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Obs Gynae & Midwifery News

Featuring this issue:

• Breast Health

Incorporating Womens’ Health Winter 2009/10

• Urology

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UK £6.00

Winter 2009/10 06 NEWS 12 PRODUCT NEWS 16 FUTURE EVENTS 20 ARTICLE

How to turn your ideas into clinical products

23 JOURNAL REVIEW 24 AN INTERVIEW WITH...

Ashley Sexton, Clinical Innovations Europe Limited (CIE)

26 FEATURE ARTICLE

Predictive factors for breast cancer in patients diagnosed atypical ductal hyperplasia at core needle biopsy

28 ARTICLE

Urological perspectives of flank pain during pregnancy

6 News 12 Product News Cover Feature: Carl Zeiss There is a lot that happens in the border area between the ectocervix and the endocervix which the naked eye cannot see. A good colposcope gives you the magnification required to reliably differentiate between physiological and pathological changes at an early stage. The Zeiss Colposcope 150FC, for example has excellent optics and a six step magnification changer to ensure reliable diagnosis and therapy. A fully integrated MediLive® video camera makes documenting your results simple, quick and reliable. The 150FC is the ultimate in convenience, with a central handgrip incorporating the fine focus control. Perfect for single handed border patrol. Carl Zeiss Ltd. Medical Division PO Box 78, Woodfield Road, Welwyn Garden City, Herts AL7 1LU

16 Future Events

23 Journal Review

In The Next Issue

Spring 2010 Pelvic Health & Gynaecological Oncology OGMN is available on subscription: £24.00 U.K. £32.00 Europe (Airmail) £42.00 elsewhere (Airmail)

Published in the UK by: Pelican Magazines Ltd Address: 2 Cheltenham Mount Harrogate HG1 1DL, England Tel: +44 (0)1423 569676 Fax: +44 (0)1423 569677 Web Site: www.ogpnews.com Group Editor: Leslie Charneca - les@pelgrp.com Assistant Editor: Matt Ng - matt@pelgrp.com Editorial Advisor: Isaac Babarinsa Deputy Assistant Editor: Richard Redwin - richard@pelgrp.com Deputy Assistant Editor: Kate Jackson - kate@pelgrp.com Design: Neil Molyneaux - neil@pelgrp.com Group Sales & Marketing Manager: Debbie Hall - debbie@pelgrp.com Accounts & Administration: Gaye Wright - gaye@pelgrp.com New Media & E-commerce - Andy Hill IT Support - Matt Wensley Lead Developer - Jonathan Hill Proof Reading - Colin Taylor Every effort is made to ensure that information given in this magazine is accurate but no legal responsibility is accepted by the Editor or Publisher for errors or omissions in that information. Readers are recommended to contact manufacturers direct. Views expressed by contributors are not necessarily shared by OGMN. Printed in the UK by Buxton Press.

Obs Gynae & Midwifery News • Winter 2009/10

FROM THE EDITOR

Editorial elcome to the Winter 09/10 issue of OGMN. In this issue, we have articles on laparoscopic sterilisation versus hysteroscopic permanent contraception techniques, urological perspectives of flank pain during pregnancy, and our topic feature on Breast Health, which examines core needle biopsy in patients with diagnosed atypical ductal hyperplasia. In addition, on page 20, we also have a guide to the innovation process in medical devices. Our author William Atiomo personally tackles the daunting challenge of developing a new medical device on the product life-cycle, from conceptualisation to launch. I am sure our readers with product ideas of their own, and do not know where to start, will find this useful. We are pleased to be able to offer you such a wide variety of articles, and we hope readers will take the time to submit a few of their own. Please address them to editor@ogpnews.com Elsewhere in the issue, we have an interview with Ashley Sexton, International Sales Manager at Clinical Innovations Europe Limited (CIE), as well as our up to date news, products and future events.Enjoy the issue, and we hope you have an excellent 2010.

Les Charneca

Editor

I’m like...one needs to adapt to change in clinical practice, to patient expectations, to the use of products…and to a wilful distortion of syntax in the English language. Take the introduction of any new technology. We are initially sceptical, we think it does not do what it says on the tin...and may just wish to stick to our comfort zone. A senior colleague had once asked; ‘Can you show me how to use this thing? I don’t know how to use it’. I was like… ‘this guy is an institution, yet he is asking to be showed how stuff works!’ When I recently used the irritating ‘I’m like’ neo pre-fix in a complex sentence, my kid gleefully observed that I was using the same phrase I had criticised him for using! I’m like, what the cheek? What does he know? Have good times in 2010.

Isaac Bab arinsa Editorial Advisor

Obs Gynae & Midwifery News • Winter 2009/10

NEWS Use of gastric bands during pregnancy not recommended According to a doctor presenting a case study at the 8 th RCOG International Scientific Meeting, gastric bands fitted to expectant women may need releasing to prevent pregnancy complications. Dr Neena Garg, a specialist trainee in obstetrics and gynaecology from Dewsbury District Hospital, dealt with a case of 33year old patient who sought help at Rotherham Hospital for severe morning sickness and significant weight loss when she was 17 weeks pregnant. Prior to falling pregnant, she underwent a laparoscopic adjustable gastric banding because of obesity. Doctors found she was severely malnourished. To correct this, parenteral nutrition was given and she received multivitamin supplements. The gastric band was released and this led to some improvement. Due to further deterioration, the gastric band was removed laparoscopically at 21 weeks. The patient was followed-up with serial growth scans and had a normal full-term vaginal delivery. Dr Garg said: “Our case study shows that women who have had bariatric surgery may require release of the band when they

become pregnant to avoid pregnancy complications. “When a woman is pregnant, she needs to take extra care of her diet. She must eat healthily so that the foetus receives the nourishment it needs to grow. This includes having well-balanced meals and the recommended nutritional supplements. A gastric

band may prevent these essential nutrients from reaching the mother and baby and has been shown to induce the unpleasant side effect of nausea. “Pregnant women who have had bariatric surgery should therefore inform their doctors and midwives so that an assessment could be made and further action taken.”

Hormonal contraceptives offer benefits beyond pregnancy prevention, reports US study Hormonal contraceptives are effective in treating menstruation-related disorders such as dysmenorrhoea and heavy menstrual bleeding, as well as preventing unplanned pregnancies, according to The American College of Obstetricians and Gynecologists (ACOG) and published in the January issue of Obstetrics & Gynecology. In addition, combined contraceptives containing both oestrogen and progesterone offer disease prevention by reducing the risk of developing endometrial, ovarian cancer, and colorectal cancer. “We’ve known for many years that hormonal contraceptives have health advantages beyond preventing pregnancy,” says Robert L. Reid, MD, of Kingston, Ontario, who led development of the document. “These recommendations examine the scientific data supporting the non-contraceptive uses of hormonal contraceptives to treat specific conditions.” For instance, both oral contraceptives and the single-rod progestin implant help relieve or reduce the symptoms of dysmenorrhoea (severe menstrual pain), the most commonly reported menstrual disorder. Dysmenorrhoea affects up to 90% of young women and is a leading cause of women missing school and work. A variety of hormonal contraceptives are also useful in treating menorrhagia (exces6

sive menstrual bleeding), which, if left untreated, can lead to anaemia. All forms of birth control that contain both oestrogen and progesterone have the potential to improve hirsutism (excess hair growth) and acne because they suppress production of the male hormone, androgen. Other potential benefits of hormonal contraceptives include prevention of menstrual migraines, treatment of pelvic pain due to endometriosis, and treatment of bleeding due to uterine fibroids. “Combined oral contraceptives are effective in normalising irregular periods, reducing

Obs Gynae & Midwifery News • Winter 2009/10

symptoms of premenstrual dysphoric disorder, improving acne, and allowing women to avoid having their period at inconvenient times, such as during a business trip, vacation, or honeymoon,” says Dr. Reid. “Although there is little data on the newer forms of hormonal contraception in terms of their off-label benefits, experts suggest that they may be as effective as the more studied ones in treating the same conditions.” Source: American College of Obstetricians and Gynecologists

NEWS The RCM welcomes positive news on infant mortality rates Commenting on the recent release of the Department of Health’s mortality target monitoring (infant mortality, inequalities) data for 2008, Cathy Warwick, general secretary of the Royal College of Midwives, said: “It is very good news that infant mortality continues to fall. The statistics released today nonetheless highlight the real and continuing need to tackle health inequalities and social deprivation. These are important and significant factors contributing to babies’ deaths, particularly in ethnic minority groups and teenagers. “We need to ensure that maternity services are of the highest quality for all women, and one of the most important things we can do is help all women to get early access to maternity services. A recent survey carried out by the RCM and Netmums, the parenting website, showed significant progress is being made in this area. We need to continue to make sure that midwives are locally-based and planted in their communities, and are easy to find. The commitment to such initiatives needs to be continued in times of public spending constraint if we are to address the areas of deprivation and health inequalities.”

Research suggests link between infertility, low egg reserve, and breast/ovarian cancer gene (BRCA1) New findings may help explain why women who carry a mutated BRCA1 gene have greater rates of infertility as well as a greater risk for breast and ovarian cancer A New York Medical College physician who speciales in restoring or preserving fertility in female cancer patients has discovered a possible link between the presence of breast cancer genes and infertility. In a paper published last week in the Journal of Clinical Oncology, Kutluk Oktay, M.D., professor of obstetrics and gynecology and principal investigator on the study, concluded that mutations in the BRCA1 gene, which have been linked with early onset breast cancer, are also associated with an early loss of egg reserves. This finding may help to explain why women who carry a mutated BRCA1 gene have greater rates of infertility as well as a greater risk for breast and ovarian cancer. Dr. Oktay’s team performed ovarian stimulation in 126 women with breast cancer for the purpose of fertility preservation by embryo or oocyte cryopreservation. The results showed that of the 82 women who met the inclusion criteria, 47 women (57 percent) had undergone BRCA testing, with 14 having a mutation in BRCA genes. In BRCA mutation-positive patients, the low ovarian response rate was significantly greater than for patients who did not show BRCA gene mutations, nor for women who had not been tested for the gene at all. If fertility drugs are not as effective in stimulating egg production in the ovaries of patients who carry BRCA1 mutations, this establishes a link between infertility and the risk of getting breast or ovarian cancer, Dr. Oktay concludes. It is estimated that in the general population, one in every 1,000 women is BRCA mutation positive, with the incidence as high as 2.5 percent in certain ethnic groups such as Ashkenazi Jews. Researchers have identified hundreds of mutations in the BRCA1 gene, many already associated with an increased risk of cancer. This means that the mutations in BRCA1 gene may affect egg reserve and fertility of a significant number of women in the U.S.

Compounds in pomegranates may prevent growth of hormone-dependent breast cancer Eating fruit, such as pomegranates, that contain anti-aromatase phytochemicals reduces the incidence of hormone-dependent breast cancer, according to results of a study published in the January issue of Cancer Prevention Research, a journal of the American Association for Cancer Research. Pomegranate is enriched in a series of compounds known as ellagitannins that, as shown in this study, appear to be responsible for the anti-proliferative effect of the pomegranate. “Phytochemicals suppress oestrogen production that prevents the proliferation of breast cancer cells and the growth of oestrogenresponsive tumours,” said principal investigator Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology and co-leader of the Breast Cancer Research Program at City of Hope in Duarte, Calif. Previous research has shown that pomegranate juice (punica granatum L) is high in antioxidant activity, which is generally attributed to the fruit’s high polyphenol content. Ellagic acid found in pomegranates inhibits aromatase, an enzyme that converts androgen to oestrogen. Aromatase plays a key role in breast carcinogenesis; therefore, the growth of breast cancer is inhibited. Chen, along with Lynn Adams, Ph.D., a research fellow at Beckman Research Institute of City of Hope, and colleagues, evaluated whether phytochemicals in pomegranates can suppress aromatase and ultimately inhibit cancer growth. After screening and examining a panel of 10 ellagitannin-derived compounds in pomegranates, the investigators found that those compounds have the potential to prevent oestrogen-responsive breast cancers. Urolithin B, which is a metabolite produced from ellagic acid and related compounds, significantly inhibited cell growth. “We were surprised by our findings,” said Chen. “We previously found other fruits, such

as grapes, to be capable of the inhibition of aromatase. But, phytochemicals in pomegranates and in grapes are different.” According to Gary Stoner, Ph.D., professor in the Department of Internal Medicine at Ohio State University, additional studies will be needed to confirm the chemopreventive action of Urolithin B against hormone-dependent breast cancer. “This is an in vitro study in which relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells,” said Stoner, who is not associated with this study. “It’s not clear that these levels could be achieved in animals or in humans because the ellagitannins are not well absorbed into blood when provided in the diet.” Stoner believes these results are promising enough to suggest that more experiments with pomegranate in animals and humans are warranted. Powel Brown, M.D., Ph.D., medical oncologist and chairman of the Clinical Cancer Prevention Department at the University of Texas M. D. Anderson Cancer Center, agreed with Stoner’s sentiments and said these results are intriguing. He recommended that future studies focus on testing pomegranate juice for its effect on oestrogen levels, menopausal symptoms, breast density or even as a cancer preventive agent. “More research on the individual components and the combination of chemicals is needed to understand the potential risks and benefits of using pomegranate juice or isolated compounds for a health benefit or for cancer prevention,” Brown said. “This study does suggest that studies of the ellagitannins from pomegranates should be continued.” Until then, Stoner said people “might consider consuming more pomegranates to protect against cancer development in the breast and perhaps in other tissues and organs.”

