Emma Crosbie - Academia.edu (original) (raw)
Papers by Emma Crosbie
Morbidly obese and super-obese women should have surgery refused for benign conditions: AGAINST: Refusing surgery is both legally and morally wrong
BJOG : an international journal of obstetrics and gynaecology, 2016
Research snippets
BJOG: An International Journal of Obstetrics & Gynaecology, 2015
Negative pressure wound therapy for treating surgical wounds healing by secondary intention
Protocols, 1996
ABSTRACT Following surgery, incisions are usually closed by fixing the edges together with suture... more ABSTRACT Following surgery, incisions are usually closed by fixing the edges together with sutures (stitches), staples, adhesive glue or clips. This process helps the cut edges heal together and is called 'healing by primary intention'. However, not all incised wounds are closed in this way: where there is high risk of infection, or when there has been significant tissue loss, wounds may be left open to heal from the 'bottom up'. This delayed healing is known as 'healing by secondary intention'. Negative pressure wound therapy (NPWT) is one treatment option for surgical wounds that are healing by secondary intention. To assess the effects of negative pressure wound therapy (NPWT) on the healing of surgical wounds healing by secondary intention (SWHSI) in any care setting. For this review, in May 2015 we searched the following databases: the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations; Ovid EMBASE; and EBSCO CINAHL. There were no restrictions based on language or date of publication. Published or unpublished randomised controlled trials (RCTs) comparing the effects of NPWT with alternative treatments or different types of NPWT in the treatment of SWHSI. We excluded open abdominal wounds from this review as they are the subject of a separate Cochrane review that is in draft. Two review authors independently performed study selection, risk of bias assessment and data extraction. We located two studies (69 participants) for inclusion in this review. One study compared NPWT with an alginate dressing in the treatment of open, infected groin wounds. and one study compared NPWT with a silicone dressing in the treatment of excised pilonidal sinus. The trials reported limited outcome data on healing, adverse events and resource use. There is currently no rigorous RCT evidence available regarding the clinical effectiveness of NPWT in the treatment of surgical wounds healing by secondary intention as defined in this review. The potential benefits and harms of using this treatment for this wound type remain largely uncertain.
Reviews in Gynaecological Practice, 2005
The possible link between ovulation-inducing agents and ovarian cancer has been the focus of cons... more The possible link between ovulation-inducing agents and ovarian cancer has been the focus of considerable research effort over the past decade. Epidemiological studies addressing this issue have varied in their ability to achieve adequate sample sizes, obtain accurate measures of subfertility and fertility drug use, and eliminate potential bias due to confounding variables. Despite these methodological challenges, nulliparity has consistently been associated with increased rates of epithelial ovarian cancer. An additional modest effect of subfertility has been suggested by some studies, particularly among women who remain childless despite prolonged non-pharmacological attempts to conceive. Type of subfertility may also impact on ovarian cancer risk: ovulatory disorders, endometriosis and unexplained subfertility have all been associated with increased rates of the disease. However, most studies have shown no overall increased risk of epithelial ovarian cancer in women exposed to ovulation-inducing agents, irrespective of the type of fertility drugs used and duration of treatment. While results are generally reassuring, there is a clear need for larger studies employing longer periods of follow-up, detailing precisely the types, doses and duration of treatments patients have received, and controlling for potential confounding reproductive factors. While uncertainties persist, patients undergoing ovulation induction should be informed of the possible increased risk of ovarian cancer following treatment, but it should be emphasised that this risk is doubled at most. Short courses of ovulation induction are probably preferable but there is no evidence for posttreatment screening for ovarian cancer in these patients. #
Commentary on 'Risk of colorectal cancer in women with pelvic inflammatory disease: a matched cohort study
BJOG : an international journal of obstetrics and gynaecology, 2014
The emerging epidemic of endometrial cancer: Time to take action
Editorials, 1996
