Dying with cancer: patients' function, symptoms, and care preferences as death approaches.

OBJECTIVE: To characterize the dying experience of patients with cancer over the last 6 months of life. STUDY DESIGN: A retrospective analysis of the last 6 months of life among patients with colon cancer and non-small cell lung cancer enrolled in a prospective cohort study from June 1989 to June 1991 and from January 1992 to January 1994. SETTING: Five geographically diverse tertiary care academic medical centers participating in the Study to Understand Patient Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) Project. PARTICIPANTS: All patients enrolled in SUPPORT who had either colon cancer, metastatic to the liver or stage III or stage IV non-small cell lung cancer and died within 1 year of their index hospitalization. This report examines 316 of 520 patients with metastatic colon cancer and 747 of 939 patients with lung cancer enrolled in SUPPORT. METHODS: Data were collected by interview and chart abstraction at several time points in the SUPPORT Project. To describe progression to death, we constructed four observational windows backward in time beginning with patients' date of death and ending with their date of entry into the SUPPORT Project or 6 months before their death, whichever came first: (1) 3 days before death, (2) 3 days to 1 month before death, (3) 1 month to 3 months before death, and (4) 3 months to 6 months before death. For each outcome, patients contributed information to all windows during which they had data collected. We describe the frequency distributions of each outcome over time and report tests for trend. OUTCOME MEASURES: We examined several outcomes over time, including: percentage of days spent in a hospital; prognosis as measured by model-based prognostic estimates of 6-month survival; severity of illness as measured by the acute physiology score; functional status as measured by dependencies in activities of daily living (ADLs); severe physical and emotional symptoms, including pain, depression, and anxiety; patients' preferences for care; and the financial impact on patients' families. RESULTS: The death rate within 1 year of study entry was high among patients with metastatic colon cancer and advanced non-small cell lung cancer enrolled in SUPPORT (61% and 80%, respectively). As patients with cancer progress toward death, their estimated 6-month prognosis decreases significantly and the severity of their disease worsens. Patients' functional status also declines significantly as they approach death, such that most patients have four or more impairments within the 3 days before death. Patients with cancer experience significantly more pain and confusion as death approaches. Severe pain is common; more than one-quarter of patients with cancer experience serious pain 3 to 6 months before death and more than 40% were in serious pain during their last 3 days of life. However, dying patients are only modestly depressed and anxious during their last 3 days of life. As death approaches, patients favor comfort measures over life-extension, and about two-thirds want to forego resuscitation within 3 days of death. Families of patients dying with cancer incurred significant financial burdens during the last 6 months of life, and much of this burden was already experienced by 3 to 6 months before death. CONCLUSIONS: The last 6 months of life for patients with cancer is characterized by functional decline and poorly controlled severe pain and confusion. Although patients increasingly prefer comfort care as they near death, many die in severe pain. These findings highlight important opportunities to improve the quality of care at the end of life for patients dying with cancer.

Passage to nonselective media transiently alters growth of mycophenolic acid-resistant mammalian cells expressing the escherichia coli xanthine-guanine phosphoribosyltransferase gene: implications for sequential selection strategies.

The Escherichia coli xanthine-guanine phosphoribosyltransferase gene (Ecogpt) rescues mammalian cells from inhibition of purine nucleotide biosynthesis by mycophenolic acid (MPA). We used Ecogpt and other selectable markers to obtain subclones of NIH 3T3 derivatives (EN/NIH) stably expressing transfected genes of interest. In their respective selective mediums, growth of MPA-resistant (MPA(R)) isolates was indistinguishable from that of aminoglycoside-resistant counterparts expressing selectable marker genes conferring resistance to protein synthesis inhibitors hygromycin B, puromycin, and G418. Growth of aminoglycoside-resistant isolates remained unaltered on passage to nonselective media. In contrast, MPA(R) cells transferred from MPA complete media to nonselective media displayed morphologic changes with static growth. These findings resolved completely by third passage in nonselective media and were independent of the gene of interest cis-linked to the selectable marker. Sequential selection strategies involving cell culture conditions resulting in these altered growth characteristics significantly impaired detection (by selection in G418) of genomic events associated with reactivation of enhancerless, transcriptionally silent neointegrants present in MPA(R) EN/NIH isolates. We explored the cause of these cell culture findings and defined transfection and sequential selection strategies for MPA(R) derivatives that successfully circumvented these effects.

