Dermatological Manifestations During Pregnancy: a Literature Review

NOVEMBER 2012 Vol. 3 No. 11 Your partner in paediatric and O&G practice JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

IN PRACTICE

JOURNAL WATCH

OBSTETRICS Primary Amenorrhoea

GYNAECOLOGY Dermatological Manifestations during Pregnancy: A Literature Review

PAEDIATRICSPAEDIATRICS The Preschool Wheezer

CASE STUDY Amelia: A Rare Case

CME ARTICLE Robotic Surgery in Gynaecology cimsasia.com get connected get addicted THE MOST POWERFUL DRUG SEARCH make CIMS your home page at the point of care

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cimsasia.com JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

NOVEMBER 2012 Vol. 3 No. 11

Journal Watch 377 • Long-acting reversible contraception in the US

• Stress incontinence surgery: Prior urodynamic testing unnecessary

• Third stage of labour: Active management with or without controlled cord traction

377

378 • Birth defects after assisted conception

• Cervical pessary to prevent preterm birth in women with a short cervix

• First-trimester abortion: Cervical preparation with misoprostol

378

Editorial Board Professor Biran Affandi Professor Hextan Yuen-Sheung Ngan Associate Professor Kok Hian Tan University of Indonesia The University of Hong Kong KK Women’s and Children’s Hospital, Singapore Board Director, Paediatrics Dr Karen Kar-Loen Chan Professor Carmencita D Padilla Dr Surasak Taneepanichskul The University of Hong Kong Professor Pik-To Cheung University of the Philippines Manila Chulalongkorn University, Thailand Associate Professor Associate Professor Oh Moh Chay Professor Seng-Hock Quak Professor Eng-Hseon Tay Department of Paediatrics KK Women’s and Children’s Hospital, National University of Singapore Thomson Women’s Cancer Centre, Singapore and Adolescent Medicine Singapore Dr Tatang Kustiman Samsi The University of Hong Kong Associate Professor Anette Jacobsen University of Tarumanagara, Indonesia Professor Gulardi H Wiknjosastro KK Women’s and Children’s Hospital, Singapore Professor Perla D Santos Ocampo University of Indonesia Board Director, Obstetrics and Gynaecology Professor Rahman Jamal University of the Philippines Dr PC Wong Professor Pak-Chung Ho Universiti Kebagsaan Malaysia Associate Professor Alex Sia National University of Singapore Head, Department of Dato’ Dr Ravindran Jegasothy KK Women’s and Children’s Hospital, Singapore Dr George SH Yeo Obstetrics and Gynaecology Hospital Kuala Lumpur, Malaysia Dr Raman Subramaniam KK Women’s and Children’s Hospital, Singapore The University of Hong Kong Associate Professor Kenneth Kwek Fetal Medicine and Gynaecology Centre, Malaysia Professor Hui-Kim Yap KK Women’s and Children’s Hospital, Singapore Professor Walfrido W Sumpaico National University of Singapore Dr Siu-Keung Lam MCU-DFT Medical Foundation, Philippines Professor Tsu-Fuh Yeh Kwong Wah Hospital, Hong Kong Professor Cheng Lim Tan Professor Terence Lao China Medical University, Taiwan KK Women’s and Children’s Hospital, Singapore Chinese University of Hong Kong Dr Kwok-Yin Leung Indian Editorial Board The University of Hong Kong Dr Tak-Yeung Leung Obstetrics & Gynaecology Paediatrics Chinese University of Hong Kong Editor Associate Professor Bharat J Parmar BJ Medical College & Civil Hospital, Ahmedabad Professor Tzou-Yien Lin Dr. JB Sharma Chang Gung University, Taiwan Assistant Professor Deepak Chawla Associate Professor, All India Institute of Professor Somsak Lolekha Government Medical College & Hospital, Chandigarh Medical Sciences, New Delhi Ramathibodi Hospital, Thailand Dr. Sangeeta Sharma Professor Lucy Chai-See Lum Dr. Ashok Kumar LRS Institute of Tuberculosis & Respiratory Disease, University of Malaya, Malaysia Professor, MAMC, New Delhi New Delhi Professor SC Ng Dr. P. Reddi Rani Dr. Asha Pherwani National University of Singapore Professor, JIPMER, Pondicherry PD Hinduja Hospital & Research Centre, Mumbai

JPOG NOVEMBER 2012 • i JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

NOVEMBER 2012 Vol. 3 No. 11

Review Article Obstetrics

379 Primary Amenorrhoea Amenorrhoea is the absence or abnormal cessation of menstruation. It is mainly classifi ced as primary amenorrhoea and secondary amenorrhoea. Primary amenorrhoea is defi ned either as absence of menses by age 14 years with the absence of growth or secondary sexual characteristics or as absence of menses by age 16 years with normal development of secondary sexual characteristics. Secondary amenorrhoea is defi ned as the cessation of menstruation for at least 6 months or for at least 3 of the previous 3 cycle intervals. Primary amenorrhoea is a common problem during adolescence. In this article authors will discuss about primary amenorrhoea in detail. Shikha Joshi, C Hariharan, SA Inamdar 379

Review Article Gynaecology

384 Dermatological Manifestation during Pregnancy: A Literature Review Pregnancy is a physiological and transient period where medical intervention is usually not required, or at least is restrained to checking expected events. However, in the ﬁ nely tuned, harmonious and extraordinarily complex cascade of molecular and cellular phenomenon that gestation brings, many signs and/or symptoms may target the cutaneous layer. Therefore, it seems logical that during pregnancy, hormonal or other less well-explained pathways may inﬂ uence one of the skin cell types. By contrast, some diseases originating in the skin may affect the course of the gestation. Prasoon Soni, Monica Soni, Ekta, Priyanka 384

In Practice

392 Case of the Month: Woman with Cyst formation in Right Breast Prabhu Prakash, Asha Mathur, Sneha Ambwani, Seema Surana

Review Article Paediatrics

393 The Preschool Wheezer This article addresses the different patterns of preschool wheeze and explains how one might differentiate 393 between them; looks at the risk factors and important preventative measures to take; reviews current therapies; and highlights the paucity of evidence supporting common use. David Cremonesini, Anne Thomson

JPOG NOVEMBER 2012 • ii JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

NOVEMBER 2012 Vol. 3 No. 11

400 In Practice (Answer)

Case Study

402 Study of Serum Homocysteine and Vitamin B12 Levels in Eclampsia, Pre-eclampsia, and the Effectiveness of Treatment with Inj.

Vitamin B12 on the Outcome of these Patients 402 Radha Yegnanarayan, GS Shekhawat, Hemant S Damle

407 Amelia: A Rare Case Varsha Deshmukh, KA Yelikar, VY Kalyankar, Neha Golechha, PS Deshmukh

Continuing Medical Education 409 409 Robotic Surgery in Gynaecology This article reviews the applications of robotics in various gynaecological procedures, including tubal reanastomosis, hysterectomy, myomectomy, sacrocolpopexy and oncological surgery. Yuen Pong Mo

The Journal of Paediatrics, Obstetrics and Gynaecology contains articles under license from UBM Medica India Pvt. Ltd.

JPOG NOVEMBER 2012 • iii JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY

NOVEMBER 2012 Vol. 3 No. 11

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PUBLISHER: Journal of Paediatrics, Obstetric & Gynaecology (JPOG) is published 12 times a year by UBM Medica, a division of United Business Media. CIRCULATION: JPOG is for medical practitioners in Asia. It is available on subscription to members of allied professions. SUBSCRIPTION: The price per copy is Rs. 200/-. The price per annum is Rs. 2040/-. EDITORIAL MATTER published herein has been prepared by professional editorial staff. Views expressed are not necessarily those of UBM Medica. Although great care has been taken in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular fi eld or fi elds. Publisher of CIMS/IDR COPYRIGHT: © 2012 UBM Medica. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, in any language, without written consent of copyright owner. Permission to reprint must be obtained from the publisher. ADVERTISEMENTS are subject to editorial acceptance and have no infl uence on editorial content or presentation. UBM Medica does not guarantee, directly or indirectly, the quality or effi cacy of any product or service described in the advertisements or other material which is commercial in nature.