ERK and AKT phosphorylation status in lung cancer and emphysema using nanocapillary isoelectric focusing
BMJ Open Respiratory Research, 2016
Emphysema is an independent risk factor for the development of lung cancer in smokers. Activation... more Emphysema is an independent risk factor for the development of lung cancer in smokers. Activation of oncogenic signalling proteins AKT and ERK by phosphorylation has an established role in the development of lung cancer and has also been implicated in the pathogenesis of emphysema. The aim of this study was to compare the protein level and phosphorylation status of AKT and ERK in paired lung cancer and emphysema tissue using a highly sensitive phosphoprotein analysis approach. An antibody-based, nanocapillary isoelectric focusing (cIEF) assay was used to determine the relative quantities and phosphorylation status of AKT and ERK in tumour and matched lung tissue from patients, with or without evidence of emphysema, undergoing curative resection for non-small cell lung cancer. 20 patients with adenocarcinoma (n=9) or squamous cell carcinoma (n=11) of the lung were included (mean age 67.3 years (SD 7.5, range 47-80 years)), 12 were men and all were current (n=10) or former smokers (n=10). Paired macroscopically normal lung tissue was either histologically normal (n=7) or showed emphysema (n=13). Total and phosphorylated AKT levels were fourfold (p=0.0001) and fivefold (p=0.001) higher in tumour compared with matched lung, respectively. There was no correlation with tumour histology, stage or differentiation; however, total AKT signal in tumour was significantly correlated with fluorodeoxyglucose avidity on positron emission tomography-CT scan (r=0.53, p=0.035). Total ERK was not differentially expressed, but doubly phosphorylated (activated) ERK was threefold higher in emphysema (23.5%, SD 9.2) than either matched tumour (8.8%, SD 8.6) or normal lung tissue (8.3%, SD 9.0) and correlated with the histological severity of emphysema (p=0.005). cIEF offers opportunities for quantifying subtle shifts in the phosphorylation status of oncoproteins in nanogram amounts of lung tissue. ERK activation is a feature of emphysema.
Developing role of HPV in cervical cancer prevention
BMJ (Clinical research ed.), 2013
A presurgical window-of-opportunity study of metformin in obesity-driven endometrial cancer
The Lancet, 2015
Metformin use is associated with reduced cancer risk in several observational studies of patients... more Metformin use is associated with reduced cancer risk in several observational studies of patients with type 2 diabetes. Results from preclinical studies in endometrial cancer show that metformin reduces cellular proliferation by inhibition of the PI3K-AKT-mTOR pathway. We tested the hypothesis that metformin would reduce cellular proliferation in vivo in atypical endometrial hyperplasia and endometrial endometrioid adenocarcinoma. We recruited women attending gynaecological oncology clinics in Manchester, UK, with atypical endometrial hyperplasia or endometrial endometrioid adenocarcinoma. Women received metformin (850 mg twice daily) or no drug (control) during the 1-4 week presurgical window between cancer diagnosis and hysterectomy according to patient preference. Paired blood and tumour samples were obtained at recruitment and hysterectomy. Cellular proliferation was assessed by Ki-67 proliferation index. Automated scoring on two separate occasions provided consistent replicate scores (SD <10%). This study is registered with the ISRCTN register, number ISRCTN81570194. Samples from 40 women have been analysed (28 metformin-treated [median age 64 years, IQR 58-69]; 12 control [70, 64-70]). 24 of the patients (60%) were obese. 22 patients (55%) had either undiagnosed diabetes (fasting glucose >7·0 mmol/L, n=4) or insulin resistance (homoeostatic model assessment of insulin resistance >2·8, n=18). Metformin was taken for a median of 20 days (IQR 17-24), and mild gastrointestinal side-effects were reported by 22 metformin-treated patients. In the metformin-treated group, Ki-67 was 12·9% lower at hysterectomy than at recruitment (95% CI 3·7-22·1, p=0·008) after adjustment for baseline Ki-67, Ki-67 change in controls, age, and body-mass index. No significant changes in phosphorylation of AKT or markers of insulin resistance after adjustment for treatment arm were seen. Undiagnosed insulin resistance or diabetes were common in our study population. Short-term presurgical metformin was associated with a reduction in Ki-67 proliferation index. We are now exploring the hypothesis that metformin reduces Ki-67 expression by inducing phosphorylation of AMP-activated kinase and subsequent mTOR proproliferative inhibition, independent of insulin and insulin-like growth factor receptor activation. Wellbeing of Women, Wellcome Trust.
