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Biomedical subjects

Victor T Chang

Publications and source records attributed to Victor T Chang.

At least 19 recordsLinked to original sources

Correlation of ZAP-70 expression in B cell leukemias to the ex vivo response to a combination of fludarabine/genistein.

The role of ZAP-70 expression on the ex vivo response of blood cells from CLL and PLL patients to a combination of fludarabine, a purine analog, and genistein, a tyrosine kinase inhibitor was studied. Patient cells were studied for the expression of ZAP-70 mRNA and its relation to the induction of apoptosis in response to treatment with genistein 15-60 muM and/or fludarabine 3 muM. The combination of genistein and fludarabine resulted in a significantly increased induction of apoptosis relative to the fludarabine alone. The ex vivo patient cells with a high ZAP-70 expression underwent more apoptosis in response to genistein than did patient cells with a low ZAP-70 mRNA expression. In contrast, basal IL-10 mRNA expression correlated negatively with apoptosis induction in response to genistein (P < 0.01). These studies suggest that, in malignant B cells that express elevated levels of the ZAP-70 signaling molecule, genistein may inhibit the ZAP-70 tyrosine kinase activity, resulting in cell death. The ZAP-70 may serve as a target for therapy. In addition, these studies suggest that the IL-10 expression by malignant B cells may not only suppress anti-tumor T cell responses in vivo, but also promote the survival of malignant B cells despite treatment with chemotherapeutic agents.

Aged↗

Metastatic acetabular fractures: evaluation and approach to management.

Although bone metastasis to the acetabulum can cause significant disability from pain and immobility, little has been written about the diagnosis and management of a pathologic acetabular fracture. We present three patients with metastatic acetabular fractures and discuss an approach to evaluation and management. When a high index of suspicion of fracture exists, further radiographic workup is warranted. Management requires a multidisciplinary approach. Factors such as age, associated comorbidities, natural history of the underlying primary cancer, general health status, prognosis, acetabular fracture characteristics, and quality of bone should be considered. We briefly discuss the options available to nonoperative candidates.

Acetabulum↗

Update in cancer pain syndromes.

Cancer pain assessment and management are integral to palliative medicine. This paper reviews recent publications in the period 1999-2004 in the broad categories of epidemiology, pain assessment, nonpharmacologic approaches to cancer pain (radiation therapy, anesthetic blocks, palliative surgery and chemotherapy, complementary and alternative medicine), and in nociceptive pain, neuropathic pain, visceral pain, and bone pain.

Humans↗

Regional cancer pain syndromes.

Cancer pain often presents in a body region. This review summarizes articles from 1999-2004 relevant to cancer pain syndromes in the head and neck, chest, back, abdomen, pelvis, and limbs. Although the evidence is limited, progress is being made in further development of the evidence base to support and guide current practice.

Anatomy, Regional↗

Study of unmet needs in symptomatic veterans with advanced cancer: incidence, independent predictors and unmet needs outcome model.

Veteran patients possess distinctive characteristics such as a higher mortality rate, lower socioeconomic status and poorer health status. We report the prevalence and predictors of unmet needs and examine the association between unmet needs and quality of life (QOL). Two hundred ninety-six male cancer patients who presented with distressing symptom(s) completed the following instruments: a 14-item multidimensional unmet needs questionnaire, Functional Assessment of Cancer Therapy (FACT-G), Memorial Symptom Assessment Scale-Short Form (MSAS-SF) and other validated measurements of function, depression, health and social support. Multiple linear regression models were used to identify independent predictors of each unmet needs domain and of total unmet needs. The relationships between total unmet needs, QOL and multidimensional variables were also explored. The median number of total unmet needs was three, and the most frequently reported unmet needs areas were physical (80.0%), activities of daily living (53.3%), nutrition (46.1%) and emotional (32.5%). Different predictors of each unmet needs domain were identified. Younger age was associated with a higher risk of unmet needs in physical, economic and medical domains. Higher psychological symptom distress was associated with more unmet needs in the emotional/social, economic and medical domains. Physical symptom distress, extent of disease and health measure were only significant in the physical unmet needs domain. The depression, psychological and physical symptom distress scores, confident and affective social support scores, total unmet needs and age independently predicted FACT-G total QOL score (R(2)=63%, P < 0.00001). Patients with higher psychological, physical symptom distress and depression scores, younger age, lower functional status and metastatic disease were more likely to report more unmet needs. The total number of unmet needs was predictive of QOL. The unmet needs and QOL outcomes model was developed but needs further validation.