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JPOG NOVEMBER 2012 • iv Journal Watch

ring, and 0.25 per 100 person-years with long-act- nosis of overactive bladder and more likely to be GYNAECOLOGY ing reversible contraception, a significant 22-fold given a diagnosis of voiding phase dysfunction, but improvement with long-acting reversible contra- this did not affect treatment selection or outcome. Long-acting reversible ception. The risk of unintended pregnancy in par- At 1-year after surgery, outcomes were no contraception in the US ticipants using pills, patches, or rings was almost worse in women who had not had urodynamic test- twice as high in younger women (< 21 years) as ing than in those who had. in older women. Among women using long-acting Nager CW et al. A randomized trial of urodynamic testing before stress- reversible contraception, age did not affect the incontinence surgery. NEJM 2012; 366: 1987–1997. failure rate. The use of long-acting reversible contraceptive methods reduces the risk of unintended preg- OBSTETRICS nancy. Third stage of labour: Active Winner B et al. Effectiveness of long-acting reversible contraception. NEJM 2012; 366: 1998–2007. management with or without controlled cord traction

The US has a particularly high rate of unintended Postpartum haemorrhage (PPH) is an important pregnancy (about half of all pregnancies), leading Stress incontinence surgery: Prior cause of maternal morbidity and mortality, espe- to many abortions and adverse consequences for urodynamic testing unnecessary cially in developing countries. Active management women’s health. About half of the unintended preg- of the third stage of labour reduces the risk of PPH nancies are a result of failure of contraception and Urodynamic testing is often performed prior to sur- by > 60%. Active management includes admin- half a result of failure to use contraception. The gery for stress incontinence in women but is costly, istration of oxytocin and controlled cord traction, annual failure rate for oral contraceptive pills is inconvenient, and uncomfortable. It increases the but the importance of controlled cord traction is about 9% overall and higher in teenagers and other risk of urinary tract infection, and there is no good unknown. Omitting controlled cord traction might high-risk groups. Long-acting reversible contracep- evidence that it influences outcomes. A multicentre simplify and improve services in resource-poor tive methods, including intrauterine devices (IUDs) US study has confirmed that urodynamic testing is countries. A randomized trial in eight countries (Ar- and subdermal implants, have failure rates of < 1%. not beneficial. gentina, Egypt, India, Kenya, the Philippines, South A low uptake of IUDs may partially explain the high A total of 630 women with stress inconti- Africa, Thailand, and Uganda) has suggested that rate of unintended pregnancy in the US. Now, a US nence were randomized at 11 centres to preopera- controlled cord traction might be omitted safely. prospective cohort study has underlined the effective office evaluation with or without urodynamic A total of 24,390 women with singleton preg- tiveness of long-acting reversible contraception. testing. Treatment was successful (Urogenital nancies were randomized to full package (FP) or In St Louis, Missouri, a total of 9,256 women Distress Inventory score reduced by at least 70% simplified package (SP) management of third stage. aged 14–45 at risk of unintended pregnancy were and ‘much better’ or ‘very much better’ on Patient All women were given oxytocin 10 IU immediately recruited between August 2007 and September Global Impression of Improvement) at 1 year in after the birth, with cord clamping at 1–3 minutes. 2011. They were provided with a contraceptive 76.9% (urodynamic testing) vs 77.2% (controls), The SP consisted of placental delivery with gravity method of their choice free of cost with an em- showing non-inferiority of the control group. There and maternal effort. The FP consisted of controlled phasis on the advantages of long-acting reversible were no significant differences between the groups cord traction immediately after uterine contraction contraception. A total of 7,486 participants were in incontinence severity, quality of life, patient sat- and cord clamping. Blood loss of 100 mL or more included in the analysis. There were 334 unin- isfaction, provocative stress test results, voiding occurred in 239/11,621 (2%) in the SP group and tended pregnancies. The contraceptive failure rate dysfunction, or adverse events. The urodynamic 219/11,621 (2%) in the FP group. The risk ratio of was 4.55 per 100 person-years with pills, patch, or testing group were less likely to be given a diag- 1.09 (0.91–1.31) had a 95% confidence interval up-

JPOG NOVEMBER 2012 • 377 p per margin exceeding the pre-stated non-inferiority Factors in the parents may be responsible for margin of 1.3. There was one case of uterine inver- much of the increased risk, but ICSI may be inde- sion in the FP group. pendently associated with increased risk. Although the pre-stated non-inferiority limit Davies MJ et al. Reproductive technologies and the risk of birth defects. was exceeded, these researchers conclude that NEJM 2012; 366: 1803–1813. omitting controlled cord traction had very little effect on the risk of severe PPH, and haemorrhage prevention programmes in non-hospital settings could safely focus on the use of oxytocin. Cervical pessary to prevent

Gülmezoglu AM et al. Active management of the third stage of labour preterm birth in women with a with and without controlled cord traction: a randomised, controlled, non- inferiority trial. Lancet 2012; 379: 1721–1727. Chong Y-S, Arulkumaran short cervix S. Keep things simple for safer childbirth and better medicine. Ibid: 1684–1685 (comment). is cheap and widely used orally, sublingually, or Cervical pessaries have been used for 50 years to vaginally. A multinational study has shown that prevent preterm births associated with short cervix, vaginal misoprostol is effective in reducing the but there has been no randomized trial. Now, a mul- risk of complications after first-trimester vacuum Birth defects after assisted ticentre trial in Spain has confirmed the effective- extraction abortion. conception ness of this method. A total of 4,972 women were randomized The trial included 385 women with a cervical at 14 centres in nine countries to vaginal miso- Evidence suggests that assisted reproduction tech- length of 25 mm or less on routine transvaginal scan- prostol (two 200-µg tablets) or vaginal placebo, nologies, ie, in vitro fertilization (IVF) and intracyto- ning at 18–22 weeks’ gestation. Randomization was 3 hours before first-trimester vacuum aspiration plasmic sperm injection (ICSI), are associated with to insertion of a cervical pessary at 20–23 weeks abortion. Follow-up was for 2 weeks, and full data increased risk of birth defects. This could be due to or no intervention. Spontaneous delivery before 34 were analysed for 4,858 women. There was a sig- factors within the technologies or to factors in the weeks occurred in 6% (pessary) vs 27% (controls), a nificant 32% reduction in risk of complications in patients who take up the technologies. A study in highly significant difference. There were no serious the misoprostol group compared with the placebo South Australia has provided more data. adverse effects from use of a pessary. group. Incomplete abortion occurred in < 1% (miso- Out of a total of 308,974 births, 6,163 were Insertion of a cervical pessary reduces the prostol) vs 2% (placebo), a significant difference. the result of assisted conception. The rate of any risk of preterm birth in women with a short cervix. Uterine re-evacuation was necessary in < 1% vs birth defect was 8.3% after assisted conception 2%. Pelvic inflammatory disease occurred in 1% of Goya M et al. Cervical pessary in pregnant women with a short cervix and 5.8% without assisted conception. Unadjusted (PECEP): an open-label randomised controlled trial. Lancet 2012; 379: each group. Three women in the placebo group, but 1800–1806; Caritis SN, Simhan H. Cervical pessary use and preterm birth: data showed a 47% increase in risk after assisted how little we know. Ibid: 1769–1770 (comment). none in the misoprostol group, had cervical tears, conception, but after adjustment for parental fac- and uterine perforation occurred in two (placebo) tors the increase fell to 28%. There was no sig- and three (misoprostol). Abdominal pain occurred nificant increase in adjusted risk after IVF, but after First-trimester abortion: Cervical in more women in the misoprostol group (55% vs ICSI this risk was increased significantly by 57% preparation with misoprostol 22%) than did vaginal bleeding (37% vs 7%). after adjustment. The risk was increased for a wide Misoprostol given 3 hours before first-tri- variety of defects including cardiovascular, muscu- Almost a third of all pregnancies worldwide end in mester vacuum extraction abortion reduces the risk loskeletal, urogenital and gastrointestinal abnor- induced abortion, often by vacuum extraction in the of complications. A Lancet commentator suggests malities and cerebral palsy. Women with a history first trimester. It is important to prepare the cervix that it should be used routinely. of infertility had an increase in risk irrespective of for cervical dilation, and osmotic dilators, mifepris- Meirik O et al. Complications of ﬁrst-trimester abortion by vacuum whether or not they had had a previous birth after tone, and prostaglandin analogues are used for this aspiration after cervical preparation with or without misoprostol: a multicentre randomised trial. Lancet 2012; 379: 1817–1824; Templeton A. assisted conception. purpose. Misoprostol, a prostaglandin E1 analogue, Misoprostol for all women seeking abortion? Ibid: 1772–1773 (comment).

