daily functioning, and the effect of such changes may be profound and long-lasting, regardless of the outcome of the disease. 3 Despite the benefits of home care in cost-saving and convenience, family caregivers must deal with many unfamiliar situations and unexpected demands throughout the treatment and progress of the disease. Because caregiving may lead to hidden costs of care (negative effects experienced by the family members), attention to caregiving issues is important in understanding how this major, unpaid component of the health care and long-term care system works and what can be done to minimize the burdens of caregiving. 15 Family involvement is also essential for the successful, comprehensive care of geriatric oncology patients; caregivers must work closely with doctors to monitor the patients' disease status, assist patients with self-care, and implement treatment regimens. With improvements in cancer diagnosis, treatment, and palliative care, cancer patients survive longer, and the length of the caregiving period has extended from days or weeks to months or years. The chronic yet progressive nature of this illness suggests that caregivers of cancer patients must face various challenges in different stages of the disease and with different levels of treatment. Greater psychosocial problems may arise when cancer metastasizes, 51 and the terminal phase, with the impending bereavement period, sees the peak impact. 15 Although one study found a moderate feeling of preparedness in spouses of recently diagnosed elderly cancer patients, 50 family caregivers also expressed unmet needs for social, volunteer, and professional support as their own physical and emotional health suffered. 61 More research is needed to document the specific issues involved in family caregiving for older patients with cancer.

Gastrointestinal abnormalities and involvement in systemic mastocytosis

Abstract: Recent studies have shown that involvement of the gastrointestinal tract is much more frequent than originally reported in patients with systemic mastocytosis. Seventy percent to 80% of patients with systemic mastocytosis are found to have gastrointestinal symptoms when a careful history is taken, and abnormalities in the gastrointestinal tract are frequently detected by endoscopic studies, functional studies of absorption, and barium studies. Because of the rarity of the disease, there are few prospective studies of gastrointestinal involvement, so the actual frequency of upper and lower gastrointestinal lesions is unknown. Furthermore, there have been no studies correlating endoscopic abnormalities of the lower gastrointestinal tract with the presence or absence of diarrhea, which is a frequent symptom (mean, 43% [range 14%-100%]). A review of gastric acid studies reveals that a proportion of patients develop gastric acid hypersecretion because of the hyperhistaminemia, which can result in ulcer disease that in turn can cause dyspeptic pain, small intestinal mucosal damage, and malabsorption. In some patients gastric acid hypersecretion in the range seen in Zollinger-Ellison syndrome can develop. A number of studies suggest that the prevalence of peptic ulcer disease has been underestimated in these patients and is certainly higher than the general population. The exact physiologic basis for the diarrhea or nondyspeptic abdominal pain remains largely unknown in these patients. Whereas some studies suggest small intestinal mucosal abnormalities are responsible for most cases of malabsorption not associated with gastric acid hypersecretion, this supposition also remains unproven. Hepatomegaly, portal hypertension, splenomegaly, and ascites occur frequently in patients with systemic mastocytosis, especially those with category II through IV disease. Whereas the histology of the liver and spleen and alterations in hepatic function studies have been well studied, the pathogenesis of each of these abnormalities has not been well studied, and almost all the information comes from a few well-studied case reports.

CANCER IN THE FRAIL PATIENT: A Coming Epidemic

Abstract: With the aging of the population, frailty has emerged as a new clinical entity. The frail person has exhausted any functional reserve. Current criteria for the recognition of frailty include age of over 85 years, dependence in one or more activities of daily living, three or more comorbid conditions, and the presence of one or more geriatric syndromes. It is calculated that there are approximately 6 million frail patients in the United States and approximately 400,000 of them have cancer. Management of cancer in the frail person is mainly comprised of palliation, which may include some forms of chemotherapy, such as navelbine, gemcitabine, or low-dose taxanes.

Kit signal transduction.

