Laparoscopic pelvic lymphadenectomy: experience of a Gynaecological Cancer Centre in the UK.

INTRODUCTION: The role of laparoscopic lymphadenectomy in the management of gynaecological cancers has been established over the last two decades, having been first described in Dargent and Selvat (L'envahissement ganglionnaire pelvin. Medsi-Mcgraw Hill, Paris, 1989). It has been shown that laparoscopic lymphadenectomy can be performed in the majority of patients and is associated with a low complication rate. However, the technique continues to be undertaken in only a relatively small number of Gynaecological Cancer Centres in the UK owing to the long learning curve and wide variations in training. MATERIALS AND METHODS: At the Royal Wolverhampton NHS Trust Gynaecological Cancer Centre in the Greater Midlands Cancer Network laparoscopic lymphadenectomy has been performed since 1999 in the management of early cervical and high grade endometrial cancers. We have undertaken a retrospective audit (1999-2009) of these 42 cases to assess the feasibility of the procedure as well as to assess the complication rate. CONCLUSION: We are presenting the first reported series of exclusive laparoscopic transperitoneal lymphadenectomies from a Gynaecological Cancer Centre in the UK.

Malignant transformation of residual endometriosis after hysterectomy: a case series.

OBJECTIVE: To explore the role of long-standing hormone replacement therapy (HRT) in the malignant transformation of endometriosis. DESIGN: Short case series. Three cases of women with pelvic clearance receiving long-standing HRT studied in detail. SETTING: Teaching hospital in the United Kingdom (Gynaecological Cancer Centre) (Institutional Review Board approval was not obtained as it was not deemed necessary, this being a case series). PATIENT(S): Women with a history of pelvic clearance for endometriosis and longstanding HRT. INTERVENTION(S): HRT. MAIN OUTCOME MEASURE(S): Malignant transformation of endometriosis. RESULT(S): Long-standing HRT in all three women with pelvic clearance for endometriosis resulted in malignant transformation of residual endometriosis many years after the initial surgery. All cases presented with a new pelvic lesion. CONCLUSION(S): The diagnosis of malignant transformation needs to be considered in women with a history of endometriosis and with long-term HRT use in whom a new pelvic lesion is detected. The risk of malignant transformation in women with endometriosis after pelvic clearance receiving HRT needs to be explored further. Surveillance with CA-125 and imaging in such cases to predict recurrence or malignant transformation needs to be studied further in a research setting.

Postexercise muscle glycogen synthesis with combined glucose and fructose ingestion.

PURPOSE: To evaluate the efficacy of using combined glucose and fructose (GF) ingestion as a means to stimulate short-term (4 h) postexercise muscle glycogen synthesis compared to glucose only (G). METHODS: On two separate occasions, six endurance-trained men performed an exhaustive glycogen-depleting exercise bout followed by a 4-h recovery period. Muscle biopsy samples were obtained from the vastus lateralis muscle at 0, 1, and 4 h after exercise. Subjects ingested carbohydrate solutions containing G (90 g x h(-1)) or GF (G = 60 g x h(-1); F = 30 g x h(-1)) commencing immediately after exercise and every 30 min thereafter. RESULTS: Immediate postexercise muscle glycogen concentrations were similar in both trials (G = 128 +/- 25 mmol x kg(-1) dry muscle (dm) vs GF = 112 +/- 16 mmol x kg(-1) dm; P > 0.05). Total glycogen storage during the 4-h recovery period was 176 +/- 33 and 155 +/- 31 mmol x kg(-1) dm for G and GF, respectively (G vs GF, P > 0.05). Hence, mean muscle glycogen synthesis rates during the 4-h recovery period did not differ between the two conditions (G = 44 +/- 8 mmol x kg(-1) dm x h(-1) vs GF = 39 +/- 8 mmol x kg(-1) dm x h(-1), P > 0.05). Plasma glucose and serum insulin responses during the recovery period were similar in both conditions, although plasma lactate concentrations were significantly elevated during GF compared to G (by approximately 0.8 mmol x L(-1), P < 0.05). CONCLUSIONS: Glucose and glucose/fructose (2:1 ratio) solutions, ingested at a rate of 90 g x h(-1), are equally effective at restoring muscle glycogen in exercised muscles during the recovery from exhaustive exercise.