JPOG NOVEMBER 2012 • 378 OBSTETRICS

Primary Amenorrhoea

Shikha Joshi, C Hariharan

AMENORRHOEA

Amenorrhoea is the absence or abnormal cessation of menstruation. It is mainly classified as primary amenorrhoea and secondary amenorrhoea.

Primary Amenorrhoea It is defined either as absence of menses by age 14 years with the absence of growth or secondary sexual characteristics or as absence of menses by age 16 years with normal development of secondary sexual characteristics.

Secondary Amenorrhoea It is defined as the cessation of menstruation for at least 6 months or for at least 3 of the previous 3 cycle intervals. Secondary amenorrhoea is more common than primary amenorrhoea.1–3 Primary amenorrhoea is a common problem during adolescence. In this article authors will discuss about primary amenorrhoea in detail.

Primary Amenorrhoea−Causes

Hypothalamic • Weight loss–anorexia nervosa • Primary hypothyroidism

JPOG NOVEMBER 2012 • 379 OBSTETRICS

History and physical exam

Uterus present Uterus absent or uncertain

FSH and LH<5 FSH >20 IU/L and IU/L LH>40 IU/L Karyotype patient

Hypergonadotropic Hypogonadotropic hypogonadism 45,XX 46,XY hypogonadism Eating disorders Brain injury or irradiation Karyotype Kallmann syndrome Mulle- Androgen patient Pituitary defect rian agenesis/ insensitivity Hyperprolactinemia Mayer-Rok- syndrome, Hemochromatosis itansky- vanishing testes 45,XO 46,XX Kuster- syndrome, Hauser 5α reductase Syndrome deﬁ ciency

Consider MRI Turner Premature syndrome ovarian failure

Figure 1. Approach to diagnosis

• Craniopharyngioma Diseases of the Outflow Tract • Cerebral/midbrain injury • Non-functional uterus with uterovaginal agen- • Encephalitis/meningitis esis Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome Pituitary Causes • Uterine adhesions–TB endometritis • Mixed pituitary tumours • Functional uterus with obstruction to the outflow • Irradiation tract, septate vagina, imperforate hymen • Post-intracranial surgery Depending on Serum FSH Levels Adrenal • Hypergonadotropic primary amenorrhoea • Congenital adrenal hyperplasia • Eugonadotropic primary amenorrhoea • Adrenal tumours • Hypogonadotropic primary amenorrhoea

Ovarian Causes • Turner syndrome (45,X0) EVALUATION AND DIAGNOSIS • Turner mosaics (45,X0/46,XX) • Premature ovarian failure Diagnostic approach for primary amenorrhoea is • Virilising ovarian tumours described in figure 1.

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History • Age at menarche of other siblings • History of excessive weight loss of 10–15% loss of body weight–Anorexia nervosa • Cyclical lower abdominal pain–Cryptomenor- rhoea • Anosmia (Kallmann’s syndrome) • Headaches, visual disturbances–Intracranialtu- mours • Meningitis, tuberculosis (hypothalamic) • Virilisation, hirsuitism, change in voice Figure 2. Vaginoplasty • Radiotherapy to the pelvis or chemotherapy

MRKH Syndrome cortisol from cholesterol by the adrenal glands Among congenital abnormalities of the (steroidogenesis) as showed in figure 3.6 female genital tract, a non-functional. • Most of these conditions involve excessive or Uterus with uterovaginal agenesis (MRKH deficient production of sex steroids and can alter syndrome) being one of the most frequent causes development of primary or secondary sex char- of primary amenorrhoea.4 acteristics in some affected infants, children or It can sometimes be associated with renal adults.7 agenesis or other renal abnormalities.5 • Genetic males with 5-ARD are born with ambigu- Uterovaginal agenesis ous genitalia (i.e., male pseudohermaphrodit- • Normal secondary development and external ism). female genitalia; absence of uterus and upper • The described clinical abnormalities range from vagina and normal ovaries • Karyotype 46,XX • Intravenous pyelography (IVP) in 30% cases suggest urinary tract abnormalities

Management Investigation with clinical examination, karyotyping, ultrasound examination, IVP for the localisation of kidneys and laparoscopy in that order followed by vaginoplasty (Figure 2).

Congenital Adrenal Hyperplasia • Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes Figure 3. Congenital adrenal hyperplasia mediating the biochemical steps of production of

JPOG NOVEMBER 2012 • 381 OBSTETRICS

infertility with normal male genital anatomy to come out through genital tract due to causes like: to underdeveloped male with hypospadias to • Imperforate hymen predominantly female external genitalia, most • Transverse vaginal septum often with mild clitoromegaly. A clitoral index • Atresia of upper third of vagina and cervix greater than 35 mm2 is evidence of increased Patient presents with periodic cyclical pain, androgen effect. A clitoral index greater than retention of urine, haematocolpos, haematometra 100 mm2 is evidence of virilisation. and haematosalphinx. • Associated with metabolic abnormalities, hyper- kalaemia and hyponatraemia • Sex chromatin study depicts positive barr bodies TURNER’S SYNDROME • Karyotype shows generally 46,XX • 17 hydroxy progesterone > 800ng/ml Turner’s syndrome (45,XO) occurs in one out of 2500 to 3000 patients. These patients have streak Cryptomenorrhoea gonads, usually short with associated somatic Cryptomenorrhoea or cryptomenorrhea, also known abnormalities and eye defects like segmental irido- as haematocolpos, a condition where menstruation goniodysgenesis without glaucoma. occurs but is not visible.8 There will be periodic • Turner’s syndrome is caused by either complete shedding of endometrium, but menstrual blood fails absence or a partial abnormality of one of the two X chromosomes. About 50% have mosaic forms such as 45,X/46,XX or 45,X/46,XY • Features short stature, poor secondary sexual characters though phenotypically female, web neck, lymphoedema, shield chest with widely spaced nipples, scoliosis, wide carrying angle, (Figure 4) coarctation of the aorta, cubitus valgus and streak ovaries

Androgen Insensitivity Syndrome/ Testicular Feminisation Syndrome Phenotypically female normal breast development without areolar pigmentation, scanty pubic and axillary hair, under-developed labial or inguinal gonads. On laparoscopy: Uterus and tubes are absent. Serum testosterone level is equal to normal male. Karyotyping: 46,XY Gonadal biopsy: Testicular structure Management includes gonadectomy due to Figure 4. Physical characteristics of patient with Turner’s Syndrome increased risk of seminoma or dysgerminoma. Hormone replacement therapy with conjugated

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equine oestrogen (premarin 0.625 mg) is adequate itary tumours along with dopamine agonists in to maintain secondary sexual characters. prolactinomas: • XY Karyotype – Gonadectomy TREATMENT–GOALS • Imperforate hymen – Cruciate incisions • Vaginal atresia/septate vagina – Vaginoplasty The treatment objective are as follows: • Correct the underlying cause Unresponsive Endometrium • Correct sexual infantilism and initiate full repro- Synechiae of tubercular origin: Antitubercular ductive potential when possible drugs with adhesiolysis. • Correct short stature • Correction of sexual infantilism Thyroid and Adrenal Dysfunction • Exogenous oestrogen and progesterone Adrenogenital syndrome with enlarged clitoris • Correction of short stature human growth treated by clitoroplasty corticosteroid replacement hormone exogenous gonadotropins are given to in 17α hydroxylase deficiency. correct short stature About the Authors Correction of Underlying Cause Dr Shikha Joshi is an Assistant Professor and Dr C Hariharan is the Head of Department and Professor, Department of Obstetrics and Gynaecol- Surgical excision of craniopharyngioma and pitu- ogy, Datta Meghe Institute of Medical Sciences Sawangi, Wardha.

