Innovations for the future of breast surgery.

BACKGROUND: Future innovations in science and technology with an impact on multimodal breast cancer management from a surgical perspective are discussed in this narrative review. The work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England. METHODS: Expert opinion was sought around themes of surgical de-escalation, reduction in treatment morbidities, and improving the accuracy of breast-conserving surgery in terms of margin status. There was emphasis on how the primacy of surgical excision in an era of oncoplastic and reconstructive surgery is increasingly being challenged, with more effective systemic therapies that target residual disease burden, and permit response-adapted approaches to both breast and axillary surgery. RESULTS: Technologies for intraoperative margin assessment can potentially half re-excision rates after breast-conserving surgery, and sentinel lymph node biopsy will become a therapeutic procedure for many patients with node-positive disease treated either with surgery or chemotherapy as the primary modality. Genomic profiling of tumours can aid in the selection of patients for neoadjuvant and adjuvant therapies as well as prevention strategies. Molecular subtypes are predictive of response to induction therapies and reductive approaches to surgery in the breast or axilla. CONCLUSION: Treatments are increasingly being tailored and based on improved understanding of tumour biology and relevant biomarkers to determine absolute benefit and permit delivery of cost-effective healthcare. Patient involvement is crucial for breast cancer studies to ensure relevance and outcome measures that are objective, meaningful, and patient-centred.

This article describes how future innovations in science and technology influence the management of breast cancer from a surgical perspective. This work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England.

A comparison of three outcome measures of the impact of vasomotor symptoms on women's lives.

Objective: Measures of the impact of vasomotor symptoms (VMS) have been used as outcomes in clinical trials but have not been compared. This study compares the Hot Flush Rating Scale (HFRS), the Hot Flash Related Daily Interference Scale (HFRDIS), and the shorter Hot Flash Interference (HFI) scale. Methods: Baseline data were taken from two studies including healthy women (menopause transition or postmenopause) and breast cancer patients experiencing VMS. Participants completed questionnaires on sociodemographics, the HFRS, the HFRDIS, the HFI, the Work and Social Adjustment Scale (WSAS), on depression (Generalized Anxiety Disorder 7), on anxiety (Patient Health Questionnaire 9), and on use of medical services. Results: A total of 169 women (129 with history of breast cancer and 40 without) aged 54.47 (standard deviation [SD] = 9.11) years took part. They had an average of 66 (SD = 40.94) VMS per week, with a mean HFRS problem-rating of 6.53 (SD = 1.99), HFRDIS score of 5.36 (SD = 2.22), and HFI score of 6.13 (SD = 2.30). The HFRS problem-rating, HFRDIS, and HFI were significantly associated (r = 0.61-0.85), had good internal reliability (α = 0.76-0.91), and had significant concurrent validity with mood, the WSAS, and use of medical services. VMS frequency was not associated with mood, the WSAS, or use of medical services. Conclusion: The HFRS problem-rating scale and the HFI are two brief, three-item measures that measure a similar concept of VMS interference/impact, with evidence of reliability and validity.

Factors associated with intentional and unintentional non-adherence to adjuvant endocrine therapy following breast cancer.

Adherence to adjuvant endocrine therapy (AET) following breast cancer is known to be suboptimal despite its known efficacy in reducing recurrence and mortality. This study aims to investigate factors associated with non-adherence and inform the development of interventions to support women and promote adherence. A questionnaire survey to measure level of adherence, side effects experienced, beliefs about medicine, support received and socio-demographic details was sent to 292 women 2-4 years post breast cancer diagnosis. Differences between non-adherers and adherers to AET were explored, and factors associated with intentional and unintentional non-adherence are reported. Approximately one quarter of respondents, 46 (22%), were non-adherers, comprising 29 (14%) intentional non-adherers and 17 (8%) unintentional non-adherers. Factors significantly associated with intentional non-adherence were the presence of side effects (p < .03), greater concerns about AET (p < .001) and a lower perceived necessity to take AET (p < .001). Half of the sample (105/211) reported that side effects had a moderate or high impact on their quality of life. Factors associated with unintentional non-adherence were younger age (<65) (p < .001), post-secondary education (p = .046) and paid employment (p = .031). There are distinct differences between intentional non-adherence and unintentional non-adherence. Differentiation between the two types of non-adherence may help tailor support and advice interventions.