POEMS syndrome with myocardial infarction: observations concerning pathogenesis and review of the literature.

A 27-year-old white man with no significant risk factors for coronary artery disease presented with a 9-month history of progressive impotence, gynecomastia, lower extremity paresthesias, and extensive myocardial infarction and subsequently developed ulcerative proctitis. A diagnosis of POEMS syndrome was made based on the clinical presentation; additional physical findings of papilledema, clubbing, and hyperpigmentation; and laboratory findings of an immunoglobulin G M component of the lambda subtype, elevated cerebrospinal fluid protein, and typical sclerotic bone lesions. Abnormal in vitro binding of the patient's serum immunoglobulin to testicular tissue was also seen. Cardiac catheterization showed evidence of diffuse coronary artery narrowing and left ventricular wall motion abnormalities. Diffuse coronary involvement and ulcerative proctitis have not been previously described in POEMS syndrome. It is hypothesized that an abnormal immunoglobin (or fragment) is responsible for both findings. Furthermore, the detection of antitesticular autoantibodies suggests the possibility of an interaction between the antibody and Leydig cells, leading to an alteration in the synthesis and release of sex steroids and thereby explaining the gonadal failure seen in this syndrome. Long-term glucocorticoid therapy for the past 5 years has resulted in marked subjective and objective improvement.

Oncogenes result in genomic alterations that activate a transcriptionally silent, dominantly selectable reporter gene (neo).

Although oncogenes and tumor suppressor genes have been implicated in carcinogenesis and tumor progression, their relationship to the development of genomic instability has not been elucidated. To examine this role, we transfected oncogenes (polyomavirus middle [Py] and large T [MT and LT]) and adenovirus serotype 5 E1A) into two NIH 3T3-derived cell lines, EN/NIH 2-4 and EN/NIH 2-20. Both cell lines contain two stable integrants of a variant of the retrovirus vector pZipNeoSV(x)1 that has been modified by deletion of the enhancer elements from the long terminal repeats. DNA rearrangements activating the silent neomycin phosphotransferase gene (neo) present in these integrants were identified by selection of cells in the antibiotic G418. Whereas control-transfected EN/NIH cell lines do not yield G418-resistant subclones (GRSs), a fraction of oncogene-transfected EN/NIH 2-4 (8 of 19 Py MT, 5 of 17 Py LT, and 11 of 19 E1A) and 2-20 (7 of 15 Py MT) cell lines gave rise to GRSs at differing frequencies (0.33 x 10(-6) to 46 x 10(-6) for line 2-4 versus 0.11 x 10(-6) to 1.3 x 10(-6) for line 2-20) independent of cell generation time. In contrast, a distinctly smaller fraction of mutant Py MT-transfected EN/NIH cell lines (1 of 10 MT23, 1 of 10 MT1015, and 0 of 10 MT59b) resulted in GRSs. Southern analysis of DNA from selected oncogene-transfected GRSs demonstrated genomic rearrangements of neo-containing cellular DNA that varied in type (amplification and/or novel fragments) and frequency depending on the specific oncogene and EN/NIH cell line used in transfection. Furthermore, only one of the two neo-containing genomic loci present in both EN/NIH cell lines appeared to be involved in these genomic events. In addition to effects related to the genomic locus, these observations support a role for oncogenes in the development of genetic changes associated with tumor progression.

Purpose of admission and resource use during cancer hospitalizations.

This study examined the role of purpose of admission (POA) in hospitalizations for lung, colon, and breast cancers, using the 1985 20-percent Medicare provider analysis and review file. Six POA categories were created from discharge abstract data. Average hospitalization charges, per diem charges, length of stay, and rates of death varied significantly by POA (p < .001). Rural and small hospitals were more likely to admit patients for palliation, while urban and large hospitals admitted relatively more patients for active interventions (p < .0001). POA and indicators of case complexity added only modestly to the ability of diagnosis-related groups to predict hospitalization charges.