REFERENCES

1. The Practice Committee of the American Society for 5. Reindollar RH, Byrd JR, McDonough AD. Delayed Reproductive Medicine. Current evaluation of amenor- sexual development; a study of 250. Am J Obstet rhea. Fertil Steril. 2004;82(suppl 1):S33–9. Gynecol. 140:371-80. 2. American College of Obstetricians and Gyne- 6 David A. Warrell (2005). Oxford textbook of medi- cologists. Amenorrhea (ACOG Technical Bulletin 128). cine: Sections 18-33. Oxford University Press. pp. Washington, DC.: ACOG, 1989. 261–Retrieved 14 June 2010. 3. Speroff L, Fritz MA. Amenorrhea. In: Clinical gyneco- 7 Aubrey Milunsky; Jeff Milunsky (29 January 2010). logic endocrinology and infertility. 7th ed. Philadelphia, Genetic Disorders and the Fetus: Diagnosis, Prevention Pa.: Lippincott Williams & Wilkins, 2005;401–64. and Treatment. John Wiley and Sons. pp. 600–. ISBN 4. Morgan T. Turner syndrome: diagnosis and manage- 978-1-4051-9087-9. Retrieved 14 June 2010. ment. Am Fam Physician. 2007;76(3):405-10. 8 “cryptomenorrhea” at Dorland’s Medical Dictionary.

JPOG NOVEMBER 2012 • 383 GYNAECOLOGY

Dermatological Manifestations During Pregnancy: A Literature Review

Prasoon Soni, Monica Soni, Priyanka, Ekta

INTRODUCTION

Pregnancy is a physiological and transient period where medical intervention is usually not required, or at least is restrained to checking expected events. However, in the finely tuned, harmonious and extraordinarily complex cascade of molecular and cellular phenomenon’s that gestation brings, many signs and/or symptoms may target the cutaneous layer. Therefore, it seems logical that during pregnancy, hormonal or other less well-explained pathways may influence one of the skin cell types. By contrast, some diseases originating in the skin may affect the course of the gestation. In this review, cutaneous modifications will be classified as physiological changes, specific dermatoses of pregnancy, cutaneous infections that may modify the prognosis of pregnancy and, finally, miscellaneous skin diseases that may be affected by pregnancy.

Physiological Changes in Pregnancy It is important to recognise and differentiate physiological changes from diseased states in order to explain them to the patient and avoid unnecessary investigations or treatments. The 3 main precipitating factors that induce the development of these changes are an increase in circulating hormones or other mediators that are secreted by ovaries and/or placenta, including oestrogens, progesterone, human placental lactogen, placental growth factor (PlGF), intravascular volume expansion and a compression from the enlarging uterus. Oestrogens display pleiotropic effects. They stimulate melanogenesis and keratinocyte growth, cause cutaneous vasodilatation, increase capillary

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permeability and probably enhance angiogenesis. Structural Changes Progesterone acts synergistically with oestrogens • Striae gravidarum on melanogenesis, but intervenes solely to reduce • Molluscum fibrosum gravidarum collagenolytic activity.1 In addition, an enlargement of the pituitary gland results in increased levels of Adnexal Changes gonadotrophins, adrenocorticotropic hormone and • Hair melanocytic-stimulating hormone that have a direct » Reversible hirsutism, postpartum telogen effect on the skin. effluvium, male pattern alopecia • Nails Physiologic Changes of the Skin and the » Distal onycholysis, transverse grooves, Mucosa during Pregnancy longitudinal melanonychia, subungual hyper- keratosis Pigmentary Changes • Glands • Non-facial hyperpigmentation » Eccrine sweat glands: Hyperhidrosis, miliara » Areolae, nipples, periumbilical skin, anogen- » Apocrine sweat glands: Decreased activity ital region, axillae, thighs » Sebaceous glands: Increased activity, Mont- » Recent scars, nevi, freckle gomery’s tubercles » Linea nigra » Pigmentary demarcation lines Non-facial Hyperpigmentation • Melasma Hyperpigmentation is the most frequent skin • Vascular changes modification found in pregnancy and is one of its » Spider telangiectasias earliest signs. It takes place usually during the » Palmar erythema first trimester. The exact pathogenesis, although • Venous hypertension signs unclear, is considered to rely on increased serum » Varicose veins and venous telangiectasias of levels of melanocytic-stimulating hormone, oestro- the legs gens and possibly progesterone, which stimulates » Hemorrhoids melanocytic activity contributing to pigmentation. » Jacquemier’s sign Changes are more pronounced in women with » Chadwick’s sign a dark complexion. Areas normally display- » Non-pitting oedema ing pigmentation become darker in pregnancy. » Purpura However, hyperpigmentation is usually more local- • Vasomotor instability ised, targeting the areola and/or nipples, which are » Episodic pallor, facial flushing, hot and cold the most commonly affected sites (40%).2 Other sensations, dermographism, cutis marmorata sites of predilection include the face, the perium- • Vascular proliferation bilical skin, the anogenital region, the axillae and » Hemangiomas, glomus tumours, hemangio- the inner thighs. Recent scars, nevi and freckles endotheliomas may also darken during gestation. Linea alba that » Hyperemia and hyperplasia of the gingival corresponds to an aponeurosis extending from the mucosa symphysis pubis to the xiphisternum often becomes » Oral pyogenic granulomas hyperpigmented during pregnancy, most markedly

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below the umbilicus. It is referred to as linea nigra nant women, but are found much less frequently in and found in 75% of pregnant females.2 Increase dark-skinned women.2,6 They are easily recognised of the pigmentary demarcation lines is frequently by their punctiform central redness-corresponding observed in black pregnant women, but very rarely to a dilated afferent arteriole with radiating capil- in white subjects.3 After delivery, pigmentation laries and surrounding erythema. Typically, spider usually resolves spontaneously even though the nevi appears at the end of the first trimester in outcome may differ widely among patients. the area of skin drained by the superior vena cava, namely the face, neck, arms and hands. Their Melasma number increases throughout pregnancy. They often Melasma, chloasma or mask of pregnancy may disappear within weeks after deliver. It should be affect up to 70% of pregnant women. Facial hyper- mentioned that when abnormally numerous spider pigmentation display various symmetrical distribu- telangiectasias manifest in pregnant women, tions. The most common is centrofacial melasma liver status should nevertheless be checked, since developing on the forehead, cheeks, upper lip, and in hepatic diseases oestrogen catabolism may chin. Maxillary and mandibulary patterns are less decrease. frequent.4 Pigmentation consists of grey-brown, poorly demarcated plaques. The diagnosis is very Acral Erythema easy. Pigmentation usually regresses in postpar- Palmar erythema appears within the first trimes- tum, but may persist in some cases and/or worsen ter along with spider telangiectasias.4 It is more again after sun exposure. Recurrence in future frequent and noticeable in white than black women. pregnancies or with oral contraception is common. Two patterns have been described; erythema may The genetic background, dark complexion and expo- either be restricted to the thenar and hypothenar sure to UV light are aggravating factors.5 eminences, the metacarpophalangeal joints and the finger pads or, by contrast, it may present as Vascular Changes a diffuse mottled redness of the entire palms.7 Various molecules can cause functional modifica- Hyperthyroidism, cirrhosis, lupus and salbutamol tions in the arteries with a decrease in smooth intake are the main differential diagnosis.4 Palmar muscle tension and consequent decrease in vascu- erythema in pregnancy is attributed to venous lar resistance. Proliferation of the cutaneous micro- capillary engorgement and fades within 1 week vasculature also occurs. Alternatively, expanding postpartum. intravascular volume and compression from the enlarging gravid uterus explains venous conges- Venous Hypertension Signs tion, dependent oedema and varicosities. Thus, Secretion of pregnancy-related hormones induces hyperemia, vasomotor instability, vascular prolif- an increased fragility of the elastic fibres in eration and venous hypertension can cause skin vessel walls. Furthermore, the enlarging uterus lesions that usually regress postpartum. compresses the pelvic and abdominal vessels, increasing venous pressure. These, as well as other Spider Telangiectasias precipitating factors, including genetic predisposi- Spider telangiectasias, also termed spider angio- tion and prolonged standing, lead to saphenous, mas, develop in approximately 60% of white preg- vulvar and anal (hemorrhoidal) varicosities.6 Start-

