The silent epidemic: tobacco and the evolution of lung cancer and its treatment.

Considered a rare disease during the 19th century, lung cancer became the most virulent and lethal cause of cancer mortality by the end of the 20th century. In this paper, lung cancer and its treatment are addressed within the social, cultural, economic, and political context of the last century. Because lung cancer is related to the consumption of cigarettes, the battles over tobacco control are highlighted. Four time periods are addressed: the early years (1900-1930), beginning of the epidemic (1930-1960), defining the problem (1960-1980), and expanding options (1980-1990s). Although improvements have been made in science and technology, attempts at finding curative treatments have met with little success. Smoking cessation and efforts to control tobacco (especially among children and adolescents) remain the most important factors if the incidence of lung cancer is to be curtailed in the future. Providing care to individuals with the illness is a current challenge. Research examining the efficacy of treatments and their effect on survival, health-related quality of life, and cost outcomes is essential and can be best achieved through the efforts of multidisciplinary teams.

Pain assessment and management.

Assessment and management of pain is crucial to the success of any program of care for dying patients and their families. With appropriate assessment and management, often using home health or hospice teams, pain can be controlled in more than 90% of patients. This article focuses on the symptomatic care of patients who are dying. The legal and regulatory issues that may inhibit delivery of adequate opioid therapy are also reviewed.

Patients with cancer referred to hospice versus a bridge program: patient characteristics, needs for care, and survival.

PURPOSE: The purpose of this study was to compare the characteristics and needs of patients with advanced cancer who were referred to hospice with those referred to a prehospice "bridge" program that is staffed by hospice nurses. PATIENTS AND METHODS: Data were gathered through retrospective review of computerized clinical records using precoded data fields of 284 patients with cancer enrolled in a bridge program and 1,000 who enrolled in a hospice program. Patient characteristics, needs for supportive care at the time of enrollment, and survival were assessed. RESULTS: Bridge patients were less likely to have Medicare or Medicaid (43% v 72%; odds ratio, 0.30; P <.001) and were younger (69 v 73 years, rank sum test; P <.001), more likely to be married (59% v 43%; odds ratio, 1.90; P <.001), and more likely to be in the highest income category (14% v 10%; odds ratio, 1.77; P =.009). Bridge patients had at least as many needs for care as did patients in hospice. Bridge patients lived significantly longer (median, 46 v 19 days; log-rank test of survivor functions, P <.001). CONCLUSION: Patients referred to this bridge program had prognoses that are significantly better than those of patients who enter hospice, but they have needs for supportive care that are at least as great. These findings underscore the importance of initiatives to extend some of the benefits of hospice care to a wider population of patients and should encourage the analysis of similar programs' ability to meet these needs.

Advances in pain management for older adult patients.

Management of pain is crucial to the success of any program of care and support for dying patients and their families. Pain can be controlled in more than 90% of older adults. Components of an effective program include comprehensive, repeated pain assessment; detection and treatment of complicating medical and psychological disorders (e.g., delirium); spiritual concerns; and the judicious use of nonpharmacologic and pharmacologic therapies, radiation, and radiopharmaceuticals. Strategies that enable clinicians to prevent and treat the expected complications of nonsteroidal anti-inflammatory and opioid therapies are reviewed. Strategies to change opioid agents or routes to minimize opioid-induced side effects and to provide effective pain relief as death nears are presented.

Development of a teaching module for quality-of-life assessment of terminal patients. The AACE Multi-Institutional Palliative Cancer Education Section. American Association for Cancer Education.

To enhance the teaching of students to assess quality of life of patients with serious disease, the AACE Palliative Cancer Education Section has developed a teaching module. The module, which focuses on four desired learning objectives, is to be used in an hour-long small-group session. The authors describe the development of the module, as well as its objectives, teaching method, evaluation, and future challenges.

Management of pain and spinal cord compression in patients with advanced cancer. ACP-ASIM End-of-life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine.