Adult↗

HER-2/neu and p53 in osteosarcoma: an immunohistochemical and fluorescence in situ hybridization analysis.

The overexpression of HER-2/neu and p53 has been associated with poor outcome in many neoplasms. Their role in patients with osteosarcoma is unclear. We studied the expression of HER-2/neu and p53 in 22 osteosarcoma samples (from 20 patients--2 had locally recurrent disease) biopsied at the University of Medicine and Dentistry of New Jersey (UMDNJ) from 1996-2000 using both immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Fourteen patients (14 samples) presented with Stage II and 6 patients (8 samples) presented with Stage III disease. Median follow-up is two years (range one year to five years). Four of 22 (18%) samples showed focal membranous or cytoplasmic positivity for HER-2/neu and six of 22 samples (27%) showed nuclear positivity for p53 by IHC analysis. In contrast, none of 22 tested samples showed gene amplification for HER-2/neu by FISH analysis. Seven of 13 HER-2/neu and p53 negative patients (54%) are currently disease free (between one year to five years). In this sample of patients, the HER-2/neu oncogene is not overexpressed or amplified in osteosarcoma; six of 22 samples (27%) showed overexpression of p53 by IHC analysis. By FISH, none of the samples demonstrated deletion of p53. Neither HER2/neu nor p53 expression was important for the biology of osteosarcoma in this population.

Adolescent↗

Shorter symptom assessment instruments: the Condensed Memorial Symptom Assessment Scale (CMSAS).

BACKGROUND: Rapid and efficient symptom assessment is an important aspect of palliative care. The objective was to determine whether a smaller number of symptoms from the 32-item Memorial Symptom Assessment Scale Short-Form (MSAS-SF) could convey equivalent quality of life (QOL) information. METHODS: Responses from 479 medical oncology patients who completed the MSAS-SF and the Functional Assessment Cancer Therapy (FACT-G) were analyzed. Canonical correlations were performed to assess the relationships of 32 MSAS-SF symptoms to quality of life (FACT-G domains) and clinical variables [age, Karnofsky performance status (KPS), stage of disease, and inpatient status]. The relation of the subscales of the Condensed MSAS (CMSAS) and FACT-G to survival was assessed in a multivariate model. RESULTS: The median age was 67 years (range, 20-89) and median KPS was 80% (range, 20-100). Primary sites were prostate in 141 (29%) patients, lung in 121 (26%) patients, colorectal in 53 (11%) patients, hematologic in 50 (10%) patients, head and neck in 30 (6%) patients and other in 84 (18%) patients. Median survival was 245 days (range, 1-2,215 days). Canonical correlation analyses identified a five-dimensional QOL factor structure. Symptoms important for QOL also correlated significantly with survival and provided the basis for the CMSAS with 14 symptoms and 3 subscales (CMSAS SUM, CMSAS PHYS, and CMSAS PSYCH). In multivariate analyses, the CMSAS PSYCH predicted survival independently of stage, performance status, and QOL. The CMSAS takes 2-4 minutes to complete. CONCLUSION: The CMSAS contains both QOL and survival information approximately equivalent to the original 32 items.

Adult↗

Prediction of survival for advanced cancer patients by recursive partitioning analysis: role of Karnofsky performance status, quality of life, and symptom distress.