Abstract: The current understanding of kit signaling is that a limited number of signaling proteins interact to build multiple interacting networks that allow diverse cellular responses. Cytoplasmic signaling proteins are increasingly seen to form networks directed through converging and interacting pathways rather than following a simple linear model. There are also numerous cross-connections between signaling proteins more distal to the receptor. Ras thus binds PI3 kinase and potentiates its activation, whereas the Rac-dependent protein kinase PAK phosphorylates MEK and thereby stabilizes its association with Raf. A signaling network with multiple intersecting pathways can obtain a single, coherent response from numerous, potentially conflicting signals. There is still limited information about the effect of activating mutations on various aspects of kit signaling. There is, however, mounting evidence that an activating mutation may enhance kit signaling and also induce factor-independent activation of kit. For instance, this activation could occur through degradation of SHP-1, the protein tyrosine phosphatase that negatively regulates kit signaling. There is also emerging evidence that inherent inhibitory factors may exist in the juxtamembrane of kit and may be suppressed as a result of a mutation in that region. Understanding the impact of these activating mutations on kit signaling is important, not only in contributing to the understanding of the pathogenesis of mastocytosis but ultimately in forming the basis for more effective therapeutic intervention in this disease.

Treatment of systemic mast cell disorders

Abstract: The heterogeneous nature of disease manifestations in mastocytosis requires the individualization of therapy to each patient's clinical presentation and prognosis. The mainstay of treatment for most categories of mastocytosis are H1 and H2 antihistamines with the addition of corticosteroids for more severe symptoms. This article presents a summary of treatment strategies for indolent and aggressive forms of mastocytosis along with a discussion of future therapeutic directions.

Antineoplastic chemotherapy of the older cancer patient.

Abstract: Cancer chemotherapy may be effective and safe in older patients if some proper provisions are made. Doses of chemotherapy should be adjusted to the patient's glomerular filtration rate, and his or her hemoglobin should be maintained for the duration of the therapy. For patients who are 70 years of age or older and who are receiving moderately toxic chemotherapy, growth factors should be used. The risk of mucositis increases with the age of the patient, so it is important to treat it aggressively at the first signs of the complication.

Assessment of the older cancer patient.

Abstract: The correct assessment of a cancer patient is a key step in the treatment process In older people, this assessment entails not only the patient's basic medical history and the standard cancer staging, but also much more comprehensive evaluation of the various facets of the patient's health and environment that may interfere with his or her therapy Patient fitness for elective surgery, radiation therapy, and chemotherapy must be considered Geriatricians have defined the relevant aspects of the general evaluation of the older person, and now this work is being adapted to cancer patients This article reviews the various aspects of a comprehensive assessment applicable to the cancer patient in settings such as academic oncology programs, cooperative group studies, and private oncology practice

Hematopoiesis and cytokines. Relevance to cancer and aging.

Abstract: Impaired hematopoiesis and dysregulated cytokine expression have important implications for cancer in the elderly. In aged people, hematopoiesis is dysregulated and becomes paradoxically down-modulated under periods of increased hematopoietic demand. This down-modulation may explain, at least in part, the increased incidence of anemia in the elderly, although the cause of anemia can usually be identified in these patients and frequently reversed with targeted therapy. An age-associated decrease in the expression of interleukin-2 may contribute to impaired cellular immunity. Additionally, the increased interleukin-6 production frequently found in the elderly may participate in promoting the survival and proliferation of malignant myeloma and in inducing resistance by myeloma cells to therapies that act through apoptosis. Dysregulation of the expression of these and other cytokines may be a mechanism contributing to age-related impairment of the hematopoietic response, the genesis and therapeutic resistance of specific malignancies, and cancer cachexia.