Proceedings of the 1997 Particle Accelerator Conference (Cat. No.97CH36167), 1998
Two accelerator configurations, the linac/compressor ring scheme and the linac/RCS scheme, are co... more Two accelerator configurations, the linac/compressor ring scheme and the linac/RCS scheme, are commonly used to provide the proton beam power for a short-pulse spallation neutron source. In one configuration, a fullpower linac provides the beam power and a compressor ring shortens the pulse length from 1-ms down to 1 µs. In the other, rapid cycling synchrotrons (RCSs) provide the beam power and also shorten the pulse length. A feasibility study of a staged approach to a 5-MW proton source utilizing RCS technology, allowing intermediate operation at 1 MW, was performed at ANL and is presented in this paper. This study is complementary to a study in progress at ORNL based on a linac and an accumulator ring. Our 1-MW facility consists of a 400-MeV injector linac that delivers 0.5-mA timeaveraged current, a synchrotron that accelerates the beam to 2 GeV at a 30-Hz rate, and two neutron-generating target stations. In the second phase, the 2-GeV beam is accelerated to 10 GeV by a larger RCS, increasing the facility beam power to 5 MW. 953 0-7803-4376-X/98/$10.00
Human Reproduction Update, 2014
S88 High Sensitivity ERK and AKT Phosphostatus Assays in Lung Cancer and Emphysema
Thorax, 2012
Surgical Oncology, 2011
Background: The surgical management of morbidly (BMI >40) and super obese (BMI >50) women with en... more Background: The surgical management of morbidly (BMI >40) and super obese (BMI >50) women with endometrial cancer is challenging. The aim of this study was to describe the short and long term outcomes of apronectomy combined with laparotomy for endometrial cancer staging and tumour debulking. Methods: A retrospective case note review of morbidly obese patients undergoing combined apronectomy and laparotomy for suspected endometrial cancer between 2007 and 2009 was performed. Short term (operating time, estimated blood loss, complication rates, duration of hospital stay) and long term outcomes (weight profile over 24-month follow up period) were evaluated. Results: Twenty-one patients were identified with a median age of 58 years and a median BMI of 49 (range 37e64). Apronectomy combined with laparotomy took 192 min on average to complete, with a mean estimated blood loss of 497 ml. There were no intra-operative complications. Postoperative complications included anaemia (14% required a blood transfusion), urinary tract infection (5%) and wound complications (wound infection in 29% and partial wound dehiscence in 5%). The median postoperative stay was 9 days. At twenty-four months, one-third of patients were heavier (mean 5 kg, range 2e8 kg) but almost two-thirds of patients were considerably lighter than they had been preoperatively (mean 13 kg lighter, range 9e17 kg). Conclusions: Apronectomy combined with laparotomy was safe and well tolerated in this group of patients. Sustained weight loss by two-thirds of the patients over the two-year follow up period may reflect lifestyle changes instigated by individual patients following surgery. Combined apronectomy and laparotomy may provide an alternative to standard surgery for this challenging group of patients.
The accuracy of the sentinel node procedure after excision biopsy in squamous cell carcinoma of the vulva
Surgical Oncology, 2010
Restricting inguinofemoral lymphadenectomy to patients with malignant nodes would reduce treatmen... more Restricting inguinofemoral lymphadenectomy to patients with malignant nodes would reduce treatment-related morbidity in vulval cancer patients. A prospective study was conducted to determine the diagnostic accuracy of the Sentinel Lymph Node (SLN) procedure in vulval cancer patients referred following either diagnostic or excision biopsy. Patients with clinical stage I and II squamous cell carcinoma of the vulva underwent SLN identification with peri-scar/lesional injection of (99m)Technetium-labelled nanocolloid (pre-operative lymphoscintigraphy and intra-operative use of a hand-held probe) and intra-operative blue dye. Radical excision of the vulval tumour or scar and formal inguinofemoral lymphadenectomy was then performed as necessary. SLN were processed separately and further examined at multiple levels to exclude micrometastases (H&E/cytokeratin staining) if negative on routine analysis. Clinical follow-up was carried out to identify and treat recurrences or treatment-related morbidity. Thirty-two women took part. Fifteen were referred following excision biopsy and seventeen following diagnostic biopsy of their primary vulval tumour. One or more SLN was successfully detected intra-operatively in 31 patients (97%) and 45 groins. An SLN could not be identified intra-operatively in one case (re-excision of scar). On average, more SLN were identified in patients with their primary vulval lesion in situ compared with those whose tumour had previously been excised (2.6 vs. 1.8, p = 0.03). Midline tumours were more likely (15/17) than lateral tumours (1/15) to have bilateral SLN identified pre-operatively. Two patients with midline tumours previously excised had unilateral SLN. Seven patients (23%) and ten groins had inguinofemoral lymph node metastases. The SLN procedure correctly identified inguinofemoral metastases in six patients (nine groins). In one case (midline tumour, re-excision of scar) the sentinel node was positive on one side but false negative on the other. The SLN procedure may be used to identify malignant groins in selected patients with vulval cancer. The extent to which previous vulval surgery might influence the accuracy of the SLN procedure deserves further investigation.
