Interventions for the physical aspects of sexual dysfunction in women following pelvic radiotherapy.

BACKGROUND: Following pelvic radiotherapy (RT), a proportion of women experience problems related to sexual function, which are multifactorial in origin. The physical components relate to distortion of the perineum and vagina, which may occur as a result of surgery and/or radiotherapy and compromise sexual activity resulting in considerable distress. OBJECTIVES: The aim of this review was to evaluate the evidence for treatment options addressing the physical components of sexual dysfunction arising from pelvic radiotherapy as prevention or treatment of acute or late complications. SEARCH STRATEGY: The concepts used included synonyms for radiation therapy and brachytherapy and synonyms for the spectrum of physical aspects of sexual dysfunction in women. randomized. We searched the Cochrane Controlled Trials Register (CENTRAL), issue 1, 2002, MEDLINE 1966 to 2002, EMBASE 1980 to 2002, CANCERCD 1980 to 2002, Science Citation Index 1991 to 2002, CINAHL 1982 to 2002, as well as sources of grey literature. We also hand searched relevant textbooks and contacted experts in the field. SELECTION CRITERIA: Any study describing the therapeutic trial of a treatment to relieve the physical aspects of female sexual dysfunction which had developed following pelvic radiotherapy was considered. The quality of each study was then assessed by two reviewers independently to determine its suitability for inclusion in statistical analysis. DATA COLLECTION AND ANALYSIS: Thirty-two references met the inclusion criteria for the search but of these only four were suitable to be included for statistical analysis. MAIN RESULTS: The strongest evidence for benefit is the grade IC data in the topical oestrogens and benzydamine sections which describes the treatment of acute radiation vaginal changes. The use of vaginal dilators to prevent the development of vaginal stenosis is supported by grade IIC evidence. The value of hyperbaric oxygen therapy and surgical reconstruction is supported by the much weaker grade IIIC evidence in the form of case series. REVIEWER'S CONCLUSIONS: These findings reflect the quality of published data regarding interventions for this aspect of the management of radiation induced complications. Although there is grade IC evidence, these studies are not recent, the allocation concealment is unclear in the text, and overall there is a variable level of assessment of the response, emphasising the need for more studies to be conducted with improved designs to clarify the investigative process and support the final result.

How useful are observational reports in the evaluation of interventions for radiation morbidity?: an analysis of formalin therapy for late radiation proctitis.

BACKGROUND AND PURPOSE: Evidence-based medicine requires the systematic and critical evaluation of published and unpublished trials. Problems arise when a clinical condition is relatively rare and the only available data relate to experiential knowledge. The way forward would be to recommend the development of good quality randomized controlled studies. Until then, we are left with the situation where some information exists, albeit in the form of case reports and small series. Should this information be used and what features would determine its strength? METHODS: Using the example of formalin therapy in haemorrhagic radiation proctitis, a treatment for a rare condition, we were able to identify 16 published studies, 13 of which were retrospective and three of which were prospective. The quality of reporting detail was assessed by comparison to the features in a 'proposed minimum dataset' for an uncontrolled study addressing this topic. RESULTS: The mean score for quality of reporting detail for these studies was 50.6% (range 25-70%). Earlier studies reported a significantly higher response rate than subsequent studies and although there was a tendency for smaller studies to report higher response rates, this was not significant. The score for detail of reporting did not improve with year of publication and the correlation between the size of the study and the detail of reporting was not statistically significant. CONCLUSIONS: The information presented is of exceedingly variable quality. If these studies are to be used, where insufficient controlled trials are available, they should be scored for methodology, and these scores used to assist interpretation of results. This would be facilitated if an accepted reporting format including specific criteria was available.

Non-surgical interventions for late radiation cystitis in patients who have received radical radiotherapy to the pelvis.