A comprehensive review of vitamin k and vitamin k antagonists

Abstract: For more than 50 years, vitamin K has been thought to be uniquely involved in blood coagulation. Unlike many other vitamins, its mode of action is known on a molecular level, and the vitamin K–dependent reaction can be mimicked in vitro using artificial substrates and a liver cell–free system. Moreover, reaction products formed by vitamin K action can be readily identified among the bulk of other proteins in tissues or body fluids. During the last decade this detailed knowledge formed the basis for the discovery that vitamin K–dependent proteins are involved in other regulatory processes as well as regulation of blood coagulation. Vitamin K antagonists are presently used worldwide to treat patients with an increased thrombosis risk, and accumulating data suggest that these drugs not only inhibit blood coagulation but also interfere with other physiologic processes in which vitamin K is involved. This article summarizes the basic knowledge and provides an update on recent developments.

BREAST CANCER AND AGING: Clinical Interactions

Abstract: The most common non–skin cancer and the most common cause of cancer death in women older than 65 years is breast cancer. 9 This article discusses the prevalence of breast cancer in the geriatric population, the biology of breast cancer in older women, prevention of and screening for breast cancer, and problems specific to older women in the management of breast cancer. Breast cancer is primarily a disease of older women. Incidence rates of female breast cancer rise with advancing age, level off between the ages of 45 and 50 years (Clemmesen's hook), increase again to a peak at 75 years, and decline thereafter (Fig. 1). 66 Over time, the incidence of breast cancer has increased, and this increase has occurred predominantly in women over the age of 50 years. Compared with an incidence curve from 1973, a curve from 1987 shows a more dramatic increase in breast cancer incidence after age 50 55 (Fig. 1). With the projected increase in the geriatric population, and especially the population of women, during the next half century breast cancer will be an even greater health concern (Fig. 2). The life expectancy of women in Western societies is relatively long, about 15.5 years at the age of 70 years and 9.2 years at the age of 80 years (Table 1). 90 Life expectancy reflects the average number of years of remaining life for a woman in a specified population. For the individual, life expectancy depends on the presence of comorbid diseases as potential causes of mortality. Older women are at elevated risk not only for breast cancer but for multiple, concurrent health conditions (Fig. 3). Comorbidity clearly is an important consideration for breast cancer screening and breast cancer management. 81 Among women with breast cancer, those over the age of 65 years have more non–breast cancer related deaths than those younger than 65 (20% versus 3%, P 37 This finding has been confirmed by a series of studies by Satariano et al. 82,83,84 The risk of death increased with the number of comorbid conditions; as the number of comorbid conditions increased, the risk of breast cancer–related death also increased; and early diagnosis of breast cancer in women with multiple coexisting illnesses did not improve prognosis. 45,64,102

Mastocytosis and the skin

Abstract: The most frequent site of organ involvement in individuals with any form of mastocytosis is the skin. Cutaneous lesions include urticaria pigmentosa, mastocytoma, diffuse and erythematous cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. The major histologic feature is an increase in the number of mast cells in the dermis. Treatment depends on the type of skin lesions.

Serum tryptase and the laboratory diagnosis of systemic mastocytosis.

Abstract: Total tryptase levels of 20 ng/mL or higher in a baseline serum sample when the ratio of total to beta-tryptase is 20 or greater strongly suggest underlying systemic mastocytosis. Whether these criteria prove to be more sensitive than a bone marrow biopsy will require further study. Although the absolute level of total tryptase does not predict disease severity, it may provide a practical method for assessing the efficacy of therapeutic interventions designed to reduce the mast cell burden.

ACUTE MYELOGENOUS LEUKEMIA AND AGING: Clinical Interactions

Abstract: Effective treatment of the elderly patient with AML remains a challenging task. Acute myelogenous leukemia is clearly a different disease in the elderly than in the young, for many reasons, both clinical and biologic, which contribute to the worse prognosis in the elderly. The elderly, as a group, have been underrepresented in clinical trials. Several important prognostic variables have been identified and described, however, that can help the physician select the appropriate treatment for any individual patient. Age itself should not preclude an attempt at therapy, especially for AML, which progresses very rapidly in the absence of treatment. After careful analysis of prognostic factors, in any individual patient, however, the outlook may be so poor that it may be desirable to withhold treatment. With a better understanding of the pathophysiology of AML in the elderly, more targeted and less toxic treatment regimens will become available. At present, however, clinicians must use an improved understanding of the disease to predict its behavior in an individual patient, so that the currently available treatment modalities are used most prudently.

