Health care for childhood cancer survivors: insights and perspectives from a Delphi panel of young adult survivors of childhood cancer.

BACKGROUND: Most children diagnosed with cancer are surviving into adulthood but are not receiving adequate or appropriate follow-up health care. However, to the authors' knowledge, there is little literature published to date exploring potential barriers to long-term risk-based follow-up care for young adult survivors of childhood cancer. METHODS: In the current study, using a modified Delphi technique, young adult cancer survivors identified barriers to utilizing appropriate follow-up care and offered suggestions for ways to enhance health care in this young adult population. RESULTS: Major barriers to health care were found to be a lack of knowledge on the part of both physicians and survivors regarding long-term health issues related to cancer. Suggestions to enhance care included self-advocacy training for survivors and advanced training for primary care physicians who may treat childhood cancer survivors as they transition into adulthood. CONCLUSIONS: The results of the current study are consistent with reports that young adult survivors of childhood cancer need or desire information regarding their medical histories, psychosocial support, and social advocacy.     

The superior prognostic value of humoral factors compared with molecular proliferation markers in renal cell carcinoma

BACKGROUND: The American Joint Committee on Cancer and the Union Internationale Contre le Cancer have acknowledged routine laboratory parameters, such as serum calcium, alkaline phosphatase, hemoglobin, and the erythrocyte sedimentation rate (ESR), as predictors of survival in patients with renal cell carcinoma. The predictive value of these parameters compared with proliferation markers, such as Ki-67, proliferating cell nuclear antigen (PCNA), topoisomerase II-alpha, and p100, has not been determined. METHODS: Forty-eight consecutive patients who underwent nephrectomy for nonmetastatic renal cell carcinoma between 1990 and 1994 were observed up to 120 months postoperatively. Ten of 48 patients developed tumor progression 6-69 months after surgery. Routine preoperative laboratory parameters as well as tumor-specific data were assessed. Findings were compared with tumor proliferation indices, which were obtained by immunohistochemical staining for nuclear antigens Ki-67, PCNA, topoisomerase II-alpha, and p100 in paraffin embedded tumor tissue. RESULTS: Univariate and multivariate statistical analyses demonstrated superiority of routine laboratory values compared with tumor proliferation indices in predicting progression-free survival and disease-specific death. The best predictor after tumor size and symptomatic presentation was ESR (P < 0.0001), with ESR values > 70 mm at 2 hours indicating a significantly poorer prognosis. Only the proliferation marker Ki-67 reached univariate significance at a threshold of 7%. CONCLUSIONS: Routine laboratory parameters, such as alkaline phosphatase, lactate dehydrogenase, thrombocyte count, and especially ESR, provided superior long-term prognostic information for patients with nonmetastatic renal cell carcinoma compared with the molecular tumor proliferation markers Ki-67, PCNA, topoisomerase II-alpha, and p100.     

Microarray analyses uncover UBE1L as a candidate target gene for lung cancer chemoprevention

Retinoids, natural and synthetic derivatives of vitamin A, are active in cancer therapy and chemoprevention. We reported previously that all-trans-retinoic acid (RA) treatment prevented carcinogen-induced transformation of immortalized human bronchial epithelial (HBE) cells. To identify cancer chemopreventive mechanisms, immortalized (BEAS-2B), carcinogen-transformed (BEAS-2B(NNK)), and RA-chemoprevented (BEAS-2B(NNK/RA)) HBE cells were used to conduct microarray analyses independently. Species increased in chemoprevented as compared with immortalized HBE cells (group I) and those augmented in chemoprevented as compared with transformed HBE cells (group II) included known RA-target genes as well as previously unrecognized RA-target genes in HBE cells. Unexpectedly, both groups were also enriched for interferon-stimulated genes. One interferon-stimulated gene of particular interest was UBE1L, the ubiquitin-activating enzyme E1-like protein. UBE1L expression was also induced after prolonged RA-treatment of immortalized HBE cells. UBE1L mRNA was shown previously as repressed in certain lung cancer cell lines, directly implicating UBE1L in lung carcinogenesis. Notably, UBE1L immunoblot expression was reduced in a subset of malignant as compared with adjacent normal lung tissues that were examined. Immunohistochemical analyses were performed using a new assay developed to detect this species using rabbit polyclonal anti-UBE1L antibodies independently raised against the amino- or carboxyl-termini of UBE1L. Studies done on paraffin-embedded and fixed tissues revealed abundant UBE1L, but low levels of cyclin D1 expression in the normal human bronchial epithelium, indicating an inverse relationship existed between these species. To study this further, cotransfection into HBE cells of wild-type or mutant UBE1L species was accomplished. In a dose-dependent manner, wild-type but not mutant UBE1L species repressed cyclin D1 expression. This implicated UBE1L in a retinoid chemoprevention mechanism involving cyclin D1 repression described previously. Taken together, these findings directly implicate UBE1L as a candidate-pharmacologic target for lung cancer chemoprevention. These findings also provide a mechanistic basis for the tumor suppressive effects of UBE1L through cyclin D1 repression.     