Obs Gynae & Midwifery News • Winter 2009/10

NEWS VIA is best alternative to cytology in poorer countries, suggests study A paper to be published in The Obstetrician & Gynaecologist (TOG) offers a cost-effective solution in the provision of effective cervical screening services in underresourced countries. Around 285,000 women worldwide die from cervical cancer each year. 80% of deaths occur in under-resourced countries. Unlike developed nations, where cervical screening programmes are well established, access to these services is limited in many countries in Africa, Asia and the Americas. The main barriers to reducing the high cervical cancer rate in under-resourced countries are poor health service infrastructures and the high costs of screening and vaccines. Researchers from University College London and University College Hospital suggest that visual inspection with acetic acid (VIA) is undertaken instead of the more expensive HPV DNA testing or liquid based cytology (LBC). VIA is a simple test where a very small dose of acetate acid solution is applied to the cervix to detect precancerous lesions. A positive result can be treated immediately with cryotherapy or a loop electrosurgical excision procedure. This is referred to as the ‘see and treat’ approach and may be

appropriate for small clinics without advanced equipment and laboratories. VIA is regarded as the best alternative to cytology and previous studies in rural settings have shown that it is accurate, leads to a reduction in the cancer mortality rate and is acceptable to women. Cost-wise, VIA screening costs approximately US$2 per woman, compared to >US$9 per woman for cytology. The authors point out that the drawback to using VIA is over-diagnoses which may lead to unnecessary treatment and health services need to ensure that appropriate training and monitoring are in place. Authors point out that even if the VIA test is in place, the ultimate hurdle that healthcare professionals need to overcome in the push to improve cervical cancer rates in under-resourced countries is the lack of awareness among women about the need for screening. Education programmes that engage local communities are needed to empower women. Researcher David McGregor, from UCL, said: “Visual Inspection with Acetic Acid (VIA) is an effective and affordable tool to screen women for pre-cancerous lesions of

the cervix in under-resourced countries. Coupled with simple treatment measures, VIA could potentially reduce these cancer deaths by a third, which means nearly 100,000 women saved each year. “The main barriers are financial and the low awareness of the benefits of screening among women. Successful implementation of VIA depends on the political will of governments to finance national screening programmes for women as a well as a comprehensive educational campaign on the benefits of screening and early treatment.” Mr Jason Waugh, TOG editor-in-chief, said: “The VIA test has been shown to be effective in resource-poor settings, but even with all the best will in the world, cervical cancer screening programmes will not work if women are not engaged. “Rising awareness about screening programmes to ensure higher uptake in the population is always a challenge; especially among rural and isolated communities. There are also other considerations such as cultural and social factors which may impede uptake. Health services and voluntary organisations must work closely with local groups to spread these messages.”

Breakthrough breast cancer therapy kills tumours & reduces mastectomies A new treatment developed and tested by US researchers not only killed large cancer tumors, but reduced the need for mastectomies by almost 90 percent. The latest results from the University of Oklahoma appear in an upcoming issue of the Annals of Surgical Oncology. Building on this success, researchers at the OU Health Sciences Center, plan to start the next phase of clinical trials this year to test the therapy on even larger tumours. “This therapy is a major advancement for women with later stage breast cancer. Right now, most patients with large tumours lose their breast. With this treatment along with chemotherapy, we were able to kill the cancer and save the breast tissue,” said William Dooley, M.D., a researcher at the OU Cancer Institute and the director of surgical oncology at OU Medicine. Dr. Dooley is leading a group of researchers from OU, the Massachusetts Institute of Technology, the Los Angeles Biomedical Research Institute, the Comprehensive Breast Center in Florida and St. Joseph’s Hospital in California. They are working on a treatment called

Focused Microwave Thermotherapy. The technique, which was approved by the U.S. Food and Drug Administration, uses a modified version of the microwave technology behind the “Star Wars” defense system. In the most recent study, researchers tested the therapy on tumours that were an inch to an inch and a half in size. These large tumours usually require mastectomies. When researchers used the heating therapy within two hours of patients receiving chemotherapy, the tumour was more susceptible to the chemotherapy and shrunk rapidly. The percentage of patients needing mastectomies was reduced from 75 percent to 7 percent. “The trial was very successful. We were able to completely reverse those odds,” Dooley said. “We redesigned the machine and will begin clinical trials this year to determine whether the therapy works on tumours that are larger than one and a half inches and smaller than 5 inches in size.”

Obs Gynae & Midwifery News • Winter 2009/10

In theory, Dooley said the technique could be used on any organ that could be “held relatively still.” Scientists are now working to integrate heat-sensitive nanotechnology that would more precisely target cancer cells. They also plan to study a byproduct of the rapid disintegration of the tumour – a boosted immune system. Dooley said it looks like the rapid release of cancer proteins into the blood stream is causing an immune response that could reduce the chance of cancer recurrence.

NEWS Should obese, smoking and alcohol consuming women receive assisted reproduction treatment? The European Society of Human Reproduction and Embryology (ESHRE) has published a position statement on the impact of the life style factors obesity, smoking and alcohol consumption on natural and medically assisted reproduction. In a literature study the ESHRE Task Force on Ethics and Law summarised the negative effects of obesity, smoking and drinking on the natural reproductive potential of patients, on IVF results, pregnancy complications and outcomes and finally on the health of the future child. The paper is published online in Europe’s reproductive medicine journal Human Reproduction. The group made five recommendations. 1) In view of the risks for the future child, fertility doctors should refuse treatment to women used to more than moderate drinking and who are not willing or able to minimise their alcohol consumption. 2) Treating women with severe or morbid obesity required special justification. The available data suggested that weight loss would incur in a positive reproductive effect, although more data was needed to establish whether assisted reproduction should be made conditional upon prior lifestyle changes for obese and smoking females. 3) Assisted reproduction should only be conditional upon life style changes, if there

was strong evidence that without behavioural modifications there was a risk of serious harm to the child or that the treatment became disproportional in terms of cost-effectiveness or obstetric risks. 4) When making assisted reproduction conditional upon life style modifications, fertility doctors should help patients to achieve the necessary results. 5) More data on obesity, smoking and alcohol consumption as well as other life style factors were necessary to assess reproductive effects. Fertility doctors should continue research in this area. ESHRE acknowledged that this was a complex issue due to personal, patient, professional and societal responsibilities and also in terms of what these responsibilities meant with regard to safety of mother and child and fair and equitable access to treatment. The respect for patient autonomy needed to be balanced with the moral weight of the interests of society and the future child. According to the group obesity negatively affected reproductive potential through interference with hormonal and metabolic mechanisms leading to lower ovulation frequency and reduced chances of conception. The risk of gestational diabetes increased from twofold in overweight women to eightfold for morbidly obese

women. The infants of obese mothers were at risk of perinatal death, congenital abnormalities such as neural tube defects (80% increase) and cardiovascular anomalies (30% increase). The risk of infertility was thought to be twice as high in smokers compared to nonsmokers. Female smokers needed more time to become pregnant, were less likely to do so spontaneously and had a higher risk of miscarriage. Having an accelerating effect on oocyte depletion, smoking was suggested to lead to an increase in 10 years with regards to IVF outcome. Lower birth weight, a higher risk of oral facial clefts and Sudden Infant Death Syndrome were associated with maternal smoking. Male smokers were at risk of producing sperm of reduced quality and concentration. Reduced conception, lower pregnancy rates and higher miscarriage rates were suggested as adverse effects of alcohol consumption. The known effects of alcohol consumption were summarised under Foetal Alcohol Spectrum Disorders (FASD) such as physical anomalies and behavioural and cognitive deficits. Other risks associated with prenatal alcohol consumption were foetal death, preterm labour and compromised foetal growth. Source: www.eshre.com

Screening and treating girls doesn't reduce prevalence of Chlamydia in teens Frequent testing and treatment of infection does not reduce the prevalence of Chlamydia in urban teenage girls, according to a long-term study carried out by US researchers. The Indiana University School of Medicine published the results in the January 2010 issue of the Journal of Infectious Diseases. Despite the fact they were screened every three months and treated when infected, the proportion of infected girls did not change over the course of the study. On entering the study, 10.9 percent of the young women were infected. After 18 months of participation, 10.6 percent were infected; 10.4 percent were infected at the four-year mark. Eighty-four percent of repeated infections were re-infections. In spite of being so highly motivated that they kept diaries of their sexual encounters and interacted at least quarterly with the study staff, some of the young women had unprotected sex with either an untreated partner or a new partner and subsequent infection occurred. The

researchers determined that 13 percent of repeated infections were due to failure of antibiotics to cure an earlier infection; considering all infections, antibiotic treatment was 92.1 percent effective. “The rate of infection we found in the 365 Indianapolis girls we followed is similar to the rates reported by other researchers for girls in Denver and Baltimore, so it is likely that our important new findings on re-infection can be generalized to urban teenage girls in other cities,” said Byron E. Batteiger, M.D., professor of medicine at the IU School of Medicine, an infectious disease specialist who is the first author of the study. The researchers obtained a biological sample from as many sex partners of the study participants as possible to determine if the boys were Chlamydia infected. “We were able to test 22.6 percent of all the partners that the girls named in the study. We determined that 26.2 percent of the participating boys were infected – a very high level of infection in this pool of young men to

whom young women in the study were exposed,” noted Dr. Batteiger. Current national recommendations call for routine Chlamydia screening of women based on age and history of sexual activity. There is no similar recommendation for screening young men. “The high rate of re-infection we found in our study strongly suggests there may be some real limits on what we can do to control Chlamydia without doing a better job of controlling Chlamydia in young men,” said J. Dennis Fortenberry M.D. M.S., professor of pediatrics at the IU School of Medicine, an adolescent medicine physician who is the senior author of the study. “We also need to make sure that sexually active teens are aware of fact that unlike some other diseases, having Chlamydia and being successfully treated for it does not give the individual immunity from reoccurrence,” said Dr. Fortenberry, who urges physicians to repeatedly screen adolescents for the disease.

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NEWS Study finds higher incidence of gynaecological cancers in urban areas New research to be published in BJOG: An International Journal of Obstetrics and Gynaecology has found a higher incidence of gynaecological cancers (uterine, ovarian and cervical cancer) in urban areas of Egypt, as compared to rural areas. The incidence of uterine cancer among urban women was six times higher than that of rural women. The study suggests that women in urban areas may have a higher exposure to environmental xenoestrogens (industrially made compounds that have an oestrogenic activity), which may increase the risk of developing hormonerelated cancers. Cancers specific to female organs such as the breasts and uterus, are associated with higher long term exposure to oestrogen. Numerous studies around the world have shown that environmental xenoestrogen presence and exposure is higher in urban areas. Previous research has shown a three to four times higher urban incidence of breast cancer and oestrogen receptor positive breast cancer. In this study, the researchers investigated the urban-rural incidences of gynaecological

cancers (uterine, ovarian and cervical cancer) to see if they demonstrate the same trend. The researchers analysed data from the Gharbiah Cancer Registry for the 4-year period of 1999-2002. The study population consisted of all women diagnosed with uterine, ovarian and cervical cancer in the Gharbiah Province of Egypt during this time. The key findings indicate that the incidence of all three cancers (uterine, ovarian and cervical cancer) was higher in urban areas. The most striking finding was the almost six times higher incidence of uterine cancer among urban women. The researchers found a gradient of increasing urban-rural differences for all female cancers. Cancers such as leukaemia (which are mainly genetically determined) had the lowest urban-rural difference, followed by that seen for all nonhormonally related cancers. The inclusion of cancers that are largely hormonally dependent increased the urban-rural difference by almost 70% (the urban-rural difference increased by 146% when only hormonal cancers were considered).

Lead author, Dr. Amr Soliman, Associate Professor of Epidemiology at the University of Michigan School of Public Health, said: “In this population, there is no significant urban-rural difference among women with respect to other risk factors for uterine and breast cancer, healthcare access, and behaviour. There is also very low use of hormonal pills or therapy among Egyptian women. The higher exposure of urban women to man-made chemicals in the environment that act as hormones is the probable risk factor.” Prof. Philip Steer, BJOG editor-in-chief, said: “This study adds to a growing body of literature demonstrating the impact of environmental chemicals on human health. The findings suggest that urban women have a much higher exposure to hormonal agents that increase the risk of them developing hormone-dependent cancers. Further research is warranted to confirm and investigate in more detail the association between xenoestrogens and hormonerelated cancers.