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ing from the second month of pregnancy, varicose reported in 5% of pregnant women.7 They develop veins and venous telangiectasias appear in 40% of at the beginning of the third month of gestation, women.7 They are localised on the legs, the pelvis particularly affecting the hand and neck. These and the perineum. Thrombosis can complicate the hemangiomas grow slowly until delivery, which is situation in less than 10% of cases.4 Varicosities followed in most cases by spontaneous involution.4 usually regress postpartum. Uses of elastic stock- Hyperaemia and hyperplasia of the gingival mucosa ings are therefore recommended to prevent this is observed in pregnant women.8 It may present phenomenon. Prevention of constipation may help with various degrees of severity, ranging from mild to prevent their exacerbation. In the same way, asymptomatic inflammation to intense pain with vascular dilatation of the vestibule and vagina bleeding. It develops in the third trimester of preg- is responsible for varicosities (the Jacquemier’s nancy and progressively resolves postpartum. sign) and a bluish purple tint of the mucosa (the Similarly, pyogenic granulomas appear to be Chadwick’s sign), two early diagnostic features relatively frequent during pregnancy.8 They are also of pregnancy.8 The increased hydrostatic venous known as pregnancy epulis, epulis gravidarum or pressure detailed above may also lead to fluid granuloma gravidarum and usually develop during leakage in the extracellular milieu. This results in the second trimester. Pyogenic granulomas are non-pitting oedema mainly affecting the legs, but painless but may bleed. Spontaneous regression is possibly affecting the face and the eyelids also. It observed in the months after postpartum, but their is more pronounced in the morning and is observed recurrence is possible in later pregnancies. Surgical in almost half of all pregnant women during the last excision is allowed if necessary (e.g., considerable few months of pregnancy.4,9 However, one has to bleeding). keep in mind that oedema of the face and hands may be indicative of pre-eclampsia. Purpura is due Structural Changes to the excessive fragility and permeability of capil- laries and is common on the legs during the second Striae Gravidarum half of pregnancy; although, it spontaneously Striae distensae (striae gravidarum) is a cause of regresses postpartum, if persists longer, other great concern for pregnant women. They occur in causes of purpura should be ruled out. 60–90% of white women, but less commonly in black or Asian women.2,4,9 However, Chang et al., Vasomotor Instability found that dark-skinned women had more striae Vasomotor instability is frequently observed and gravidarum than Caucasian females.10 The most includes alternating episodes of pallor, facial flush- significant risk factors for striae in primiparous ing, hot and cold sensations and dermographism. women include young maternal age and elevated Exaggerated response to cold is sometimes associ- maternal BMI, as well as maternal weight gain and ated with a reticulate bluish erythema of the lower high neonatal birth weight.11 Women with a history legs, referred to as cutis marmorata, which usually of breast or thigh striae, or a family history of striae resolves after delivery. gravidarum are also at higher risk.10 The diagnosis is readily performed, but the mechanisms remain Vascular Proliferation poorly known. These seem to be multifactorial and Superficial or subcutaneous hemangiomas are include physical trauma, such as stretching of the

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skin, and hormonal mediation through steroids, sis. Most of these conditions are uncommon and oestrogens and relaxin, leading to reduction in the resolve postpartum.4 elastic fibre network.12 Sudoral and Sebaceous Glands Molluscum Pendulum (Acrochordons) Sebaceous gland activity appears to increase in Molluscum fibrosum gravidarum corresponds to the the third trimester since many pregnant women skin tags or acrochordons that grow during preg- complain of greasy skin, especially on the face, and nancy. As in non-pregnant females, these appear as in many of these, acne develops for the first time multiple small, cutaneous, fibrous, pedunculated, during pregnancy. However, the effect of gestation lightly pigmented polyps located on skin folds, and hormonal disturbances is unpredictable on such as the neck, the axillary, inframammary and pre-existing acne.4 In approximately half of preg- inguinal folds. They begin during the second half nant women, the sebaceous glands on the areola of pregnancy and often shrink after delivery. When enlarge and appear as multiple elevated brown persisting, these may enlarge in future pregnan- papules called Montgomery’s glands or tubercles.4 cies.4 They have no malignant potential. They are visible starting from the 6th week of gestation, representing an early sign of pregnancy.7 Adnexal Changes Regression is classical after delivery.

Hair Specific Dermatoses of Pregnancy During pregnancy, hair cycle changes resulting in These conditions are peculiar in the way they repre- fewer anagen hair follicles entering the telogen sent cutaneous diseases strictly developing during phase. This leads to thickening and brightening of pregnancy or shortly after. They may, or may not hairs. In addition to the thickening of scalp hair, recur in later pregnancies. Their mechanisms are, body hair follicles increase in size and number, therefore, related to the development of the gesta- especially on the face, and less often on the arms, tion, although the precise pathways are not yet legs, and back. This kind of hirsutism is reversible well understood. within 6 months postpartum.4 Postpartum, scalp hair enters a prolonged telogen phase causing increased shedding (telo- Polymorphic Eruption of Pregnancy gen effluvium), that may begin 2–4 weeks after (PEP)/Pruritic urticarial papules and delivery and last 3–4 months. After this period, plaques of pregnancy (PUPPP) hair completely grows again within 6–15 months.7 • Urticarial papules and plaques, usually develops Evaluation of the possibility of an iron deficiency during late term. This disease is characterised by should usually be performed. the development of pruritic disseminated cutaneous lesions that usually begin on the lower Nails abdomen, particularly on the striae distensae. Nails grow faster during pregnancy and rapidly Unlike pemphigoid gestationis (PG), the perium- become brilliant and brittle. Pregnant women may bilical area is nearly constantly spared in PEP notice distal onycholysis, transverse grooves, longi- • Most frequent in primiparous women tudinal melanonychia and subungual hyperkerato- • No maternal or foetal risks

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• Resolves spontaneously and rapidly postpartum women with PEP.16 Recurrences of PG may occur • Rarely recurs either if an oestroprogestative contraception is given or at later pregnancies, at levels of 20–50% Pemphigoid Gestationis and 50–70%, respectively. Intensely pruritic vesiculobullous eruption developing during late pregnancy or the immediate post- Prurigo of Pregnancy partum period. The disease usually develops in Prurigo of pregnancy (PP) was formerly known as multiparous women, in contrast to PEP, and mainly prurigo gestationis of Besnier or early PP. The inci- during the second or the third trimester. Pruritus dence of PP varies from one in 300 to one in 450 classically precedes skin manifestations. Later, pregnancies.14,19 It presents as excoriated papules urticarial lesions develop initially on the abdomen and affects the extensor surfaces of the extremi- and the umbilical skin (50–80% of cases). These are ties and the abdomen. As previously mentioned, erythematous and pruritic papular plaques some- such manifestations are part of other skin diseases times displaying an annular pattern. The lesions related to atopy or various other causes (e.g., secondarily extend to the trunk, the limbs, and more scabies). rarely the palms and soles. Clear and tense bullae may rise on the edematous plaques. The face and Pruritic Folliculitis of Pregnancy mucous membranes are usually unaffected. Then, Pruritic folliculitis of pregnancy (PFP) is a very more recent series gave much higher figures, rais- rare eruption, with only 24 reported cases, which ing the incidence up to one in 1600.17 If PG is not develops during the third trimester of pregnancy. treated, it regresses after delivery, although a flare It is characterised by papules and sterile follicular in postpartum is frequently reported (75–85% of pustules on the trunk and sometimes the upper the cases). Persistent PG with a protracted autono- limbs.15 PFP clears spontaneously after delivery. mous course may evolve for several years after There are no risks for the mother or the baby except pregnancy. PG relapses in 50–70% of later preg- a decrease in the foetal birth weight.15 nancies, appearing earlier in gestation and in a more severe form. Recurrences have been reported Intrahepatic Cholestasis of Pregnancy in 20–50% of cases with subsequent use of oral Intrahepatic cholestasis of pregnancy (ICP) is not contraceptives. The foetal prognosis is good in PG. strictly part of the dermatoses of pregnancy since Neonatal vesicles may appear but the eruption is there are no primary skin lesions. The aetiology usually mild, self-limited and linked to the tran- of ICP is complex and not fully understood, but it sient passage of maternal antibodies. At least 4 is likely to result from the cholestatic effects of studies found high percentages of preterm labour reproductive hormones and their metabolites in ranging from 7–43%.16,19-21 Reduced birth weight genetically susceptible women. ICP usually mani- and low birth weight were associated in one series fests in the third trimester by nocturnal itching. with early onset of disease and blister formation.18 Skin lesions are found in only a third of cases. Caesarean section incidence was also high, rang- These are secondary to scratching and correspond ing from 3–39%.16 Of note, the case-control study to excoriated lesions or prurigo. Symptoms resolve of Mascaro et al., found a significantly higher inci- after delivery. Recurrence occurs in 60–70% of dence of preterm labour and caesarean sections in subsequent pregnancies. Hepatitis C infection was