Intermenstrual and post-coital bleeding
Obstetrics, Gynaecology & Reproductive Medicine, 2011
Abnormal or unscheduled bleeding from the lower genital tract is common. In some women it can be ... more Abnormal or unscheduled bleeding from the lower genital tract is common. In some women it can be the first symptom of genital tract malignancy. However in majority of women there is a benign or idiopathic cause. The investigation for the abnormal bleeding is dependent on a number of factors, including age, co-existing medical conditions and cervical smear history. Based on
Journal of Obstetrics & Gynaecology, 2009
Objectives: Evaluation results laparoscopic paraortic lymphadenectomy. Methods: The group is cons... more Objectives: Evaluation results laparoscopic paraortic lymphadenectomy. Methods: The group is constituted by 34 consecutive-patients technique laparoscopy outpost by oncological cervix-endometrial-ovary processes. Procedure: Evaluation of operability with intention to try. Lymphadenectomy took place paraortic transperitoneal from primitive iliac artery to left renal vein. We realise retrospective analysis. Results: The indication of lymphadenectomy was endometrial adenocarcinoma (high degree, serous papillary, cel. Clear) 64%cases, advanced cervix cancer (IB2, IIandIII) 22% and the rest are initial stage ovary cancer. The average was 51 years (rank 30-81); the average body index of mass was of 32. The procedure was completed in all the cases, one case was made to laparotomy by vascular accident. The sanguineous lost estimation was of 120 cc (70-350) with an average reduction of the number of haemoglobin of 1,7 (0,1-3.9) The average time of the procedure was 72 minutes (50-110), the number average of lymphatic nodules was 8 (4-14). one case we found metastasis preaortic ganglion that also he was positive in the pelvic ones. We had two vascular complications (5,8%) one of theme was resolute by laparoscopyc by injury in cava vein digs and other injury, in right ovarian artery in aorta exit, was sutured by laparotomy.
Gastrointestinal stromal tumour presenting as an ovarian tumour
Journal of Obstetrics & Gynaecology, 2010
Clinical performance of RNA and DNA based HPV testing in a colposcopy setting: Influence of assay target, cut off and age
Journal of Clinical Virology, 2014
As HPV testing is used increasingly for cervical disease management, there is a demand to optimis... more As HPV testing is used increasingly for cervical disease management, there is a demand to optimise the performance of HPV tests, particularly with respect to specificity. To compare the clinical performance of an HPV DNA and a RNA based test in women with cytological abnormalities. The influence of age and assay cut off on test performance was also assessed. A prospective comparison of the Hybrid Capture 2 test (HC2) and the Aptima HPV assay (AHPV) was performed within a colposcopy setting. Clinical sensitivity and specificity were determined for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse. Both assays were >90% sensitive for the detection of CIN2+. AHPV was slightly more specific than HC2 [49.9% (46.8-53.1) vs 45.9% (42.8, 49.1), p<0.0001]. Raising HC2 cut off to 2 RLU did not improve specificity. A cut-off of 10 RLU increased specificity by approximately 10% - although this led to a reduction in sensitivity of 6.3% which equated to 24 missed cases of CIN2+. Both assays were more specific in women over 30 years of age, compared to women under 30 (p<0.001). Although AHPV was more specific than HC2 in the total cohort (p<0.001), we found this difference to be smaller than other studies. This could be attributed to different indications for colposcopic referral across different settings. This study also confirms the relatively poor specificity of commercial HPV assays in women under 30.
Human papillomavirus as a target for management, prevention and therapy
International Journal of Hyperthermia, 2012
The discovery that human papillomavirus (HPV) is the necessary causal factor in cervical carcinog... more The discovery that human papillomavirus (HPV) is the necessary causal factor in cervical carcinogenesis has made it a target for prophylactic and therapeutic vaccines, as well as a diagnostic tool in cervical screening. Whilst prophylactic vaccination has proven very effective in terms of preventing cervical cancer precursor lesions, therapeutic strategies have presented far greater challenges. HPV testing has shown itself to be extremely valuable in the triage of low grade cytological abnormalities, test of cure following treatment of cervical intraepithelial neoplasia (CIN), and will, over the next 10 years, gradually replace cytology as the mainstay of primary cervical screening. In this review, the latest evidence supporting HPV as both a biomarker of risk for cervical cancer and a target for prophylactic and therapeutic vaccination is presented.
