Rajesh Varma

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer.

Histopathology and epidemiology studies have consistently demonstrated a strong link between endometriosis and endometriosis‐associated ovarian cancers (EAOCs)—in particular, the endometrioid and clear cell subtypes. However, it is still unclear whether endometriosis is a precursor to EAOCs, or whether there is an indirect link because similar factors predispose to both diseases. In order to search for evidence of clonal progression, we analyzed 10 EAOCs (endometrioid = 4; clear cell = 6) with coexisting endometriosis for common molecular genetic alterations in both the carcinoma and corresponding endometriosis. We used 82 microsatellite markers spanning the genome to examine loss of heterozygosity (LOH) in the coexisting carcinoma and endometriosis samples. A total of 63 LOH events were detected in the carcinoma samples; twenty two of these were also detected in the corresponding endometriosis samples. In each case, the same allele was lost in the endometriosis and cancer samples. Interestingly, no marker showed LOH in the endometriosis alone. These data provide evidence that endometriosis is a precursor to EAOCs.

Determining the quality of educational climate across multiple undergraduate teaching sites using the DREEM inventory

BackgroundOur obstetrics and gynaecology undergraduate teaching module allocates 40–50 final year medical students to eight teaching hospital sites in the West Midlands region. Based on student feedback and concerns relating to the impact of new curriculum changes, we wished to objectively assess whether the educational environment perceived by students varied at different teaching hospital centres, and whether the environment was at an acceptable standard.MethodsA Dundee Ready Education Environment (DREEM) Questionnaire, a measure of educational environment, was administered to 206 students immediately following completion of the teaching module.ResultsThe overall mean DREEM score was 139/200 (70%). There were no differences in the education climate between the teaching centres.ConclusionFurther research on the use of DREEM inventory, with follow up surveys, may be useful for educators to ensure and maintain high quality educational environments despite students being placed at different teaching centres.

The effectiveness of a levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of endometrial hyperplasia--a long-term follow-up study.

OBJECTIVES Medical treatment of non-atypical endometrial hyperplasia with oral progestogens has limited efficacy and poor compliance. A levonorgestrel-releasing intrauterine system (LNG-IUS) has been shown to successfully treat hyperplasia in small-sized studies. Our aim was to examine the effectiveness of LNG-IUS in a larger study with long-term follow up. STUDY DESIGN Prospective observational study of 105 women diagnosed with endometrial hyperplasia and treated with LNG-IUS between 1999 and 2004 at a University Teaching hospital. Baseline characteristics and outpatient endometrial Pipelle sampling were undertaken at 3 and 6 months post LNG-IUS insertion and 6-monthly intervals thereafter in all cases. Outcome included histological data derived from both Pipelle and uterine histologies at 1 and 2 years LNG-IUS therapy. RESULTS LNG-IUS achieved endometrial regression in 90% (94/105) of cases by 2 years, with a significant proportion (96%, 90/94) achieving this within 1 year. Regression occurred in 88/96 (92%) of non-atypical and 6/9 (67%) of atypical hyperplasias, and in all 22 cases of endometrial hyperplasia associated with HRT. Regression rates did not differ between histological types of hyperplasia. Twenty-three women (22%) underwent hysterectomy of which 13 were indicated and 10 were performed at patient request despite regressed endometrium. Two cases of cancer (one uterine and one ovarian) were identified. CONCLUSION LNG-IUS is highly effective in treating endometrial hyperplasia. Beneficial effects are observed by the majority within 1 year. Treatment can be reliably monitored through regular 6-montly outpatient endometrial Pipelle surveillance. LNG-IUS treatment of non-atypical hyperplasias is likely to reduce the number of hysterectomies performed in this subgroup.

Laparoscopic entry techniques: clinical guideline, national survey, and medicolegal ramifications

BackgroundThis study aimed to establish criteria for safe laparoscopic entry through a systematic literature search and evidence-based medicine appraisal, to determine surgeon preferences for laparoscopic entry in the United Kingdom, and to appraise the medicolegal ramifications of complications arising from laparoscopic entry.MethodsA systematic literature search of MEDLINE and EMBASE (1996–2007) was performed as well as a national surgeon survey by questionnaire (May–December 2006).ResultsLaparoscopic entry criteria involving 10 steps were established based on the systematic literature search and evidence-based critical appraisal. The national survey had 226 respondents, with the majority aware of the Middlesbrough consensus or Royal College of Obstetricians and Gynaecologists [RCOG]-sourced guidance. There was considerable variation in preferred laparoscopic entry techniques. Currently, there is clear judicial guidance on the medicolegal stance toward laparoscopic entry-related complications.ConclusionsDespite widespread awareness of laparoscopic entry guidelines, there remains considerable variation in the techniques adopted in clinical practice. Unless practice concurs with recommended guidance, women undergoing laparoscopy will be exposed to increased unnecessary operative risk. Laparoscopic entry-related injury in an uncomplicated woman is considered negligent practice according to UK legal case law.