Clinical application of argatroban as an alternative anticoagulant for extracorporeal circulation.

Abstract: To avoid systemic thromboembolization and clot formation in the extracorporeal circulation (ECC) equipment in open-heart surgery, full heparinization or an activated clotting time (ACT) longer than 450 seconds has been considered essential. This requirement has been determined both empirically and from hematologic studies of abnormal fibrin monomer or fibrinopeptide A (FPA) production. 8,42 Although ECC materials such as polypropylene and silicone used in the gas-exchange membrane of the oxygenator and polyvinyl chloride tubing retain some degree of thrombogenicity, 6,35,36 improved biocompatibility between these materials and the blood components achieved with heparin coating, improved connector and cannula designs, and use of the centrifugal pump have made it possible to perform some ECC procedures without full systemic anticoagulation therapy. The risk of thrombus formation within the circuit has not yet been eliminated, however, especially in cases of prolonged low-flow perfusion. 6,37 Stagnation or turbulence of the blood flow in the ECC circuit 35 can also increase the thrombotic risk. Therefore, low-dose heparin therapy is commonly used to prolong the ACT to 150 to 200 seconds.

Cancer surgery in the elderly.

Abstract: Surgery is still the most important treatment for solid tumors, regardless of the age of the patient. For lymphomas and leukemias, surgery is needed for diagnosis and sometimes for resection. Because the population of the United States is both growing and aging, and because the incidence of tumors increases with age, the number of elderly patients with cancers requiring surgical intervention can be expected to rise markedly in the next decade. Life expectancy for the elderly is often underestimated. According to the Metropolitan Life Insurance Tables, the life expectancy of a girl born in 1992 is 79.1 years, and that of a boy is 72.2 years. Furthermore, the life expectancy of a person reaching the age of 65 is an additional 17.5 years; and an 85-year-old person has a life expectancy of an additional 6 years. Because clinicians often underestimate the life expectancy of elderly patients, cancer in these patients is frequently undertreated. Inadequate initial therapy for an older patient diagnosed with cancer can result in recurrence or metastases and death from cancer, outcomes which might have been preventable with correct treatment at the outset. The most common tumors in elderly patients, colorectal, breast, gastric, and pancreatic cancers, all require surgery for cure. Melanoma and hepatobiliary tumors are seen less frequently but also require surgery for optimal therapy. The optimal surgical therapy for the elderly patient is not always accurately known, nor is it known whether treatment for elderly patients should differ from the standard treatment provided to younger patients, because the elderly have been severely underrepresented in most clinical trials. Therefore, scientific data from randomized studies are not available for the older population. Most available studies are retrospective and many display considerable bias in choosing patients for certain treatments, especially for surgical procedures. Many factors influence the selection of therapy for elderly patients, including comorbid disease, decreased functional status, alterations in mental status, limitations in economic resources, perceived limited life expectancy, and assumed inability to tolerate treatment. These biases may affect the elderly patient's survival of cancer. Factors influencing survival in the elderly include health status (comorbidity, functional status, level of activity), socioeconomic status (income and education level), cognitive status, and the availability of social support. Also, failure to obtain the definitive therapy for a cancer has been associated with a poorer outcome. To treat the elderly most effectively, all these factors should be considered, but they should not be the basis for withholding appropriate therapy. Surgery, in particular, has often been considered as carrying a prohibitive risk for the elderly patient. The literature does not support this viewpoint, however, and many studies indicate that surgical procedures can be performed safely in the elderly. The balance between the surgical risk and the expected cure or palliation is important when treating any patient with cancer but is especially important in the elderly cancer patient. The effect of treatment on quality of life is also of prime importance. Many cancer operations are complex, extensive, and have significant morbidity and mortality when attempted for cure. This article reviews the current knowledge regarding risk assessment, breast cancer, gastrointestinal cancers, melanoma, and laparoscopic surgery as it pertains to the elderly population.