Managing fatigue after cancer treatment: development of RESTORE, a web-based resource to support self-management.

OBJECTIVE: The aim of this study is to co-create an evidence-based and theoretically informed web-based intervention (RESTORE) designed to enhance self-efficacy to live with cancer-related fatigue (CRF) following primary cancer treatment. METHODS: A nine-step process informed the development of the intervention: (1) review of empirical literature; (2) review of existing patient resources; (3) establish theoretical framework; (4) establish design team with expertise in web-based interventions, CRF and people affected by cancer; (5) develop prototype intervention; (6) user testing phase 1; (7) refinement of prototype; (8) user testing phase 2; and (9) develop final intervention. RESULTS: Key stakeholders made a critical contribution at every step of intervention development, and user testing, which involved an iterative process and resulted in the final intervention. The RESTORE intervention has five sessions; sessions 1 and 2 include an introduction to CRF and goal setting. Sessions 3-5 can be tailored to user preference and are designed to cover areas of life where CRF may have an impact: home and work life, personal relationships and emotional adjustment. CONCLUSIONS: It is feasible to systematically 'co-create' an evidence-based and theory-driven web-based self-management intervention to support cancer survivors living with the consequences of cancer and its treatment. This is the first account of the development of a web-based intervention to support self-efficacy to manage CRF. An exploratory trial to test the feasibility and acceptability of RESTORE is now warranted.

Recovery and self-management support following primary cancer treatment.

BACKGROUND: Around 2 million people are living with or beyond cancer in the UK. However, experiences and needs following primary treatment are relatively neglected. Following treatment, survivors may feel particularly vulnerable and face threats to their identity. We present a conceptual framework to inform areas of self-management support to facilitate recovery of health and well-being following primary cancer treatment. METHODS: To explain the framework, we draw on data from two studies: UK-wide consultation about cancer patients' research priorities and survivors' self-management in the year following primary cancer treatment. RESULTS: Self-confidence may be low following treatment. Recovery includes rebuilding lost confidence. Support to manage the impact of cancer on everyday life was a priority. Self-management support included health professionals, peers, employers, family, friends and online resources. However, support was not always available and confidence to access support could be low. CONCLUSION: Cancer survivors may struggle to self-manage following primary treatment where confidence is low or support is lacking. Low confidence may be a significant barrier to accessing support. Supporting recovery of self-confidence is an important aspect of recovery alongside physical and psychosocial problems in the context of changing health care and cancer follow-up.

A survey of provision of breast care nursing for patients with metastatic breast cancer--implications for the role.

The role of the breast care nurse was developed in the UK and is now being adopted internationally. Although evidence is available to suggest that the role is beneficial in the care of women with primary breast cancer, it is emerging that women with metastatic breast cancer do not receive the same level of support. This study aimed to develop an understanding of the role of the breast care nurse in the provision of care for patients with metastatic breast cancer. A cross-sectional survey of 276 breast care nurses in the UK found that 91% of breast care nurses stated that they provided care for patients with metastatic disease and 81% provided ongoing information and support. However 57% of breast care nurses acknowledged that the provision of care for this population was inadequate and many reported feeling ill equipped to care for women with progressive disease. Care pathways for this patient group are unstructured and ill defined complicating the efforts of breast care nurses to identify and provide care for them. In conclusion, the current nursing service for women with metastatic breast cancer is inadequate but many breast care nurses are working to address this.

Menopausal hot flushes after breast cancer.

The study aimed to improve understanding of the natural history and impact of hot flushes after breast cancer. Data were collected from women participating in an RCT of relaxation to reduce the incidence of flushes from breast cancer follow-up clinics from two hospitals in South-East England. Repondents were 150 women experiencing hot flushes following completion of primary treatment for breast cancer. This study utilized a flush diary, the Hot Flushes and Night Sweats Questionnaire (HFNSQ), Functional Assessment of Cancer Therapy with Endocrine Subscale (FACT-ES) and Spielberger State/Trait Anxiety Index (STAI) as the main outcome measures. The study found that in this sample, 51 (34%) women experienced flushes more than five years after diagnosis and 75 (50%) more than 5 years after menopause. Sleep disruption occurred in 90 women (72% of those that returned diaries), affecting half of the nights they recorded. The mean problem rating on the HFNSQ was 4.85 out of 10. A peak incidence of flushes was apparent around 10 a.m. in women taking tamoxifen. It was concluded that hot flushes after breast cancer may be long-lasting and cause sleeping difficulties for many women. Tamoxifen may affect the diurnal pattern of flushes. After breast cancer, the duration of flushes, potential distress and disruption to women's lives should not be underestimated and appropriate interventions should be offered.

