High-Risk Merkel Cell Carcinoma of the Skin Treated With Synchronous Carboplatin/Etoposide and Radiation: A Trans-Tasman Radiation Oncology Group Study-TROG 96:07

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy was prospectively assessed in a group of patients with high-risk Merkel cell carcinoma (MCC) of the skin. Patients and Methods: Patients were eligible if they had disease localized to the primary site and nodes, and were required to have at least one of the following high risk features: recurrence after initial therapy, involved nodes, primary tumor size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks and synchronous carboplatin (area under the curve, 4.5) and intravenous etoposide 80 mg/m(2) days 1 to 3 was given in weeks 1, 4, 7, and 10. The median age of the group was 67 (range, 43-86) years, and there were 39 males and 14 females. Involved nodes (stage II) were present in 33 cases (62%). The sites involved were head and neck (22 patients), occult primary (13 patients), upper limb (eight patients), lower limb (eight patients), and trunk (two patients). Results: Fifty-three patients were entered between 1996 and 2001. The median potential follow-up was 48 months. There were no treatment related deaths. The 3-year overall survival, locoregional control, and distant control were 76%, 75%, and 76%, respectively. Tumor site and the presence of nodes were factors that were predictive for local control and survival. Multivariate analysis indicated that the major factor influencing survival was the presence of nodes; however, this was not a significant factor in locoregional control. Conclusion: High levels of locoregional control and survival have been achieved with the addition of chemotherapy to radiation treatment for high-risk MCC of the skin. The role of chemoradiotherapy for high-risk MCC warrants further investigation. (C) 2003 by American Society of Clinical Oncology.

Cervical Cancer Control, Priorities and New Directions

Cervical cancer is caused by infection with a range of high risk oncogenic human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than I in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, Screening for persistent HPV infection is effective in reducing the incidence of cervical cancer. Infection can be detected by molecular techniques or by cytological examination of exfoliated cervical cells. Persistent infection is the single best predictor of risk of cervical cancer.(1) The latest findings of HPV and cervical cancer research need to be widely disseminated to the scientific and medical societies that are updating screening and management protocols, public health professionals, and to women and clinicians. This report reviews current evidence, clinical implications and directions for further research in the prevention, control and management of cervical cancer. We report the conclusions of the Experts' Meeting at the EUROGIN 2003 conference. (C) 2003 Wiley-Liss, Inc.

Analyzing checkpoint controls in human skin

A short-term whole-skin organ culture model has been established to enable the investigation of cell cycle perturbations in epidermal layer cells following exposure to ultraviolet radiation (UVR). This model affords the opportunity to manipulate the growth and nutrient conditions, and to perform detailed biochemical and immunohistochemical analysis of skin cells in their normal epidermal layer microenvironment. The use of this model is described in this chapter.

Comparability of skin screening histories obtained by telephone interviews and mailed questionnaires: A randomized crossover study

The comparability of information collected through telephone interviews and information collected through mailed questionnaires has not been well studied. As part of the first phase of a randomized controlled trial of population screening for melanoma in Queensland, Australia, the authors compared histories of skin examination reported in telephone interviews and self-administered mailed questionnaires. A total of 1,270 subjects each completed a telephone interview and a mailed questionnaire 1 month apart in 1999; 564 subjects received the interview first, and 706 received the mailed questionnaire first. Agreement between the two methods was 91.2% and 88.6% for whole-body skin examination by a physician in the last 12 months and the last 3 years, respectively, and 81.9% for whole-body skin self-examination in the last 12 months. Agreement was lower for any skin self-examination. Agreement between the two methods was similar regardless of whether the interview or the questionnaire was administered first. Missing data were less frequent for interviews (0.5%) than for mailed questionnaires (3.8%). Costs were estimated at A$9.55 (US$6.21) per completed interview and A$3.01 (US$1.96) per questionnaire. The similarity of results obtained using telephone interviews and mailed questionnaires, coupled with the substantially higher cost of telephone interviews, suggests that self-administered mailed questionnaires are an appropriate method of assessing this health behavior.

A randomized, controlled trial to determine the efficacy of paper tape in preventing hypertrophic scar formation in surgical incisions that traverse Langer's skin tension lines

Background: How a scar is managed postoperatively influences Its cosmetic outcome. After Suture removal, scars are susceptible to skin tension, which may be the trigger for hypertrophic scarring. Paper tape to support the scar may reduce multidirectional forces and prevent hypertrophic scarring. Methods: Seventy patients who had under gone cesarean section at the Royal Brisbane and Women's Hospital were randomized to treatment and control groups. Patients in the control group received no postoperative intervention. Patients in the treatment group applied paper tape to their scars for 12 weeks. Scars were assessed at 6 weeks, 12 weeks, and 6 months after surgery using Ultrasound to measure intradermal scar volume. Scars were also assessed using the International Clinical Recommendations. Results: Paper tape significantly decreased scar volume by a mean of 0.16 cm(3), (95 percent confidence Interval, 0.00 to 0.29 cm(3)) At 12 weeks after surgery, 41 percent of the control group developed hypertrophic scars compared with none in the treatment group (exact test, p = 0.003). In the treatment group, one patient developed a hypertrophic scar and four developed stretched scars only after the tape was removed. The odds of developing a hypertrophic scar were 13.6 times greater in the control than in the treatment group (95 percent confidence interval, 3.6 to 66.9). Of the 70 patients randomized, 39 completed the study. Four patients in the treatment group developed a localized red rash beneath the tape. These reactions were minor and transient and resolved without medical intervention. Conclusions: The development of hypertrophic and stretched scars in the treatment group only after the tape was removed suggests that tension acting on a scar is die trigger for hypertrophic scarring. Paper tape is likely to be an effective modality for the prevention of hypertrophic scarring through its ability to eliminate scar tension.