Morbidly obese and super-obese women should have surgery refused for benign conditions: AGAINST: Refusing surgery is both legally and morally wrong
BJOG : an international journal of obstetrics and gynaecology, 2016
Research snippets
BJOG: An International Journal of Obstetrics & Gynaecology, 2015
Negative pressure wound therapy for treating surgical wounds healing by secondary intention
Protocols, 1996
ABSTRACT Following surgery, incisions are usually closed by fixing the edges together with suture... more ABSTRACT Following surgery, incisions are usually closed by fixing the edges together with sutures (stitches), staples, adhesive glue or clips. This process helps the cut edges heal together and is called 'healing by primary intention'. However, not all incised wounds are closed in this way: where there is high risk of infection, or when there has been significant tissue loss, wounds may be left open to heal from the 'bottom up'. This delayed healing is known as 'healing by secondary intention'. Negative pressure wound therapy (NPWT) is one treatment option for surgical wounds that are healing by secondary intention. To assess the effects of negative pressure wound therapy (NPWT) on the healing of surgical wounds healing by secondary intention (SWHSI) in any care setting. For this review, in May 2015 we searched the following databases: the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations; Ovid EMBASE; and EBSCO CINAHL. There were no restrictions based on language or date of publication. Published or unpublished randomised controlled trials (RCTs) comparing the effects of NPWT with alternative treatments or different types of NPWT in the treatment of SWHSI. We excluded open abdominal wounds from this review as they are the subject of a separate Cochrane review that is in draft. Two review authors independently performed study selection, risk of bias assessment and data extraction. We located two studies (69 participants) for inclusion in this review. One study compared NPWT with an alginate dressing in the treatment of open, infected groin wounds. and one study compared NPWT with a silicone dressing in the treatment of excised pilonidal sinus. The trials reported limited outcome data on healing, adverse events and resource use. There is currently no rigorous RCT evidence available regarding the clinical effectiveness of NPWT in the treatment of surgical wounds healing by secondary intention as defined in this review. The potential benefits and harms of using this treatment for this wound type remain largely uncertain.
Reviews in Gynaecological Practice, 2005
The possible link between ovulation-inducing agents and ovarian cancer has been the focus of cons... more The possible link between ovulation-inducing agents and ovarian cancer has been the focus of considerable research effort over the past decade. Epidemiological studies addressing this issue have varied in their ability to achieve adequate sample sizes, obtain accurate measures of subfertility and fertility drug use, and eliminate potential bias due to confounding variables. Despite these methodological challenges, nulliparity has consistently been associated with increased rates of epithelial ovarian cancer. An additional modest effect of subfertility has been suggested by some studies, particularly among women who remain childless despite prolonged non-pharmacological attempts to conceive. Type of subfertility may also impact on ovarian cancer risk: ovulatory disorders, endometriosis and unexplained subfertility have all been associated with increased rates of the disease. However, most studies have shown no overall increased risk of epithelial ovarian cancer in women exposed to ovulation-inducing agents, irrespective of the type of fertility drugs used and duration of treatment. While results are generally reassuring, there is a clear need for larger studies employing longer periods of follow-up, detailing precisely the types, doses and duration of treatments patients have received, and controlling for potential confounding reproductive factors. While uncertainties persist, patients undergoing ovulation induction should be informed of the possible increased risk of ovarian cancer following treatment, but it should be emphasised that this risk is doubled at most. Short courses of ovulation induction are probably preferable but there is no evidence for posttreatment screening for ovarian cancer in these patients. #
Commentary on 'Risk of colorectal cancer in women with pelvic inflammatory disease: a matched cohort study
BJOG : an international journal of obstetrics and gynaecology, 2014
The emerging epidemic of endometrial cancer: Time to take action
Editorials, 1996
ERK and AKT phosphorylation status in lung cancer and emphysema using nanocapillary isoelectric focusing