Supportive care needs of patients following treatment for colorectal cancer: risk factors for unmet needs and the association between unmet needs and health-related quality of life-results from the ColoREctal Wellbeing (CREW) study.

PURPOSE: To investigate unmet needs of patients with colorectal cancer (CRC) at the end of treatment and whether unmet needs improve over time. Identify predictors of need following treatment and whether unmet need is associated with worse health-related quality of life (HRQoL). METHODS: As part of the UK ColoREctal Wellbeing (CREW) cohort study, patients treated for CRC completed the Supportive Care Needs Survey Short Form-34 (SCNS SF-34) 15 and 24 months following surgery, along with questionnaires measuring HRQoL, wellbeing, life events, social support, and confidence to manage their cancer before surgery, 3, 9, 15, and 24 months post-surgery. RESULTS: The SCNS SF-34 was completed by 526 patients at 15 months and 510 patients at 24 months. About one-quarter of patients had at least one moderate or severe unmet need at both time points. Psychological and physical unmet needs were the most common and did not improve over time. Over 60% of patients who reported 5 or more moderate or severe unmet needs at 15 months experienced the same level of unmet need at 24 months. HRQoL at the beginning of treatment predicted unmet needs at the end of treatment. Unmet needs, specifically physical, psychological, and health system and information needs, were associated with poorer health and HRQoL at the end of treatment. CONCLUSIONS: Unmet needs persist over time and are associated with HRQoL. Evaluation of HRQoL at the start of treatment would help inform the identification of vulnerable patients. Assessment and care planning in response to unmet needs should be integrated into person-centred care. IMPLICATIONS FOR CANCER SURVIVORS: Early identification of CRC patients at risk of unmet needs will help infrom personalised survivorship care plans. The implementation of personalised and tailored services are likely to confer HRQoL gains.

Preoperative chemotherapy for resectable thoracic esophageal cancer.

BACKGROUND: Surgery has been the treatment of choice for localized esophageal cancer. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates but the individual reports have been conflicting. An explicit systematic update of the role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer is, therefore, warranted. OBJECTIVES: The objective of this review is to determine the role of preoperative chemotherapy on patients with resectable thoracic esophageal carcinomas. SEARCH STRATEGY: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2006), EMBASE (1988 to 2006) and CANCERLIT (1993 to 2002). There were no language restrictions. SELECTION CRITERIA: All trials of patients with potentially resectable carcinomas of the esophagus (of any histologic type) who were randomised to having either chemotherapy or no chemotherapy before surgery. DATA COLLECTION AND ANALYSIS: The primary outcome was survival, which was assessed using hazard ratios. This is an amendment to the original review which used relative risks to assess survival at yearly intervals. Hazard ratios (HR) have now been introduced to summarise the complete survival experience in a single analysis. The risk ratio (relative risk; RR) was used to compare rates of resections, tumour recurrences and treatment morbidity and mortality. MAIN RESULTS: There were eleven randomised trials involving 2019 patients. Eight trials (1729 patients) reported sufficient detail on survival to be included in a meta-analysis for the primary outcome. There was some evidence to suggest that preoperative chemotherapy improves survival, but this was inconclusive (HR 0.88; 95% CI 0.75 to 1.04). There was no evidence to suggest that the overall rate of resections (RR 0.96, 95% CI 0.92 to 1.01) or the rate of complete resections (R0) (RR 1.05; 95% CI 0.97 to 1.15) differ between the preoperative chemotherapy arm and surgery alone. There is no evidence that tumour recurrence (RR 0.81, 95% CI 0.54 to 1.22) or non-fatal complication rates (RR 0.90; 95% CI 0.76 to 1.06) differ for preoperative chemotherapy compared to surgery alone. Trials reported risks of toxicity with chemotherapy that ranged from 11% to 90%. AUTHORS' CONCLUSIONS: In summary, preoperative chemotherapy plus surgery may offer a survival advantage compared to surgery alone for resectable thoracic esophageal cancer, but the evidence is inconclusive. There is some evidence of toxicity and preoperative mortality associated with chemotherapy.