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over 3 folds more common in patients with ICP Impetigo Herpetiformis than in controls.22 As for PG, oral contraceptive The onset of impetigo herpetiformis (IH) occurs intake may also cause recurrences, and this raised most commonly in primiparous women during the the hypothesis that oestrogens are mediating the third trimester of pregnancy. IH presents with development of this disease. The diagnosis relies symmetric, erythematous patches the borders of on biochemical tests. Alanine aminotransferase which sterile pustules secondarily develop. The level is increased in 95% of cases, and the serum lesions start in the folds and extend centrifugally. fasting bile salts level is always increased. Bile Hyperthermia, nausea, vomiting and diarrhoea are acid synthesis appears to be reduced in patients common. Hypocalcaemia, hypoalbuminemia or low with ICP, in whom primary conjugated bile acids serum levels of vitamin D should be systematically are retained in the blood. The major bile acid in sought. True hypocalcaemia remains rare and is the blood and urine of these patients is cholic acid usually the reflection of hypoalbuminemia. Recur- instead of chenodeoxycholic acid present in normal rence in successive pregnancies may occur with pregnancies.23 This test is essential for diagnos- earlier onset. Oral contraception can be another ing cholestasis and quantifying its intensity. It has triggering factor. Replacement treatment is mandatory if low levels of calcium are found. been demonstrated that for the evaluation of foetal status, increased total bile acid levels in the mother CONCLUSION and increased exposure time for the foetus to these increased values of total bile acid within the mater- Skin is constantly modified during pregnancy and/ nal circulation system help to predict increased or postpartum. These changes are usually only risk of asphyxia in newborns to ICP mothers.24 In physiological, expressing changes in hormones or contrast with other dermatoses of pregnancy, ICP other factors secreted though the placenta, ovaries harbors a risk of intrauterine growth retardation or enlarged pituitary gland. However, various (17–50%), stillbirth (0.75–3.2%), perinatal death dermatoses may specifically develop during this (0.75-6.4%) and preterm delivery (12-50%).24,25 period and may influence the foetal outcome or, Indeed, most authors recommend the induction of more rarely, the mother’s health. Therefore, being labour in week 38 of gestation in mild cases and able to diagnose and manage them is of high impor- even earlier (in week 36) in severe cases. Mean- tance. Of note, to perform skin biopsy with direct while, cholestyramine, a resin that binds bile salts, immunofluorescence remains requested when may be given, a partial response being observed facing urticarial or eczematous plaques. In the in 70% of patients. Furthermore, cholestyramine same way, it is mandatory to evaluate the bile salts is responsible for a malabsorption of vitamin K, levels when facing generalised pruritus. inducing a risk of haemorrhage. Ursodeoxycholic

acid seems to work faster than cholestyramine and About the Authors also controls pruritus and plasma abnormalities. It Dr Prasoon Soni is a Senior Resident, Department Skin and VD, Dr Monica Soni is an Assistant Professor, Dr Priyanka is a Senior appears to be safe for mother and foetus and may Demonstrator and Dr Ekta is a Medical Ofﬁ cer, Department Obstetrics decrease foetal mortality associated with ICP. and Gynaecology, SP Medical College and PBM Hospital Bikaner.

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REFERENCES

1. Huber J, Gruber C. Immunological and of the physiologic modifi cations of the skin cal characteristics of specifi c dermatoses second husband. J. Fam. Pract. 2006;55, dermatological impact of progesterone. with discussion of potential mechanisms. of pregnancy. 953-956. Gynecol. Endocrinol. 2001;15(S6):18-21. 8. Torgerson RR, Marnach ML, Bruce AJ, 14. Roger D, Vaillant L, Fignon A et al. 20. Shornick JK, Black MM. Fetal risks in 2. Estève E, Saudeau L, Pierre F, Barruet Rogers RS 3rd. Oral and vulvar changes Specifi c pruritic diseases of pregnancy: a herpes gestationis. J. Am. Acad. Dermatol. K, Vaillant L, Lorette G. Signes cutanés in pregnancy. Clin. Dermatol. 2006;24, prospective study of 192 pregnant women. 1992;26:63-68. lors des grossesses normales. Étude de 60 122-132. Detailed review of various physi- Arch. Dermatol. 1994;30:734-739. 21. Shornick JK, Bangert JL, Freeman RG, 15. Vaughan Jones SA, Hern S, Nelson- cas. Ann. Dermatol. Vénéréol. 2004;121: ologic and pathologic conditions of the Gilliam JN. Herpes gestationis: clinical and Piercy C, Seed PT, Black MM. A prospective 227-231. mucosa during pregnancy. histologic features of twenty-eight cases. study of 200 women with dermatoses of 3. Bonci A, Patrizi A. Pigmentary demarca- 9. Kroumpouzos G, Cohen LM. Dermato- J. Am. Acad. Dermatol. 1983;8:214-224. pregnancy correlating clinical fi ndings with 22. Saidi W, Joly P. Topical or systemic tion lines in pregnancy. Arch. Dermatol. ses of pregnancy. J. Am. Acad. Dermatol. hormonal and immunopathological profi les. corticosteroids in patients with pemphi- 2002;138:127-128. 2001;45:1-19. Br. J. Dermatol. 1999;141:71-81. •• goid gestationis and polymorphic eruption 4. Elling SV, Powell FC. Physiological 10. Chang AL, Agredano YZ, Kimball AB. Prospective study of clinical, obstetrical, of pregnancy. Ann. Dermatol. Venereol. changes in the skin during pregnancy. Clin. Risk factors associated with striae gravi- and biological data of various dermatoses 2008;135:865-866. Dermatol. 1997;15:35-43. darum. J. Am. Acad. Dermatol. 2004;51, of pregnancy. 23. Ropponen A, Sund R, Riikonen S, 5. Costin GE, Hearing VJ. Human skin 881-885. 16. Yancey KB, Hall RP, Lawley TJ. Pruritic Ylikorkala O, Aittomäki K. Intrahepatic pigmentation: melanocytes modulate 11. Atwal GS, Manku LK, Griffi ths CE, urticarial papules and plaques of preg- cholestasis of pregnancy as an indicator skin color in response to stress. FASEB J. Polson DW. Striae gravidarum in primipa- nancy: clinical experience of patients. J. of liver and biliary diseases: a population- Am. Acad. Dermatol. 1984;10:473-480. 2007;21:976-994. rae. Br. J. Dermatol. 2006;155:965-969. based study. Hepatology 2006;43:723-728. 6. Henry F, Quatresooz P, Valverde-Lopez 12. Salter SA, Kimball AB. Striae gravi- 17. Jenkins RE, Hern S, Black MM. Clinical features and management of 87 patients 24. Geenes V, Williamson C. Intrahepatic JC, Piérard GE. Blood vessel changes during darum. Clin. Dermatol. 2006;24:97-100. with pemphigoid gestationis. Clin. Exp. cholestasis of pregnancy. World J. Gastro- pregnancy: a review. Am. J. Clin. Dermatol. 13. Ambros-Rudolph CM, Müllegger RR, Dermatol. 1999;24:255-259. enterol. 2009;15, 2049-2066. 2006;7:65-69. Vaughan-Jones SA, Kerl H, Black MM. The 18. Castro LA, Lundell RB, Krause PK, 25. Oztekin D, Aydal I, Oztekin O, Okcu S, 7. Roger D, Boudrie JL, Vaillant L, Lorette specifi c dermatoses of pregnancy revisited Gibson LE. Clinical experience in pemphi- Borekci R, Tinar S. Predicting fetal asphyxia G. Peau et Grossesse. In: Encyclopédie and reclassifi ed: results of a retrospective goid gestationis: report of 10 cases. J. Am. in intrahepatic cholestasis of pregnancy. Médico-Chirurgicale (Dermatologie). Scien- two-center study on 505 pregnant patients. Acad. Dermatol. 2006;55:823-828. Arch. Gynecol. Obstet. DOI: 10.1007/ tifi ques et Médicales Elsevier SAS. 200198- J. m. Acad. Dermatol. 2006;54:395-404. 19. Villegas M, Goff HW, Kraus EW, Usatine s00404-009-1052-x (2009) (Epub ahead of 858-A-10 (2001). •• Comprehensive review •• Large recent study that detailed clini- RP. Blisters during pregnancy-just with the print).