Isolation and stress identified as contributing to breast cancer risk Social isolation and related stress could contribute to human breast cancer susceptibility, research from a rat model designed at the University of Chicago, USA, to identify environmental mechanisms contributing to cancer risk shows. The researchers found that isolation and stress result in a 3.3-fold increase in the risk of developing cancer among rats with naturally occurring mammary tumours. The research establishes, for the first time, that isolation and stress could be a factor in human breast cancer risk, said Martha McClintock, a psychologist at the University of Chicago and an author of a paper in current issue of the Proceedings of the National Academy of Sciences. Researchers at the University have been studying social isolation in the context of breast cancer development after having found that that many women living in high-crime neighbourhoods must deal with a variety of stressors, including social isolation. In particular, African American women have been noted to have an earlier onset of breast cancer, although total incidence is similar to women from other ancestries. “We need to use these findings to identify potential targets for intervention to reduce cancer and other and its psychological and social risk factors,” said McClintock, the David Lee Shillinglaw Distinguished Service Professor in Psychology and Comparative Human Development at the University. “In

order to do that, we need to look at the problem from a variety of perspectives, including examining the sources of stress in neighbourhoods as well as the biological aspects of cancer development.” The results of the study are published in a PNAS paper titled, “Social Isolation Dysregulates Endocrine and Behavioral Stress While Increasing Malignant Burden of Spontaneous Mammary Tumors.” Gretchen Hermes, a former researcher at the University and now a resident in psychiatry at the Yale University School of Medicine, is lead author of the study. The paper is part of a series of publications by University of Chicago researchers exploring the connection between social isolation and breast cancer biology, and part of an ongoing research program at Chicago where work is being done on cancer by researchers from a wide number of disciplines. That work was enabled by the University’s Biopsychological Sciences Building, designed for such interdisciplinary research on behaviour and biology and enhanced when the University received a $10 million grant from the National Institutes of Health to finance its Center for Interdisciplinary Health Disparities Research and is supported by the University of Chicago Cancer Research Center. The study published in PNAS found that isolation led to a higher production of a stress hormone, corticosterone, among rats that were kept alone and subjected to the disturbances of

Obs Gynae & Midwifery News • Winter 2009/10

colony life as well as stressful situations, such as the smell of a predator or being briefly constrained. Additionally, the isolated rats took longer to recover from a stressful situation than rats that lived together in small groups. The study also suggests a causal relationship between social interaction and disease by showing that living alone first causes rats to have higher stress hormones, beginning in young adulthood, become fearful, anxious and vigilant and then prone to malignancy in latemiddle age. The study further showed that the stress hormone receptor entered the nucleus of mammary tumour cells in isolated rats, where gene regulation occurs, something that happened less often in the cells of the nonisolated rats. The researchers further found that rats living in isolation experienced a 135 percent increase in the number of tumours and a more than 8,000 percent increase in their size. The impact of isolation was much larger than the impact another environmental source of tumour formation—the unlimited availability of high-energy food. In natural situations, oestrogen and progesterone produced from ovaries play a role in the majority of naturally occurring mammary and breast cancers tumours. In the rat study, tumours naturally developed in late middle age, while ovaries were no longer fully functioning, further suggesting the role of isolation and stress hormones in cancer development.

NEWS Leading doctor calls for the urgent need to study the consequences of premature ovarian failure Data from the WHO global survey on maternal and perinatal health shows that risk of maternal death and serious complications is higher for women undergoing caesarean section that is not medically indicated than for those where there is a medical indication. Therefore the study suggests that to improve medical outcomes, caesarean section should be done only when there is a medical indication. The findings of the survey are reported in an article in an edition of The Lancet, written by Dr A Metin Gülmezoglu, Department of Reproductive Health and Research, WHO, Switzerland, and colleagues. The survey took data from nine Asian countries: Cambodia, China, India, Japan, Nepal, Philippines, Sri Lanka, Thailand, and Vietnam. In each country, the capital city and two other regions or provinces were randomly selected. A detailed description of each health facility, and its resources for obstetric care, was obtained. Women’s medical records were also scrutinised to summarise obstetric and perinatal events. Data was obtained for 109 101 of 112 152 deliveries reported in 122 recruited facilities (97% coverage), and 107 950 deliveries were studied. The overall rate of caesarean section was 27.3%. The overall

rate of operative vaginal delivery (which includes vacuum and forceps assisted vaginal deliveries) was 3.2%. Risk of maternal mortality and morbidity index (at least one of: maternal mortality, admission to intensive care unit [ICU], blood transfusion, hysterectomy, or internal iliac artery ligation) was increased for both operative vaginal delivery and caesarean section in various scenarios. The increased risk, compared with normal birth, was for operative vaginal delivery 2.1 times, antepartum caesarean without indication 2.7; antepartum caesarean with indication 10.6, intrapartum without indication 14.2; intrapartum with indication 14.5. For breech presentation, caesarean section reduced the risk of perinatal mortality—both for antepartum (by 80%) and intrapartum (by 70%) caesarean deliveries; but caesarean section in this situation also increased risk of stay in neonatal ICU (doubled for both antepartum and intrapartum deliveries). The authors say: “In the 122 Asian health facilities studied, more than one in four women underwent caesarean section. Facilities in China, Sri Lanka, Vietnam, and Thailand had higher aggregated rates of caesarean section than did those in Cambodia, India, Japan, Nepal, and the

Philippines. Operative vaginal delivery and caesarean section were independently associated with increased risk of maternal mortality and morbidity index. Caesarean section without a medical indication was associated with increased risk of maternal mortality and morbidity. Caesarean section for breech presentation was associated with improved perinatal outcomes.” They conclude: “Caesarean section should be done only when there is a medical indication to improve the outcome for the mother or the baby. Women and their carers who plan to undertake caesarean section delivery should discuss the potential risks to make an informed decision if they still wish to have a caesarean delivery.” In an accompanying comment, Dr YapSeng Chong, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, and Dr Kenneth Y C Kwek, Department of Maternal Fetal Medicine, KK Women’s and Children’s Hospital, Singapore, say: “There is little wrong with medical interventions when indicated, but for those who are still inclined to consider caesarean delivery a harmless option, they need to take a cold hard look at the evidence against unnecessary caesarean section.”

Possible ovarian cancer treatment target identified A multi-institutional study has identified a potential personaled treatment target for the most common form of ovarian cancer. In the December issue of Cancer Cell, the research team describes finding that a gene called MAGP2 – not previously associated with any type of cancer – was over-expressed in papillary serous ovarian tumours of patients who died more quickly. They also found evidence suggesting possible mechanisms by which MAGP2 may promote tumour growth. “Ovarian cancer is typically diagnosed at an advanced stage when it is incurable, and the same treatments have been used for virtually all patients,” says Michael Birrer, MD, PhD, director of medical gynecologic oncology in the Massachusetts General Hospital (MGH) Cancer Center, the study’s corresponding author. “Previous research from my lab indicated that different types and grades of ovarian tumours should be treated differently, and this paper now shows that even papillary serous tumours have differences that impact patient prognosis.” Birrer was with the National

Institutes of Health when this study began and is now at the MGH Cancer Center.. The fifth most common malignancy among U.S. women, ovarian cancer is expected to cause close to 15,000 deaths during 2009. Accounting for 60 percent of ovarian cancers, papillary serous tumours are typically diagnosed after spreading beyond the ovaries. The tumours typically return after initial treatment with surgery and chemotherapy, but while some patients die a few months after diagnosis, others may survive five years or longer while receiving treatment. To search for genes expressed at different levels in patients with different survival histories, which could be targets for new treatments, the researchers conducted whole-genome profiling of tissue samples that had been microdissected, reducing the presence of non-tumour cells from 53 advanced papillary serous ovarian tumours. The gene for microfibril-associated glycoprotein 2 (MAGP2) had the strongest correlation with reduced patient survival. Further analysis confirmed that MAGP2

expression was elevated in another group of malignant ovarian tumours but not in normal tissue. The gene’s expression was also reduced in patients whose tumours responded to chemotherapy. Recombinant expression of MAGP2 in samples of the endothelial cells that line blood vessels caused the cells to migrate and invade other tissues, which combined with the observation that MAGP2-rich tumours have increased microvessel density suggests a potential role for the protein in the growth of a tumour’s blood supply. “By confirming that different ovarian tumours have distinctive gene signatures that can predict patient prognosis, this study marks the beginning of individualed care for ovarian cancer,” says Birrer, a professor of Medicine at Harvard Medical School. “MAGP2 and the biochemical pathways it contributes to are definitely targets for new types of therapies, and we plan to pursue several strategies to interfere with tumourassociated pathways. But first we need to validate these findings in samples from patients treated in clinical trials.”

Obs Gynae & Midwifery News • Winter 2009/10

PRODUCT NEWS The following pages provide details of new or recently launched products supplied to us by manufacturers. We are happy to provide this as a service to our readers. If you have a product you’d like to promote, please email editor@ogpnews.com.

ELA – Electronically, Illuminating Amnioscope

N ew – Pelican 3/4mm Dilator & Pelican Thread Retriever

ELA is a completely self-illuminating, self-contained Amnioscope which provides a shadow-free light source ready for immediate use straight out of the packet. ELA contains its very own LED light inside, so as soon as you remove the obutrator, the light source automatically switches on. When you have finished collecting the sample, you simply replace the obutrator to switch the light off. ELA is for single patient use, but contains adequate light to allow you to take multiple samples. Using ELA means there is no need for any additional light source or external power. All the light you need is in the ELA that you can hold in one hand. For more detailed information about ELA, please contact us at Clinical Innovations (Europe) or visit www.clinicalinnovationseurope.com

Pelican Healthcare Limited, UK manufacturer of the market leading PELIspec vaginal speculum, is pleased to announce the launch of two brand new additions to our extensive range of single-use Feminine Healthcare products. The Pelican 3/4mm Dilator joins our existing Pelican 5/6mm Dilator designed to gently dilate the cervix. The tapered ends allow gradual dilatation from the two size options allowing 1mm increments from 2mm-6mm. The Pelican Dilator features a central thumb hold for ease of use and smooth rounded ends to minimize discomfort. Two pack sizes are also available for convenience. The Pelican Thread Retriever is designed to locate lost IUD threads and can also be used to sound the uterus for the presence of the intra-uterine device. The Pelican Thread Retriever has a flexible stem to sound the uterus and specifically designed notches for accurate location and retrieval of the IUD threads. The Pelican Thread Retriever has a thumb recess for enhanced grip and control. For further information on the full range of products available from Pelican Healthcare and to request your complimentary sample, please see our advert within this edition of Obs Gynae & Midwifery News.

Clinical Innovations (Europe) Tel: 01235 530022 Web: www.clinicalinnovationseurope.com Email: info@cieuropean.com

Pelican Healthcare Ltd Tel: 0800 052 1394 Email: contactus@pelicanhealthcare.co.uk Web: www.pelicanhealthcare.co.uk

PROMPT Birthing Simulator

Cory Bros Add The Secure Catch Tissue Retrieval Pouch To Their Laparoscopic Essentials Portfolio

This Simulator provides a platform for the teaching and acquisition of many of the practical skills required for the successful management of childbirth. It has been developed for multiple professional training, in conjunction with midwives and obstetricians from Southmead Hospital, Bristol (UK) and Gloucestershire Royal Hospital (UK). It incorporates a number of features which enhance training: an anatomically correct bony pelvis in the mother (modelled from patient CT scan data), silicone pelvic floor musculature and a stretchable perineum. The baby is of newborn size and weight, is fully articulated, and features anatomical landmarks e.g. fontanelles, clavicles and scapula. It was designed to improve training for the manoeuvres required to accurately manage both routine and difficult deliveries. A recent study has proved that training with mannequins, both low and high fidelity improves management of shoulder dystocia. Results published showed that training with the PROMPT Birthing Simulator was associated with a higher successful delivery rate than training with traditional low fidelity mannequins : 94% compared with 72%. For more information on this product and the study please visit www.limbsandthings.com

Cory Bros introduce the Secure Catch Tissue Retrieval Pouch for the quick, simple, secure capture and removal of resected tissue such as ovaries, gall bladder, fibroids, myomas, omentum, spleen, appendices and bowel. The Cory Bros Secure Catch Tissue Retrieval Pouch is manufactured from secure ‘rip-stop’ nylon which ensures pouch integrity even during vigorous removal. The non porous nature of the pouch material minimises port site infection and carcinoma seeding whilst the radio-opaque tethers enable secure grasper fixation during insertion and removal. The product is available in small, medium and large size options. For further information on the Cory Bros Secure Catch Tissue Retrieval Pouch or any product within their entire Laparoscopic Essentials ranges contact:

Limbs & Things Ltd Tel: +44 (0)117 311 0500 Web: www.limbsandthings.com

Cory Bros Tel: +44 (0)1923 839333 Web: www.corybros.co.uk

Obs Gynae & Midwifery News • Winter 2009/10

PRODUCT NEWS Excellent image quality for clear and detailed fetal scans at New Cross Hospital

Aesculap Endoscopy Launch New 3 Chip Full HD Camera For Laparoscopic Surgery

Obstetric patients at New Cross Hospital, part of The Royal Wolverhampton Hospitals NHS Trust, are receiving accurate and detailed scans following the installation of three ACUSON S2000™ ultrasound systems and a SpatioTemporal Imaging Correlation (STIC) application from Siemens Healthcare. One S2000 system has been installed into the Fetal Medicine Department and includes STIC for obtaining images of fetal hearts. STIC provides an automated acquisition of a high quality fetal heart volume using a sophisticated algorithm that compensates for variability in heart rate. Multi-planar reformatted images are easily obtained for detailed anatomical evaluation. STIC also features real-time heart rate display and preview mode to improve workflow. “The S2000’s excellent image quality provides a clear and detailed representation of any cardiac abnormalities, enabling us to accurately diagnose and treat as many problems as possible,” said David Churchill, Consultant Obstetrician at New Cross Hospital. “The STIC package will significantly increase our yield detection rate in small hearts to uncover problems early such as ventricular septal defects.” The other two S2000 systems have been installed into the maternity department for paediatric, obstetric and gynaecological work. “We selected the systems based on excellent image quality and the variety of different probes available,” said Sue Burford, Clinical Ultrasound Manager at New Cross Hospital. “We are very pleased with the lightweight and comfortable first trimester 9L4 probe, which we are using to obtain highly detailed obstetric and baby hip scans.” The S2000 system in the maternity department at the hospital also features the syngo® Auto OB application, which enables automated measurements from knowledge-based fetal biometrics. It uses advanced statistical pattern recognition from a large database of ultrasound images to provide the sonographer with instant measurements without the need for manual calculations. This ensures that all measurement results are standardised and not subject to individual influences, by cross checking against thousands of annotated images of fetal biometric measurements inside the Auto OB database engine for a standard and consistent result. “The S2000 ultrasound system is a versatile solution for obtaining detailed obstetric and fetal scans,” said Bernadette Leonard, Regional Sales Manager for Ultrasound Products at Siemens Healthcare. “The range of applications such as STIC and Auto OB provides quick and accurate information that clinicians need for detecting the smallest of abnormalities, enabling any problems to be accurately diagnosed and treated at an early stage.”