Tubal evaluation in the investigation of subfertility: A structured comparison of tests

Fallopian tube obstruction is thought to play a role in 12% to 33% of subfertile couples. Assessing the patency of the fallopian tubes is, therefore, an important part of the work-up of a subfertile couple. There are several tests available for this purpose, including hysterosalpingography, laparoscopy and dye test, selective salpingography and hysterosalpingo-contrast sonography (Table 1). Each one of these tests differs in interand intra-observer reliability, diagnostic accuracy to predict blockage or other tubal disease, the prognostic information for treatmentindependent pregnancy, potential complications and costs. Moreover, some of these tests would allow assessment of the possible functioning of the tubes (e.g. measurement of tubal perfusion pressures during selective salpingography), evaluation of other pelvic pathology that may have an impact on fertility (e.g. laparoscopy to assess for endometriosis) or improve pregnancy rates in their own right (e.g. oil-based hysterosalpingography). Currently, there is a wide variation in the choice, combinations and ordering of tubal evaluation tests in different assisted conception units. While there could be several reasons for such variation in practice, one reason may be a lack of collated information that allows an easy comparison of the available tests. We, therefore, reviewed tubal evaluation tests for their interand intra-observer reliability, accuracy to predict tubal blockage and disease, prognostic value for treatment-independent pregnancies, effectiveness to improve pregnancy outcome and possible complications. We limited our review to visual tests only—non-visual tests such as chlamydial antibody testing were not considered in this review.

Outpatient Thermachoice Endometrial Balloon Ablation: Long-Term, Prognostic and Quality-of-Life Measures

Study Objective: To evaluate short- and long-term treatment outcomes of outpatient local anaesthetic thermal balloon endometrial ablation (LA-TBEA) and identify any prognostic factors. Study Design: Prospective observational study in a UK teaching hospital involving 102 menorrhagic women undergoing LA-TBEA between 2001 and 2005. Women underwent either Gynecare® Thermachoice I (n = 51) or Thermachoice III (n = 51) TBEA performed in the outpatient setting under local anaesthesia without conscious sedation. The main outcome measures were: treatment completion, pain and analgesia, duration of stay (from admission to discharge), duration of follow-up, primary treatment success and nature of any secondary treatment, menstrual symptoms and amenorrhoea, patient satisfaction, and quality of life. Results: TBEA was completed in 97% of women. Mean duration of stay was 8.0 h (95% CI 6.6–9.3). Mean follow-up was 30 months (95% CI 26–32). Secondary treatment with the levonorgestrel intrauterine system, repeat TBEA or hysterectomy occurred in 19/102 (19%). Overall, 50% of surgical re-interventions occurred by 19 months. There were high rates of amenorrhoea (29%) and treatment satisfaction (76%). Higher mean intrauterine ablation pressure was associated with increased treatment satisfaction. Conclusion: TBEA can be successfully performed in the outpatient setting. Higher endometrial ablation pressure may improve long-term treatment outcome.

Hysteroscopic myomectomy for menorrhagia using Versascope™ bipolar system: Efficacy and prognostic factors at a minimum of one year follow up

OBJECTIVE To evaluate the effectiveness of hysteroscopic submucous myomectomy for women with heavy menstrual bleeding (HMB) over a minimum 1-year period and assess prognostic factors associated with treatment success. STUDY DESIGN Prospective observational study set in a university teaching hospital in UK involving 92 women symptomatic of HMB with submucous myomas consecutively recruited between June 2003 and November 2006. Hysteroscopic myomectomy was performed under outpatient local anaesthetic (n=35, 38%) or daycase general anaesthesia (n=57, 62%) using Gynecare Versascope bipolar system. The main outcome measures were: the need for secondary surgical or medical re-intervention, menstrual improvement and patient satisfaction. Other outcome measures include: successful completion of primary resection, type of secondary treatment. RESULT Mean follow up was 2.6 years (95% CI 2.3-2.9). Complete fibroid excision was achieved in 66%. Secondary surgical re-intervention was required in 27 (29%) of which 11 (12%) were repeat hysteroscopic myomectomy and 10 (11%) were hysterectomy procedures. Multiple uterine fibroids and adenomyosis were identified in 80% of hysterectomies. At follow up, improved menstrual symptoms and patient satisfaction were reported by 91% and 86%, respectively. Irregular cycle HMB and incomplete fibroid excision were associated with secondary retreatment. Size of the submucous fibroid resected, presence of intramural and subserosal fibroids, or LA vs. GA setting were unrelated to treatment success. CONCLUSION HMB with submucous myomas may be successfully treated by completely removing the intracavity myoma component, irrespective of co-existent intramural or subserosal fibroids or size of fibroid resected. This effect remains sustained over at least a 1-2 year period.