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Case of the Month Women with Cyst Formation in Right Breast Prabhu Prakash, Asha Mathur, Sneha Ambwani, Seema Surana, PC Gupta

A 32 years female, came to surgical OPD, the cyst was done under local anaesthesia brown area, measuring 2–2.5 cm. HPE was with a complaint of cyst in right breast and sent for histopathological examina- done and it showed encysted larvae of since last 6 month, which was gradually tion. As patient was not having any other Trichinella spiralis with its characteristic increasing in size and was tender. The cyst complaints, she was not hospitalised. morphological features and scanty muscle was fixed to chest wall (not freely movable On gross examination, received grey- tissue was also seen (Figure 1, 2). like lipoma or fibroadenosis). Excision of ish white cystic soft tissue piece with grey

Figure 1 Figure 2

Cyst formation on breast wall

(Continued on page 400)

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The Preschool Wheezer

David Cremonesini, BA, MRCPH

Anne Thomson, MD, FRCP, FRCPH

ll children cough and around 50% of children will wheeze before reaching school age, but the majority of these children will be normal. Up to 40% of A 1 infants experience wheeze in the first year of life. A UK population-based study showed the prevalence of reported wheeze in 1998 was 29%, a significant increase from the same survey in 1990 when it was 16%.2 The cost of treating preschool wheezing children is a considerable one, estimated to be 0.15% of the UK National Health Service budget.3 An asthma diagnosis is more common in this age group than in older children.4 (Figure 1) There is good evidence-based treatment for asthma in older children, but only a proportion of preschool wheezers fit an asthma diagnosis. Different patterns (or phenotypes) of preschool wheeze have been determined and are described below. These evolve with time and it can be difficult to distinguish one from another at presentation.

PHENOTYPES OF WHEEZING IN YOUNG CHILDREN

A series of studies from Tucson, Arizona, United States, on a cohort of over 1,000 newborn babies followed throughout childhood has clarified the natural history.5–7 In the first 6 years of life, 50% of children never wheezed, small numbers (approximately 1%) had atypical wheezing related to other abnormalities or disease states (see Table 1) and the remainder with typical wheeze could be divided into three groups: transient early wheeze, persistent atopic wheeze and late-onset non-atopic wheeze.

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Figure 1. The average weekly incidence of ﬁrst and new wheezing before the age of 3 years, and asthma episodes of asthma in patients presenting to GPs in England and Wales between 1976 and 2000 persisted through childhood. They had normal lung function in infancy but developed airways obstruction in the first years of life. These children wheezed without viral infections and were more likely to have a family history of asthma, elevated serum IgE and peripheral eosinophilia. Early allergic sensitization plays an important role in persistent wheeze/asthma. A European cohort of 1,300 children studied from birth to 13 years found that sensitization to perennial (eg, house dust mite, cat and dog hair) but not sea- sonal allergens developing in the first 3 years of life was associated with a loss of lung function at school age.8 Such exposure to high levels of allergens in early life led to the development of airway hyper- responsiveness with wheeze in sensitized children. Exposure in later years had a much weaker effect. Reproduced with permission from Asthma UK. Out in the open: a true picture of asthma in the United Interestingly, there is evidence that factors which Kingdom today. Asthma J 2001;6(suppl):3–14. decrease the risk of atopic sensitization include exposure to other children and farm animals.9 Transient Early Wheeze In the Tucson study, the largest group had transient Late-onset Non-atopic Wheeze early wheeze, making up 20% of the cohort. These These made up 15% of the Tucson cohort. Their cu- children generally started wheezing in their first year mulative prevalence increased in the first 6 years but of life and stopped by 3 years of age. The primary then started to decline. These children had normal risk factor is reduced pulmonary function in infancy, lung function early in life before any respiratory in- with lung function tests shortly after birth showing sult. Then, as they were exposed to viral respiratory reduced forced expiratory flow indicating small air- agents,7 they developed wheeze independently of ways. This is not associated with a family history of allergic sensitization. This phenotype appears to be asthma or atopy, and airway function in this cohort almost as common as atopic wheezing in the pre- remained low up to the age of 16 years. school group but is associated with less severe and Other risk factors for transient early wheez- less persistent wheeze and becomes less common ing include prematurity, male gender, exposure to among school-aged children. (Figure 2) siblings and other children at day-care centres, prenatal maternal smoking and post-natal exposure to CLINICAL FEATURES tobacco smoke. The child is likely to present with a history of noisy Persistent Atopic Wheeze breathing but may not be making any noise when Children with persistent ‘atopic’ wheezing made up seen. It is important to determine what the family 14% of the Tucson cohort. More than half started means by the word wheeze as parents often use

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this word to describe other noises, such as hear- cystic fibrosis is suspected. Where there is suspicion ing or feeling a loose rattle on the chest or nasal of structural abnormalities or unusual diagnosis, snuffling. Studies using a video questionnaire10 or then special investigations including bronchoscopy objective recording of lung sounds have shown poor and CT scanning are carried out in secondary/tertiary parental recognition of wheeze. From the history, it centres. Further tests should be guided by the history is important to determine the pattern and duration and examination if other causes of ‘atypical wheeze’ of wheezy episodes and the severity when they oc- are suspected. (Table 1) cur. Any precipitants of episodes should be identified (eg, viral infections). History and examination should TREATMENT OPTIONS elicit whether the child or family are atopic (eg, evidence of eczema) and whether there is evidence of The pathophysiology of wheeze in young children any other systemic disease (eg, cystic fibrosis, heart may be multifactorial with bronchospasm, mucus disease). At acute presentation, the child will be oedema, mucus plugging, abnormal airway archi- tachypnoeic and hyperinflated with lower intercostal tecture and mechanics all contributing.11 These indrawing and widespread expiratory wheeze. In ad- mechanisms may not be receptive to pharmacologi- dition, generalized inspiratory crackles may be heard cal manipulation and so the response to conven- in children with viral infections. Severe respiratory tional asthma treatments may be highly variable. distress, evidence of hypoxia (SaO2 <92%) or poor response to treatment warrants referral to hospital. Preventative Measures Between episodes, the child may be entirely normal. Passive prenatal smoking results in underdevelop- Persistence or recurrence of focal signs, evidence of ment of the fetal bronchial tree leading to diminished inspiratory wheeze or stridor, hypoxia between epi- lung function from birth.12 This is the most important sodes or failure to thrive are all indications for further investigation in secondary care. It may be difficult at Figure 2. Hypothetical yearly peak prevalence of wheezing presentation to fit the child into the phenotypes de- according to phenotype in childhood scribed above, but for management purposes, there are two main patterns: s !CUTEEPISODICWHEEZEANDCOUGHWITHNOINTERVAL symptoms; main/only trigger viral infections and no evidence of atopy s #HRONICSYMPTOMSORFREQUENTEPISODESWITHINTER- val symptoms; evidence of atopy and a variety of triggers which may include viral infections

INVESTIGATION

Most preschool children with wheeze do not require any investigation. A chest X-ray should be performed if there are persistent signs. Oximetry is useful during Adapted from Stein RT, et al. Thorax 1997;52:946–952. acute episodes. A sweat test should be performed if

