Functional Capacity and Self-Esteem of People With Cerebral Palsy.

OBJECTIVE: We assessed whether functional capacity predicts self-esteem in people with cerebral palsy (CP). METHOD: We conducted a cross-sectional observational study of 108 people with CP, ages 16-65 yr, who were residents of Spain. Self-esteem was captured using the Rosenberg Self-Esteem Scale (RSES), and functional capacity using the Barthel Index (BI). Sociodemographic characteristics were recorded. The relationship between the RSES score and the BI score was analyzed using linear regression. RESULTS: RSES scores increased significantly as BI scores increased (regression coefficient = 0.047, 95% confidence interval [0.017, 0.078], p = .003). People with a higher level of education, active employment, and independent living arrangements tended to have better functional capacity and higher self-esteem. CONCLUSION: Greater functional capacity predicted higher self-esteem; this effect is probably partly mediated by education, employment, and living arrangements.

Self-reported quality of life of adolescents with cerebral palsy: a cross-sectional and longitudinal analysis.

BACKGROUND: Children with cerebral palsy who can self-report have similar quality of life (QoL) to their able-bodied peers. Is this similarity also found in adolescence? We examined how self-reported QoL of adolescents with cerebral palsy varies with impairment and compares with the general population, and how factors in childhood predict adolescent QoL. METHODS: We report QoL outcomes in a longitudinal follow-up and cross-sectional analysis of individuals included in the SPARCLE1 (childhood) and SPARCLE2 (adolescent) studies. In 2004 (SPARCLE1), a cohort of 818 children aged 8-12 years were randomly selected from population-based cerebral palsy registers in nine European regions. We gathered data from 500 participants about QoL with KIDSCREEN (ten domains); frequency of pain; child psychological problems (Strengths and Difficulties Questionnaire); and parenting stress (Parenting Stress Index). At follow-up in 2009 (SPARCLE2), 355 (71%) adolescents aged 13-17 years remained in the study and self-reported QoL (longitudinal sample). 76 additional adolescents self-reported QoL in 2009, providing data for 431 adolescents in the cross-sectional sample. Researchers gathered data at home visits. We compared QoL against matched controls in the general population. We used multivariable regression to relate QoL of adolescents with cerebral palsy to impairments (cross-sectional analysis) and to childhood QoL, pain, psychological problems, and parenting stress (longitudinal analysis). FINDINGS: Severity of impairment was significantly associated (p<0·01) with reduced adolescent QoL on only three domains (Moods and emotions, Autonomy, and Social support and peers); average differences in QoL between the least and most able groups were generally less than 0·5 SD. Adolescents with cerebral palsy had significantly lower QoL than did those in the general population in only one domain (Social support and peers; mean difference -2·7 [0·25 SD], 95% CI -4·3 to -1·4). Pain in childhood or adolescence was strongly associated with low adolescent QoL on eight domains. Childhood QoL was a consistent predictor of adolescent QoL. Child psychological problems and parenting stress in childhood or their worsening between childhood and adolescence predicted only small reductions in adolescent QoL. INTERPRETATION: Individual and societal attitudes should be affected by the similarity of the QoL of adolescents with and without cerebral palsy. Adolescents with cerebral palsy need particular help to maintain and develop peer relationships. Interventions in childhood to alleviate psychological difficulties, parenting stress, and especially pain, are justified for their intrinsic value and for their longer term effect on adolescent QoL. FUNDING: SPARCLE1 was funded by the European Union Research Framework 5 Program (grant number QLG5-CT-2002-00636), the German Ministry of Health GRR-58640-2/14, and the German Foundation for the Disabled Child. SPARCLE2 was funded by: Wellcome Trust WT086315 A1A (UK and Ireland); Medical Faculty of the University of Lübeck E40-2009 and E26-2010 (Germany); CNSA, INSERM, MiRe-DREES, and IRESP (France); Ludvig and Sara Elsass Foundation, The Spastics Society and Vanforefonden (Denmark); Cooperativa Sociale "Gli Anni in Tasca" and Fondazione Carivit, Viterbo (Italy); Göteborg University-Riksforbundet for Rorelsehindrade Barn och Ungdomar and the Folke Bernadotte Foundation (Sweden).