The hyper-cvad regimen in adult acute lymphocytic leukemia

Abstract: The regimen of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) has demonstrated significant activity in adult lymphocytic leukemia (ALL) and in other hematologic malignancies, including Burkitt's disease, lymphoblastic lymphoma, mantle cell lymphoma, and multiple myeloma. This article presents the rationale for the development of this regimen, describes the program, summarizes the results of the large clinical trials developed at the University of Texas M. D. Anderson Cancer Center, and discusses strategies to improve the results.

Iron deficiency in pregnancy, obstetrics, and gynecology

Abstract: Iron deficiency remains a major health risk in the United States, despite the apparent availability of a high-quality diet. In the United States, at least 7.8 million adolescent girls and premenopausal women are iron-deficient. Worldwide, the challenge of identifying and treating iron deficiency is enormous. Physicians involved in the primary care and in the obstetric and gynecologic care of women of all ages must be aware of the nature of the problem and the correct approach to screening, diagnosis, and treatment. The potential benefit to newborns and infants and to their mothers is substantial. Furthermore, a thorough diagnostic evaluation has considerable potential for uncovering a potentially lethal disease, such as gastrointestinal malignancy, in a curable phase.

Mechanisms of thrombosis in spinal cord injury.

Abstract: Deep vein thrombosis (DVT) and pulmonary emboli remain the major complications in spinal cord injuries associated with motor complete or motor nonfunctional paralysis. Two findings set complete spinal cord injury apart from other risk factors for venous thrombosis. The first concerns the incidence of leg DVT and pulmonary embolism in complete spinal cord injury, which is three times higher than in the general population. The second is the surprising finding that DVT and pulmonary embolism persist and recur despite adequate anticoagulation. Numerous studies failed to identify a hypercoagulable imbalance in blood coagulation factors or a decrease in anticoagulant activity. On the other hand, fibrinolysis, a process unrelated to hypercoagulability but closely related to endothelial cell integrity, is predictably altered and contributes to the persistence of venous occlusion by thrombosis. There is considerable evidence that in spinal cord injury patients interruption of neurologic impulses and the ensuing paralysis cause profound metabolic changes in blood vessels accountable for venous thrombosis. Altered venous competence with complete spinal cord injury manifests by a decrease in venous distensibility and capacity and an increase in venous flow resistance. Vascular adaptations to inactivity and muscle atrophy, rather than the effect of a nonworking leg-muscle pump and sympathetic denervation, cause thrombosis, indicating that thrombosis established through venous incompetence cannot be reversed by anticoagulation alone. Measures to increase venous distensibility and decrease flow resistance are also required and can be provided by exercise or intermittent pneumatic compression. Therapeutic approaches aimed at restoring nerve signals to skeletal muscles would be more appropriate. Such measures are not yet available to humans. In incomplete spinal cord injury, reorganization in spared pathways does occur, and capability of the CNS to remyelinate axons after a lesion has been well documented. A new mouse model of contusive spinal cord injury promises to shed light on the effect of genetic modifications produced by specific mutations on nerve injury and recovery process after spinal trauma. Spinal cord injuries with paralysis result in an immobile state with retardation of the blood flow caused by the relaxation of muscle and the atony of blood vessels. It is not surprising that spinal cord injuries are frequently complicated by the development of venous thrombosis, which is inevitably linked to hospitalization, immobilization, vein wall damage, stasis, and hypercoagulability. Deep vein thrombosis and pulmonary emboli remain the major complications in spinal cord injuries below the C2 through T12 vertebrae associated with motor complete or motor nonfunctional paralysis. 9,13,27,28,33,42,48 Two surprising findings set spinal cord injury apart from other risk factors for venous thrombosis: incidence of leg DVT and pulmonary embolism in spinal cord injury is three times higher than in the general population. The annual incidence of venous thromboembolism in the general population in the western world is about 1 per 1,000 2,9,10,42 ; and occurrence of DVT and pulmonary embolism persists and recurs despite adequate anticoagulation. 49 The focus of this article is to determine the nature of factors that contribute to the initiation and persistence of vascular occlusion by thrombosis in the legs of paralyzed individuals, and in what regards the paralysis makes them different from the general population. Information is presented in three sections. The first section makes available the scope of spinal cord injury and the associated incidence of technically documented venous thrombosis. The second section reviews changes in nerves, muscles, and blood vessels following spinal cord injury and paralysis. Due attention is given to the condition of the muscle pump and the venous valves, two important factors that propel venous blood from leg veins to the right heart. The third section discusses the effectiveness of approaches used to combat blood stasis, changes in blood fluidity, and skeletal muscle denervation in the paralyzed patient. These include prevention or treatment with anticoagulation, vena cava filter placement, compression devices, and electric and magnetic stimulators. Approximately 450,000 people live with the consequences of traumatic spinal cord injuries in the United States with 10,000 new cases added each year. The total cost per patient for objective diagnosis and treatment of acute venous thromboembolic disease has been estimated at approximately US $4000. This figure does not include costs for patients who incur long-term sequelae. 48 Unfortunately, there is not an appropriate intervention or prophylaxis to be recommended yet.