BACKGROUND: Chronic radiation cystitis occurs a minimum of three months after completion of pelvic radiotherapy and represents a range of clinical symptoms for which there is as yet no recommended standard management. OBJECTIVES: The aim of this review was to identify the various non-surgical treatment options for the management of late chronic radiation cystitis and evaluate the evidence. SEARCH STRATEGY: Synonyms for radiation therapy and for the spectrum of radiation toxicity to the bladder in both text and MeSH terms were combined and applied to a range of databases without restriction of year of publication, methodology or language. SELECTION CRITERIA: The inclusion criteria included studies of interventions for the non-surgical management of all grades of late radiation cystitis. DATA COLLECTION AND ANALYSIS: Out of 80 relevant studies, there were no RCTs that met the inclusion criteria, but there were three prospective case series and two non-randomised studies which assessed different interventions and were not comparable. MAIN RESULTS: Sixty-three reports met the stated inclusion criteria. The majority were predominantly retrospective case series with the exception of two trials which were unrandomised and unblinded studies with a control group for comparison of effect. Although these two trials, Micic 1988, (intravesical placental extract) and Milani 1988, (flavoxate) provided the strongest evidence they were not randomised and were essentially isolated controlled studies. REVIEWER'S CONCLUSIONS: In such a relatively rare condition there are obvious difficulties in identifying sufficient patients to participate in a randomised controlled trial. The number of published reports is a reflection of the degree of medical interest that exists in providing therapeutic solutions for late radiation cystitis. However, in spite of the two studies of level IIA evidence, the absence of randomised controlled trials makes it impossible to draw any firm conclusions.

Systematic review for non-surgical interventions for the management of late radiation proctitis.

Chronic radiation proctitis produces a range of clinical symptoms for which there is currently no recommended standard management. The aim of this review was to identify the various non-surgical treatment options for the management of late chronic radiation proctitis and evaluate the evidence for their efficacy. Synonyms for radiation therapy and for the spectrum of lower gastrointestinal radiation toxicity were combined in an extensive search strategy and applied to a range of databases. The included studies were those that involved interventions for the non-surgical management of late radiation proctitis. Sixty-three studies were identified that met the inclusion criteria, including six randomised controlled trials that described the effects of anti-inflammatory agents in combination, rectal steroids alone, rectal sucralfate, short chain fatty acid enemas and different types of thermal therapy. However, these studies could not be compared. If the management of late radiation proctitis is to become evidence based, then, in view of its episodic and variable nature, placebo controlled studies need to be conducted to clarify which therapeutic options should be recommended. From the current data, although certain interventions look promising and may be effective, one small or modest sized study, even if well-conducted, is insufficient to implement changes in practice. In order to increase recruitment to trials, a national register of cases with established late radiation toxicity would facilitate multi-centre trials with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data.

Treatment-related morbidity and hospital league tables: experience from a national audit of radiotherapy-induced morbidity in cervical carcinoma.

Data are now available from a U.K. audit of survival and late morbidity following curative radiotherapy for cancer of the cervix treated in 1993. The complication rate per centre ranges from 0 to 67%. Although the frequency of complications following curative radiotherapy for cancer of the cervix might be considered to be an indicator of clinical performance, variation in treatment outcomes can be explained by sampling variability rather than real differences in quality of care. In the present study we have asked the question: could the disparity in complication rates between centres be no more or less than would be expected by chance? Our analysis suggests that this is the case, and for this reason it would be premature to use such outcome data to produce league tables or to assess institutional differences. Thus, ranking centres according to complication rate would not be valid, as the differences in rates observed are probably not significantly different from the national average. It is important that audit data are not used inappropriately and this analysis further highlights the need for reliable prospective collection of clinical information and the importance of considering sampling variability in interpreting the results of such studies.

National audit of the management and outcome of carcinoma of the cervix treated with radiotherapy in 1993.