A systematic review of tests for lymph node status in primary endometrial cancer.

BACKGROUND: The lymph node status of a patient is a key determinate in staging, prognosis and adjuvant treatment of endometrial cancer. Despite this, the potential additional morbidity associated with lymphadenectomy makes its role controversial. This study systematically reviews the accuracy literature on sentinel node biopsy; ultra sound scanning, magnetic resonance imaging (MRI) and computer tomography (CT) for determining lymph node status in endometrial cancer. METHODS: Relevant articles were identified form MEDLINE (1966-2006), EMBASE (1980-2006), MEDION, the Cochrane library, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 18 relevant primary studies (693 women). Data was extracted for study characteristics and quality. Bivariate random-effect model meta-analysis was used to estimate diagnostic accuracy of the various index tests. RESULTS: MRI (pooled positive LR 26.7, 95% CI 10.6 - 67.6 and negative LR 0.29 95% CI 0.17 - 0.49) and successful sentinel node biopsy (pooled positive LR 18.9 95% CI 6.7 - 53.2 and negative LR 0.22, 95% CI 0.1 - 0.48) were the most accurate tests. CT was not as accurate a test (pooled positive LR 3.8, 95% CI 2.0 - 7.3 and negative LR of 0.62, 95% CI 0.45 - 0.86. There was only one study that reported the use of ultrasound scanning. CONCLUSION: MRI and sentinel node biopsy have shown similar diagnostic accuracy in confirming lymph node status among women with primary endometrial cancer than CT scanning, although the comparisons made are indirect and hence subject to bias. MRI should be used in preference, in light of the ASTEC trial, because of its non invasive nature.

Endometriosis and the primary care consultation.

OBJECTIVES: Endometriosis is a long term, disabling condition, and a common cause of chronic pelvic pain. Symptomatic disease is usually characterised by pelvic and abdominal pain, lower back pain, and dyspareunia, all of which may be severe and debilitating. Yet the time between onset of symptoms and diagnosis is frequently a number of years, and many women report negative experience within the primary care setting. This paper explores the experience of women with endometriosis in the primary care setting. STUDY DESIGN: A qualitative research design was considered appropriate to elicit the experience of endometriosis and the impact on women's lives. Semi-structured interviews were conducted with 30 women who suffer with endometriosis. The sample was recruited via a dedicated endometriosis clinic in the English Midlands, and participants had all been diagnosed laparoscopically with endometriosis. RESULTS: Participants described diverse experiences within the primary care setting. Although some women reported a positive relationship with their general practitioner, over half had had negative experiences, which they felt had contributed to delays in them receiving a diagnosis of endometriosis. CONCLUSION: The delay in diagnosis can be reduced and perceived attitudes of general practitioners towards women presenting with endometriosis can be improved by being alert to certain symptomology, and by detailed and sensitive history taking.

A clinical overview of endometriosis: a misunderstood disease.

Endometriosis is the presence of endometrial glands and stroma outside the endometrial cavity and is the most common known cause of pelvic pain. The number of women being diagnosed with the disease is increasing, but this may be reflective of improved diagnostic techniques. The aetiology is unknown, although the theory of retrograde menstruation remains dominant. Although pain around menstruation is the most frequently experienced symptom, dyspareunia, dyschezia, cyclical dysuria and extreme fatigue are all common. The 'gold standard' diagnostic technique is laparoscopic visualization, and the Royal College of Obstetricians and Gynaecologists (2006) recommends that surgical removal of all endometriotic lesions is the ideal. The experience of endometriosis can negatively affect all aspects of a woman's life and relationships, and this is consistently reported in research studies. This article discusses the aetiology and clinical aspects of endometriosis as well as giving an overview of empirical literature surrounding the experience of the disease. It provides nurses with the knowledge to be alert to the possibility of endometriosis as a diagnosis in women with a certain set of symptoms, in whatever healthcare setting they work.

Endometriosis-associated dyspareunia: the impact on women's lives.