Stability of motor function and associated impairments between childhood and adolescence in young people with cerebral palsy in Europe.

AIM: The aim of the study was to investigate whether impairments associated with cerebral palsy were stable between childhood and adolescence. METHOD: The Study of Participation of Children with Cerebral Palsy Living in Europe (SPARCLE) longitudinal study was conducted in nine European regions. In total, 818 children aged 8 to 12 years were randomly selected from population-based registers; 594 (73%) were followed up at the age of 13 to 17 years (344 males, 250 females; median age 10 y 4 mo) Research associates visited them in their homes and recorded their motor function and additional impairments. Stability of impairment was assessed using the weighted kappa coefficient. RESULTS: The proportion of participants whose level of impairment remained unchanged varied from 63% for fine motor function to 98% for hearing. For gross motor function, communication, and cognitive level, the kappa and the lower bound of its 95% confidence interval (CI) were above 0.75, indicating stability between childhood and adolescence; for fine motor function and feeding, the kappa was above 0.75 but the lower bound of the 95% CI was below 0.75, indicating probable stability; for seizures and vision, the kappa was below 0.75, although the upper bound of the 95% CI was above 0.75, indicating possible change; for hearing the kappa and its entire CI were below 0.75, indicating change. Overall, 81% of participants had no seizures in childhood, of whom 93% were seizure-free in adolescence. INTERPRETATION: Motor function and additional impairments were generally stable between childhood and adolescence.

Surgical interventions for high-grade vulval intraepithelial neoplasia.

BACKGROUND: This is an updated version of an original Cochrane review published in The Cochrane Library, 2011, Issue 1.Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its multicentric and multifocal nature. The incidence of this condition appears to be rising, particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for the surgical treatment of VIN has been to treat the symptoms and exclude any underlying malignancy, with the continued aim of preserving the vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity, thus impacting he individual's quality of life. OBJECTIVES: To evaluate the effectiveness and safety of surgical interventions in women with high-grade VIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register and the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 11,2013 and MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared surgical interventions in adult women diagnosed with high-grade VIN. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. MAIN RESULTS: We identified one RCT, including 30 women, that met our inclusion criteria; this trial reported data on carbon dioxide (CO2) laser surgery versus cavitational ultrasonic surgical aspiration (CUSA). There were no statistically significant differences in the risks of disease recurrence after one year of follow-up, pain, scarring, dysuria or burning, adhesions, infection, abnormal discharge or eschar between women who underwent CO2 laser surgery and those who received CUSA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias. AUTHORS' CONCLUSIONS: The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. The absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of VIN therefore precludes any definitive guidance or recommendations for clinical practice.

Surgery for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Atypical squamous changes occur in the transformation zone of the cervix with mild, moderate or severe changes described by their depth (CIN 1, 2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the grade and extent of the disease. OBJECTIVES: To assess the effectiveness and safety of alternative surgical treatments for CIN. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to November 2012). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of alternative surgical treatments in women with cervical intraepithelial neoplasia. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risks of bias. Risk ratios that compared residual disease after the follow-up examination and adverse events in women who received one of either laser ablation, laser conisation, large loop excision of the transformation zone (LLETZ), knife conisation or cryotherapy were pooled in random-effects model meta-analyses. MAIN RESULTS: Twenty-nine trials were included. Seven surgical techniques were tested in various comparisons. No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity. Morbidity was lower than with laser conisation, although the trials did not provide data for every outcome measure. There were not enough data to assess the effect on morbidity when compared with laser ablation. AUTHORS' CONCLUSIONS: The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity.

Centralisation of services for gynaecological cancers - a Cochrane systematic review.