We performed an exploratory recursive partitioning analysis (RPA) in 429 metastatic cancer patients who had completed a Functional Assessment of Cancer Therapy-General (FACT-G) and a Memorial Symptom Assessment Scale-Short Form (MSAS-SF) to define survival prognostic groups. The Cox model analysis also was performed. Both RPA and Cox models included Karnofsky performance status (KPS), age, FACT-G subscales, and MSAS-SF subscales as survival predictors. Of 429 patients, 348 patients (81.1%) had expired at time of analysis. The median age was 67 years (27-89), with median length of survival of 147 days. The RPA identified four distinct survival groups (p < .0001) with three variables: KPS, physical well-being, and physical symptom distress. The most significant split was KPS of 50%, followed by physical well-being score of 25 and physical symptom distress score of 0.6. The median survival time was 29 days for patients with KPS < 50%; 146 days for patients with KPS > or = 50% and physical well-being < 25; 292 days for patients with KPS > 50%, physical well-being > or = 25, and physical symptom distress score > 0.6; and 610 days for patients with KPS > or = 50%, physical well-being > or = 25, and physical symptom distress score < or = 0.6. The Cox model found, in addition to KPS (p < .0001) and physical well-being (p = .08), different predictors: psychological symptom distress (p = .0007), global distress index (p = .02), and age (p < .0001). We concluded that the KPS, quality of life, and symptom distress scores can be combined to define prognostic groups. Such models may be helpful for clinical decision making.

Adult↗

Study of hormone refractory prostate cancer: hospital care and palliative care resource use at a VA medical center.

Palliative care plays a central role in the management of hormone refractory prostate cancer patients (HRPC), yet little is known about palliative care resource use. Computerized medical records of a retrospective cohort of 89 consecutive HRPC patients seen at a VA medical center from 1994 to 1999 were reviewed for hospital and palliative care resource use in the last 6 months of life. There were 51 Caucasian and 38 African American patients; 95% of patients were admitted to the hospital for symptom management (median of 2 admissions); 98% visited clinics (median 19 visits); 35% went to the emergency room (median of 1 visit); 60% died in the hospital (median length of last hospitalization of 22 days); 49% received palliative radiation; 52% used rehabilitation; 57% received blood transfusion (median 2 units). Thirty-five patients (40%) received hospice care (median stay 35 days). The most frequently prescribed medications included opioids (90%), laxatives (89%), H2-blockers (57%), antiemetics (55%), diuretics (49%), and corticosteroids (43%). The prevalence of patients receiving opioids, as well as the dose of opioids increased over time. There was no difference in categories of palliative care resource use or survival by race. The median survival for all patients was 13 months. The results begin to highlight the extent of care and resources needed by patients with end-stage HRPC. This information will be of importance in planning palliative care for patients with HRPC and in designing future prospective studies.

Black or African American↗

Acute myelogenous leukemia associated with extreme symptomatic thrombocytosis and chromosome 3q translocation: case report and review of literature.

Acute leukemias with thrombocytosis have been recently linked with structural abnormalities of the short arm of chromosome 3. A 46-year-old man with a 2-month history of recurrent transient ischemic attacks and abdominal pain developed an ischemic left foot and a gangrenous toe as his initial symptoms. Platelet count was 3.5 x 10(6)/microL, and despite plateletpheresis, the patient required left-leg amputation. Pathologic examination was remarkable for arterial thrombosis in the absence of atherosclerotic lesions. A diagnosis of acute myeloid leukemia with a novel translocation between chromosomes 3q21, 16, and 7 was made. Induction therapy was unsuccessful, and the patient died of overwhelming sepsis within 5 weeks of diagnosis. The striking features of this case were extreme symptomatic thrombocytosis, peripheral gangrene without atherosclerosis, and a novel three-way chromosomal translocation involving chromosome 3q21.

Acute Disease↗

Cancer breakthrough pain characteristics and responses to treatment at a VA medical center.