BACKGROUND AND METHODOLOGY: Endometriosis is a chronic condition in which endometrial glands and stroma are present outside of the uterus. Whereas chronic pelvic pain is the most commonly experienced pain of endometriosis, many women also suffer from deep dyspareunia. In order to determine how much of an impact endometriosis-associated dyspareunia has on the lives and relationships of women a qualitative study using semi-structured interviews, supplemented with quantitative data on the extent of dyspareunia, was conducted in a dedicated endometriosis clinic in the West Midlands, UK with 30 women aged from 19 to 44 years. RESULTS: The main outcome measures were the extent of dyspareunia within the sample of women, and the impact of dyspareunia on quality of life. The experience of dyspareunia was found to be higher than in previous research. Three main themes emerged. The experience of pain was found to limit sexual activity for the majority of the sample, with a minority ceasing to be sexually active. Lack of sexual activity resulted in a lowering of self-esteem and a negative effect on relationships with partners, although the experience differed between younger and older women. DISCUSSION AND CONCLUSIONS: The experience of dyspareunia is a significant factor in the quality of life and relationships for women living with endometriosis. For most of the women in the study it was very severe and resulted in their reducing or curtailing sexual activity. Qualitative research can produce salient data that highlight the impact of dyspareunia on self-esteem and sexual relationships.

Efficacy of laparoscopic excision of visually diagnosed peritoneal endometriosis in the treatment of chronic pelvic pain.

OBJECTIVE: To determine the efficacy of laparoscopic excision of visually diagnosed endometriosis in the treatment of chronic pelvic pain. STUDY DESIGN: Sixty-two women with chronic pelvic pain and who underwent laparoscopic excision of visually diagnosed peritoneal lesions suggestive of endometriosis returned postal questionnaires. The main outcomes measures were change in pelvic pain symptoms measured on a continuous and ordinal scale and patient satisfaction following treatment. Secondary outcomes were quality of life, time off work and use of health service resources. RESULTS: 42/62 (68%) women with an average follow up time of 13 months (range 6-38 months) returned completed outcome questionnaires. The mean amount of pelvic pain was reduced following surgery compared to immediately prior to treatment, regardless of the nature of the pain (P<0.05). Overall, 67% (95% CI 50-80%) of women reported improvement in pain symptoms and 71% (95% CI 55-84%) were satisfied with the results of treatment. Satisfaction with treatment was comparable whether the visual diagnosis of peritoneal endometriosis was confirmed histologically or not (62% versus 64%, P=1.0). CONCLUSION: Laparoscopic excision of visually diagnosed endometriosis appears to be efficacious in the treatment of women with chronic pelvic pain. The launch of a long-term randomised controlled trial to confirm these provisional results is now required.

Exogenous carbohydrate oxidation rates are elevated after combined ingestion of glucose and fructose during exercise in the heat.

The first purpose of this study was to investigate whether a glucose (GLU)+fructose (FRUC) beverage would result in a higher exogenous carbohydrate (CHO) oxidation rate and a higher fluid availability during exercise in the heat compared with an isoenergetic GLU beverage. A second aim of the study was to examine whether ingestion of GLU at a rate of 1.5 g/min during exercise in the heat would lead to a reduced muscle glycogen oxidation rate compared with ingestion of water (WAT). Eight trained male cyclists (maximal oxygen uptake: 64+/-1 ml.kg-1.min-1) cycled on three different occasions for 120 min at 50% maximum power output at an ambient temperature of 31.9+/-0.1 degrees C. Subjects received, in random order, a solution providing either 1.5 g/min of GLU, 1.0 g/min of GLU+0.5 g/min of FRUC, or WAT. Exogenous CHO oxidation during the last hour of exercise was approximately 36% higher (P<0.05) in GLU+FRUC compared with GLU, and peak oxidation rates were 1.14+/-0.05 and 0.77+/-0.08 g/min, respectively. Endogenous CHO oxidation was significantly lower (P<0.05) in GLU+FRUC compared with WAT. Muscle glycogen oxidation was not different after ingestion of GLU or WAT. Plasma deuterium enrichments were significantly higher (P<0.05) in WAT and GLU+FRUC compared with GLU. Furthermore, at 60 and 75 min of exercise, plasma deuterium enrichments were higher (P<0.05) in WAT compared with GLU+FRUC. Ingestion of GLU+FRUC during exercise in the heat resulted in higher exogenous CHO oxidation rates and fluid availability compared with ingestion of GLU and reduced endogenous CHO oxidation compared with ingestion of WAT.