OBJECTIVE: Gynaecological cancers are the second most common cancers among women. It has been suggested that centralised care improves outcomes but consensus is lacking. This systematic review assesses the effectiveness of centralisation of care for patients with gynaecological cancer, in particular, survival advantage. METHODS: A comprehensive search of the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL (The Cochrane Library, Issue 4, 2010), MEDLINE, and EMBASE up to November 2010 was conducted. Registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies were also searched. Randomised controlled trials (RCTs), quasi-RCTs, controlled before-and-after studies, interrupted time series studies, and observational studies were included and multivariable analysis to adjust for baseline case mix were used. RESULTS: Five retrospective observational studies met the inclusion criteria. Meta-analysis of three studies assessing over 9000 women suggested that institutions with gynaecologic oncologists on site may prolong survival in women with ovarian cancer, compared to community or general hospitals: hazard ratio (HR) of death was 0.90 (95% confidence interval (CI) 0.82 to 0.99). Similarly, another meta-analysis of three studies assessing over 50,000 women, found that teaching centres or regional cancer centres may prolong survival in women with any gynaecological cancer compared to community or general hospitals (HR 0.91; 95% CI 0.84 to 0.99). The largest of these studies included all gynaecological malignancies and assessed 48,981 women, so the findings extend beyond ovarian cancer. One study compared community hospitals with semi-specialised gynaecologists versus general hospitals and reported non-significantly better disease-specific survival in women with ovarian cancer (HR 0.89; 95% CI 0.78 to 1.01). The findings of included studies were highly consistent. CONCLUSIONS: The meta-analysis provides evidence to suggest that women with gynaecological cancer who received treatment in specialised centres had longer survival than those managed elsewhere.

Centralisation of services for gynaecological cancer.

BACKGROUND: Gynaecological cancers are the second most common cancers among women. It has been suggested that centralised care improves outcomes but consensus is lacking. OBJECTIVES: To assess the effectiveness of centralisation of care for patients with gynaecological cancer. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL (The Cochrane Library, Issue 4, 2010), MEDLINE, and EMBASE up to November 2010. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs, controlled before-and-after studies, interrupted time series studies, and observational studies that examined centralisation of services for gynaecological cancer, and used multivariable analysis to adjust for baseline case mix. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data, and two assessed risk of bias. Where possible, we synthesised the data on survival in a meta-analysis. MAIN RESULTS: Five studies met our inclusion criteria; all were retrospective observational studies and therefore at high risk of bias.Meta-analysis of three studies assessing over 9000 women suggested that institutions with gynaecologic oncologists on site may prolong survival in women with ovarian cancer, compared to community or general hospitals: hazard ratio (HR) of death was 0.90 (95% confidence interval (CI) 0.82 to 0.99). Similarly, another meta-analysis of three studies assessing over 50,000 women, found that teaching centres or regional cancer centres may prolong survival in women with any gynaecological cancer compared to community or general hospitals (HR 0.91; 95% CI 0.84 to 0.99). The largest of these studies included all gynaecological malignancies and assessed 48,981 women, so the findings extend beyond ovarian cancer. One study compared community hospitals with semi-specialised gynaecologists versus general hospitals and reported non-significantly better disease-specific survival in women with ovarian cancer (HR 0.89; 95% CI 0.78 to 1.01). The findings of included studies were highly consistent. Adverse event data were not reported in any of the studies. AUTHORS' CONCLUSIONS: We found low quality, but consistent evidence to suggest that women with gynaecological cancer who received treatment in specialised centres had longer survival than those managed elsewhere. The evidence was stronger for ovarian cancer than for other gynaecological cancers.Further studies of survival are needed, with more robust designs than retrospective observational studies. Research should also assess the quality of life associated with centralisation of gynaecological cancer care. Most of the available evidence addresses ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers within different healthcare systems.

Radiotherapy and chemoradiation after surgery for early cervical cancer.