The purpose of this study is to analyze cancer breakthrough pain (BP) characteristics and how BP responds to conventional cancer pain management. Seventy-four cancer pain patients with worst pain severity >or=4 out of 10 completed the Brief Pain Inventory (BPI), Memorial Symptom Assessment Scale-Short Form, Functional Assessment Cancer Therapy and Breakthrough Pain Questionnaires (BPQ) at an initial interview. Agency for Health Care Policy and Research (AHCPR) cancer pain management guidelines were followed. Pain syndromes and morphine equivalent daily dose (MEDD) orally were determined. One-week follow-up assessments were obtained in 66 patients with BPI and BPQ. The BP characteristics were similar at both time points. On day 1, 52 patients (70%) had BP, and the BP was unpredictable in 30 patients (58%). The median time to worst BP severity was 3 min. Patients with BP had significantly higher worst pain (P<0.001). At week 1, the median MEDD doubled from 60 to 120 mg orally, and the number of patients who received adjuvant analgesics doubled from 31.1% (23 patients) on day 1 to 62.2% (41 patients). At week 1, 21 patients (32%) remained without BP, 21 patients (32%) were classified as BP responders and 24 patients (36%) were BP non-responders. The mean pain relief was similar for all three subgroups, i.e. around 80%. Compared to BP responders, BP non-responders had significantly higher worst pain (P<0.0001), average pain (P<0.004), and higher BPI interference parameters and shorter time to worst pain severity. The study confirmed the applicability of the BPQ to an US veteran population, and that pain management following the AHCPR guidelines is effective for a group of patients with cancer related BP. Underlying pain syndromes and the BP location may influence the response of BP to treatment. Patients with bone pain located in the spine, back, and pelvis may be at risk for resistant BP.

Adult↗

Longitudinal quality of life in advanced cancer patients: pilot study results from a VA medical cancer center.

To document quality-of-life (QOL), symptom distress and Karnofsky Performance Status (KPS) over time, 67 advanced cancer patients completed the Functional Assessment of Cancer Therapy (FACT-G) and Memorial Symptom Assessment Scale - Short Form (MSAS-SF) from the time of determination of no active anti-cancer treatment to death at 3-6 week intervals. The KPS was determined at each time point. Statistical analyses with mixed effects models were performed to examine the association between changes in QOL, symptom distress and KPS at selected time points in the advanced cancer trajectory. Median survival for the population was 115 days, and a median of 5 interviews was completed per patient. Slow steady changes in KPS, MSAS-SF and FACT-G QOL parameters started 6 months prior to death, with accelerated decline in the last 2 to 3 months and dramatic increase in psychological symptoms during the last month. Different domains changed at different rates at different selected time points. The correlation between changes in KPS, FACT-G parameters and MSAS-SF subscales at enrollment and near death suggests that when patients were stable, changes in KPS correlated significantly with changes in sum FACT-G QOL and physical well being, and with changes in the MSAS-SF subscales. However, when patients were near death, changes in KPS did not correlate with any other changes, and only emotional well being reflected changes in physical and psychological symptom distress. The sequence of changes, and how determinants of symptom distress and QOL change over time, may help clinicians assess the prognosis of terminally ill patients and plan appropriate interventions.

Humans↗

Multidimensional independent predictors of cancer-related fatigue.

The purpose of this study was to identify independent predictors of clinically significant fatigue based upon a multidimensional model. A total of 180 cancer patients completed the Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), Memorial Symptom Assessment Scale Short Form (MSAS-SF), and the Zung Self-Rating Depression Scale (SDS). Additional data included Karnofsky Performance Status (KPS) score, laboratory tests, and demographic information. The BFI usual fatigue severity > or =3/10 was defined as clinically significant fatigue. Possible independent variables were identified from a biopsychosocial model of fatigue. Fisher's exact test was used to univariately assess the association of each variable with clinically significant fatigue. Multiple logistic regression analyses were used to identify independent predictors of fatigue within each dimension, and then across dimensions. Fatigue was present in 113 (62%) patients, and 80 (44.4%) patients had usual fatigue > or =3/10. The unidimensional independent predictors were use of analgesics (situation dimension); hemoglobin and serum sodium (biomedical dimension); feeling drowsy, dyspnea, pain and lack of appetite (physical symptom dimension); and feeling sad and feeling irritable (psychological symptom dimension). In a multidimensional model, dyspnea, pain, lack of appetite, feeling drowsy, feeling sad, and feeling irritable predicted fatigue independently with good calibration (Hosmer Lemeshow Chi Square=5.73, P=0.68) and discrimination (area under the receiver operating characteristic curve=0.88). Physical and psychological symptoms predict fatigue independently in the multidimensional model, and superseded laboratory data. These findings support a symptom-oriented approach to assessment of cancer-related fatigue.