Radiation therapy of the older patient

Abstract: Radiotherapy has a major role in the multidisciplinary approach to cancer therapy. It is widely used for curative and palliative treatment of cancer involving various sites. Radiotherapy is of particular benefit to older and frail cancer patients as an alternative to surgery and to systemic therapy. The available data on the sensitivity of normal tissues to radiotherapy in elderly patients strongly suggest that older patients with good functional status tolerate radiotherapy as well as younger patients and have comparable tumor response and survival rates. Aggressive radiotherapy should not be withheld from older patients because of chronological age alone.

Evidence-based medicine. Interpreting studies and setting policy.

Abstract: The ascendancy of EBM has been accompanied by a greater awareness of its shortcomings. It is increasingly evident from the cost, length, and difficulty of performing RCTs that studies cannot be launched to address every question in medicine. Good evidence is often lacking in medicine. Epistomologists question the very notions of evidence and the suitability of current study designs and measurement tools to research the salient issues of concern to patients and others concerned with quality. Lack of evidence of effectiveness does not prove ineffectiveness, yet, in reaction to EBM, insurance companies and government often make this inference to justify decisions to withhold coverage or research support. The unbridled enthusiasm for the evidence-based practice guideline of the early 1990s has been tempered by a more mature understanding of its limitations. Not many practice guidelines are developed well, and the implementation of flawed guidelines can cause harm. The seven-step process outlined earlier is slow, laborious, and expensive (sometimes costing hundreds of thousands of dollars). Moreover, there is little evidence that either the rigor of the methods or the guidelines themselves have a meaningful effect on practice behavior or patient outcomes. To the most cynical observers, the only consistent beneficiaries of guidelines are payers, who use guidelines with considerable success in reducing costs, lengths of stay, and utilization rates. Even ardent advocates of guidelines acknowledge the evidence that disseminating reviews and recommendations, by itself, fails to motivate clinicians to increase delivery of effective interventions and to abandon ineffective ones. This absence of response has stimulated a closer look at the barriers to behavior change and the design of thoughtful implementation strategies that begin with, but reach beyond, simple guidelines. Tools such as reminder systems, standing orders, academic detailing, peer review and audit, feedback, and health system changes recognize that knowing what to do is only one piece of an increasingly complex puzzle. The competitive marketplace of managed health care has added new economic influences on clinician behavior but is also fueling private-sector interest in good research. Patients, clinicians, and policy makers will continue to seek better data concerning what works in medicine and what does not.