Today’s laparoscopic surgeon demands the very best quality pictures from a camera system, and Aesculap’s new high definition camera establishes the benchmark standard for image quality. Camera features include: • 5 times higher resolution, compared to standard definition cameras • 1080p60 - Offers maximum possible quality & lag free images • Impressive colour depth and differentiation • Remote control functions • 5 x Zoom (Optical & Digital) • Multi-specialty surgery setting options • 16:9 ratio images offers wider field of view • Camera cable can be replaced on-site • HD laparoscopes complement the HD camera and ensure the highest quality images all the way from the patient to the monitor Surgical images can be archived on the “EDDY” digital storage system, and transferred onto external USB storage media or CD /DVDs, as well as creating instant printable patients reports, including still pictures with commentary. We also offer innovative finance options to make it easy for hospitals to “advance to HD”, where current funding may be limited, inhibiting existing equipment upgrades.

Siemens Healthcare Web: www.siemens.co.uk/healthcare

For further information, please contact: B. Braun Medical Ltd Tel: 0114 225 9020 Fax: 0114 225 9062 Email: customercare.bbmuk@bbraun.com

DiOne - The Complete Lap an d D ye procedure Pack Clinical Innovations (Europe) has introduced a completely disposable “Latex Free” Lap and Dye Procedure Pack, DiOne. The pack contains all the things that you require in an ergonomically designed and easily accessible tray. The pack contains the following: • A flexible sound dilator to assess the length of the uterus • A single use Teals Tenaculum • An atraumatic Spackman Cannula. The softer tip and a moveable cervical bung reduce the risk of dye leakage and the potential to rupture the uterus during the procedure. The unique Spackman Cannula ensures that the placement of the tip inside the uterus allows exact alignment of the dye holes with the fallopian tubes. The moveable bung reduces the rick of dye leakage and provides a more reliable result. For more information on how this new and interesting DiOne can aid you in your procedure please contact us at 01235 530022 or email info@cieuropean.com. Clinical Innovations (Europe) Tel: 0123 530022 Web: www.clinicalinnovationseurope.com Email: info@cieuropean.com Obs Gynae & Midwifery News • Winter 2009/10

PRODUCT NEWS Cover Feature: Carl Zeiss There is a lot that happens in the border area between the ectocervix and the endocervix which the naked eye cannot see. A good colposcope gives you the magnification required to reliably differentiate between physiological and pathological changes at an early stage. The Zeiss Colposcope 150FC, for example has excellent optics and a six step magnification changer to ensure reliable diagnosis and therapy. A fully integrated MediLive® video camera makes documenting your results simple, quick and reliable. The 150FC is the ultimate in convenience, with a central handgrip incorporating the fine focus control. Perfect for single handed border patrol. Carl Zeiss Ltd. Tel: 01707 871231 Email: med-sales@zeiss.co.uk Web: www.zeiss.co.uk

DGL Practice Man ager Professional

Aesculap Endoscopy AdTec comBi® AdTec comBi ® , from Aesculap Endoscopy, is a combination instrument for laparoscopic surgery. It combines dissecting forceps / bipolar grasping forceps with mechanical scissors. The integrated functions allow: • Precise dissection • Secure grasping and manipulation of tissue • A high level of safety through bipolar coagulation • Effective mechanical cutting The fine instrument tips allow for excellent visualisation. Colour coding is used for instant recognition of the active function. (scissors or forcep functions) “4 in 1” cost efficiency (grasping, dissecting, coagulating, and cutting) – Fewer instrument changes. Aesculap Endoscopy provides the most comprehensive range of products and services for today’s minimally invasive surgery. We have developed products and services with our customers in mind, offering innovative solutions for procuring everything from camera drapes, through to high quality reusable instrumentation and leading edge HD camera technology.

COST EFFECTIVE with CLINICAL EXCELLENCE! For further information, please contact: B. Braun Medical Ltd Tel: 0114 225 9020 Fax: 0114 225 9062 Email: customercare.bbmuk@bbraun.com DGL are the authors of Practice Manager Professional, the UK’s best selling software for Consultants in private practice. With over 4000 licences sold throughout the UK, the software provides unrivalled features for managing the business of today’s private practice both from a business and clinical aspect. The software briefly comprises; • A complete or modular Medical Accounting Suite from Patient Registration through to full Accounts Production and Automated Debtor Management. • Clinical Audit & Electronic Patient Records, generic facilities can be customised quickly and easily to reflect individual clinical interests. • Very flexible Document Production, Management and Archiving facilities – including integrated Digital Dictation allowing for remote dictation and transcription. • Comprehensive Clinic & Theatre Diaries facilities including Multiple Practitioner diaries, Recourse Booking and Web Booking. For further information or a no-obligation demonstration contact DGL: DGL Telephone: +44 (0)1280 824600 Email: sales@dglit.com Web: www.dglit.com 14

Obs Gynae & Midwifery News • Winter 2009/10

EZIplug™ 3 Foetal Scalp Electrode System Malvern Healthcare have recently launched the latest product in their range of Foetal Scalp Electrodes. The EZIplug™ 3 System was developed following concerns raised by midwives regarding contamination and possible cross infection from insufficient cleaning and disinfecting of adaptor cables. These adaptor cables form part of the connection systems supplied by all manufacturers of FSEs and are attached to the mother’s leg during delivery and are susceptible to contamination by amniotic and body fluids. The new EZIplug™ 3 disposable Electrode has three wires, two for the foetal scalp electrode and a third which attaches to the mother’s leg by a press stud and ECG pad. The electrode is connected to the EZIplug™ 3 adaptor cable away from the birth area. If the adaptor cable does become soiled by handling it is fully sealed and can be immersed in cleaning fluid and disinfectant. Malvern Healthcare Limited Tel: +44 (0)1684 566539 Web: malvernhealthcare.co.uk

PRODUCT NEWS Boston Scientific Capio

How do you accurately adjust a sling?

Boston Scientific’s mission is to improve the quality of patient care and the productivity of health care delivery through the development and advocacy of less-invasive medical devices and procedures. This is accomplished through the continuing refinement of existing products and procedures and the investigation and development of new technologies that can reduce risk, trauma, cost, procedure time and the need for aftercare. The Capio™ suture capture device is a proven tool, and has been designed as an ease of use device to automatically throw, catch and retrieve the suture. Thereby ensuring precise uniform suture placement, with efficient tying and reloading when compared to traditional suturing methods. The Capio™ suture capture device allows for a single step procedure. Thereby extending the reach of the surgeon and assisting in difficult to access procedures eliminating the need for secondary surgical instruments. This increases procedural control for the surgeon, and creates the potential for reducing the vaginal dissection required, and potentially reducing operation time and time for patient recovery post surgery. The Capio™ suture capture device is available for both vaginal approach and laparoscopic approach. For more information please contact Ian Logan, Marketing Manager on 07887 830721.

Women with recurrent stress incontinence due to failed prior corrective surgery pose a dilemma for many Surgeons. What are the treatment options...? For these difficult to treat patients the solution is the TRT® Remeex System (Tension-free Readjustable Tape) now being distributed by Dantec Medical in the UK. The sling system eliminates the guesswork from sling tensioning and provides the Surgeon with the flexibility of increasing or decreasing urethral support with their patient awake, standing and actively participating in achieving continence. The TRT® system is also ideal for difficult ISD cases that may require slight compression to achieve continence while minimising the risk of retention. Further fine tuning in the mid to long term is easily accomplished with a Readjustment set, through a small suprapubic incision carried out under local anesthesia. With its unique capabilities and long term safety and efficacy, validated in over 65 studies and abstracts, the TRT® Remeex system should be included in the range of treatments offered by every Surgeon who treats significant numbers of incontinent patients. To arrange a demonstration or discuss the innovative system in more detail, please contact Robin Benson, Business Development ExecutiveSUI on 07814-596912 or email robin.benson@dantecdynamics.co.uk

Boston Scientific Tel: 07887 830721 Web: www.bostonscientific.com

Dantec Medical Tel: 07814 596912 Email: robin.benson@dantecdynamics.co.uk

Obs Gynae & Midwifery News • Winter 2009/10

FUTURE EVENTS January 2010 29-30 January 7 t h European Congress: Perspectives in Gynecologic Oncology Venue: Barcelona, Spain meetings@imedex.com Contact: Organiser Tel: 678 242 0906

February 2010 1-4 February RCOG: Theoretical Courses for Obstetric Ultrasound Modules, Fetal Medicine and Advanced Antenatal Practice Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 1-6 February Society for Maternal-Fetal Medicine 30t h Annual Scientific Meeting Venue: Chicago, IL, USA Contact: Society for Maternal-Fetal Medicine E-mail: smfm@smfm.org Tel: +1 202 863 2476 Fax: +1 202 554 1132 Chicago

11 February RCOG: Training Course in Manual Vacuum Aspiration Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 12 February RCOG: Workplace-based Assessment Symposium Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 23-25 February The 3t h National & First International Safe Pregnancy and Motherhood Venue: Tehran, Iran Contact: Nahid Khodakarami E-mail: safpregnancy@gmail.com Tel: +98 21 2243 2558 25-26 February 1 s t European Conference on Simulation in Womenâ&#x20AC;&#x2122;s Health Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 25-28 February First International Meeting on Cardiac Problems in Pregnancy Venue: Valencia, Spain Contact: Shlomit Benartzy E-mail: secretariat@cpp2010.com Tel: +41 0225 330 948 Fax: +41 0225 802 953

March 2010 5-6 February ISUOG Congenital Anomalies and Fetal Echocardiology Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 10-11 February British Maternal and Fetal Medicine Society 14t h Annual Conference Venue: Gateshead, UK Contact: Conference Manager E-mail: fetal@hamptonmedical.com Tel: 0208 979 8300 Fax: 0208 979 6700

3-5 March The 19t h Annual International Congress of The Egyptian Society of Gynecology and Obstetrics (ESGO): Advances and Debates in Clinical Obstetrics and Gynecology Venue: Hurghada, Egypt Contact: Mr. Alaa Abdalla E-mail: egyicc@link.net Tel: 2010 666 1172 9 March RCOG: Treatment-induced Female Infertility Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200

Obs Gynae & Midwifery News â&#x20AC;˘ Winter 2009/10

10 March Female Sexual Dysfunction Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 12 March PROMPT: Training the Trainers Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 16-18 March RCOG: Understanding Clinical Research Methods Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 19 March RCOG: Guideline for the Management of Obesity in Pregnancy Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 22-23 March Current Management of PCOS Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 22-24 March Basic Practical Skills Course, RCOG Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 24 March RCOG: Early Pregnancy and Emergency Gynaecology Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 25-28 March The First International Congress on Global Reproductive Tourism Venue: Vienna, Austria Contact: Meital Fridenzon E-mail: mfridenzon@paragon-

FUTURE EVENTS conventions.com Tel: +41 225 330 948 Fax: +41 225 802 953 25-29 March ISUOG Cairo 2010 - 6t h International Scientific Meeting Venue: Cairo, Egypt Contact: Congress Secretariat E-mail: info@pioneer-events.com Tel: 20 24 053 575 Fax: 20 24 020 609 Cairo

and Workshops Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 20-21 April RCOG: Postmenopausal Health Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 26-30 April RCOG: Subfertility and Reproductive Endocrinology and Assisted Conception Theoretical Courses Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200

26-28 March International Neonatal and Maternal Immunization Symposium (INMIS) Venue: Antalya, Turkey Contact: Ener Cagri Dinleyici E-mail: timboothtr@yahoo.com

April 2010 8-10 April 8 t h Annual Meeting of the Mediterranean Society of Pelvic Floor Disorders Venue: Cairo, Egypt www.mspfd2010.org Contact: Congress Secretariat E-mail: info@mspfd2010.org Tel: +202 3762 5077 Fax: +202 3749 8851 9-10 April The 3rd Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2010) Venue: Bangkok, Thailand Contact: KENES International E-mail: aspire2010@kenes.com Tel: +41 229 080 488 15-16 April RCOG: Training the Trainers Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 15-16 April BSGI Annual Scientific Meeting 18

www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 17-19 May Basic Practical Skills Course, RCOG Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 18-19 May Urodynamics - Joint RCOG/BSUG Meeting Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 London

28-30 April MRCOG OSCE Revision Course Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200

May 2010 6 May RCOG: How to be a College Tutor Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 9-11 May SpROGs 2010 Bournemouth Venue: Bournemouth, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200 12-13 May RCOG: Maternal Medicine: Medical Complications in Pregnancy Venue: London, UK

27-28 May Surgical Masterclass - Joint RCOG/BSUG Meeting Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200

June 2010 8-9 June RCOG: Intermediate/Advanced Colposcopy Venue: London, UK www.rcog.org.uk Contact: Royal College of Obstetricians and Gynaecologists Tel: +44 (0)20 7772 6200

For dates further in the future, please see the future events section at www.OGPNews.com I f you would like your event listed free of charge in Future Events, please forward details to: The Editor, Obs Gynae & Midwifery News, 2 Cheltenham Mount, Harrogate. HG1 1DL Tel: +44 1423 569676 Fax: +44 1423 569677 E-Mail: editor@ogpnews.com If you would like to reproduce our list, please place an acknowledgement to OGMN in your text.