Failed sterilisation: evidence-based review and medico-legal ramifications

Sterilisation is one of the most common procedures in the world. Around 50,000 female sterilisations are performed every year in the UK, although there is a suggestion of a worldwide downward trend in sterilisation procedures. Surgical techniques used in female sterilisation are designed to prevent pregnancy by occluding tubal patency through mechanical device application, electrocautery or by tubal excision and separation. These are shown in Table 1. Laparoscopic tubal occlusion by clip or ring is the preferred method of female sterilisation in the UK, and has replaced the earlier preference for tubal electrocautery. Laparoscopic sterilisation using the Filshie clip is the principal method in Europe, Canada and Australia and is becoming popular in the USA since licensing in 1996. Conception occurring after sterilisation is termed failed sterilisation, and can occur several years after the procedure; one case was described after an interval of 23 years. Complications can occur during sterilisation. The complication rate of interval laparoscopic sterilisation in one large multicentre study was 4.5 per 1000, with vascular or bowel injury, or inability to complete sterilisation laparoscopically, cited as the main reasons for conversion to laparotomy. Other complications include intractable localised pelvic pain, mesosalpingeal tears, tubal transection, tubal torsion and necrosis, tubo-ovarian abscess, uterine perforation, thermal bowel injury by electrocoagulation, pelvic or wound infection, delayed migration of Filshie clips (urethra, rectum, vagina), psychological symptoms and regret. Mortality attributed to the sterilisation procedure is extremely low, and has been estimated to vary from 1 to 2 per 100,000 for procedures performed in the United States, to 4 per 100,000 in developing countries, and is consequent to operative and anaesthetic related complications. Of significance, sterilisation decreases the risk of ovarian cancer but increases the risk of subsequent hysterectomy and ectopic pregnancy.

Prognostic significance of estrogen and progesterone receptor expression in LNG-IUS (Mirena®) treatment of endometrial hyperplasia: an immunohistochemical study

We performed immunohistochemical analysis of estrogen (ERα) and progesterone receptors (PRA and PRB), phosphatase and tensin homolog (PTEN) and aromatase in endometrial hyperplasia treated with Mirena® (levonorgestrel‐releasing intrauterine system; LNG‐IUS) and explored their prognostic significance. The baseline pre‐treatment endometrial hyperplasia of a selected prospective cohort was analyzed [complex (n = 29) and atypical (n = 5)]. Study participants were categorized into those that showed endometrial regression (responders, n = 28) and those that showed non‐regression or histological progression to atypia or malignancy (non‐responders, n = 6). Immunohistochemical expression was expressed as a histological score (HS). Responders compared to non‐responders showed significantly higher HSs for estrogen and progesterone receptors. Absence of estrogen and progesterone receptors predicted non‐responder status with likelihood ratios of 9.33 (95% CI 2.19–39.81) and 2.92 (95% CI 1.47–5.79), respectively. Neither PTEN nor aromatase expression were associated with LNG‐IUS therapy responsiveness. Responsiveness of endometrial hyperplasia to LNG‐IUS therapy may be determined through analysis of baseline estrogen and progesterone receptors, but these exploratory findings require confirmation in a larger dataset.

Hospital recovery following Thermachoice ablation is not dependent on setting (outpatient or daycase) or rescue analgesia: Unexpected result

BACKGROUND Thermal balloon endometrial ablation (TBEA) is increasingly being performed in the outpatient setting under local anaesthesia (LA) rather than in a daycase setting under general anaesthesia (GA). Our aim was to compare the post operative rescue analgesia requirements and duration of hospital stay in women undergoing outpatient (LA) and daycase (GA) TBEA. METHODS Prospective observational study of consecutively recruited women who underwent outpatient (LA) TBEA (n=51) and daycase (GA) TBEA (n=50) over the same time period. Analgesia that was provided additional to the standard administered analgesic regimen was considered rescue analgesia. The main outcome measures were requirement for rescue analgesia and duration of hospital stay in both cohorts. RESULT(S) LA compared to GA cohorts had shorter hospital stays (11 h [95% CI 9-13] vs. 17 h [95% CI 14-20]) and lower analgesia requirements. However, multivariate regression, correcting for all known confounders, showed that duration of stay was independent of setting for ablation or amount of rescue analgesia. CONCLUSION(S) Duration of hospital stay is not entirely dependent on whether outpatient or daycase endometrial ablation is considered. This unexpected preliminary finding deserves to be validated in future confirmatory trials that compare outpatient and daycase treatments. We also discuss the confounding factors that should be considered when designing such trials.