The aim of the study was to investigate the UK prevalence of late, severe side-effects associated with radical radiotherapy for cancer of the cervix and try to identify associated factors. All patients treated for cancer of the cervix with radical radiotherapy in 1993 were identified and retrospective case notes studied to determine mortality and severe complications occurring following treatment. Of the 55 radiotherapy departments in the UK that were treating gynaecological malignancy in 1993, 53 participated in the study. There were 1558 patients with carcinoma of the cervix receiving radical radiotherapy as part of their treatment regimen in 1993, whose patterns of treatment were assessed. The main outcome measures were the development of late severe complications as defined by the Franco-Italian Glossary and mortality. Of the patients receiving surgery and radiotherapy, 58.5% underwent Wertheim's procedure. The crude rate of late severe complications in all patients with cervical cancer treated with radical radiotherapy in 1993 was 6.1% (actuarial rate 8%) at 5 years, and only four of the 91 patients who developed complications died as a result of their morbidity. There was no significant correlation of stage, centre size, surgery or radiotherapeutic approach with late morbidity in univariate analysis. The overall survival at 5 years was 47% and was lower than that of the European data from FIGO's 1990-92 cohort, for all stages. Increasing FIGO stage was the only factor significantly associated with mortality. The absence of variables that were significantly associated with late complications may well be related to the relatively low event rate compared to the sample size. Differences in surgical treatment prior to radiotherapy and radiation technique may be confounding the comparison of outcomes. The relatively poor survival for locally advanced disease and the difficulty with which these data were collated indicates that national prospective data collection is urgently required to monitor performance and hence derive best practice.

Management of malignancy in HIV infection.

The prevalence of HIV-related malignant disease is increasing, probably due to more effective management of opportunistic infection. The most frequent tumours are Kaposi's sarcoma, systemic non-Hodgkin's lymphoma and primary central nervous system lymphoma. Management of these conditions must take into account host indicators of immunosuppression and prognostic outcome in order to minimise treatment associated complications.

AIDS-related lymphoma: an emerging epidemic.

Acquired immunodeficiency syndrome-related lymphoma is a serious opportunistic complication of human immunodeficiency virus (HIV) infection which is predicted to increase in frequency over the next few years. The presence of this malignant process in HIV-related individuals, who are already immunocompromised, constitutes a major cause of morbidity and mortality, determining both therapy and prognosis.

Radiotherapy is a useful treatment for lymphangioma circumscriptum: a report of two patients.

Lymphangioma circumscriptum is a rare non-malignant skin tumour, conventionally treated by surgical resection, but with variable results. We report two cases, which, although unsuitable for excision, were treated successfully by radiotherapy and consider the place of this modality in managing this disorder. We conclude that radiotherapy is an effective treatment for unresectable lesions, or for patients who are unwilling to consider surgery.

Effects on pulmonary function of two regimens of chemotherapy for AIDS related Kaposi's sarcoma.

We retrospectively analysed serial pulmonary function tests in 14 HIV infected patients receiving either bleomycin and vincristine or liposomal doxorubicin therapy (Doxil) for AIDS related Kaposi's sarcoma. There was a significant reduction in the carbon monoxide transfer coefficient in bleomycin treated patients compared with patients treated with Doxil. No other significant changes in pulmonary function, including the carbon monoxide diffusing capacity, were observed. These preliminary findings suggest that HIV infected patients with Kaposi's sarcoma, who are receiving bleomycin, may be at risk of accelerated pulmonary dysfunction. A larger prospective study should be performed to enable further investigation.

Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma.

Kaposi sarcoma-associated herpesvirus (KSHV) is consistently found in biopsy samples from patients with AIDS-related and "classical" Kaposi's sarcoma (KS). Although highly suggestive of a causal role of KSHV in the pathogenesis of KS, this observation does not exclude the possibility that KSHV, like other herpesviruses, is widely distributed and is a mere "passenger" in these lesions. Here we report that KSHV was detectable in peripheral blood mononuclear cells of 24/46 (52%) of KS patients, but in none of 134 blood donors or 26 HIV-uninfected hospital controls. KSHV detection increased with immunosuppression, as shown by a correlation with a reduced number of CD4-positive T-cells. Moreover, KSHV detection in peripheral blood cells of HIV-infected individuals without KS predicted the subsequent appearance of KS lesions. 143 patients who did not have KS at the time of their first (or only) blood sample were followed up for a median of 30 months. Of the 11 who had been KSHV positive 6 developed KS compared with only 12 out of 132 who were KSHV negative. These findings are compatible with a causative role of KSHV in KS. KSHV was rarely detected in sputum and throat swabs of HIV-infected patients, providing a potential explanation for the apparently limited spread of this virus.

Management of pulmonary Kaposi's sarcoma: new perspectives.

Pulmonary Kaposi's sarcoma is a frequent complication of human immunodeficiency virus infection. This article reviews the current approaches to the management of this difficult condition.