BMJ Open Respiratory Research, 2016
Emphysema is an independent risk factor for the development of lung cancer in smokers. Activation... more Emphysema is an independent risk factor for the development of lung cancer in smokers. Activation of oncogenic signalling proteins AKT and ERK by phosphorylation has an established role in the development of lung cancer and has also been implicated in the pathogenesis of emphysema. The aim of this study was to compare the protein level and phosphorylation status of AKT and ERK in paired lung cancer and emphysema tissue using a highly sensitive phosphoprotein analysis approach. An antibody-based, nanocapillary isoelectric focusing (cIEF) assay was used to determine the relative quantities and phosphorylation status of AKT and ERK in tumour and matched lung tissue from patients, with or without evidence of emphysema, undergoing curative resection for non-small cell lung cancer. 20 patients with adenocarcinoma (n=9) or squamous cell carcinoma (n=11) of the lung were included (mean age 67.3 years (SD 7.5, range 47-80 years)), 12 were men and all were current (n=10) or former smokers (n=10). Paired macroscopically normal lung tissue was either histologically normal (n=7) or showed emphysema (n=13). Total and phosphorylated AKT levels were fourfold (p=0.0001) and fivefold (p=0.001) higher in tumour compared with matched lung, respectively. There was no correlation with tumour histology, stage or differentiation; however, total AKT signal in tumour was significantly correlated with fluorodeoxyglucose avidity on positron emission tomography-CT scan (r=0.53, p=0.035). Total ERK was not differentially expressed, but doubly phosphorylated (activated) ERK was threefold higher in emphysema (23.5%, SD 9.2) than either matched tumour (8.8%, SD 8.6) or normal lung tissue (8.3%, SD 9.0) and correlated with the histological severity of emphysema (p=0.005). cIEF offers opportunities for quantifying subtle shifts in the phosphorylation status of oncoproteins in nanogram amounts of lung tissue. ERK activation is a feature of emphysema.
Developing role of HPV in cervical cancer prevention
BMJ (Clinical research ed.), 2013
A presurgical window-of-opportunity study of metformin in obesity-driven endometrial cancer
The Lancet, 2015
Metformin use is associated with reduced cancer risk in several observational studies of patients... more Metformin use is associated with reduced cancer risk in several observational studies of patients with type 2 diabetes. Results from preclinical studies in endometrial cancer show that metformin reduces cellular proliferation by inhibition of the PI3K-AKT-mTOR pathway. We tested the hypothesis that metformin would reduce cellular proliferation in vivo in atypical endometrial hyperplasia and endometrial endometrioid adenocarcinoma. We recruited women attending gynaecological oncology clinics in Manchester, UK, with atypical endometrial hyperplasia or endometrial endometrioid adenocarcinoma. Women received metformin (850 mg twice daily) or no drug (control) during the 1-4 week presurgical window between cancer diagnosis and hysterectomy according to patient preference. Paired blood and tumour samples were obtained at recruitment and hysterectomy. Cellular proliferation was assessed by Ki-67 proliferation index. Automated scoring on two separate occasions provided consistent replicate scores (SD <10%). This study is registered with the ISRCTN register, number ISRCTN81570194. Samples from 40 women have been analysed (28 metformin-treated [median age 64 years, IQR 58-69]; 12 control [70, 64-70]). 24 of the patients (60%) were obese. 22 patients (55%) had either undiagnosed diabetes (fasting glucose >7·0 mmol/L, n=4) or insulin resistance (homoeostatic model assessment of insulin resistance >2·8, n=18). Metformin was taken for a median of 20 days (IQR 17-24), and mild gastrointestinal side-effects were reported by 22 metformin-treated patients. In the metformin-treated group, Ki-67 was 12·9% lower at hysterectomy than at recruitment (95% CI 3·7-22·1, p=0·008) after adjustment for baseline Ki-67, Ki-67 change in controls, age, and body-mass index. No significant changes in phosphorylation of AKT or markers of insulin resistance after adjustment for treatment arm were seen. Undiagnosed insulin resistance or diabetes were common in our study population. Short-term presurgical metformin was associated with a reduction in Ki-67 proliferation index. We are now exploring the hypothesis that metformin reduces Ki-67 expression by inducing phosphorylation of AMP-activated kinase and subsequent mTOR proproliferative inhibition, independent of insulin and insulin-like growth factor receptor activation. Wellbeing of Women, Wellcome Trust.