Helping Patients to Help Themselves after Breast Cancer Treatment.

There is a rise in the number of women living with the long-term consequences of cancer and continuing to suffer unmet need as breast cancer survival improves. This paper includes an introduction to self-management and a discussion of the evidence around the effectiveness of the key intervention types that could help patients to help themselves after treatment. Self-management interventions are particularly beneficial in reducing bother from symptoms, without patients having to take on the additional burden of more unwanted side-effects frequently seen with pharmacological interventions. There is a need to prioritise the funding of these financially viable self-management strategies to ensure equity of access and that these interventions are available for those in need.

Cancer survivors' self-efficacy to self-manage in the year following primary treatment.

PURPOSE: Cancer survivors are increasingly expected to manage the consequences of cancer and its treatment for themselves. There is evidence that self-efficacy is important for successful self-management and that this can be enhanced with support. The purpose of this study was to assess self-efficacy to manage problems in the year following primary treatment. METHODS: This cross-sectional online survey included cancer survivors who had completed their treatment within the past 12 months. Self-efficacy was assessed and variables expected to be associated with self-efficacy were measured using validated scales including quality of life, well-being, illness perceptions, depression and social support. RESULTS: One hundred eighty-two respondents (mean age 50; 81% female) completed the survey. They had been treated for a range of cancers; most commonly breast (45%). Self-efficacy scores varied between individuals and according to the illness-related task to be managed. Respondents were least confident in managing fatigue and most confident in accessing information about their cancer. Individuals most likely to report low self-efficacy were women, those experiencing higher levels of pain and/or depression, lower well-being scores, lower socio-economic status, low levels of social support, or a more negative perception of cancer. CONCLUSIONS: Self-efficacy to self-manage problems faced as a consequence of cancer and its treatment can vary widely in the year following treatment. Fatigue may be particularly difficult to manage. IMPLICATIONS FOR CANCER SURVIVORS: Variations in self-efficacy highlight the importance of assessing specific problems faced and people's confidence to manage them in order to tailor appropriate self-management support.

Modelling the vector pathway and infection of humans in an environmental outbreak of Escherichia coli O157.

Quantifying the transfer of Escherichia coli O157 from the environment to humans is essential for understanding outbreaks, establishing the infectious dose of the organism and proposing safeguards. We modelled the pathogen loading shed onto a field by sheep immediately prior to a scout camp where 18 scouts and two adults were infected with E. coli O157. We estimated the dose ingested (4-24 organisms) which is in agreement with the low infective dose reported previously for this organism in food outbreaks. These data closely fit a surrogate Shigella dose-response model which can be used as a basis for risk assessment.

The fate of Escherichia coli O157 in soil and its potential to contaminate drinking water.

The survival and transport of Escherichia coli and E. coli O157 after cattle slurry application were studied on drained plots in both grassland and arable stubble at three sites in Scotland. Leaching losses were between 0.2% and 10% of total E. coli and were dependent on rainfall. Recovery of E. coli in grass and soil declined with approximately first order kinetics. Residual numbers, in excess of background declined more slowly. The pattern was similar for both grass and arable plots. Laboratory incubations of soil cores, with applied slurry containing E. coli and E. coli O157 were performed in soils with different moisture contents at two temperatures for clay loam and sandy loam soils. Both E. coli populations were measured over a 4-week period. Using a dual population approach, the die off of the susceptible pool was linear with a half-life of 3-4 days, and was faster at the higher temperature and lowest moisture content. The resistant pool was not strongly affected by temperature or moisture and had a half-life for die off of between 18 and 24 days. After a 4-week period, < 100 cfu g/soil of E. coli and E. coli O157 remained. The die off rate of E. coli O157 was the same or slightly faster than that of the commensal E. coli population, indicating that the field behaviour of E. coli O157 can be studied by monitoring the total population of E. coli applied with slurry. The risk of significant pollution of water by E. coli is highest immediately after application of slurry, and the first increments of drainflow carry significant concentrations. Thereafter, the risk of pollution is very low. If weather conditions are dry after application on well-drained sandy soils, it is unlikely that any significant losses of organisms to drains will occur. Such data can be used to control and minimise the risk of E. coli O157 contaminating drinking water.