Elevated levels and distinct patterns of expression of A-type cyclins and their associated cyclin-dependent kinases in male germ cell tumors

Aberrant expression of several key regulators controlling the G1/S phase of the cell cycle has been implicated in human male germ cell tumorigenesis. Given the critical role of cyclin A2 at both the G1/S and G2/M transitions and the essential role for cyclin A1 in male germ cell development, our present study focused on the involvement of the A-type cyclins in the transformation and progression of male germ cell tumors (GCTs). The expression of the A-type cyclins and their catalytic partners Cdk1 and Cdk2 was examined in all types and stages of human male GCTs, including carcinoma in situ(CIS), seminoma and non-seminoma GCTs, along with normal testis samples. Elevated levels of cyclin A2, Cdk1 and Cdk2 were detected in the majority of GCTs and were correlated with the invasiveness of the tumors (p < 0.05). Cyclin A1 expression was virtually undetectable in CIS and seminoma, but was aberrantly expressed in all non-seminomatous GCTs. Cyclin A2 expression was strongly correlated with that of its catalytic partners Cdk1 and Cdk2 in all types of testicular tumors examined (p < 0.05), whereas a strong correlation between cyclin A1 and Cdk1 or Cdk2 was only seen in non-seminomatous GCTs (p < 0.05). Histone kinase activities of cyclin A1/Cdks and cyclin A2/Cdks were found to be elevated in tumors. Our data suggest that aberrant expression of A-type cyclins and their Cdks is a significant factor in male germ cell tumorigenesis. The abundant ectopic expression of cyclin A1 in non-seminomatous GCTs and its absence in CIS and seminomas is likely linked to the tumor transformation and progression and may be relevant to clinical prognosis.     

Pilot evaluation of black cohosh for the treatment of hot flashes in women

Background. Hot flashes cause significant morbidity in postmenopausal women, including women with breast cancer. We undertook a pilot study to estimate the effectiveness of black cohosh to reduce hot flashes. Methods. Women who reported significant hot flashes (≥ 14 per week) were enrolled. Black cohosh was given in the form of the commercial product Remifemin. The first week was a no-treatment baseline period, and therapy was given for the subsequent 4 weeks. Hot flash data were collected by daily questionnaires during baseline and treatment weeks. Adverse effects were recorded. Results. Twenty-one women completed the study. Their mean age was 56 years (range, 38-80). Thirteen patients had a history of breast cancer. Six patients were taking tamoxifen or raloxifene. Patients reported an average of 8.3 hot flashes per day during the baseline week. The reduction in mean daily hot flash frequency was 50% (95% CI, 34%-65%), while weekly hot flash scores were reduced 56% (95% CI, 40%-71%) at completion of the study. Overall, patients reported less trouble with sleeping, less fatigue, and less abnormal sweating. No patients stopped therapy because of adverse effects. Conclusions. Black cohosh appeared to reduce hot flashes and had a low toxicity. The efficacy found in this trial seems to be more than would be expected by a placebo effect (20%-30% hot flash reduction in previous trials). These results suggest that further evaluation of this black cohosh preparation with a phase III randomized trial is indicated.     