Proceedings of the 1997 Particle Accelerator Conference (Cat. No.97CH36167), 1998
Two accelerator configurations, the linac/compressor ring scheme and the linac/RCS scheme, are co... more Two accelerator configurations, the linac/compressor ring scheme and the linac/RCS scheme, are commonly used to provide the proton beam power for a short-pulse spallation neutron source. In one configuration, a fullpower linac provides the beam power and a compressor ring shortens the pulse length from 1-ms down to 1 µs. In the other, rapid cycling synchrotrons (RCSs) provide the beam power and also shorten the pulse length. A feasibility study of a staged approach to a 5-MW proton source utilizing RCS technology, allowing intermediate operation at 1 MW, was performed at ANL and is presented in this paper. This study is complementary to a study in progress at ORNL based on a linac and an accumulator ring. Our 1-MW facility consists of a 400-MeV injector linac that delivers 0.5-mA timeaveraged current, a synchrotron that accelerates the beam to 2 GeV at a 30-Hz rate, and two neutron-generating target stations. In the second phase, the 2-GeV beam is accelerated to 10 GeV by a larger RCS, increasing the facility beam power to 5 MW. 953 0-7803-4376-X/98/$10.00
Human Reproduction Update, 2014
S88 High Sensitivity ERK and AKT Phosphostatus Assays in Lung Cancer and Emphysema
Thorax, 2012
Surgical Oncology, 2011
Background: The surgical management of morbidly (BMI >40) and super obese (BMI >50) women with en... more Background: The surgical management of morbidly (BMI >40) and super obese (BMI >50) women with endometrial cancer is challenging. The aim of this study was to describe the short and long term outcomes of apronectomy combined with laparotomy for endometrial cancer staging and tumour debulking. Methods: A retrospective case note review of morbidly obese patients undergoing combined apronectomy and laparotomy for suspected endometrial cancer between 2007 and 2009 was performed. Short term (operating time, estimated blood loss, complication rates, duration of hospital stay) and long term outcomes (weight profile over 24-month follow up period) were evaluated. Results: Twenty-one patients were identified with a median age of 58 years and a median BMI of 49 (range 37e64). Apronectomy combined with laparotomy took 192 min on average to complete, with a mean estimated blood loss of 497 ml. There were no intra-operative complications. Postoperative complications included anaemia (14% required a blood transfusion), urinary tract infection (5%) and wound complications (wound infection in 29% and partial wound dehiscence in 5%). The median postoperative stay was 9 days. At twenty-four months, one-third of patients were heavier (mean 5 kg, range 2e8 kg) but almost two-thirds of patients were considerably lighter than they had been preoperatively (mean 13 kg lighter, range 9e17 kg). Conclusions: Apronectomy combined with laparotomy was safe and well tolerated in this group of patients. Sustained weight loss by two-thirds of the patients over the two-year follow up period may reflect lifestyle changes instigated by individual patients following surgery. Combined apronectomy and laparotomy may provide an alternative to standard surgery for this challenging group of patients.
The accuracy of the sentinel node procedure after excision biopsy in squamous cell carcinoma of the vulva
Surgical Oncology, 2010
Restricting inguinofemoral lymphadenectomy to patients with malignant nodes would reduce treatmen... more Restricting inguinofemoral lymphadenectomy to patients with malignant nodes would reduce treatment-related morbidity in vulval cancer patients. A prospective study was conducted to determine the diagnostic accuracy of the Sentinel Lymph Node (SLN) procedure in vulval cancer patients referred following either diagnostic or excision biopsy. Patients with clinical stage I and II squamous cell carcinoma of the vulva underwent SLN identification with peri-scar/lesional injection of (99m)Technetium-labelled nanocolloid (pre-operative lymphoscintigraphy and intra-operative use of a hand-held probe) and intra-operative blue dye. Radical excision of the vulval tumour or scar and formal inguinofemoral lymphadenectomy was then performed as necessary. SLN were processed separately and further examined at multiple levels to exclude micrometastases (H&E/cytokeratin staining) if negative on routine analysis. Clinical follow-up was carried out to identify and treat recurrences or treatment-related morbidity. Thirty-two women took part. Fifteen were referred following excision biopsy and seventeen following diagnostic biopsy of their primary vulval tumour. One or more SLN was successfully detected intra-operatively in 31 patients (97%) and 45 groins. An SLN could not be identified intra-operatively in one case (re-excision of scar). On average, more SLN were identified in patients with their primary vulval lesion in situ compared with those whose tumour had previously been excised (2.6 vs. 1.8, p = 0.03). Midline tumours were more likely (15/17) than lateral tumours (1/15) to have bilateral SLN identified pre-operatively. Two patients with midline tumours previously excised had unilateral SLN. Seven patients (23%) and ten groins had inguinofemoral lymph node metastases. The SLN procedure correctly identified inguinofemoral metastases in six patients (nine groins). In one case (midline tumour, re-excision of scar) the sentinel node was positive on one side but false negative on the other. The SLN procedure may be used to identify malignant groins in selected patients with vulval cancer. The extent to which previous vulval surgery might influence the accuracy of the SLN procedure deserves further investigation.