Preoperative chemotherapy for resectable thoracic esophageal cancer.

BACKGROUND: Surgery has been the treatment of choice for localized esophageal cancer. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates, but the individual reports have been conflicting. An explicit systematic update of the role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer is therefore warranted. OBJECTIVES: The objective of this review is to determine the role of preoperative chemotherapy on patients with resectable thoracic esophageal carcinomas. SEARCH STRATEGY: Trials were identified by searching the Cochrane Controlled Trials Register, MEDLINE (1966 - 2003), EMBASE (1988 - 2003) and CancerLit (1993 - 2003). There were no language restrictions. SELECTION CRITERIA: Types of studies. Studies that randomised patients with potentially resectable carcinomas of the esophagus (of any histologic type) to chemotherapy or no chemotherapy before surgeries were included in this review. Types of participants. The participants consisted of patients with localized potentially resectable thoracic esophageal carcinomas. Trials involving patients with carcinomas of the cervical esophagus were excluded. Types of interventions. Trials that compared chemotherapy before surgery (esophagectomy) with surgical resections alone (esophagectomy) were included. Types of outcome measures. The primary outcome was overall survival at yearly intervals after randomisation. Secondary outcomes of interest included rates of resections, response to chemotherapy, rates of local and distant recurrences, quality-of-life, and treatment morbidity and mortality. DATA COLLECTION AND ANALYSIS: All analyses were carried out on intention-to-treat. Survival at 1, 2, 3, 4 and five years were used as endpoints of clinical relevance along with the median survival. The risk ratio (relative risk; RR) was the primary measure of effect for survival, rates of resections, and tumour recurrences. The risk difference (RD) was used to describe differences in response to chemotherapy, treatment morbidity and mortality. MAIN RESULTS: There were 11 randomised trials involving 2051 patients. At 1- year and 2-year the risk ratios showed no difference in survival between preoperative chemotherapy and surgery alone. The 3-year risk ratios found a 21% increase in survival (RR = 1.21; 95% CI 0.88 to 1.68; p = 0.25) and a 24% increase in survival with preoperative chemotherapy at 4 years (RR = 1.24; 95% CI 0.92 to 1.68; p = 0.15) but they did not reach statistical significance. Only at 5 years did the results become significant (RR = 1.44; 95% CI 1.05 to 1.97; p = 0.02). The overall rate of resections and the rate of complete resections (R0) did not differ between the preoperative chemotherapy arm and surgery alone. The pooled clinical response to chemotherapy was about 36% (RD = 0.36; 95% CI 0.26 to 0.47) but the complete pathologic response was a disappointing 3% (RD = 0.03; 95% CI 0.01 to 0.04). No single agent or combination of chemotherapeutic agents was found to be superior to the others. There was a 19% reduction in local recurrence with preoperative chemotherapy, but this was not significant (RR = 0.81; 95% CI 0.54 to 1.22; p = 0.3). Preoperative chemotherapy was somewhat more harmful to patients than surgery alone. REVIEWER'S CONCLUSIONS: In summary, preoperative chemotherapy plus surgery appears to offer a survival advantage at 3, 4, and 5 years, which reached significance only at 5 years compared to surgery alone for resectable thoracic esophageal cancer of any histologic type. The number needed to treat for one extra survivor at five years is eleven patients. The results are tempered by the increased toxicity and mortality associated with chemotherapy. The most beneficial chemotherapy combination appears to be cisplatin and 5-flurouracil based, however, the dosing is unclear.

Preoperative chemotherapy for resectable thoracic esophageal cancer.