General internists often care for patients with advanced cancer. These patients have substantial morbidity caused by moderate to severe pain and by spinal cord compression. With appropriate multidisciplinary care, pain can be controlled in 90% of patients who have advanced malignant conditions, and 90% of ambulatory patients with spinal cord compression can remain ambulatory. Guidelines have been developed for assessing and managing patients with these problems, but implementing the guidelines can be problematic for physicians who infrequently need to use them. This paper traces the last year of life of Mr. Simmons, a hypothetical patient who is dying of refractory prostate cancer. Mr. Simmons and his family interact with professionals from various disciplines during this year. Advance care planning is completed and activated. Practical suggestions are offered for assessment and treatment of all aspects of his pain, including its physical, psychological, social, and spiritual dimensions. The methods of pain relief used or discussed include nonpharmacologic techniques, nonopioid analgesics, opioids, adjuvant medications, radiation therapy, and radiopharmaceutical agents. Overcoming resistance to taking opioids; initiating, titrating, and changing opioid routes and agents; and preventing or relieving the side effects they induce are also covered. Data on assessment and treatment of spinal cord compression are reviewed. Physicians can use the techniques described to more readily implement existing guidelines and provide comfort and optimize quality of life for patients with advanced cancer.

The oncologist's expanding role.

Advances in the assessment and management of pain have made it possible for over 90% of oncology patients to have a pain free death at home. Oncologists have a unique opportunity, as clinical role models, teachers, and participants in research, to insure proper management of patients' symptoms at diagnosis, during treatment, and as death approaches.

Promoting symptom control in palliative care.

OBJECTIVES: To describe management of common physical problems that occur in patients with advanced cancer. DATA SOURCES: Research and review articles, book chapters, and published guidelines. CONCLUSIONS: Effective symptom control for patients with advanced cancer requires the coordinated efforts of a multidisciplinary team. Excellent palliation can be achieved in patients suffering from pain, as well as from gastrointestinal, respiratory, or dermatologic disorders. IMPLICATIONS FOR NURSING PRACTICE: Nursing is the cornerstone of effective palliative care. Through accurate assessments and expertise in delivering pharmacologic and nonpharmacologic treatments, nurses ensure optimal palliation of physical symptoms.

A survey of physicians' education in caring for the dying: identified training needs.

BACKGROUND: Physicians receive limited systematic training in caring for dying people. The majority of training focuses on technical skills. METHODS: This study surveyed medical students, residents, fellows, and attending physicians to identify physician needs and current types of training in caring for the terminally ill. The study questionnaire was designed to determine whether and when physicians were trained in caring for dying people, the nature of such training, and possible areas to be included in future training. Also requested was a description of a personal experience involving caring for a terminally ill person. RESULTS: One hundred twenty-three questionnaires were distributed and 90 were returned. Data indicate a lack of standardized training in dealing with terminally ill people and an expressed need for periodic, continuous training. The training needs to be mandatory, be ongoing, and use multiple formats, including the integration of theoretical information and clinical practice. Physicians in this study desired training in the following topic areas: 1) pain management; 2) death and dying; 3) the quality of life and death; 4) DNR status. CONCLUSIONS: Physicians in this study indicated a need for more training in how to care for the terminally ill. A model for training should start in medical school and continue throughout one's career. Providing a framework for lifelong professional development that integrates theoretical information and clinical practice with a multidisciplinary approach to patient care should form the basis of a training model.

The impact of a hospice consultation team on the care of veterans with advanced cancer.

To address the needs of patients with advanced cancer, all Veterans' Affairs hospitals were asked to establish teams of clinicians whose focus was to deliver expert palliative care. At the Philadelphia Veterans' Affairs Medical Center, our Hospice Consultation Team brought together professionals who had worked together informally in some of the outpatient oncology clinics. We conducted a prospective study of all consults received during the first year of the team's operation to determine whether or not the team approach would duplicate already available services or provide improved care. We identified 164 new medical/ nursing problems in 75 patients, 85% of which we were able to resolve. There were 152 new psychosocial/spiritual problems, but only 40%-61% were resolved. Of 22 patients followed in oncology clinics, new problems were identified and resolved in 21. We conclude that the expertise of the Hospice Consultation Team members along with the team process provided improved care to these patients.

Elevated methylmalonic acid and total homocysteine levels show high prevalence of vitamin B12 deficiency after gastric surgery.

