Cancer rehabilitation approaches to neurologic pain syndromes in malignancy.

Pain is a common symptom in cancer patients. Thirty to fifty percent of patients will experience pain while undergoing cancer treatment, and 70 to 90% of patients with advanced disease report pain.1-7 In addition, greater than 50% of patients state their pain is incompletely controlled. In part, this is due to the difficulty physicians have in accurately assessing the patient's level of pain and response to treatment, as well as utilizing a treatment approach that is agreeable to the patient. It is common that patients underreport the severity of the pain that they are experiencing, as well as their inability to achieve pain control. There are many possible reasons for this, including their wish to appease the physician; the fear of confirming progression of their disease by admitting to having increased pain; and the concern of possible narcotic addiction. To address these problems, the World Health Organization, the American Pain Society, and the American Society of Clinical Oncology's Ad Hoc Committee on Cancer Pain have published guidelines for assessing and treating pain.8-10Pain is one of the most disabling conditions experienced by cancer patients.7,11-14 This disabling effect is exacerbated by the patient's fear of the loss of control of both the ability to regulate his/her pain and loss of control of his physical mobility due to the pain. Therefore, it affects the patient both physically and emotionally and further compromises the ability of the patient and family to deal with the disease.The perceived intensity of the pain as well as the level of disability experienced by the patient can be influenced by many variables such as family support and cultural background of the patient. These influences in the patient's life can magnify or diminish his/her perception of pain and disability. Therefore, in the same way that patients tolerate pain differently, the treatment approach must to some extent be appropriately individualized, periodically reviewed, and frequently altered to change with the needs of the patient. This is one reason why those involved with cancer rehabilitation use an individualized interdisciplinary approach to the patients' needs, including pain control. In addition to the traditional use of analgesics, chemotherapy, radiation therapy, surgery, and nerve blocks to palliate pain, cancer rehabilitation employs a wide range of other modalities, both physical and cognitive behavioral, in its treatment approach. Physical and occupational therapy utilize positioning, strengthening, transcutaneous electrical nerve stimulation (TENS), and other electrical stimulation modalities, orthotics, and other assistive devices to alleviate pain and maximize function. In addition, psychological support in its various forms, with both patient and family counseling, affords better handling of the disease. In some cases biofeedback and/or hypnosis can be utilized as an adjunct to pain control. Since the pathophysiology of cancer pain and its pharmacologic, surgical, and radiation treatments were dealt with in a previous issue, they will not be addressed further. This article will focus primarily on the more unique aspects of cancer rehabilitation, and the physical, nonpharmacologic, and behavioral approaches to pain management that practitioners commonly use in relation to neurological pain syndromes in cancer.

Dehydroepiandrosterone and related steroids induce multilamellar lipid structures in cultured human endothelial cells.

Pharmacologic doses of dehydroepiandrosterone (DHEA), a steroid hormone produced naturally by the adrenal cortex, may lower plasma lipoprotein levels in humans and reduce the severity of experimental atherosclerosis in rabbits. Effects of DHEA on cells of the vascular wall, particularly endothelial cells (EC), which are in direct contact with the plasma, have not been documented. The authors have found that micromolar doses of DHEA induce a consistent and reversible morphologic change in cultured EC derived from the human umbilical vein. During 24 hours of exposure to DHEA, cultured EC became loaded with phase-dense, perinuclear cytoplasmic granules, which persisted while DHEA remained in the culture medium. Certain steroids related to DHEA, particularly 17-ketosteroids, also induced perinuclear cytoplasmic granules. The granules lost their phase-density after fixed monolayers were extracted using ethanol or methanol. The granules did not form in media made with lipoprotein-deficient serum, suggesting that serum lipoproteins were involved in formation of the granules. Ultrastructurally, the granules were identical to multilamellar lipid structures, a type of pleomorphic lipid-containing lysosome found in foam cells. The granules were identified as lysosomes by positive reaction for acid phosphatase. The mechanism by which DHEA induces formation of lysosomal lipid structures remains to be determined.

Nonspecific cytotoxicity of recombinant interleukin-2 activated lymphocytes.

The administration of interleukin-2 (IL-2) and lymphokine activated killer (LAK) cells to patients with advanced metastatic cancer has yielded encouraging results. The purported ability of LAK cells to be discriminatively tumoricidal, thus sparing normal host tissue, represents a major advance over conventional chemotherapy. However, IL-2 adoptive immunotherapy results in dose-limiting toxicity characterized by weight gain, dyspnea, ascites, and peripheral-pulmonary edema suggestive of a vascular leak syndrome. It is unclear whether the observed toxicity is directly related to IL-2 and/or LAK cells. The authors examined the cytolytic nature of human LAK cells against human endothelial, epithelial, and fibroblast cell lines. Bovine endothelial cells also were studied. Using a 51Cr release assay, the cytolytic potential, time course, and effect of reactive oxygen intermediate inhibitors were studied. LAK cells were uniformly toxic against all cell lines, in contrast to high dose rIL-2 and excipient. Significant cytolysis was observed within 30 minutes and increased over the first 2 hours of LAK cells coming in contact with target cells. Reactive oxygen intermediate inhibitors did not reduce cytolytic activity. The authors thus found human LAK cells to be rapidly cytolytic against a variety of human and bovine cell lines. This cytolysis was independent of reactive oxygen intermediates.