BACKGROUND: Carcinoma of the esophagus is a relatively uncommon but lethal cancer that continues to kill over 90% of its victims within 5 years. Surgery is the treatment of choice for most localized esophageal cancer patients. However, despite curative resection, the 5-year survival rate ranges from 15% to 39%. The failure of surgery to cure clinically localized esophageal cancer is because of the advanced state of the disease before symptoms occur, high frequency of lymph node involvement, and the common occurrence of submucosal spread and extension to surrounding structures. Preoperative chemotherapy has been used in an attempt to decrease tumour activity, increase resectability, and improve disease-free and overall survival. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates, but the individual reports have not been encouraging. The role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer remains undefined. OBJECTIVES: The objective of this review is to determine the role of preoperative chemotherapy on overall survival and/or quality-of-life for patients with resectable thoracic esophageal carcinoma. SEARCH STRATEGY: Trials were identified by searching the Cochrane Controlled Trials Register (Issue 2 - 2000), MEDLINE (1966 - 2000), EMBASE (1988 - 2000) and CancerLit (1993 - 2000). The references of all identified studies, review articles, and standard textbooks were examined. Members of the Cochrane UGPD Group and experts in the oncology field were contacted and asked to supply details of any outstanding clinical trials and relevant unpublished materials. There were no language restrictions. The searches were updated in June 2000. The clinical trial registers of the National Cancer Institute and the Radiation Therapy Oncology Group were consulted for ongoing trials. SELECTION CRITERIA: Types of studies Studies (published or unpublished) that randomised patients with potentially resectable carcinoma of the esophagus (of any histologic type) to chemotherapy or no chemotherapy before surgery were included in this review. Studies were excluded if they were not truly randomised (phase I or II trials), earlier versions of updated trials, if other treatment modalities (e.g. radiotherapy, hyperthermia) were used, or if there was not a surgery alone control arm. Types of participants The participants consisted of patients with potentially resectable thoracic esophageal carcinoma (of any histologic type). Trials involving patients with carcinoma of the cervical esophagus were excluded. Types of interventions Trials that compared chemotherapy before surgery (esophagectomy) with surgical resection alone (esophagectomy). Types of outcome measures The primary outcome was death at yearly intervals. Morbidity (complications), and quality-of-life were secondary outcomes. DATA COLLECTION AND ANALYSIS: Overall mortality at yearly intervals was determined by extracting the total number of patients randomised to the treatment and control groups and the number of deaths in each group. All analyses were carried out on intention-to-treat that is patients were analyzed according to their allocated treatment, irrespective of whether they received that treatment. Mortality at 1, 2, 3, 4 and 5 years were used as endpoints of clinical relevance. If survival numbers at the specified time intervals were not given, they were estimated from the published survival curves. The number of deaths in the treatment groups (preoperative chemotherapy plus surgery) was compared to the number of deaths in the control groups (surgery alone). Treatment modalities as well as patient demographics and characteristics and side-effects were also recorded. Trials meeting the inclusion criteria were evaluated by two independent reviewers using the Jadad method MAIN RESULTS: A total of 14 randomised controlled trials and 1 meta-analysis of preoperative chemotherapy versus surgery alone for esophageal carcinoma were identified to be potentially eligible for review. This review is based on 7 randomised trials and 1653 patients. At 1 year the Peto odds ratio based on the fixed-effects models showed no difference in mortality between preoperative chemotherapy and surgery alone (OR = 1.03). At 2 years there was a 20% significant decrease in mortality for preoperative chemotherapy (OR = 0.80; 95% C.I. 0.65 to 0.99) but the results were not robust. The results at 3, 4, and 5 years found odds ratios tending to favour preoperative chemotherapy, but wide confidence intervals that included 1. None of the published trials reported on quality-of-life outcomes. There appeared to be an increased risk of morbidity with chemotherapy. REVIEWER'S CONCLUSIONS: The results of this review suggest that there is no strong evidence to recommend preoperative chemotherapy in the treatment of surgically resectable carcinomas of the thoracic esophagus. (ABSTRACT TRUNCATED)

Iloprost and cisaprost for Raynaud's phenomenon in progressive systemic sclerosis.