OBJECTIVE: To determine the prevalence of vitamin B12 deficiency in patients who have had gastric surgery. DESIGN: Cross-sectional study. SETTING: Philadelphia Veterans Affairs Medical Center. PARTICIPANTS: 61 patients who had had gastric surgery and 107 controls. MEASUREMENTS: Serum levels of vitamin B12, folate, methylmalonic acid, and total homocysteine measured before and after treatment in participants with vitamin B12 deficiency. Vitamin B12 deficiency was defined as one of the following: 1) a serum vitamin B12 level less than 221 pmol/L and an elevated methylmalonic acid level; 2) a serum vitamin B12 level less than 221 pmol/L and an elevated total homocysteine level that decreased with vitamin B12 treatment; or 3) in patients unavailable for treatment, a serum vitamin B12 level less than 221 pmol/L, a folate level greater than 9 nmol/L, and an elevated total homocysteine level. RESULTS: Study patients and controls were similar in age, sex, and racial distribution. Nineteen patients (31%) and 2 controls (2%) had vitamin B12 deficiency (P < 0.001). Twelve (63%) of the 19 vitamin B12-deficient patients had elevated total homocysteine levels. In all participants with vitamin B12 deficiency who received treatment (15 of 21), methylmalonic acid and total homocysteine levels decreased substantially, confirming the deficiency before treatment. CONCLUSION: Patients who have had gastric surgery have a high prevalence of vitamin B12 deficiency. Prompt recognition and treatment of the deficiency with resultant normalization of elevated total homocysteine and methylmalonic acid levels may prevent the development of cardiovascular, hematologic, and neurologic abnormalities. Our data support both frequent screening and vitamin B12 replacement therapy in patients who have had gastric surgery and have serum vitamin B12 levels less than 221 pmol/L.

A pain syndrome associated with large adrenal metastases in patients with lung cancer.

We report two cases of a pain syndrome caused by large adrenal metastases in patients with lung cancer. A review of the literature identified 23 previously reported patients with primary lung cancers who appear to have had a similar syndrome, although in none of these cases were other likely causes of the pain syndrome carefully excluded. The syndrome characteristically includes unilateral flank pain but may have abdominal components as well, and has only been reported in patients with large metastases (> or = 5 cm in largest diameter). Although the mechanism by which large adrenal metastases cause the pain syndrome is not clear, we suggest that treatment that includes local anesthetic agents or steroids may be effective. The pain syndrome caused by large adrenal metastases is not included in reviews of cancer pain syndromes but needs to be considered in the differential diagnosis of patients with lung cancer and flank or abdominal pain.

Efficacy of an educational bereavement program for families of veterans with cancer.

Clinicians working with cancer patients often continue to help their surviving family members through the bereavement process. To develop an educational bereavement program for survivors, the authors used information available about the process of grieving, its psychological and physical manifestations, the most stressful times for the bereaved, and the most helpful interventions. They telephoned bereaved survivors and sent letters, a "what-to-expect" sheet, bibliographies, and listings of support services to them at specified times. One year after the program's inception, they assessed its efficacy with a chart and telephone audit. Most survivors felt the letters and "what-to-expect" sheet had been helpful. Most had not used the bibliographies, and half had not needed the support group listings. However, 30% of the survivors who had not initially requested the educational materials did so a median of eight months later. The authors conclude that the program was beneficial for the vast majority of survivors, and they plan to modify it to respond to the deficiencies identified.

Treatment with 13-cis-retinoic acid in transfusion-dependent patients with myelodysplastic syndrome and decreased toxicity with addition of alpha-tocopherol.

PURPOSE: The purpose of this study was to determine the response and tolerance to long-term treatment using 13-cis-retinoic acid (13-CRA) in transfusion-dependent patients with the myelodysplastic syndrome (MDS) and to determine the effects of therapy on the natural history of the disease. PATIENTS AND METHODS: Sixty-six consecutive patients with transfusion-dependent MDS seen in a medical school hospital and outpatient clinic from 1981 to 1988 were studied. The first 21 patients were treated with 13-CRA alone and the next 45 patients with 13-CRA plus alpha-tocopherol (AT). We compared responses to and toxicities of therapy, rates of transformation, and survival from onset of therapy in 20 evaluable patients treated with 13-CRA alone and 43 patients treated with 13-CRA plus AT. RESULTS: Four patients responded (20%) at 4 to 8 months to 13-CRA alone, but this response was associated with considerable toxicity and resulted in cessation of therapy. Among the responders, only one continued therapy and is currently in remission, whereas three discontinued therapy because of toxicity and have had a relapse and died. In the 13-CRA plus AT group, we observed one prolonged complete remission and 10 partial remissions (26%), with a decrease in skin and constitutional toxicities by the addition of AT, which enabled the continuation of 13-CRA indefinitely. Although the response rates were similar in both groups, fewer patients (28% versus 60%) experienced progression to acute leukemia in the 13-CRA plus AT group than in the group receiving 13-CRA alone, who terminated treatment (p = 0.018). A twofold increase in median survival of the RA/RARS and RAEB/CMML patient groups was observed with 13-CRA plus AT but was not significant (p greater than 0.5). CONCLUSION: This study shows a 20% to 26% response rate to 13-CRA and suggests that 13-CRA, if given continuously, decreases the rate of progression or transformation to acute leukemia in patients with MDS. The addition of AT ameliorates the toxicity of 13-CRA and allows for long-term treatment with 13-CRA. Since the standard treatment for MDS is currently unsatisfactory, these findings indicate that longer treatment with a non-marrow-suppressive agent such as 13-CRA is important, and further trials to determine the role of 13-CRA plus AT in combination with new recombinant growth factors in the therapy for transfusion-dependent MDS should offer a new approach to a disease common in the elderly population.