BACKGROUND: This is an updated version of the original Cochrane review first published in Issue 4, 2009. There is an ongoing debate about the indications for, and value of, adjuvant pelvic radiotherapy after radical surgery in women with early cervical cancer. Certain combinations of pathological risk factors are thought to represent sufficient risk for recurrence, that they justify the use of postoperative pelvic radiotherapy, though this has never been shown to improve overall survival, and use of more than one type of treatment (surgery and radiotherapy) increases the risks of side effects and complications. OBJECTIVES: To evaluate the effectiveness and safety of adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, chemoradiation) after radical hysterectomy for early-stage cervical cancer (FIGO stages IB1, IB2 or IIA). SEARCH METHODS: For the original review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 4, 2008. The Cochrane Gynaecological Cancer Group Trials Register, MEDLINE (January 1950 to November 2008), EMBASE (1950 to November 2008). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For this update, we extended the database searches to September 2011 and searched the MetaRegister for ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, or chemoradiation) with no radiotherapy or chemoradiation, in women with a confirmed histological diagnosis of early cervical cancer who had undergone radical hysterectomy and dissection of the pelvic lymph nodes. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Information on grade 3 and 4 adverse events was collected from the trials. Results were pooled using random-effects meta-analyses. MAIN RESULTS: Two RCTs, which compared adjuvant radiotherapy with no adjuvant radiotherapy, met the inclusion criteria; they randomised and assessed 397 women with stage IB cervical cancer. Meta-analysis of these two RCTs indicated no significant difference in survival at 5 years between women who received radiation and those who received no further treatment (risk ratio (RR) = 0.8; 95% confidence interval (CI) 0.3 to 2.4). However, women who received radiation had a significantly lower risk of disease progression at 5 years (RR 0.6; 95% CI 0.4 to 0.9).Although the risk of serious adverse events was consistently higher if women received radiotherapy rather than no further treatment, these increased risks were not statistically significant, probably because the rate of adverse events was low. AUTHORS' CONCLUSIONS: We found evidence, of moderate quality, that radiation decreases the risk of disease progression compared with no further treatment, but little evidence that it might improve overall survival, in stage IB cervical cancer. The evidence on serious adverse events was equivocal.

Association between participation in life situations of children with cerebral palsy and their physical, social, and attitudinal environment: a cross-sectional multicenter European study.

OBJECTIVE: To evaluate how participation of children with cerebral palsy (CP) varied with their environment. DESIGN: Home visits to children. Administration of Assessment of Life Habits and European Child Environment Questionnaires. Structural equation modeling of putative associations between specific domains of participation and environment, while allowing for severity of child's impairments and pain. SETTING: European regions with population-based registries of children with CP. PARTICIPANTS: Children (n=1174) aged 8 to 12 years were randomly selected from 8 population-based registries of children with CP in 6 European countries. Of these, 743 (63%) agreed to participate; 1 further region recruited 75 children from multiple sources. Thus, there were 818 children in the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Participation in life situations. RESULTS: For the hypothesized associations, the models confirmed that higher participation was associated with better availability of environmental items. Higher participation in daily activities-mealtimes, health hygiene, personal care, and home life-was significantly associated with a better physical environment at home (P<.01). Mobility was associated with transport and physical environment in the community. Participation in social roles (responsibilities, relationships, recreation) was associated with attitudes of classmates and social support at home. School participation was associated with attitudes of teachers and therapists. Environment explained between 14% and 52% of the variation in participation. CONCLUSIONS: The findings confirmed the social model of disability. The physical, social, and attitudinal environment of disabled children influences their participation in everyday activities and social roles.

Surgical interventions for high grade vulval intraepithelial neoplasia.

BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its' multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group.There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients' quality of life. OBJECTIVES: To evaluate the effectiveness and safety of surgical interventions for high grade VIN. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. MAIN RESULTS: We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO(2) laser) versus ultrasonic surgical aspiration (USA).There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO(2) laser and those who received USA. The trial lacked statistical power due to the small number of women in each group and the low number of observed events, but was at low risk of bias. AUTHORS' CONCLUSIONS: The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore in the absence of reliable evidence regarding the effectiveness and safety of the two surgical techniques for the management of vulval intraepithelial neoplasia precludes any definitive guidance or recommendations for clinical practice.

Medical interventions for high grade vulval intraepithelial neoplasia.