Obs Gynae & Midwifery News â&#x20AC;˘ Winter 2009/10

ARTICLE How to turn your ideas into clinical products: A guide to the innovation process in medical devices

William Atiomo MBBS, MA (Distinction) DM, FHEA, FRCOG Institutional Affiliation School of Clinical Sciences, University of Nottingham, Nottingham, UK N.G.D. Limited, Nottingham Gynaecological Devices ( www.ngd.uk.com) Address for correspondence and reprints Mr William Atiomo Clinical Associate Professor / Consultant Gynaecologist & Ex-Medici Fellow School of Human Development, University of Nottingham D Floor, East Block, Queens Medical Centre Campus Nottingham University Hospitals, Nottingham NG7 2UH Email: William.atiomo@nottingham.ac.uk Fax:+44(0)1158230704

Abstract Information Points • You can protect a new idea / intellectual property for a clinical product by not telling anyone about it (secrecy), copyright, patents, design rights or trademarks. • In general terms, two models exist for getting a product into clinical use. These options include licensing the idea out to a company, or starting a company yourself to make and sell the product(s). • A new product then has to be proved to be clinically effective and safe and approved by a regulatory body before it is marketed and sold. • The benefits of a new product have to be demonstrated to colleagues and hospital managers and it has to be competitively priced to get it into clinical use. Objectives • To provide a guide to the process of converting an innovative idea to a clinical product. • Intellectual property protection, evaluation and transfer into clinical practice, in medical devices. Ethical issues raised • Should a potentially life-saving idea should be kept secret or commercially exploited? • Will a potentially life-saving idea not get into clinical use and benefit patients because of an absence of intellectual property protection and a promise of commercial benefit? Keywords Intellectual, Property, Patent, Copyright, Licensing.

Introduction In early 2005, during the process of performing a laparoscopy and dye test for infertilty, I found that on using a certain cannula, there was a lot of leakage of dye from the cervix back into the vagina because of a poor cervical seal. It was therefore not possible to accurately assess the patency of the patient’s fallopian tubes. This caused a delay in the operation because I had to use a Leech Wilkinson cannula to ensure that I made an accurate diagnosis. A less experienced or hasty surgeon may have made a wrong diagnosis.

My experience was not unique. Almost every gynaecological surgeon I had, and have since, spoken to shared that same frustration. On this occasion however, I did something different because I was a Medici Fellow at the time, learning about intellectual property exploitation in relation to my research program developing new biomarkers in Polycystic Ovary Syndrome. I drew a rough draft of a device that I thought would solve the problem. That simple sketch evolved into a prototype, patent application and finally a clinical product, the AtiomoDyeSeal™ Uterine Manipulator which

Obs Gynae & Midwifery News • Winter 2009/10

provides a better cervical seal during laparoscpy and dye test miniming the chances of a false diagnosis of blocked fallopian tubes. Because of my experience in creating and successfully licensing the device to a manufacturing and distribution company, I have formed a gynaecological devices company . This has led to the invention of other gynaecological devices for example the “Atiomo Laparoscopic Assistant™” which enables one surgeon manipulate the laparoscope as well as the uterine manipulator during laparoscopic surgery, potentially saving manpower costs

ARTICLE as an assistant sitting between the patients legs during laparoscopic surgery is no longer required. Using my experience as the framework, this article begins by exploring some approaches to generating an idea for a new product. It then provides a guide to ways of carrying out an initial evaluation to check the viability of the idea. Next, important ways of protecting these ideas are considered, followed by the process of making a prototype, licensing the idea to another company or forming a new company to manufacture and sell the device. Regulatory issues are also discussed. The process of launching a new product into clinical use, product sales, marketing and distribution are briefly outlined. Finally, some of the important personal attributes for success are highlighted. The Best Ideas Start from a Problem At an innovation networking day organed by Medilink East Midlands in 2008, I heard the after dinner speaker say that the perfect way of developing an idea was to look for the pain in people’s lives and find a solution to it. “How appropriate”, I thought. It is important to position your ideas for new products around the solution of a problem because it is more likely to be in demand and it makes it easier to find a commercial partner to help with product development. In obstetrics and gynaecology, several opportunities arise, for the generation of new solutions to existing problems. These situations may arise in the context of trying to solve a common clinical or surgical problem, developing innovative ways of teaching / learning or it may arise from novel research findings. However, not all new ideas will survive the journey from a concept in your mind(s) to a viable clinical product. The next section offers some quick first steps you can take to evaluate the viability of your new idea. Will This Work? Initial Evaluation The first step in establishing if an idea will be viable is determining whether it has already been made or patented. There are easily accessible online patent databases such as those of the European patent office and the US patent office where a quick search using the right keywords can establish whether or not your idea is unique. A search on any commercially available search engine such as “Google ®”, “Yahoo®” or “MSN®” is also useful. A discreet enquiry from colleagues and experts in the field is also useful. It is however important to note that not all innovations will be visible on these sites as some patents may have not been published. Others may require a detailed search using unique keywords or a search of other national patent databases

through a patent agent. However, if you have been working in a particular field and you and other experts in your discipline have not come across a similar product and you haven’t found a similar device by searching the above patent databases and websites, there is a very good chance that you have got an innovation that is unique. Having established the uniqueness of your product, the next step is to obtain an initial assessment of the commercial potential of the product. This information will be useful in convincing a medical device manufacturer to work with you on developing the product or in deciding if you want to form a company to manufacture and sell your products. The important bits of information required at this point are how often the product will be used in a geographical territory (say a country, continent or globally) in a year and how much you estimate each unit will sell for based on the price of similar products. With specific regard to medical devices, I often find the United Kingdom Hospital Episode Statistics website an excellent resource. The section on hospital episode statistics provides the number of times a particular operation is performed in a given year within the National Health Service. Having convinced yourself that the product is unique and that there is a stable market for it, you must take the necessary steps to formally protect the idea (your intellectual property). Protecting Your Intellectual Property You can protect your idea by not telling anyone about it (secrecy), copyright, patents, design rights and trademarks. In developing your idea for a clinical product it is important that you keep the idea secret, only disclosing it after you have some sort of intellectual property protection. Until then, it is advisable to have anyone you discuss the idea with to sign and date a confidentiality non-disclosure agreement. This is extremely important as any public disclosure (including research presentations and publications) can jeopardise the chances of a successful subsequent patent claim. Copyright protects material such as literature, art, music, sound recordings, films, software and broadcasts. In developing a clinical product, the initial concept drawings of your idea are often your first tangible intellectual property (copyright) and are of commercial value. This means they can be licensed or sold. Taking a simple step such as signing and dating the drawings is therefore very important. Always have back-up copies should you lose your original document. It is amazing how often in discussions; people draw sketches of potentially new products and discard the piece of paper

unaware of the potential commercial value of that piece of paper. Patents, on the other hand, protects the technical and functional aspects of products and processes. For a patent to be granted, the patent examiner must be satisfied that the invention is new, has an inventive step that is not obvious to someone with knowledge and experience in the subject, and it must be applicable in some kind of industry. It is advisable to seek the services of a patent attorney. However, the UK patent office has very useful information on the patent application process. Other ways of protecting your idea are through trademarks and registered designs. Once you have protected your intellectual property, your idea now has commercial value and it is possible to sell the idea to a commercial partner. However, in my experience, it is easier to sell the idea to others if you also have a tangible physical product to show (prototype). From an Idea to a Product - Prototypes A prototype is a preliminary model of your final product. You can either choose to make a prototype yourself or form a partnership with a local medical engineering unit or manufacturer. The costs of a prototype can vary ranging from a couple of hundred pounds to thousands depending on the nature of the device you want to build. To keep expenses down, a shared risk model can be used where the engineer builds your prototypes at no up-front costs but gets a proportion of the royalties due back from the device once it is fully commercialised. However it is important to agree upfront, revenue sharing arrangements that will apply if you choose to go down this route. Changes to the original design arising from the intellectual input of your collaborator may warrant a co-inventor status on any future patents. Government grants may fund the costs of building a prototype for a promising product and it is worth investigating the prospects with your local commercialisation agency, business link or technology transfer office. Having gotten an idea, carried out an initial evaluation, protected the intellectual property and developed a prototype, the next key decision an inventor has to make is how the product into clinical use and generate revenue. In general terms, two models exist although some variants of each model occur. These options include licensing the idea out to a company, or starting a company yourself to make and sell the product(s). Licensing & Company Formation Licensing involves giving the rights to your intellectual property to a commercial partner who will take on the tasks of manu-

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ARTICLE facturing and selling the product for you in return for a royalty. The advantage of licensing is that you do not have to create your own manufacturing facilities and develop your own sales force. However, the down side is that royalty payments are not always as profitable as creating your own company for making and selling your product. Licensing is a very attractive option if you want to limit your risks and if time is an issue. Potential licensees can be found from a variety of sources. These include trade shows, conferences, personal contacts, internet web listings, local university or NHS technology transfer officers, business directories, business links and local chambers of commerce. Governmentoperated business support agencies can also help to match inventors with potential licensees. Some large companies also advertise for new ideas on their websites. It is advisable to have a legal/licensing expert go through the process and look over the contracts with you. The alternative to licensing your idea to another company is to consider forming your own company to make and sell the product. The potential commercial returns of forming a company can be higher than a licensing deal. Forming and running a company can be time consuming, require a significant upfront financial investment and involve a significant amount of administrative burden. The process of forming a company should start with writing a detailed business plan to help you clarify the process you want to embark on in your own mind and communicate the plan to partners and potential investors. This should include the goals and vision of the business, the products or services that will be sold, the commercial potential, the proposed legal structure of the business (including directors and shareholders), how the business will be managed and run on a daily basis (including a Gantt chart), which employees are required, the marketing plan, projected costs of starting the business, a financial forecast of the running costs and

the anticipated exit strategy (when and how you intend to sell your business) . What Next; Clinical Testing, Regulatory Approval, Product Launch, Marketing and Sales Regardless of whether you have licensed your idea or formed a company, to actually get your product into clinical use it has to be clinically tested, approved by the relevant regulatory body, launched, marketed and sold. Clinical Testing This is required to show that your product is safe and the intended benefits are proven. Depending on the regulatory structures in your hospital / work place, you need to have the clinical test approved by the local research and development and ethics committees. Initially, a simple proof of concept study to demonstrate that the device is safe is useful. The study can also determine the best design for the product because changes may be needed after it is tested. Regulatory Approval The national regulatory approval process in the UK involves getting the product CE marked. This provides some reassurance that the safety aspects of the product have been evaluated and defined and that there is ongoing monitoring of the product whist in clinical use. This process is overseen by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. In general medical devices are classified as Class I, II or III. Class I devices are low risk, Class II are moderate and Class III are high risk. The Food and Drug Administration (FDA) regulates the US market . Similar regulatory bodies exist for most countries and geographical regions where you want your device to be used. To ensure acceptance of your device, guidelines for each country and region will need to be followed. Again, regulatory consultants are helpful in providing important guidance on these issues. However in the UK/Europe further information can be found on the MHRA website.