Differential effects of phorbol esters on normal myeloid precursors and leukemic cells: basis for autologous bone marrow reconstitution in acute nonlymphocytic leukemia using phorbol ester-treated bone marrow from patients in remission.

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces macrophage-like differentiation of HL60 cells and cells from patients with acute nonlymphocytic leukemia (ANLL). We assessed the use of TPA as a means of eradicating residual leukemia from remission bone marrow prior to autologous bone marrow reconstitution. A 30-min incubation with TPA led to marked growth arrest in HL60 cells and in cells from most patients with acute myelogenous leukemia and acute myelomonocytic leukemia, whereas cells from most patients with acute promyelocytic leukemia and acute undifferentiated leukemia demonstrated a lesser degree of growth arrest. Freezing and thawing, a necessary step in autologous reconstitution, had no effect on the cessation of proliferation induced in HL60 or ANLL cells preincubated with TPA for 30 min. Virtually normal myeloid precursor growth occurred in normal or remission bone marrow cells preincubated with TPA and then frozen and thawed. Based on these observations, two patients with advanced ANLL in remission underwent marrow ablative therapy followed by autologous reconstitution using TPA-treated bone marrow. Limited normal hematopoiesis was reestablished in both patients, although they subsequently experienced leukemic relapse. These studies demonstrate that in ANLL cells, TPA stimulates growth arrest; in contrast, hematopoiesis is able to proceed both in vitro and in vivo.

A prospective study of prolonged central venous access in leukemia.

A three-year prospective study was conducted to evaluate right atrial silicone elastomer catheters for long-term venous access in adults with acute leukemia. Objectives included establishing the safety of catheter insertion in thrombocytopenic patients and the feasibility of maintaining the catheter during septicemia. Seventy-one catheters were placed in 57 consecutive patients entering intensive leukemia therapy. Excessive bleeding occurred at three catheter insertion sites. Eight catheter-related infections occurred. In 34 of 36 noncatheter-related and two catheter-related bacteremias, catheters were left in place with intensive monitoring. In 20, bacteremia cleared. Fourteen patients died; in eight autopsies, no evidence of catheter-related mortality was found. Catheters were in use 6,799 days, including 3,932 home use and 2,570 granulocytopenic days. The data indicate that thrombocytopenia does not preclude catheter insertion and that catheters can be safely maintained in septicemic granulocytopenic patients.

Modification of normal human myelopoiesis by 12-0 tetradecanoylphorbol-13-acetate (TPA).

The tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), induces macrophage characteristics in the HL-60 promyelocytic leukemia cell line. These same cells can be induced to develop mature myeloid characteristics with a variety of other stimuli. Since normal colony-forming units-culture (CFU C) also have the dual capability of developing colonies with myeloid or monocyte characteristics, the effect of TPA on normal human CFU-C development was studied. To carry out these studies, a method was developed to identify cells histochemically within agar cultures as containing either the myeloid marker, chloroacetate esterase (CAE), or the monocyte marker, nonspecific esterase (NSE). Cells from normal donors were placed into agar cultures with placenta conditioned medium (PCM), TPA in various concentrations, or combinations of PCM and TPA as stimulating materials, and examined after 7-14 days of incubation. TPA alone at concentrations of 5 x 10(-7) M to 10(-9) M stimulated cluster formation. With increasing concentrations of TPA, the percentage of clusters positive for NSE progressively increased, while CAE-positive clusters decreased. I contrast, when TPA at concentrations greater than 10(-9) M was added to PCM, the total number of clusters and colonies decreased. This resulted from a decrease in the number of clusters and colonies that contained the myeloid marker CAE, whereas the number positive for the monocyte marker NSE remained unchanged. These studies demonstrate two effects of TPA on normal CFU-C. In the absence of other sources of colony stimulating activity (CSA), TPA induces clusters. In the presence of PCM, it inhibits the production of myeloid colonies and clusters. Under both conditions, it favors the development of colonies and/or clusters containing predominantly monocytes.