BACKGROUND: Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. OBJECTIVES: To evaluate the effectiveness and safety of medical interventions for high grade VIN. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. MAIN RESULTS: Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one  trial reported adverse events, which were more common in the imiquimod group. One trial found no significant differences in quality of life (QoL) or body image between the imiquimod and placebo groups. AUTHORS' CONCLUSIONS: Imiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored.

Cardioprotective interventions for cancer patients receiving anthracyclines.

BACKGROUND: Anthracyclines are among the most effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent this cardiotoxicity, different cardioprotective agents have been studied. OBJECTIVES: The objective of this review was to assess the efficacy of different cardioprotective agents in preventing heart damage in cancer patients treated with anthracyclines. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE (1966 to November 2010) and EMBASE (1980 to November 2010) databases. In addition, we handsearched reference lists, conference proceedings of the International Society of Paediatric Oncology (SIOP) and American Society of Clinical Oncology (ASCO) meetings (1998 to 2010) and ongoing trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which any cardioprotective agent was compared to no additional therapy or placebo in cancer patients (children and adults) receiving anthracyclines. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection, risk of bias assessment and data extraction including adverse effects. MAIN RESULTS: We identified RCTs for the eight cardioprotective agents N-acetylcysteine, phenethylamines, coenzyme Q10, a combination of vitamins E and C and N-acetylcysteine, L-carnitine, carvedilol, amifostine and dexrazoxane (mostly for adults with advanced breast cancer). All studies had methodological limitations and for the first seven agents there were too few studies to allow pooling of results. None of the individual studies showed a cardioprotective effect. The 10 included studies on dexrazoxane enrolled 1619 patients. The meta-analysis for dexrazoxane showed a statistically significant benefit in favour of dexrazoxane for the occurrence of heart failure (risk ratio (RR) 0.29, 95% CI 0.20 to 0.41). No evidence was found for a difference in response rate or survival between the dexrazoxane and control groups. The results for adverse effects were ambiguous. No significant difference in the occurrence of secondary malignancies was identified. AUTHORS' CONCLUSIONS: No definitive conclusions can be made about the efficacy of cardioprotective agents for which pooling of results was impossible. Dexrazoxane prevents heart damage and no evidence for a difference in response rate or survival between the dexrazoxane and control groups was identified. The evidence available did not allow us to reach any definite conclusions about adverse effects. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in patients with cancer treated with anthracyclines. However, clinicians should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects for each individual patient.

Ultra-radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer.

BACKGROUND: Ovarian cancer is the sixth most common cancer among women and the leading cause of death in women with gynaecological malignancies. Opinions differ regarding the role of ultra-radical (extensive) cytoreductive surgery in ovarian cancer treatment.  OBJECTIVES: To evaluate the effectiveness and morbidity associated with ultra-radical/extensive surgery in the management of advanced stage ovarian cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE and EMBASE (up to November 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) or non-randomised studies, analysed using multivariate methods, that compared ultra-radical/extensive and standard surgery in adult women with advanced primary epithelial ovarian cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed the risk of bias. One non-randomised study was identified so no meta-analyses were performed. MAIN RESULTS: One non-randomised study met our inclusion criteria. It analysed retrospective data for 194 women with stage IIIC advanced epithelial ovarian cancer who underwent either ultra-radical (extensive) or standard surgery and reported disease specific overall survival and perioperative mortality. Multivariate analysis, adjusted for prognostic factors, identified better disease specific survival among women receiving ultra-radical surgery, although this was not statistically significant (Hazard ratio (HR) = 0.64, 95% confidence interval (CI): 0.40 to 1.04). In a subset of 144 women with carcinomatosis, those who underwent ultra-radical surgery had significantly better disease specific survival than women who underwent standard surgery (adjusted HR = 0.64, 95% CI 0.41 to 0.98). Progression-free survival and quality of life (QoL) were not reported and adverse events were incompletely documented. The study was at high risk of bias. AUTHORS' CONCLUSIONS: We found only low quality evidence comparing ultra-radical and standard surgery in women with advanced ovarian cancer and carcinomatosis. The evidence suggested that ultra-radical surgery may result in better survival.  It was unclear whether there were any differences in progression-free survival, QoL and morbidity between the two groups. The cost-effectiveness of this intervention has not been investigated. We are, therefore, unable to reach definite conclusions about the relative benefits and adverse effects of the two types of surgery.In order to determine the role of ultra-radical surgery in the management of advanced stage ovarian cancer, a sufficiently powered randomised controlled trial comparing ultra-radical and standard surgery or well-designed non-randomised studies would be required.

Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation.

BACKGROUND: Anticoagulation may improve survival in patients with cancer through an antitumor effect in addition to the perceived antithrombotic effect. OBJECTIVES: To evaluate the efficacy and safety of parenteral anticoagulants in patients with cancer with no therapeutic or prophylactic indication for anticoagulation. SEARCH STRATEGY: A comprehensive search included (1) an electronic search (February 2010) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2010, MEDLINE, EMBASE and ISI the Web of Science; (2) handsearch of conference proceedings; (3) checking of references of included studies; and (4) use of the 'related citation' feature in PubMed. SELECTION CRITERIA: Randomized controlled trials (RCTs) assessing the benefits and harms of parenteral anticoagulation in patients with cancer but no therapeutic or prophylactic indication for anticoagulation. DATA COLLECTION AND ANALYSIS: Using a standardized form we extracted in duplicate data on methodological quality, participants, interventions and outcomes of interest including all-cause mortality, symptomatic thromboembolism, major bleeding, minor bleeding and quality of life (QoL). MAIN RESULTS: Of 8187 identified citations, nine RCTs enrolling 2857 patients fulfilled the inclusion criteria. In all included RCTs the intervention consisted of heparin (either unfractionated heparin or low molecular weight heparin). Overall, the effect of heparin therapy on mortality was not statistically significant at 12 months (risk ratio (RR) 0.93; 95% CI 0.85 to 1.02) but it was statistically significant at 24 months (RR 0.92; 95% CI 0.88 to 0.97). Heparin therapy was associated with a statistically and clinically important reduction in venous thromboembolism (RR 0.55; 95% CI 0.37 to 0.82). There were no statistically significant effects on major bleeding (RR 1.30; 95% CI 0.59 to 2.88), minor bleeding (RR 1.05; 95% 0.75 to 1.46) or QoL. The quality of evidence was high for symptomatic venous thromboembolism, moderate for mortality, major bleeding and minor bleeding, and low for QoL. AUTHORS' CONCLUSIONS: Heparin was associated with a significant reduction of death at 24 months but not 12 months. It was also associated with a reduction in venous thromboembolism but based on the RCTs in this review it had no significant effect on major bleeding, minor bleeding or QoL. Future research should further investigate the survival benefit of different types of anticoagulants in patients with different types and stages of cancer. The decision for a patient with cancer to start heparin therapy for survival benefit should balance the benefits and downsides and integrate the patient's values and preferences.

Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation.

BACKGROUND: Anticoagulation may improve survival in patients with cancer through an antitumor effect in addition to the perceived antithrombotic effect. OBJECTIVES: To evaluate the efficacy and safety of parenteral anticoagulants in patients with cancer with no therapeutic or prophylactic indication for anticoagulation. SEARCH STRATEGY: A comprehensive search included (1) an electronic search (February 2010) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2010, MEDLINE, EMBASE and ISI the Web of Science; (2) handsearch of conference proceedings; (3) checking of references of included studies; and (4) use of the 'related citation' feature in PubMed. SELECTION CRITERIA: Randomized controlled trials (RCTs) assessing the benefits and harms of parenteral anticoagulation in patients with cancer but no therapeutic or prophylactic indication for anticoagulation. DATA COLLECTION AND ANALYSIS: Using a standardized form we extracted in duplicate data on methodological quality, participants, interventions and outcomes of interest including all-cause mortality, symptomatic thromboembolism, major bleeding, minor bleeding and quality of life (QoL). MAIN RESULTS: Of 8187 identified citations, nine RCTs enrolling 2857 patients fulfilled the inclusion criteria. In all included RCTs the intervention consisted of heparin (either unfractionated heparin or low molecular weight heparin). Overall, the effect of heparin therapy on mortality was not statistically significant at 12 months (risk ratio (RR) 0.93; 95% CI 0.85 to 1.02) but it was statistically significant at 24 months (RR 0.92; 95% CI 0.88 to 0.97). Heparin therapy was associated with a statistically and clinically important reduction in venous thromboembolism (RR 0.55; 95% CI 0.37 to 0.82). There were no statistically significant effects on major bleeding (RR 1.30; 95% CI 0.59 to 2.88), minor bleeding (RR 1.05; 95% 0.75 to 1.46) or QoL. The quality of evidence was high for symptomatic venous thromboembolism, moderate for mortality, major bleeding and minor bleeding, and low for QoL. AUTHORS' CONCLUSIONS: Heparin was associated with a significant reduction of death at 24 months but not 12 months. It was also associated with a reduction in venous thromboembolism but based on the RCTs in this review it had no significant effect on major bleeding, minor bleeding or QoL. Future research should further investigate the survival benefit of different types of anticoagulants in patients with different types and stages of cancer. The decision for a patient with cancer to start heparin therapy for survival benefit should balance the benefits and downsides and integrate the patient's values and preferences.