Product Launch, Marketing and Sales Launching, marketing and sales are the key to the successful translation of your idea into a clinical product. You may have invented the best life saving device on the planet, but I am afraid it still has to be marketed and sold. You still have to convince colleagues to use it instead of sticking with what they are used to even if the existing device is slow and painful. Careful planning, implementation and longterm sustainability are required. The exact nature of the launch, marketing and implementation will vary from product to product. Its success will depend on several factors including the benefits of the product, the nature of the marketing campaign, and the response of the competition, pricing and ultimately, the wider environmental / economic climate. Conclusion This article was written to provide an outline guide to colleagues in obstetrics and gynaecology on the innovation process based on my personal experience. More details can be found in an e-book I have written on the topic . I have found that some generic attributes are also important in the process. These include skilled people management, persistence, patience, focus and determination. There are also ethical issues which you may need to deal with such as whether a potentially lifesaving idea should be kept secret or commercially exploited. Focus is important because things don’t always go as planned and new challenges arise. It’s like a game of chess. You make an opening move and think a few moves ahead. You do not know how your opponent is going to respond so you change your strategy in response to the moves of your opponents. The key is to remain focused on the outcome. Even if you do not win that specific game, you just shake hands and start a new game (or in the innovation process, “new idea”). The important thing is that you enjoy it.

References

3 4 5

Simon Mosey, Andy Lockett, Paul Westhead, Building the Foundations for Academic EnterpriseSimon Mosey et al. In New Technology-Based Firms in the New Millenium Emerald Group Publishing Limited. 2008. 6;69-83. Nottingham Gynaecological Devices. N.G.D. Limited. www.ngd.uk.com. The Sir Colin Campbell Building University of Nottingham Innovation Park (UNIP) Triumph Road Nottingham, UK. Medilink East Midlands. www.medilinkem.com/ European Patent Office. http://ep.espacenet.com United States Patent and Trade Mark Office. http://www.uspto.gov

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Hospital Episode Statistics. www.hesonline.nhs.uk/ UK Intellectual Property Office. http://www.ipo.gov.uk/. Business Link. Prepare a Business Plan. Available at http://www.businesslink.gov.uk/ USA Food and Drug Administration Agency http://www.fda.gov Medicines and Healthcare products Regulatory Agency www.mhra.gov.uk/ William Atiomo. 2008. How to turn your idea into clinical products. E-book. Available at http://store.payloadz.com/go?id=193498

JOURNAL REVIEW The Journal Review section gives you the latest findings from current Obstetrics and Gynaecology journals. Written entirely by industry professionals, each summarises clinical research in a clear, concise and easy-to-digest manner. OGMN wishes to thank all the contributors involved. If you wish to submit a review in OGMN, please email editor@ogpnews.com.

Journal of Obstetrics and Gynaecology Canada (2009) 31(10) 974-979. Midwifery care in eight industrialised countries: how does Canadian midwifery compare? Malott AM, Davis B, McDonald H and Hutton E. Journal of Obstetrics and Gynaecology Canada (2009) 31(10) 974-979.

This study was aimed at comparing and contrasting Canadian midwifery with the practice in other developed countries. The authors selected eight countries with comparable maternal mortality rates [Australia, Denmark, France, New Zealand, Sweden, the Netherlands, the United Kingdom and Canada], and assessed scope of practice, educational preparation and the role of midwives in maternity care. Information was gathered by survey information from key midwifery informants, document analysis of relevant literature and a questionnaire survey of a convenient sampling of midwifery educators and clinicians. There was a 75% response to the questionnaire survey. Canadian midwives attended the least number of births (<10%). There were only 720 midwives to a population of 33,212,696 in Canada compared to 33,363 midwives to a population of 60,943,912 in the United Kingdom! United Kingdom midwives ticked all the boxes in selected ‘elements of care’, including assisting at Caesarean sections. Australia and Denmark ticked the least. In France, the caregivers were not known ‘throughout’. A training in Nursing was a pre-requisite to Midwifery training in Sweden. This was a revealing study in its own way, although the limitations are to be noted. The discussion was rather brief for a study of this importance, thereby raising more questions than answering them. For example, why was Italy or Germany not included? Nevertheless, many UK midwives and Obstetricians will find this article informative.

British Journal Of Obstetrics and Gynaecology (2009) 116: 1506-1514. After-effects reported by women following Colposcopy, cervical biopsies and LLETZ: results from the TOMBOLA trial. The TOMBOLA (Trial of Management of Borderline and Other Low-grade Abnormal Smears) Group. British Journal Of Obstetrics and Gynaecology (2009) 116: 1506-1514.

Women resident in Grampian, Tayside and Nottingham ; aged between 20 and 59years, who had had Colposcopy for low-grade cervical smear abnormalities were surveyed using two self-completed questionnaires. The survey tools were informed by extensive review of the relevant literature as well as clinical opinion. The response rate was satisfactory (80%). The majority of respondents (38%) were aged between 20 and 29 years. It was striking to note that among the women who had Colposcopy only: about 5% complained of moderate pain, and the same proportion complained of vaginal discharge. Half the number of women who had LLETZ had moderate to severe vaginal bleeding thereafter. The authors did a good job by identifying the limitations of the study, and state that Colposcopy, punch biopsies (of the cervix) and LLETZ ‘are not trivial interventions. The data from this study say it all.

This issue’s review was kindly written by: Isaac Babarinsa Editorial Advisor

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INTERVIEW Interview with... Ashley Sexton International Sales Manager Clinical Innovations Europe Limited (CIE)

OGMN: How long have you been with the company? AS: I joined the company in January 2009 OGMN: What made you choose a career in this industry? AS: My previous role had lots of contact with the medical industry and providing marketing ideas for them. I was most attracted to the very ‘pro-life’ ethos Clinical Innovations has developed. As one of my customers at the time, we both agreed that we saw great potential for further successes in working directly together. OGMN: What is your professional background? AS: I studied initially in Business, then to date my career has primarily been focused on the sales management and marketing within the UK and Europe. I have a sound background in the marketing and key account management of various commercial and consumer brands over a total of 12 years. I have a wealth of experience within the private and public sectors, having worked closely with healthcare professionals, specialists, medical distributors and internal sales teams, both national and international. My experience has enabled me to work successfully at all levels and functions. OGMN: Do you find your job rewarding and if so how? AS: I mentioned that Clinical is a very pro life company. This is mostly because we pride ourselves on the value that the products we distribute can bring, measured not just in the value of the product, but also in the advantages provided to both patient and consultant. Each product we design and take to the marketplace must provide benefits to both. We also pride ourselves on our strength and the response of our customer service’s clinical and technical backup. OGMN: Does your job involve a lot of travelling?

AS: Just a little! We currently have 25 distributors who look after 27 countries in Europe. I visit each of them at least twice a year in order to provide training to their own consultants and help to develop strategies for each individual marketplace. I also support our own sales team with regular visits across the UK which enables me to keep ‘a finger on the pulse’ here at home. The Company OGMN: How did the company begin and how long has it been running? AS: The company has been running since March 2001. After a few changes in structure, the organisation is now headed up and owned by Phil Barclay (CEO). Whilst Phil was finishing an MBA in Oxford, an opportunity arose to investigate the Obstetric marketplace in Europe. With a colleague, he wrote an academic report, developed a new scoring system to help in decision making for market entry, then formed a new company to service the marketplace. Phil was fortunate to be introduced to a new and innovative product– Kiwi Omnicup (USA). and a team of employees dedicated to the support of our customers. We now have 11 employees in the UK and 25 distributors who look after 27 countries throughout Europe. Although the organisation has a set structure, we operate as a team, working together to answer customer queries and solve problems together. OGMN: Where is the company based? AS: Our main offices which house all of our administrative functions are based in Abingdon, Oxfordshire, with a second building dedicated to warehousing and logistics less than 1 mile away. OGMN: What is the company focus? AS: Our main focus for 2010 is to to continue working towards helping Clinical Innovations (Europe) develop across the UK, Europe, but mostly internationally,

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and to continue providing products and services that give positive outcomes for patients wherever they are in the world. OGMN: What makes you different from your competitors? AS: Each product in our portfolio has been developed by assessing current products and solutions in the marketplace and improving on them, by solving a problem or filling a need. This means that everything we offer has a unique advantage over our competitors. CIE is a forward thinking company and is always striving to develop its product range to meet the customer’s needs. We are currently developing new products or more advanced products to replace the current out of date technology, which are inadequate for the jobs they were designed for. As a company we offer complimentary training for all customers that are new to the product and training is repeated as and when necessary I believe this is an essential part of the medical business. OGMN: How important are good customer relations? AS: As an organisation and as individuals, we care about what our customers think of our performance and the products, services and support we provide. We encourage all of our customers to communicate any feedback and issues they may have, so that proactive steps can be taken. Listening to our customers is also our main source of ideas for new products and helps us to continue to deliver benefits in many procedures for both patient and Consultant. Clinical Innovations (Europe) Limited 28 Blacklands Way, Abingdon, Oxfordshire OX14 1DY United Kingdom Tel: 01235 530022 Email info@cieuropean.com Web: www.clinicalinnovationseurope.com

ARTICLE Predictive factors for breast cancer in patients diagnosed atypical ductal hyperplasia at core needle biopsy Byung Joo Chae1,3 Ahwon Lee2,3 Byung Joo Song1,3 and Sang Seol Jung1,3 1 Department of Surgery, Catholic University of Korea, Seoul, Korea 2 Department of Pathology, Catholic University of Korea, Seoul, Korea 3 Breast Center Multidisciplinary Team, Department of Surgery, Seoul St Mary’s Hospital, Seoul, Korea World Journal of Surgical Oncology 2009, 7:77doi:10.1186/1477-7819-7-77 © 2009 Chae et al; licensee BioMed Central Ltd.

Abstract Background Percutaneous core needle biopsy (CNB) is considered to be the standard technique for histological diagnosis of breast lesions. But, it is less reliable for diagnosing atypical ductal hyperplasia (ADH). The purpose of the present study was to predict, based on clinical and radiological findings, which cases of ADH diagnosed by CNB would be more likely to be associated with a more advanced lesion on subsequent surgical excision. Methods Between February 2002 and December 2007, consecutive ultrasound-guided CNBs were performed on suspicious breast lesions at Seoul St. Mary’s Hospital. A total of 69 CNBs led to a diagnosis of ADH, and 45 patients underwent follow-up surgical excision. We reviewed the medical records and analyses retrospectively. Results Sixty-nine patients were diagnosed with ADH at CNB. Of these patients, 45 underwent surgical excision and 10 (22.2%) were subsequently diagnosed with a malignancy (ductal carcinoma in situ, n = 8; invasive cancer, n = 2). Univariate analysis revealed age (? 50-years) at the time of core needle biopsy (p = 0.006), size (> 10 mm) on imaging (p = 0.033), and combined mass with microcalcification on sonography (p = 0.029) to be associated with underestimation. When those three factors were included in multivariate analysis, only age (p = 0.035, HR 6.201, 95% CI 1.135-33.891) was an independent predictor of malignancy. Conclusion Age (> 50) at the time of biopsy is an independent predictive factor for breast cancer at surgical excision in patients with diagnosed ADH at CNB. For patients diagnosed with ADH at CNB, only complete surgical excision is the suitable treatment option, because we could not find any combination of factors that can safely predict the absence of DCIS or invasive cancer in a case of ADH.