Adult↗

Knowledge and attitudes toward end-of-life care in veterans with symptomatic metastatic cancer.

OBJECTIVES: The purposes of this study were to study symptomatic metastatic cancer patients' knowledge and attitudes toward end-of-life (EOL) care and to examine how patient-perceived health status affects attitudes toward EOL care and survival. METHODS: From 1999 to 2002, 254 symptomatic metastatic cancer patients at the VA New Jersey Health Care System completed the Vermont Voices on Care of the Dying Questionnaire. Survival status and location of death were obtained. Descriptive statistics and the chi square method were used to assess the differences between African Americans (N=109) and Caucasians (N=135), and between different patient-perceived health status groups. A log-rank test was performed to assess for differences in median survival length between different patient-perceived health-status groups. RESULTS: Veterans' responses to the Vermont questionnaire showed knowledge deficits regarding EOL care. There was wide variation in self-rankings of health status: 45.6% of patients rated their illness as serious and life threatening, 18.9% considered their health problem significant but not life threatening, 2.8% thought they were in good health, and one-third of patients were unsure about their health status. Most patients (86.2%) preferred physician frankness when communicating bad news and 61.8% preferred family involvement in EOL discussions. African American patients were less likely to have completed advance directives (p < 0.0001), to have knowledge about hospice programs (p < 0.00001), and to feel capable of assessing their health situation (p = 0.04). Patient-rated health status affected completion rates of advance directives and survival. SIGNIFICANCE OF THE RESEARCH: These findings demonstrate knowledge deficits and racial differences in attitudes and values toward EOL care in veterans with cancer. The Vermont questionnaire enables patients to state their EOL preferences but may not be detailed enough for clinical applications. Patient-rated health status may be an important explanatory variable for EOL preferences and length of survival.

Adult↗

Caregiver unmet needs, burden, and satisfaction in symptomatic advanced cancer patients at a Veterans Affairs (VA) medical center.

OBJECTIVES: Caregiver outcomes among those caring for symptomatic advanced cancer patients at VA Medical Centers have not been well reported. The purposes of this study were (1) to identify the caregiver characteristics and their unmet needs; (2) to examine the association between caregiver unmet needs, caregiver burden, and caregiver satisfaction; and (3) to identify the independent predictors of different caregiver outcomes. METHODS: One hundred caregivers completed three caregiver outcomes instruments: Family Inventory of Needs (FIN), Care Strain Index (CSI), and Family Satisfaction with Advanced Cancer Care (FAMCARE). The caregivers' demographics and their function, depression, health status, and social support status as well as the caregivers' perception of the patients' unmet needs (PPUN) were obtained. Principal component analysis was performed to examine the underlying dimensions of caregiver outcome measures. Pearson correlation and stepwise multivariate regression analyses were performed. RESULTS: The median number of unmet needs was 2 and the median CSI score was 4. Most of unmet needs were related to information needs (needing more information related to home care, finding help with the problems at home, and disease prognosis) and symptom management. The majority of caregivers were satisfied or very satisfied by the care patients received. Spouse caregivers (N = 60, 60%) were significantly older (p = 0.006) with higher unemployment rates (p = 0.001), higher depression scores (p = 0.04), and lower social support scores (p < 0.0001) than nonspouse caregivers (N = 40, 40%). The PPUN predicted caregiver burden and the presence of caregiver unmet needs independently. The presence of caregiver unmet needs was the only independent predictor of caregiver satisfaction. Caregivers with a high PPUN and higher depression score experienced a higher burden. SIGNIFICANCE OF THE RESEARCH: The caregiver outcome model is proposed and needs to be further validated in a new cohort of caregivers.

Adult↗

Rehabilitation needs of an inpatient medical oncology unit.