Management of drainage for malignant ascites in gynaecological cancer.

BACKGROUND: Most patients with advanced ovarian cancer and some patients with advanced endometrial cancer need repeated drainage for malignant ascites. Guidelines to advise those involved in the drainage of ascites are usually produced locally and are generally not evidence-based but mainly based on clinicians' anecdotal evidence and experience. To discover whether there are ways of managing drains that have been demonstrated to improve the efficacy and quality of the procedure is key in making recommendations which could improve the quality of life (QOL) for women at this critical period of their lives. OBJECTIVES: To evaluate the benefit and harms of different practices in the management of drains for malignant ascites in the care of women with advanced or recurrent gynaecological cancer. The review aimed to evaluate the evidence regarding the following questions; How long should the drain stay in place? Should the volume of fluid drained be replaced intravenously? Should the drain be clamped to regulate the drainage of fluid? Should any particular vital observations be regularly recorded? SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2009, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE1950 to February Week 3 2009, Embase 1980 to 2009 Week 8 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), quasi-RCTs and non-randomised studies that compared a range of interventions for management of multiple paracentesis in women with malignant ascites who had a confirmed histological diagnosis of gynaecological cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed. MAIN RESULTS: The search strategy identified 1664 unique references of which 1646 were excluded on the basis of title and abstract. The remaining 18 articles were retrieved in full, but none satisfied the inclusion criteria. AUTHORS' CONCLUSIONS: Since no relevant studies were identified, we are unable to make recommendations regarding the management of drains for malignant ascites in women with gynaecological cancer. Large, multi-centre RCTs are required to evaluate the efficacy and safety of the management of ascitic drains when in situ and their impact on QOL.

Interventions for the treatment of borderline ovarian tumours.

BACKGROUND: The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. OBJECTIVES: To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. MAIN RESULTS: We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed.Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intra-peritoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias.One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral cystectomy) than in those who had conservative surgery (cystectomy and contralateral oophorectomy). This trial was at low risk of bias.Quality of life (QoL) was not documented in any included trial. We did not find any trials that compared radical with conservative surgery or laparoscopy with laparotomy. AUTHORS' CONCLUSIONS: We did not find evidence to support the use of any specific type of adjuvant therapy for borderline ovarian tumours. RCTs evaluating the benefit of adjuvant therapy with optimally dosed chemotherapy and newer targeted drugs are necessary, particularly for advanced borderline ovarian tumours. The low mortality from borderline ovarian tumours should make recurrence-free survival, time to recurrence and morbidity important end points in such trials.Bilateral cystectomy may be offered to women with bilateral borderline ovarian tumours diagnosed intra-operatively who are wishing to preserve their fertility. Similarly, women who had RCTs comparing radical with conservative surgery and comparing laparoscopy with laparotomy are needed.