Background Percutaneous core needle biopsy (CNB) is the standard technique for histological diagnosis of breast lesions. It has become the procedure of choice to investigate suspicious lesions of the breast and has been shown to be an effective means to rule out cancer, alleviating the cost and discomfort of surgery. Overall, CNB histological findings are in agreement with surgical biopsy in more than 95% of the cases1-3. But, CNB is less reliable for diagnosing atypical ductal hyperplasia (ADH). ADH is a proliferative lesion of the breast epithelium, which fulfils some but not all the criteria of low grade ductal carcinoma in situ (DCIS)4. ADH carries a 4-5 times increased risk of subsequent development of invasive carcinoma in either breast,5,6 and there is genetic evidence in cell populations associated with cancer suggesting it may even be a direct precursor of malignancy7. Significant discordance has been reported isn CNB diagnosis of ADH, with 7%-87% of cases proving to be 26

DCIS or invasive carcinoma on subsequent surgical excision8-14. This problem arises from the difficulty in differentiating between ADH and low grade DCIS on the small volume of tissue obtained from core biopsy15. In addition, foci of ADH may be present at the periphery of areas of DCIS16 and, thus, even an unequivocal diagnosis of ADH does not preclude the presence of an adjacent and more advanced lesion. Because of this underestimation (which means presence of DCIS or invasive cancer) risk, some authors have recommended a mandatory surgical biopsy, while others have discussed options between surgery and follow-up17. Identification of patients with ADH diagnosed by CNB who can be spared surgical excision is an area of active investigation. However, the clinical, radiologic, and pathologic parameters on which to base this decision have not been consistently identified. The purpose of the present study was to predict, based on clinical and radiological findings, which cases of ADH diagnosed by CNB

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would be more likely to be associated with a more advanced lesion on subsequent surgical excision. Materials and methods Between February 2002 and December 2007, 3476 consecutive ultrasound-guided CNBs were performed on suspicious breast lesions at the Seoul St. Mary’s Hospital. A total of 69 CNBs led to a diagnosis of ADH, and 45 patients underwent follow-up surgical excision. Seven patients refused surgical excision and were only followed up and 12 patients were transferred other hospital as per their request while 5 were lost to follow-up. The definition employed for “histological underestimation” was a lesion diagnosed as ADH at CNB that was revealed to harbor malignant foci at follow-up surgical excision, including DCIS and invasive cancer. All patients in this study underwent clinical and radiological examination, including mammography and ultrasound. The radiological appearance of the lesion was characterised

ARTICLE according to the American College of Radiology Breast Imaging Reporting and Data System lexicon and the final assessment categories. All lesions were evaluated for size on imaging and presence of microcalcification. Lesion size was defined as the greatest dimension on ultrasound imaging for most patients, or mammography size for patients with microcalcification dominant lesions. Ultrasound-guided biopsies were used for sonographically visible lesions, and were performed with patients in a supine or decubitus position using high-resolution sonography. The biopsy was performed using a device with a 14-gauge automated needle or with an 11-gauge vacuum assisted biopsy device. The core biopsy tissue sections were fixed in 10% formaldehyde and embedded in paraffin. Each biopsy specimen was stained with hematoxylin and eosin. The biopsy slides were reviewed by experienced pathologists and diagnosed according to the ADH diagnostic criteria of the World Health Organization guidelines. The data were analyzed using Chi-square and logistic regression, as well as Fisher exact test for the small sample. P values < 0.05 were considered statistically significant. Results Sixty-nine patients were diagnosed with ADH at CNB. Of these, 45 underwent surgical excision at our institution. Of the 45 patients, 10 (22.2%) were diagnosed with a malignancy after surgical excision (DCIS, n = 8; invasive cancer, n = 2). Table 1 summarises the underestimation rates and distribution in all patients according to clinical, radiological, and pathological variables, and compares the accurate diagnoses (n = 35) and underestimations (n = 10) according to patient, lesion, and biopsy variables. Six (13.3%) underwent 11-gauge stereotactic vacuum assisted biopsy because lesions were seen mainly by mammography rather than ultrasound. Women in the accurate diagnosis group were younger than those in the underestimation group (p = 0.003). Nine of the 39 ADH lesions (23.1%) found with 14-gauge automated gun biopsies were upgraded to carcinoma, and one of the six ADH lesions (16.7%) found with 11-gauge vacuum-assisted biopsies were upgraded to carcinoma. The underestimation rate for the 11gauge vacuum-assisted biopsy (16.7%) was not significantly lower than that for the 14-gauge automated gun biopsy (23.1%) (p = 0.725). Univariate analysis revealed that age (> 50 years) at the time of core needle biopsy (p = 0.006), size on imaging (> 10 mm; p = 0.033), and combined mass with microcalcification on sonography (p = 0.029) were associated with underestimation (Table 2). When those three factors were included in multivariate analysis, only age at the time of core needle biopsy (p = 0.035, HR 6.201, 95% CI 1.135-33.891) was found to be an independent predictor of malignancy, whereas size on imaging and combined mass with microcalcification on sonography were negative predictors. (Table 3) Discussion In the present study, clinico-pathological and radiological findings of ADH diagnosed by 28

Table 1. Pathologic results after surgical excision according to clinical, radiological and histological variables.

CNB were assessed to clarify predictors that could be useful in distinguishing between ADH and cancer containing DCIS. ADH is a borderline lesion on histology that is difficult to distinguish from low grade DCIS on the small tissue sample provided by CNB. Because of this difficulty, clinico-pathologic and radiologic findings that can help discriminate between ADH and DCIS are valuable in planning patient management. Although some variables like lesion size, combined mass, and microcalcification on sonography also tended to increased underestimation, only age at the time of biopsy (> 50 years) was presently determined to be an independent predictive factor for breast cancer at surgical excision in patients with diagnosed ADH at CNB. Consistent with our findings, Ko et al18 observed an increase in underestimation rates in subjects aged 50 years and older, microcalcification on mammography and, lesion size > 15 mm. Several studies have examined various mammographic, clinical, and pathological factors that may predict the presence of a more significant lesion on surgical excision after a CNB diagnosis of ADH12,19-21. It is believed that the variability of cancer rates depends on the size and features of the mammographic lesion, size of the biopsy needle, extent and completeness of sampling of the mammographic target

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lesion, histological criteria used to diagnose ADH versus DCIS and/or usual hyperplasia, and the threshold for surgical excision. Use of vacuum assistance and more extensive sampling have improved the underestimation of carcinoma on surgical biopsy after a diagnosis of ADH on CNB from 33%-48%2,21 to 7%-35%14,22-25. Although reduced underestimation with use of an 11-gauge vacuum-assisted device is explained by larger sample volumes, the number of specimens obtained presently appeared not to be correlated with a lower rate of underestimation. These results are similar to those of a previous study12, in which the investigators found that specimen numbers per lesion did not correlate with underestimation, but that complete lesion removal did correlate with degree of underestimation. These findings indicate that targeting precision is more important than sample numbers. Further studies with more cases are needed to determine whether complete lesion removal at sonographically guided 11gauge vacuum-assisted biopsy can reduce the rate of underestimation of ADH. Jackman et al,26 recognised that as the maximum diameter of the mammographic lesion increased, so does the rate of ADH underestimation. Also, in the present study, lesion size on imaging of > 1 cm increased underestimation rates. However, lesion size was not an independent predictor upon multivariate analysis.

ARTICLE Table 2. Results of univariate analysis.

Table 3. Results of Multivariate analysis.

Microcalcification with or without a mass has been reported to be the most common finding for both ADH (58% 88%) and DCIS (68% 98%)8,27-29. On histological examination, Helvie et al10 found that the calcifications in mammary ducts within areas of ADH, without cell necrosis. In DCIS, the calcifications develop in secretions and are dystrophic calcifications secondary to necrotic tumor cells30,31. These histological differences could potentially be associated with different mammographic findings. But, those detailed variables were not addressed in the present study. Presently, only the combined sonographic finding of mass and microcalcifications was a significant predictive factor for underestimation in the univariate analysis. It has been suggested that microcalcification on mammography is an independent predictor of malignancy at follow-up surgical excision in patients diagnosed with ADH at CNB18. Our results did not reveal statistical significance in this regard. Limitations of the present study include its retrospective nature and that it did not involve a randomised series of patients. Furthermore, 24 (34.8%) of the 69 ADH cases did not undergo surgical excision and were therefore excluded. It is possible that cases with a lower possibility of malignancy were recommended for imaging follow-up rather than surgical excision, which could affect the underestimation rate and other results.

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ARTICLE Conclusion Only age at the time of biopsy (> 50 years) is an independent predictive factor for breast cancer at surgical excision in patients with diagnosed ADH at CNB. Identification of patients with ADH diagnosed by CNB who can be spared surgical excision is an area of active investigation. However, at present, clinical, radiologic, and pathologic factors on which to base this decision have not been consistently identified. So, for

patients diagnosed with ADH at CNB, only complete surgical excision is a suitable treatment option because we could not find any combination of factors that can safely predict the absence of DCIS or invasive cancer in a case of ADH. Competing interests The authors declare that they have no competing interests.

Authors’ contributions BJC carried out the statistical analysis, participated in the sequence alignment and drafted and described the manuscript. AL carried out the Pathologic diagnosis. BJS and SSJ conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

References 1

Dahlstrom JE, Sutton S, Jain S: Histological precision of stereotactic core biopsy in diagnosis of malignant and premalignant breast lesions. Histopathology 1996, 28:537-541. Jackman RJ, Nowels KW, Shepard MJ, Finkelstein SI, Marzoni FA Jr: Stereotaxic large-core needle biopsy of 450 nonpalpable breast lesions with surgical correlation in lesions with cancer or atypical hyperplasia. Radiology 1994, 193:91-95. Parker SH, Lovin JD, Jobe WE, Burke BJ, Hopper KD, Yakes WF: Nonpalpable breast lesions: stereotactic automated large-core biopsies. Radiology 1991, 180:403-407. Page DL, Dupont WD, Rogers LW, Rados MS: Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985, 55:2698-2708. Dupont WD, Page DL: Risk factors for breast cancer in women with proliferative breast disease. New England Journal of Medicine, The 1985, 312:146-151. Rosen PP: Proliferative breast “disease”. An unresolved diagnostic dilemma. Cancer 1993, 71:3798-3807. Shackney SE, Silverman JF: Molecular evolutionary patterns in breast cancer.Advances in anatomic pathology 2003, 10:278-290. Liberman L, Cohen MA, Dershaw DD, Abramson AF, Hann LE, Rosen PP: Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy. AJR Am J Roentgenol 1995, 164:1111-1113. Renshaw AA, Cartagena N, Schenkman RH, Derhagopian RP, Gould EW: Atypical ductal hyperplasia in breast core needle biopsies. Correlation of size of the lesion, complete removal of the lesion, and the incidence of carcinoma in follow-up biopsies. Am J Clin Pathol 2001, 116:92-96. Harvey JM, Sterrett GF, Frost FA: Atypical ductal hyperplasia and atypia of uncertain significance in core biopsies from mammographically detected lesions: correlation with excision diagnosis. Pathology 2002, 34:410-416. Bonnett M, Wallis T, Rossmann M, Pernick NL, Bouwman D, Carolin KA, Visscher D: Histopathologic analysis of atypical lesions in image-guided core breast biopsies. Mod Pathol 2003, 16:154-160. Jackman RJ, Birdwell RL, Ikeda DM: Atypical ductal hyperplasia: can some lesions be defined as probably benign after stereotactic 11-gauge vacuum-assisted biopsy, eliminating the recommendation for surgical excision? Radiology 2002, 224:548-554. Ely KA, Carter BA, Jensen RA, Simpson JF, Page DL: Core biopsy of the breast with atypical ductal hyperplasia: a probabilistic approach to reporting. Am J Surg Pathol 2001, 25:1017-1021. Sneige N, Lim SC, Whitman GJ, Krishnamurthy S, Sahin AA, Smith TL, Stelling CB: Atypical ductal hyperplasia diagnosis by directional vacuum-assisted stereotactic biopsy of breast microcalcifications. Considerations for surgical excision. American journal of clinical pathology 2003, 119:248-253. Darling ML, Smith DN, Lester SC, Kaelin C, Selland DL, Denison CM, DiPiro PJ, Rose DI, Rhei E, Meyer JE: Atypical ductal hyperplasia and ductal carcinoma in situ as revealed by large-core needle breast biopsy: results of surgical excision. AJR Am J Roentgenol 2000, 175:1341-1346. Lennington WJ, Jensen RA, Dalton LW, Page DL: Ductal carcinoma in situ of the breast. Heterogeneity of individual lesions. Cancer 1994, 73:118-124.

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Forgeard C, Benchaib M, Guerin N, Thiesse P, Mignotte H, Faure C, Clement-Chassagne C, Treilleux I: Is surgical biopsy mandatory in case of atypical ductal hyperplasia on 11-gauge core needle biopsy? A retrospective study of 300 patients. Am J Surg 2008, 196:339-345. Ko E, Han W, Lee JW, Cho J, Kim EK, Jung SY, Kang MJ, Moon WK, Park IA, Kim SW, et al.: Scoring system for predicting malignancy in patients diagnosed with atypical ductal hyperplasia at ultrasound-guided core needle biopsy. Breast Cancer Res Treat 2008, 112:189-195. Brown TA, Wall JW, Christensen ED, Smith DV, Holt CA, Carter PL, Patience TH, Babu SS, Williard WC: Atypical hyperplasia in the era of stereotactic core needle biopsy. J Surg Oncol 1998, 67:168-173. Hoang JK, Hill P, Cawson JN: Can mammographic findings help discriminate between atypical ductal hyperplasia and ductal carcinoma in situ after needle core biopsy? Breast 2008, 17:282-288. Moore MM, Hargett CW 3rd, Hanks JB, Fajardo LL, Harvey JA, Frierson HF Jr, Slingluff CL Jr: Association of breast cancer with the finding of atypical ductal hyperplasia at core breast biopsy. Ann Surg 1997, 225:726-731. discussion 731-723. Philpotts LE, Lee CH, Horvath LJ, Lange RC, Carter D, Tocino I: Underestimation of breast cancer with II-gauge vacuum suction biopsy. AJR Am J Roentgenol 2000, 175:1047-1050. Adrales G, Turk P, Wallace T, Bird R, Norton HJ, Greene F: Is surgical excision necessary for atypical ductal hyperplasia of the breast diagnosed by Mammotome? Am J Surg 2000, 180:313-315. Rao A, Parker S, Ratzer E, Stephens J, Fenoglio M: Atypical ductal hyperplasia of the breast diagnosed by 11-gauge directional vacuum-assisted biopsy. Am J Surg 2002, 184:534-537. discussion 537. Burak WE Jr, Owens KE, Tighe MB, Kemp L, Dinges SA, Hitchcock CL, Olsen J: Vacuum-assisted stereotactic breast biopsy: histologic underestimation of malignant lesions. Arch Surg 2000, 135:700-703. Jackman RJ, Burbank F, Parker SH, Evans WP 3rd, Lechner MC, Richardson TR, Tocino I, Wray AB: Atypical ductal hyperplasia diagnosed at stereotactic breast biopsy: improved reliability with 14-gauge, directional, vacuum-assisted biopsy. Radiology 1997, 204:485-488. Helvie MA, Hessler C, Frank TS, Ikeda DM: Atypical hyperplasia of the breast: mammographic appearance and histologic correlation. Radiology 1991, 179:759-764. Stomper PC, Cholewinski SP, Penetrante RB, Harlos JP, Tsangaris TN: Atypical hyperplasia: frequency and mammographic and pathologic relationships in excisional biopsies guided with mammography and clinical examination. Radiology 1993, 189:667-671. Dershaw DD, Abramson A, Kinne DW: Ductal carcinoma in situ: mammographic findings and clinical implications. Radiology 1989, 170:411-415. Slanetz PJ, Giardino AA, Oyama T, Koerner FC, Halpern EF, Moore RH, Kopans DB: Mammographic appearance of ductal carcinoma in situ does not reliably predict histologic subtype. The breast journal 2001, 7:417-421. Holland R, Hendriks JH: Microcalcifications associated with ductal carcinoma in situ: mammographic-pathologic correlation. Seminars in diagnostic pathology 1994, 11:181-192.