Intermenstrual and post-coital bleeding
Obstetrics, Gynaecology & Reproductive Medicine, 2011
Abnormal or unscheduled bleeding from the lower genital tract is common. In some women it can be ... more Abnormal or unscheduled bleeding from the lower genital tract is common. In some women it can be the first symptom of genital tract malignancy. However in majority of women there is a benign or idiopathic cause. The investigation for the abnormal bleeding is dependent on a number of factors, including age, co-existing medical conditions and cervical smear history. Based on
Journal of Obstetrics & Gynaecology, 2009
Objectives: Evaluation results laparoscopic paraortic lymphadenectomy. Methods: The group is cons... more Objectives: Evaluation results laparoscopic paraortic lymphadenectomy. Methods: The group is constituted by 34 consecutive-patients technique laparoscopy outpost by oncological cervix-endometrial-ovary processes. Procedure: Evaluation of operability with intention to try. Lymphadenectomy took place paraortic transperitoneal from primitive iliac artery to left renal vein. We realise retrospective analysis. Results: The indication of lymphadenectomy was endometrial adenocarcinoma (high degree, serous papillary, cel. Clear) 64%cases, advanced cervix cancer (IB2, IIandIII) 22% and the rest are initial stage ovary cancer. The average was 51 years (rank 30-81); the average body index of mass was of 32. The procedure was completed in all the cases, one case was made to laparotomy by vascular accident. The sanguineous lost estimation was of 120 cc (70-350) with an average reduction of the number of haemoglobin of 1,7 (0,1-3.9) The average time of the procedure was 72 minutes (50-110), the number average of lymphatic nodules was 8 (4-14). one case we found metastasis preaortic ganglion that also he was positive in the pelvic ones. We had two vascular complications (5,8%) one of theme was resolute by laparoscopyc by injury in cava vein digs and other injury, in right ovarian artery in aorta exit, was sutured by laparotomy.
Gastrointestinal stromal tumour presenting as an ovarian tumour
Journal of Obstetrics & Gynaecology, 2010
Clinical performance of RNA and DNA based HPV testing in a colposcopy setting: Influence of assay target, cut off and age
Journal of Clinical Virology, 2014
As HPV testing is used increasingly for cervical disease management, there is a demand to optimis... more As HPV testing is used increasingly for cervical disease management, there is a demand to optimise the performance of HPV tests, particularly with respect to specificity. To compare the clinical performance of an HPV DNA and a RNA based test in women with cytological abnormalities. The influence of age and assay cut off on test performance was also assessed. A prospective comparison of the Hybrid Capture 2 test (HC2) and the Aptima HPV assay (AHPV) was performed within a colposcopy setting. Clinical sensitivity and specificity were determined for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse. Both assays were >90% sensitive for the detection of CIN2+. AHPV was slightly more specific than HC2 [49.9% (46.8-53.1) vs 45.9% (42.8, 49.1), p<0.0001]. Raising HC2 cut off to 2 RLU did not improve specificity. A cut-off of 10 RLU increased specificity by approximately 10% - although this led to a reduction in sensitivity of 6.3% which equated to 24 missed cases of CIN2+. Both assays were more specific in women over 30 years of age, compared to women under 30 (p<0.001). Although AHPV was more specific than HC2 in the total cohort (p<0.001), we found this difference to be smaller than other studies. This could be attributed to different indications for colposcopic referral across different settings. This study also confirms the relatively poor specificity of commercial HPV assays in women under 30.
Human papillomavirus as a target for management, prevention and therapy
International Journal of Hyperthermia, 2012
The discovery that human papillomavirus (HPV) is the necessary causal factor in cervical carcinog... more The discovery that human papillomavirus (HPV) is the necessary causal factor in cervical carcinogenesis has made it a target for prophylactic and therapeutic vaccines, as well as a diagnostic tool in cervical screening. Whilst prophylactic vaccination has proven very effective in terms of preventing cervical cancer precursor lesions, therapeutic strategies have presented far greater challenges. HPV testing has shown itself to be extremely valuable in the triage of low grade cytological abnormalities, test of cure following treatment of cervical intraepithelial neoplasia (CIN), and will, over the next 10 years, gradually replace cytology as the mainstay of primary cervical screening. In this review, the latest evidence supporting HPV as both a biomarker of risk for cervical cancer and a target for prophylactic and therapeutic vaccination is presented.