Central reassessment of GH concentrations measured at local treatment centers in children with impaired growth: consequences for patient management

OBJECTIVE: GH deficiency is diagnosed in children if serum GH fails to rise above a predefined cutoff value in response to at least two stimuli. Diagnostic decisions based on this testing are highly variable between centers and depend on the GH assays used. Considering the large spectrum of commercially available GH assays, we wanted to evaluate the agreement between assays, and to test whether assay-related variability of diagnostic decisions could be reduced by reassessment of peak GH concentrations in a reference center. DESIGN: We reanalysed 699 peak GH serum samples obtained after GH testing of 382 children and adolescents from 19 centers using three reference assays and compared these results with those obtained with the local assays. A subgroup of 132 patients tested with the combination of insulin hypoglycemia test and arginine test was evaluated for changes in the assignment to the diagnostic group of GH deficiency. RESULTS: The mean difference between methods ranged from 5.4 to 10.3 mU/l, slopes of the regression lines from 1.28 to 1.65. Significant non-linearity was detected in five of six assay comparisons, indicating that most assay results cannot be interconverted by the use of a factor. Overall agreement between reference and local assays was only moderate. Significant changes in diagnostic assignment occurred when different assays were used on the same patient (P<0.0001-P<0.0023). Based on GH remeasurement by one reference assay, 36 of 132 patients were categorized differently, with 35 patients changing into the GH-deficient group. Similar findings were obtained with the other reference assays. CONCLUSIONS: To decrease variability in GH testing related to assays and cutoff values, we recommend nationwide reassessment of GH peak sera in reference centers. Decisions to treat GH deficiency should incorporate the reference center results.     

Illness behavior and social support in patients with chronic venous ulcers

Venous ulcers are a chronic and costly condition for providers and payors, as well as for patients, particularly the elderly. To examine the association between chronic venous ulceration, illness behavior, and levels of social support, patients drawn from a separate clinical trial (N = 74) were interviewed using the Illness Behaviour Questionnaire and the Social Support Questionnaire. Results indicate that women had higher hypochondriasis (1.70 versus 1.03, P = 0.19), affective disturbance (2.70 versus 1.42, P = 0.08), and number of supports (Social Support Questionnaire, 2.41 versus 1.81, P = 0.056) than men, although no score achieved a standard level of statistical significance. Patients under 70 years of age had significantly higher hypochondriasis (1.96 versus 1.17, P = 0.021) and irritability (1.38 versus 0.90, P = 0.026) scores than those older than 70 years, although denial was significantly higher in those older than 70 years (3.97 versus 3.46, P = 0.045). The level of satisfaction with social support was significantly higher in those under 70 years of age (5.13 versus 4.97, P = 0.042). These results underscore the psychological and social cost imposed by chronic venous ulceration on older women. They also support previous studies implying a greater psychological burden on younger patients. The association between illness behavior and social support remains unclear, but examining the association between illness behavior and social support among patients with venous ulceration provides an opportunity to increase understanding of the psychological, physical, and social dynamics of this chronic condition.     

An outreach geriatric medication advisory service in residential aged care: a randomised controlled trial of case conferencing

BACKGROUND: efficient strategies are needed to provide specialist advice in nursing homes to ensure quality medical care. We describe a case conference intervention involving a multidisciplinary team of health professionals. OBJECTIVES: to evaluate the impact of multidisciplinary case conferences on the appropriateness of medications and on patient behaviours in high-level residential aged care facilities. DESIGN: cluster-randomised controlled trial. SETTING: ten high-level aged care facilities. PARTICIPANTS: 154 residents with medication problems and/or challenging behaviours were selected for case conference by residential care staff. INTERVENTION: two multidisciplinary case conferences involving the resident's general practitioner, a geriatrician, a pharmacist and residential care staff were held at the nursing home for each resident. MEASUREMENTS: outcomes were assessed at baseline and 3 months. The primary outcome was the Medication Appropriateness Index (MAI). The behaviour of each resident was assessed via the Nursing Home Behaviour Problem Scale. RESULTS: 45 residents died before follow-up. Medication appropriateness improved in the intervention group [MAI mean change 4.1, 95% confidence interval (CI) 2.1-6.1] compared with the control group (MAI mean change 0.4, 95% CI -0.4-1.2; P < 0.001). There was a significant reduction in the MAI for benzodiazepines (mean change control -0.38, 95% CI -1.02-0.27 versus intervention 0.73, 95% CI 0.16-1.30; P = 0.017). Resident behaviours were unchanged after the intervention and the improved medication appropriateness did not extend to other residents in the facility. CONCLUSION: multidisciplinary case conferences in nursing homes can improve care. Outreach specialist services can be delivered without direct patient contact and achieve improvements in prescribing.