ARTICLE Urological perspectives of flank pain during pregnancy Dr. C. C. Patrick, BSc (Hons) MB.ChB Specialist Registrar, Urology Milton Keynes General Hospital United Kingdom Mr. H. O. Andrews, FRCS, FRCSi, FRCS (Urol), MBA Consultant Urological and Laparoscopic Surgeon, Milton Keynes General Hospital United Kingdom

Background There are various causes of flank pain during pregnancy, either singly or in combination. These may be urological and / or non-urological in aetiology. The non- urological causes include musculoskeletal, neurological and gastrointestinal conditions. The latter causes are beyond the scope of this article; however it is important that the managing obstetrician and midwife bear these differentials in mind. The commoner urological diagnoses for loin pain during pregnancy include urolithiasis, pyelonephritis, hydronephrosis and the ‘loin pain haematuria syndrome’. Pyelonephritis and urolithiasis account for up to 50% of these cases1. Kidney, ureter and bladder (KUB) ultrasound scan is the usual investigation to exclude hydronephrosis and obstructive nephropathy due to calculus disease. KUB ultrasound is sensitive and specific for renal stones: 81% and 100%; and between 93% and 100% for hydronephrosis. Its sensitivity to detect ureteric stones and hydroureter is however lower (46% and 50% respectively). Thus in such cases, the addition of X-ray KUB would be of benefit2. Xray KUB is not strictly contraindicated in pregnancy, but should be undertaken only if there are no alternatives to making a diagnosis or in a patient in whom symptoms are unrelenting. Other investigations should be individualised, and may include urine microscopy, urine and blood cultures, IVU (15 mins single shot) and MRI scans, depending on patients’ presentation and identified co-morbidities. The management of flank pain during pregnancy is largely medical in over 80% of women, with about 5% will requiring surgical intervention in terms of a nephrostomy tube, antegrade or retrograde JJ stent insertion, and very rarely, a ureteroscopy with or without stone fragmentation.

Pyelonephritis Routine testing for asymptomatic bacteruria (AB) in pregnancy is now standard practice, and the treatment of AB has reduced the incidence of pyelonephritis in pregnancy3. Pyelonephritis is caused by infection within the renal pelvis, with or without infection of the renal parenchyma. Escherichia coli is the commonest bacteria more than 87% of cases, this bacterial ascent complicating 1 – 2% of all pregnancies, resulting in significant foetal and maternal morbidity. A recent cohort study found that 21% of cases occur during the first trimester4. Typical presentation includes flank pain, vomiting, rigors, and fever. Yet, urinary symptoms may be minimal or absent5. Laboratory testing for culture and sensitivity should be performed in all pregnant women with suspected pyelonephritis. There is no clear consensus as per antibiotic of choice or duration of treatment, however, for pregnant women not requiring admission, i.e. apyrexial women who may be managed in primary care, treatment with Cefalexin 500mg twice daily for between 10 and 14 days is advised, together with Antipyretic-analgesics and hydration. The Health Protection Agency recommends Ciprofloxacin or Co-Amoxiclav for the empirical treatment of acute pyelonephritis. This can be modified later according to sensitivity. Cefalexin has a reduced spectrum of activity, but is considered to be safer during pregnancy. Expert consensus recommends hospital admission for those 32

unable to take fluids and medications orally, or those who have signs of sepsis and fail to improve within 24 hours of starting antibiotics6. Low-dose antibiotic prophylaxis is recommended for recurrent infections with no treatable cause. Urolithiasis Urolithiasis is challenging in terms of diagnosis and management during pregnancy. It presents a risk both to the mother and the foetus, and can induce preterm labour in up to 40% of cases; it is nevertheless uncommon7. Studies have shown that there is no significant difference in the incidence of urinary calculi disease in pregnancy when compared to the non-pregnant state. The incidence of symptomatic urinary calculi in pregnancy ranges from between 1 in 1500 to 1 in 25008,9. Even though there is a two- to three-fold increase in urinary calcium excretion caused by absorptive hypercalciuria and serum oxalate super saturation as a result of increased production of 1,25-dihydroxycholecalciferol by the placenta, there is no increased incidence. This increased calcium excretion is probably counter-balanced by an increased secretion of urinary stone inhibitors such as citrates, and glycosaminoglycans, and dilution from hypervolaemia of pregnancy7. Patients with acute ureteric obstruction may present with symptoms of abdominal / flank pain, hematuria, nausea and vomiting, dysuria, polyuria, voiding difficulties and a fever.

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Initial investigations should include the following; white cell count, serum electrolytes, urine microscopy, culture and sensitivity, and ultrasonography of the urinary tract1, 10, 11, 12. The accuracy of ultrasound scan in predicting the presence of a stone improved when there is the absence of ureteric jet, and an elevated resistive index3. Expectant management with pain relief (an analgesic and an antispasmodic) is effective in 63 to 85% of patients3. The indications for surgical intervention include: P – persistent pain, I – infection, D - deteriorating renal function especially in a solitary kidney, and O - persistent Obstruction. Traditionally, the options of treatment of obstructing renal calculi during pregnancy included percutaneous nephrostomy (PCN) tube placement, or double JJ stent insertion, either antegrade or retrograde. The stones either pass spontaneously or are removed postpartum. There is now a body of evidence to show that uretero-renoscopic stone extraction in selected patients is not only safe, but a very effective modality of treatment for this group of patients. Several studies have indicated that there is no increased complication rate compared to the normal population, and therefore should be considered as an appropriate first line therapy in pregnant patients with stone disease13, 14.

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ARTICLE Hydronephrosis Gestational hydronephrosis is a physiological condition occurring in 90% of pregnant women, commencing from between the 6th and 11th week of pregnancy, and resolving at about 6 weeks post-partum. It is thought to occur as a result of hormonal relaxation of ureteric smooth muscles and mechanical compression of the ureters by the gravid uterus15. The right side is more commonly affected than the left, and the following theories account for this. Dextrorotation of the uterus and sigmoid colon with a cushioning effect on the left ureter, results in reduced compression on the left, and the congestion of the right ovarian veins lead to a higher right sided incidence1. The clinical significance of symptomatic hydronephrosis in pregnancy is its possible association with imminent complications. These include ureteric obstruction and pain, infection and deteriorating renal function. These may lead to maternal sepsis and threatened miscarriage or preterm labour. Asymptomatic hydronephrosis should be monitored perhaps every 6 weeks with an ultrasound scan and a urological referral made if symptoms develop. Management The management of loin pain during pregnancy is mainly conservative in the majority of patients. Only those who do not respond the medical management will thus require intervention16, 17.

Medical management involves out-patient treatment or a short admission to an observation ward with treatment strategies described above. Patients with known pre-operative diagnoses including PUJ obstruction, ureterocoeles, and urolithiasis can also be thus managed. If there is recurrence of urinary infections with any of these causes, then prophylactic antibiotics should be continued after a therapeutic course. The need for surgical intervention is determined by the Urological Surgeon, with due consideration of gestational age, anaesthetic risks, and a measured risk of either an immediate undertaking or of delaying the procedure until the patient is delivered. Sometimes, such decisions are not as straight-forward as they might appear. • Percutaneous nephrostomy with or without antegrade stenting: Recovery is dramatic in patients with sepsis and renal failure. This is usually performed in the intervention suite under local anaesthetic and sedation. The presence of an external tube and a collecting device is usually undesirable, as these may fall out inadvertently. There is <5% complication rate of sepsis and haematuria and a double J stent can be placed at the same time as the nephrostomy, or as a two stage process. • Double J stents are usually placed in the operating theatre under general or regional anaesthesia with targeted and limited fluoroscopy with lead shielding of

the abdomen to minimise exposure to the foetus. • Ureteroscopy and lithotripsy – either by lithoclast, or electrohydraulic methods and stone extraction is now known to be safe in pregnancy18. A double J stent is usually placed after this procedure as a safety measure in the event that hydronephrosis of pregnancy is also a contributory factor. This represents a definitive management of stones. Complication rate is <5% and usually includes abrasions, bleeding and infection. Major complication such as major ureteric injuries and avulsion are <1%. Flexible ureterorenoscopy and holmium lasertripsy in pregnancy is not widespread but may well become more utilised in the future. Conclusion Flank pain during pregnancy is not an uncommon phenomenon. There may be renal and non-renal causes. Ultrasonography remains the first line of investigation for patients with persistent symptoms necessitating admission. The majority of patients can be managed medically regardless of whether or not a surgical cause has been found. There are absolute indications for a surgical intervention. Ureteroscopic stone extraction is safe, and emerging technologies of flexible ureterorenoscopy and lasertripsy will become more important in future management of these patients as they are less invasive.

References 1

Charalambous S, Fotas A. Rizk D. E. E. Urolithiasis in pregnancy International Urogynaecology Journal: (2009) 20; 113-1136 Ather H. M, Jafri A. H, Sulaiman N. M. Diagnostic accuracy of ultrasonography compared to unenhanced CT for stones and obstruction in patients with renal failure. BMC Medical Imaging: (2004) 4:2; 1-5 Olesen F, Oestergaard I. Patients with urinary tract infection: Proposed management strategies of general practitioners, microbiologists and urologists. British Journal of General Practice: (1995) 45(400); 611-613 Archabald K. L, Friedman A, Raker C. A, Anderson B. L. Impact of trimester on morbidity of acute pyelonephritis in pregnancy American Journal of Obstetrics and Gynaecology; (2009) 201: 406-409. Cunningham F. G, Lucas M. J. Urinary tract infections complicating pregnancy. Baillieres Clinical Obstetrics & Gynaecology; (1994) 8 (2): 353-73 HPA – Health Protection Agency (2008) www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1194947340160 For management of infection guidance Gulmi F, Felsen D, Vaughan E. D. (2002) Pathophysiology of urinary tract obstruction. Campbell’s Urology, 8th Edition. Saunders, Philadelphia. McAleer S. J, Loughlin K. R. Nephrolithiasis and pregnancy Current Opinion in Urology; (2004)14: 123-127 Lewis D. F, Robichaux A. G, Jaekle R. K, Marcum N. G, Stedman C. M. Urolithiasis in pregnancy. Diagnosis, management and pregnancy outcome.

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Journal of Reproductive Medicine; (2003) 48: 28-32 Cheriachan D, Arianayagam M, Rashid P. Symptomatic urinary stone disease in pregnancy. Australia and New Zealand J. of Obstetrics & Gynaecology. (2008) 48:34-39. Enkin M, Keirse M. J, Neillson J. P. (2000) Infections in Pregnancy. A Guide to Effective Care in Pregnancy and Childbirth, 3rd Edition, Oxford, UK, Oxford University Press. Stothers L, Lee L. M. Renal colic in pregnancy. Journal of Urology. (1992)148: 1383-1387 Semins M. J, Trock B. J, Matlaga B. R. The safety of uretoscopy during pregnancy: a systematic review and meta-analysis. Journal of Urology: (2009)181(1); 139-143 Lingerman J, Lifshitz D. A, Evan A. P. (2002) Surgical management of urinary lithiasis.Campbell’s Urology, 8th Edition. Philadelphia, PA, Saunders Andreoiu M, MacMahon R. Renal colic in pregnancy: lithiasis or physiological hydronephrosis? Urology: (2009) 74(4); 757-761 Guichard G, Fromajoux C, Cellarier D, Loock P. Y et al. Management of renal colic in pregnant women, based on a series of 48 cases. Progress in Urology: (2008)18(1); 29-34 Srirangam S. J, Hickerton B, Van Cleynenbreugel B. Management of urinary calculi in pregnancy: a review. Journal of Endourology: (2008) 22; 867-875 Swanson S. K, Heilman R. L, Eversman W. G. Urinary tract stones in pregnancy. Surgical Clinics of North America; (1995) 75: 123-142.