RISK FACTORS FOR VENOUS THROMBOEMBOLISM FOLLOWING PROLONGED AIR TRAVEL: Coach Class Thrombosis

Abstract: Venous thromboembolism (VTE) in legs and lungs is a potentially life-threatening condition. The incidence of VTE associated with air travel is still unknown, but it may have increased. Most travelers who develop symptoms do so within 24 hours after their flight takes off. Predisposing risk factors may be divided into patient-related and cabin-related factors, both of which are described. It is emphasized that better information and better inflight precautions can minimize these risk factors.

The Medical Research Council trials in adult acute lymphocytic leukemia.

Abstract: Overall, the MRC Adult Leukaemia Trials have been successful, in that since the 1970s they have demonstrated a stepwise improvement in outcome. Examination of the survival curves shows the DFS rate at 5 years in UKALL Trial 1 of 5% rising to 38% in UKALL Trial XII (year 2000). Unfortunately, compared with children with ALL, these results in adults must be regarded as poor, because in the UKALL children's trials the EFS rate at 5 years for a child entered in the year 2000 is expected to be above 80%. With a low proportion of all adults entered into randomized trials, one cannot be certain that improvements result from treatment rather than patient selection. Only recently have randomized trials in adults become large enough to detect plausible treatment effects. The authors believe that the main contribution of these trials so far, confirmed by other groups, is in examining prognostic features in al patients and finding that age and the presence of the Ph chromosome, independent of WBC count, gender, and cell type, is the main feature for predicting outcome. The UKALL XII trial will provide valuable information on the relative merits of transplantation and molecular studies of MRD. An in-depth study of a large number of Ph chromosome-positive ALL leukemias will also provide information on which to base future studies. Preliminary data suggest that all Ph-positive patients should undergo some sort of allograft early after CR is achieved, because these patients are not rescued by BMT after relapse. At the time of the publication of this article, preliminary studies suggest that STIs may not be as effective in Ph-positive ALL as in chronic granulocytic leukemia. The challenge for the future is to understand the biologic role of age and its impact on outcome so as to overcome "ageism" in adult ALL.

A proposed classification of mastocytosis incorporating molecular genetics

Abstract: As an understanding of the molecular genetic causes of different forms of mastocytosis is developed, the therapy of choice may depend on the specific genetic abnormalities expressed by a patient's neoplastic mast cells. The authors propose a new classification system for mastocytosis that incorporates both molecular-genetic and clinical data. This system provides a theoretic framework for mast cell researchers and helps practicing physicians in estimating prognosis and determining therapeutic options for individual patients.

Recurrent miscarriage syndrome and infertility caused by blood coagulation protein or platelet defects

Abstract: Recurrent miscarriage syndrome and infertility are common problems in the United States. Recurrent miscarriage affects more than 500,000 women annually. If properly screened through a cost-effective protocol, the cause will be found in almost all women. The most common singular defect in women with RMS is a hemostasis defect, and if a thorough APLS evaluation is performed, the most common of these is found to be APLS. Other hereditary and acquired procoagulant defects are also commonly found, if looked for. It is important to evaluate women with RMS appropriately, because if a cause for the RMS is found, most women will achieve normal-term delivery. Hemorrhagic defects are rare hemostasis causes of RMS, but these defects also are treatable in many instances and should be considered in appropriate women. Treatment of the common procoagulant defects consists of preconception low-dose ASA at 81 mg/day followed by immediate postconception low-dose unfractionated porcine heparin. LMWH may be a suitable alternative.

Recent clinical trials in acute lymphocytic leukemia by the cancer and leukemia group b

Abstract: The Cancer and Leukemia Group B (CALGB) has performed a series of studies evaluating different aspects of remission induction and postremission treatment in adults with acute lymphocytic leukemia (ALL). In recent years, these clinical trials have been supplemented by systematic morphologic, immunophenotyping, cytogenetic, and molecular genetic studies leading to the identification of different risk groups of patients who may warrant individualized treatments. These protocols have enrolled all adult patients older than 15 years with ALL, without an upper age restriction, and did not exclude Philadelphia (Ph) chromosome-positive patients.