OBJECTIVES: To assess the effects and toxicity of the following agents:Prostaglandin analogues together with other agents proposed for the treatment of Raynaud's phenomenom (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized controlled trials comparing prostaglandin analogues versus placebo were eligible if they reported clinical outcomes within the start of therapy, and if the dropout rate was less than 35%. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous, respectively. MAIN RESULTS: Seven randomized trials and 332 patients were included. Five of the seven trials were of parallel design. Five trials compared I.V. Iloprost and one trial studied p.o. Iloprost and another p.o. Cisaprost. Some trials were dose finding trials so various doses of Iloprost were used. Due to different efficacies of I.V. Iloprost, oral Iloprost and oral Cisaprost, the overall efficacy of these drugs was somewhat diluted. Intravenous Iloprost appears to be effective in the treatment of secondary Raynaud's phenomenon. REVIEWER'S CONCLUSIONS: Intravenous Iloprost is effective in the treatment of Raynaud's phenomenon secondary to scleroderma at decreasing the frequency and severity of attacks and preventing or healing digital ulcers. The effect seems to be prolonged after the intravenous infusion is given. Oral Iloprost may have less efficacy than intravenous Iloprost. However, Cisaprost has minimal or no efficacy when given orally for the treatment of Raynaud's phenomenon secondary to scleroderma.

Ketanserin for Raynaud's phenomenon in progressive systemic sclerosis.

OBJECTIVES: To assess the effects and toxicity of the following agent: ketanserin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systematic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized controlled trials comparing ketanserin versus placebo were eligible if they reported clinical outcomes of interest. Trials with dropout rates greater than 35% were excluded. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios (OR) were calculated for all dichotomous outcomes, and a weighted mean difference (WMD) was carried out on all continuous outcomes. A fixed effects or random effects model were used if the data was homogeneous or heterogeneous, respectively. MAIN RESULTS: Three trials and 66 patients were included. The proportion improved was significantly better in the group on ketanserin with an odds ratio (OR) of 4.80 (95% CI 1.33, 17.37). However, when comparing ketanserin to placebo, the decrease in severity of RP attacks favoured placebo but this was not statistically significant. Side effects were significantly more common in the group using active treatment with an OR of 5.96 (95% CI 1.61, 22.06). Frequency of attacks did not change, but the duration of attacks decreased significantly in the ketanserin group. REVIEWER'S CONCLUSIONS: Ketanserin may have some efficacy in the treatment of Raynaud's phenomenon secondary to scleroderma. Overall, ketanserin is not significantly different from placebo for the treatment of Raynaud's phenomenon except for some decrease in the duration of attacks and more subjects improved on ketanserin compared to placebo. However, there were more side effects. It can be concluded that ketanserin treatment in Raynaud's phenomenon secondary to scleroderma is not clinically beneficial.

Cyclofenil for Raynaud's phenomenon in progressive systemic sclerosis.

OBJECTIVES: To assess the effects and toxicity of Cyclofenil versus placebo for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or Vasospasm, Scleroderma or Progressive Systematic Sclerosis or Connective Tissue Disease or Autoimmune Disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized trials comparing cyclofenil versus placebo were eligible if they reported any clinical outcomes within the trial. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratio (OR) was calculated for all dichotomous outcomes, and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous respectively. MAIN RESULTS: One trial with 38 patients was included. There was a trend for Cyclofenil to demonstrate more improvement and more dropouts compared to placebo, but there were no statistically significant differences. REVIEWER'S CONCLUSIONS: Cyclofenil is not effective in the treatment of Raynaud's phenomenon secondary to scleroderma.

Prazosin for Raynaud's phenomenon in progressive systemic sclerosis.

OBJECTIVES: To determine the effects and toxicity of prazosin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to December 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: Randomized controlled trials comparing prazosin versus placebo were eligible if they reported clinical outcomes from the start of therapy. Trials with a greater than 35% dropout were excluded. Trials were included if patients with diffuse or limited scleroderma were the subjects. If patients with other connective tissue diseases or primary Raynaud's were included, the trial was used if the data on the scleroderma patients could be extracted from the paper. DATA COLLECTION AND ANALYSIS: All data were abstracted by two independent and trained reviewers (DF, AT), and verified by a third reviewer (JP). Each trial was assessed independently by the same two reviewers for its quality using a validated quality assessment tool (Jadad 1996). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was carried out on all continuous outcomes. Fixed effects and random effects model were used if the data was homogeneous or heterogeneous, respectively. MAIN RESULTS: Two trials with a total of 40 patients were included. Prazosin has been found in two randomized controlled cross-over trials to be more effective than placebo in the treatment of Raynaud's secondary to scleroderma. However, the positive response is modest and side effects are not rare in those taking prazosin. REVIEWER'S CONCLUSIONS: Prazosin is modestly effective in the treatment of Raynaud's phenomenon secondary to scleroderma.