Exogenous carbohydrate oxidation during ultraendurance exercise.

The purposes of this study were: 1) to obtain a measure of exogenous carbohydrate (CHO(Exo)) oxidation and plasma glucose kinetics during 5 h of exercise; and 2) to compare CHO(Exo) following the ingestion of a glucose solution (Glu) or a glucose + fructose solution (2:1 ratio, Glu+Fru) during ultraendurance exercise. Eight well-trained subjects exercised three times for 5 h at 58% maximum O2 consumption while ingesting either Glu or Glu+Fru (both delivering 1.5 g/min CHO) or water. The CHO used had a naturally high 13C enrichment, and five subjects received a primed continuous intravenous [6,6-2H2]glucose infusion. CHO(Exo) rates following the ingestion of Glu leveled off after 120 min and peaked at 1.24 +/- 0.04 g/min. The ingestion of Glu+Fru resulted in a significantly higher peak rate of CHO(Exo) (1.40 +/- 0.08 g/min), a faster rate of increase in CHO(Exo), and an increase in the percentage of CHO(Exo) oxidized (65-77%). However, the rate of appearance and disappearance of Glu continued to increase during exercise, with no differences between trials. These data suggest an important role for gluconeogenesis during the later stages of exercise. Following the ingestion of Glu+Fru, cadence (rpm) was maintained, and the perception of stomach fullness was reduced relative to Glu. The ingestion of Glu+Fru increases CHO(Exo) compared with the ingestion of Glu alone, potentially through the oxidation of CHO(Exo) in the liver or through the conversion to, and oxidation of, lactate.

Human papillomavirus (HPV) type 16-specific CD8+ T cell responses in women with high grade vulvar intraepithelial neoplasia.

Human papillomavirus (HPV)-associated vulvar intraepithelial neoplasia (VIN) has serious sequelae for the sufferer. Current treatments are associated with poor response and high relapse rates. The development of HPV-specific T cell immunotherapies offers a new approach to treatment. This will require a detailed understanding of the spectrum of T cell responses induced by HPV antigens, and how effectively viral antigens can be accessed by the immune system. We have investigated the frequency and spectrum of HPV16-specific CD8+ T cell responses to three HPV16 antigens in 9 women with high grade VIN (VIN3). CD4-depleted populations of responder cells were screened against overlapping 30-35mer peptides covering the sequences of HPV16 E6, E7 and E4 using ELISPOT assays of IFN-gamma release. We demonstrated CD8+ T cell reactivity to one or more of the proteins in 6 of 9 patient samples. All 6 of these responders recognised peptides covering the E7 protein, 3 of 9 women responded to E6 peptides, but no reactivity was seen to E4. Our results suggest that HPV16-specific cytotoxic T cells (CTLs) are relatively common in women with persistent VIN3. The HPV-specific CTL response, however, seems to be ineffective. There is some evidence that there are problems associated with the processing and presentation of HPV antigens by the infected vulvar epithelium. It will be crucial to address this in the design of any T cell based therapy for HPV-associated VIN and vulval cancer.

Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review.

OBJECTIVE: To determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial cancer in women with abnormal uterine bleeding. DESIGN: A systematic quantitative review of published research. METHODS: Studies were selected if accuracy of outpatient endometrial biopsy was estimated compared with a reference standard. Diagnostic accuracy was determined by pooled likelihood ratios for positive and negative test results. There were 1013 subjects in 13 diagnostic evaluations reported in 11 primary studies. RESULTS: A positive test result on outpatient biopsy diagnosed endometrial cancer with a pooled likelihood ratio of 66.48 (95% CI 30.04-147.13) while a negative test result had a pooled likelihood ratio of 0.14 (95% CI 0.08-0.27). The post test probability of endometrial cancer was 81.7% (95% CI 59.7%-92.9%) for a positive test and 0.9% (95% CI 0.4%-2.4%) for a negative test. CONCLUSION: Outpatient endometrial biopsy has a high overall accuracy in diagnosing endometrial cancer when an adequate specimen is obtained. A positive test result is more accurate for ruling in disease than a negative test result is for ruling it out. Therefore, in cases of abnormal uterine bleeding where symptoms persist despite negative biopsy, further evaluation will be warranted.