OBJECTIVE: To identify prospectively functional impairments and rehabilitation needs in an acute care medical oncology unit. DESIGN: Prospective cohort study. SETTING: Inpatient medical oncology unit at a Veterans Affairs hospital. PARTICIPANTS: Fifty-five patients admitted over a 6-month period. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FIM instrument, functionally based physical examination, Rehabilitation Needs Assessment, and Recreational Needs Assessment. RESULTS: On admission, the mean FIM total score was 105 out of 126, the FIM motor score was 72 out of 91, and the FIM cognitive score was 34 out of 35. The functionally based physical examination did not generally correlate with scores obtained on the FIM. Forty-eight (87%) patients had rehabilitation needs on admission. Forty-six (84%) patients had rehabilitation needs on discharge. Rehabilitation Needs Assessment on admission showed deconditioning in 42 (76%) patients; mobility impairment in 32 (58%) patients; a significant decrease in range of motion in 23 (42%) patients; deficits in activities of daily living in 12 (22%) patients; a need for recreational therapy in 7 (13%) patients; potential for benefit from patient education in 30 (55%) patients; and a need for modalities, edema control, or wound care in fever than 5% of patients. The most commonly requested recreational activity was reading. CONCLUSIONS: Patients admitted to inpatient medical oncology units have many unmet, remediable rehabilitation needs that may not be recognized by nonrehabilitation physicians and other clinical staff. These findings suggest that assessment of medical oncology patients may be enhanced by consultation with rehabilitation medicine specialists.

Activities of Daily Living↗

A comparison of three fatigue measures in veterans with cancer.

Fatigue is a highly prevalent and distressing symptom in cancer patients. The purpose of this study was to assess the validity of three fatigue measures [the Brief Fatigue Inventory (BFI), the Functional Assessment of Cancer Therapy Fatigue Subscale (FACT-F), and the lack of energy item from the Memorial Symptom Assessment Scale Short Form (MSAS-SF)] and compare these measures in relation to broader quality-of-life (QOL) constructs and clinical factors in veteran cancer patients. One-hundred-eighty cancer patients completed the BFI, FACT-F, FACT-G, MSAS-SF, and the Zung depression scale with concurrent Karnofsky performance status (KPS), laboratory tests, and demographic data. The Cronbach alpha coefficient was from 0.93 to 0.94 for BFI fatigue scales and 0.94 for FACT-F. There were significant correlations between BFI subscales, FACT-F, and lack of energy from MSAS-SF (p < 0.0001). All three fatigue measures showed significant correlation with MSAS-SF symptom subscales (p < 0.0001), FACT-G subscales (p < 0.0001), depression (p < 0.0001), KPS (p < 0.0001), inpatient status (P < 0.0001), insomnia (p < 0.05), hemoglobin (p < 0.05), and albumin levels (p < 0.01). Distress from lack of energy discriminated among levels from the BFI, FACT-F, and FACT-G subscales and MSAS-SF subsclea by one-way of variance analysis. Patient responses to BFI, FACT-F, and the lack of energy item yielded similar information about broader QOL constructs and clinical factors. Single questions about lack of energy, or fatigue severity, may provide a simple and acceptable way to assess fatigue.

Adult↗

Symptom control.

Symptom control has become increasingly recognized as an important goal in patient care. In this article, advances in symptom assessment, and various definitions of symptom improvement are reviewed. Theoretical concepts underlying symptom control and clinically significant change are presented, as well as the role of symptom control as an endpoint in clinical trials. Symptom control is then surveyed in two broad categories for selected symptoms. The first area is therapy related symptoms, secondary to chemotherapy, radiation, hormonal therapy, and surgery. Symptoms reviewed include chemotherapy related mucositis, emesis, fatigue; hot flashes; and radiation related dermatitis, xerostomia, and mucositis. The second area is palliative oncologic approaches to disease-related symptoms. Results in palliative chemotherapy, palliative radiation therapy, cancer pain, and lack of appetite are summarized. Areas requiring further research are noted. Findings are presented in both a clinical and research context to help guide the reader with interpreting symptom control studies.

Antineoplastic Agents↗