Surgery for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Atypical squamous changes occur in the transformation zone of the cervix with mild, moderate or severe changes described by their depth (CIN 1, 2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the grade and extent of the disease. OBJECTIVES: To assess the effectiveness and safety of alternative surgical treatments for CIN. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to April 2009). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of alternative surgical treatments in women with cervical intraepithelial neoplasia. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risks of bias. Risk ratios that compared residual disease after the follow-up examination and adverse events in women who received one of either laser ablation, laser conisation, large loop excision of the transformation zone (LLETZ), knife conisation or cryotherapy were pooled in random-effects model meta-analyses. MAIN RESULTS: Twenty-nine trials were included. Seven surgical techniques were tested in various comparisons. No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity. Morbidity was lower than with laser conisation, although the trials did not provide data for every outcome measure. There were not enough data to assess the effect on morbidity when compared with laser ablation. AUTHORS' CONCLUSIONS: The evidence suggests that there is no obvious superior surgical technique for treating cervical intraepithelial neoplasia in terms of treatment failures or operative morbidity.

Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer.

BACKGROUND: Most women with advanced epithelial ovarian cancer will ultimately develop recurrent disease after completion of initial treatment with primary surgery and adjuvant chemotherapy. Secondary cytoreductive surgery may have survival benefits in selected patients. However, a number of chemotherapeutic agents are active in recurrent ovarian cancer and the standard treatment of patients with recurrent ovarian cancer remains poorly defined. OBJECTIVES: To evaluate the effectiveness and safety of secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Register of Controlled Trials, (CENTRAL) Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field. SELECTION CRITERIA: We searched for RCTs, quasi-randomised trials and non-randomised studies that compared secondary cytoreductive surgery and chemotherapy to chemotherapy alonein women with recurrent epithelial ovarian cancer. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed. MAIN RESULTS: The search strategy identified 1431 unique references of which all were excluded on the basis of title and abstract. AUTHORS' CONCLUSIONS: We found no evidence from RCTs to inform decisions about secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Ideally, a large randomised controlled trial or, at the very least, well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare these treatment modalities.

Palliative surgery versus medical management for bowel obstruction in ovarian cancer.

BACKGROUND: Ovarian cancer is the sixth most common cancer among women and is usually diagnosed at an advanced stage. Bowel obstruction is a common feature of advanced or recurrent ovarian cancer. Patients with bowel obstruction are generally in poor physical condition with a limited life expectancy. Therefore, maintaining their QoL with effective symptom control is the main purpose of the management of bowel obstruction. OBJECTIVES: To compare the effectiveness and safety of palliative surgery (surgery performed to control the cancer, reduce symptoms and improve quality of life for those whose cancer is not able to be entirely removed) and medical management for bowel obstruction in women with ovarian cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled trials (CENTRAL), Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Studies that compared palliative surgery and medical interventions, in adult women diagnosed with ovarian cancer who had either full or partial obstruction of the bowel. Randomised controlled trials (RCTs) and non-RCTs that used multivariable statistical adjustment for baseline case mix were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed risk of bias. One non-randomised study was identified so no meta-analyses were performed. MAIN RESULTS: The search strategy identified 183 unique references of which 22 were identified as being potentially eligible on the basis of title and abstract. Only one study met our inclusion criteria and was included in the review. It analysed retrospective data for 47 women who received either palliative surgery (n = 27) or medical management with Octreotide (n = 20) and reported overall survival and perioperative mortality and morbidity. Women with poor performance status were excluded from surgery. Although six (22%) women who received surgery had serious complications of the operation and three (11%) died of complications, multivariable analysis found that women who received surgery had significantly (p < 0.001) better survival than women who received Octreotide, after adjustment for important prognostic factors. However, the magnitude of this effect was not reported. Quality of life (QoL) was not reported and adverse events were incompletely documented. AUTHORS' CONCLUSIONS: We found only low quality evidence comparing palliative surgery and medical management for bowel obstruction in ovarian cancer. Therefore we are unable to reach definite conclusions about the relative benefits and harms of the two forms of treatment, or to identify sub-groups of women who are likely to benefit from one treatment or the other. However, there is weak evidence in support of surgical management to prolong survival.