Optimization of a transplant model to assess skin reconstitution from stem cell-enriched primary human keratinocyte populations

Given that an important functional attribute of stem cells in vivo is their ability to sustain tissue regeneration, we set out to establish a simple and easy technique to assess this property from candidate populations of human keratinocyte stem cells in an in vivo setting. Keratinocytes were inoculated into devitalized rat tracheas and transplanted subcutaneously into SCID mice, and the epithelial lining regenerated characterized to establish the validity of this heterotypic model. Furthermore, the rate and quality of epidermal tissue reconstitution obtained from freshly isolated unfractionated vs. keratinocyte stem cell-enriched populations was tested as a function of (a) cell numbers inoculated; and (b) the inclusion of irradiated support keratinocytes and dermal cells. Rapid and sustained epidermal tissue regeneration from small numbers of freshly isolated human keratinocyte stem cells validates the utilization of this simple and reliable model system to assay for enrichment of epidermal tissue-reconstituting cells.

Effectiveness of topical skin care provided in aged care facilities

Background The 2001 Australian census revealed that adults aged 65 years and over constituted 12.6% of the population, up from 12.1% in 1996. It is projected that this figure will rise to 21% or 5.1 million Australians by 2031. In 1998, 6% (134 000) of adults in Australia aged 65 years and over were residing in nursing homes or hostels and this number is also expected to rise. As skin ages, there is a decreased turnover and replacement of epidermal skin cells, a thinning subcutaneous fat layer and a reduced production of protective oils. These changes can affect the normal functions of the skin such as its role as a barrier to irritants and pathogens, temperature and water regulation. Generally, placement in a long-term care facility indicates an inability of the older person to perform all of the activities of daily living such as skin care. Therefore, skin care management protocols should be available to reduce the likelihood of skin irritation and breakdown and ultimately promote comfort of the older person. Objectives The objective of this review was to determine the best available evidence for the effectiveness and safety of topical skin care regimens for older adults residing in long-term aged care facilities. The primary outcome was the incidence of adverse skin conditions with patient satisfaction considered as a secondary outcome. Search strategy A literature search was performed using the following databases: PubMed (NLM) (1966–4/2003), Embase (1966–4/2003), CINAHL (1966–4/2003), Current Contents (1993–4/2003), Cochrane Library (1966–2/2003), Web of Science (1995–12/2002), Science Citation Index Expanded and ProceedingsFirst (1993–12/2002). Health Technology Assessment websites were also searched. No language restrictions were applied. Selection criteria Systematic reviews of randomised controlled trials, randomised and non-randomised controlled trials evaluating any non-medical intervention or program that aimed to maintain or improve the integrity of skin in older adults were considered for inclusion. Participants were 65 years of age or over and residing in an aged care facility, hospital or long-term care in the community. Studies were excluded if they evaluated pressure-relieving techniques for the prevention of skin breakdown. Data collection and analysis Two independent reviewers assessed study eligibility for inclusion. Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data. Results The resulting evidence of the effectiveness of topical skin care interventions was variable and dependent upon the skin condition outcome being assessed. The strongest evidence for maintenance of skin condition in incontinent patients found that disposable bodyworn incontinence protection reduced the odds of deterioration of skin condition compared with non-disposable bodyworns. The best evidence for non-pressure relieving topical skin care interventions on pressure sore formation found the no-rinse cleanser Clinisan to be more effective than soap and water at maintaining healthy skin (no ulcers) in elderly incontinent patients in long-term care. The quality of studies examining the effectiveness of topical skin care interventions on the incidence of skin tears was very poor and inconclusive. Topical skin care for prevention of dermatitis found that Sudocrem could reduce the redness of skin compared with zinc cream if applied regularly after each pad change, but not the number of lesions. Topical skin care on dry skin found the Bag Bath/Travel Bath no-rinse skin care cleanser to be more effective at preventing overall skin dryness and most specifically flaking and scaling when compared with the traditional soap and water washing method in residents of a long-term care facility. Information on the safety of topical skin care interventions is lacking. Therefore, because of the lack of evidence, no recommendation on the safety on any intervention included in this review can be made.

Does chemotherapy improve survival in high-risk Stage I and II Merkel cell carcinoma of the skin?

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m(2) i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For disease-specific survival, recurrent disease was the only significant factor. Primary site on the lower limb had an adverse effect on locoregional control. For distant control, the only significant factor was residual disease. Conclusions: The multivariate analysis suggests chemotherapy has no effect on survival, but because of the wide confidence limits, a chemotherapy effect cannot be excluded. A study of this size is inadequately powered to detect small improvements in survival, and a larger randomized study remains the only way to truly confirm whether chemotherapy improves the results in high-risk MCC. (c) 2006 Elsevier Inc.

Measurement of community beliefs about colorectal cancer

Few educational campaigns have focused on bowel cancer, though studies have indicated that members of the community need and want current information about relevant issues. In order to facilitate research in this area, reliable and valid measures of community attitudes are needed. Content validity of a survey instrument was obtained through use of a Delphi process with Directors of Education from the Australia Cancer Council and focus group discussions with informed members of the public. The subsequent survey of community perceptions about colorectal cancer included a broad range of content areas related to the risk of bowel cancer, preventing and coping with bowel cancer and beliefs about susceptibility and severity. The construct validity of these content areas was investigated by use of a factor analysis and confirmation of an association with related predictor variables. Two measures related to personal influence and anticipated coping responses showed favourable psychometric properties, including moderate to high levels of internal consistency and test-retest reliability. A test of the concurrent validity of these measures requires further development of instruments related to colorectal cancer or adaptation of measures from other areas of health research. (C) 2000 Elsevier Science Ltd. All rights reserved.