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Table 1. Causes of wheeze in young children Cochrane review17 published in 2002 looked at the efficacy of inhaled short-acting beta agonists for Typical wheeze Atypical wheeze ‘recurrent wheeze’ in children under 2 years old Transient early wheeze Upper airway abnormalities and could not find clear evidence of benefit. The Persistent atopic wheeze Gastro-oesophageal reﬂux data from the right randomized trials were mark- Late-onset non-atopic wheeze Bronchopulmonary dysplasia edly heterogeneous, which severely limited the per- Pulmonary oedema secondary to cardiac disease formance of between-study comparisons. In clinical Foreign-body aspiration practice, it is worth undertaking a therapeutic trial Tuberculosis of beta-2 agonists to assess benefit. Ipratropium Causes of pulmonary suppuration bromide is no more effective than beta-2 agonists in preschool children. The younger the child, the preventable risk factor for early transient wheeze. less likely a response to either agent, but in reality, Although parents rarely admit to smoking in front of it is difficult to predict who will respond. There is their child, urinary cotinine (a metabolite of nicotine) no evidence that drugs given by a nebulizer are any studies consistently reveal that wheezing children of more effective than those given through a spacer parents who smoke are significantly exposed. Pas- and mask. sive post-natal smoking constitutes a significant risk factor for infection, worsening asthma symptoms and Inhaled Corticosteroids and Oral Steroids decreased lung function in young children. Unfortu- There is no doubt that inhaled corticosteroids (ICS) nately, interventions to decrease parental smoking are beneficial for preventing daily symptoms and are often unsuccessful.13 Breastfeeding is associated improving lung function in schoolchildren. Such ef- with lower asthma rates during childhood.14 Primary fectiveness has not been proven in children with prevention by reducing the allergen burden in the viral-induced wheeze.18 ICS maintenance therapy is environment has not been very successful. For sec- not effective in preventing or treating asthma ex- ondary prevention, it is clear that if the child is sen- acerbations secondary to viral infections in older sitized to an aeroallergen (eg, cat), then it should be schoolchildren or adults with established, atopic removed from their environment. There is evidence asthma. In young children, the use of high-dose ICS that environments rich in microbacteria, such as at the onset of viral colds does not reduce the risk farms, protect against the development of allergies. of hospital admission and need for oral steroids but Two bacterial species identified in cowsheds pos- does have a modest beneficial effect on severity of sess strong allergy protective properties.15 Antibiotic symptoms.19 use in the first 2 years of life may be implicated in In preschool children with persistent wheezing, the development of asthma, and careful antibiotic the efficacy of ICSs is less clear. Some studies show prescribing is warranted.16 clinical and physiological benefits, particularly if the child is atopic, whereas others show no benefit. The Bronchodilator Therapy effect of high-dose ICS on growth is well known, but There is good evidence that beta-2 receptors are in animal models, recent evidence suggests nebulized present in the airway from birth, and there is defi- steroids can impair alveolar development,20 implying nite physiological evidence that at least some chil- the need for increased caution in infants. There is dren respond to inhaled beta agonists. However, a recent evidence that long-term use of ICS has no ef-

JPOG NOVEMBER 2012 • 396 PAEDIATRICS

fect on the natural history of asthma or wheeze in vide some reassur- Studies show that 80% of children who 21 wheeze during the ﬁrst year of life stop later childhood. This important conclusion means ance. Eighty percent of wheezing after the age of 3 years. ICSs should be prescribed only if the current symp- children who wheeze toms are severe enough and then are only continued during the first year of if shown to be beneficial. life do not wheeze af- The role of systemic corticosteroids is con- ter the age of 3 years. troversial. A recent randomized controlled trial of Sixty percent of chil- parent-initiated oral prednisolone at the time of viral dren who wheeze in infection showed no evidence of benefit.22 However, the second year of life another randomized trial showed that systemic ster- and 30–40% of those oids given to children presenting to the emergency in the third year have department with preschool viral wheeze reduced stopped wheezing by the need for additional asthma medication in hos- school age.7 Children pital and reduced length of stay from 3 to 2 days.23 who are clearly atopic A trial of systemic steroids is sensible in a severely are more likely to con- wheezing young child, especially when there are risk tinue with symptoms factors for atopic asthma and the child responds to during childhood. bronchodilators. CONCLUSION Leukotriene Receptor Antagonists The use of leukotriene receptor antagonists seems The pattern of wheeze in preschool children is an logical as there is increased production of cysteinyl indicator of both likely treatment response and leukotrienes at the time of viral infection, and viral prognosis. infections are a major trigger in preschool children. Physiological studies of the oral leukotriene antago- s &OR CHILDREN WITH ACUTE EPISODIC WHEEZE AND nist montelukast have shown bronchoprotection and cough with no interval symptoms, a trial of treat- a reduction in exacerbations in preschool children.24 ment during the acute episode is appropriate. These Montelukast has a rapid onset of action, and a re- children are unlikely to benefit from prophylactic cent study of a 7-day course given from the day of treatment with inhaled steroids, but exacerbations onset of viral symptoms reduced symptoms by 14% may be ameliorated in some by the intermittent use and days off childcare or school by 37%.25 A trial of of leukotriene receptor antagonists (montelukast). montelukast is an appropriate first-line preventative strategy for young children with persistent wheeze s &OR CHILDREN WITH CHRONIC SYMPTOMS THERAPY IS and can be considered as an intermittent therapy for dependent on severity. Mild symptoms that do not those with frequent viral exacerbations. disturb sleep or feeding may not require treatment. For troublesome chronic symptoms and particularly PROGNOSIS where there is evidence of atopy, it is reasonable to trial step-wise treatment with leukotriene recep- The most common parental question is ‘Will he grow tor antagonists (montelukast) as first line followed out of it, doctor?’ The long-term cohort studies pro- by low-dose inhaled steroids. Therapy that is not

JPOG NOVEMBER 2012 • 397 PAediAtriCsPAEDIATRICS

Figure 3. Management of preschool wheeze in a primary care setting

Presenting features Detailed history Detailed history • Wheeze • Risk factors • Failure to thrive • Cough • Age of onset • Persistent wet cough • Breathlessness • Only with colds • Recurrent bacterial infections • Respiratory distress • Other triggers • Abnormal stool pattern • Continuous symptoms • Severe symptoms requiring hospitalization

Examination Examination • Generalized wheeze • Persistent focal chest signs • May have clear chest • Stridor • Eczema • Clubbing • Normal ENT examination • Asymmetric signs • No significant chest deformity • Fixed monophonic wheeze

Symptoms only with viral colds Chronic symptoms which are that completely resolve associated with atopy or are Normal examination significant Atypical wheeze likely May worsen with viral colds but persist • Chest X-ray Nothing else in history • Refer to paediatrician or resolve for only short periods

Management Management • Trial of bronchodilator via a spacer • Trial of bronchodilator via a spacer • Consider montelukast at onset • Consider allergen avoidance if of symptoms clear association • Reassure family • Consider daily montelukast • No chest X-ray • Consider chest X-ray

Severe symptoms Severe symptoms • Oral prednisolone at onset • Oral prednisolone at onset • Consider ICS if frequent and • ICSs and continue only if clear responsive to treatment therapeutic response • Stop ICS after 3 months and consider • Use lowest possible restarting if symptoms worsen therapeutic dose of ICS • Use lowest possible therapeutic dose of ICS

Referral to paediatrician • Diagnosis in doubt • Treatment not working • Parental or doctor anxiety

ICS = inhaled corticosteroids

JPOGJPOG Jan/FebNOVEMBER 2009 2012 • 16 • 398

JPOG_CR_Paed_Presch Wheezer-3.indd 16 1/23/09 7:38:06 PM PAEDIATRICS

helpful should be stopped. A referral to an expert in Figure 3. There is room for new evidence-based in paediatric respiratory disease should be made therapy for preschool wheeze. before escalating therapy. © 2008 Elsevier Ltd. Initially published in Medicine 2008;36:191–195. Some children may have a poor response to pharmacological treatment and avoidance of trig- About the Authors gers, and supportive treatment for severe exacerba- Dr Cremonesini is Specialist Registrar and Dr Thomson is Consultant, both in Paediatric Respiratory Medicine, Oxford Children’s Hospital, tions (with oxygen ± oral steroids) may be a main- Oxford, UK. Dr Thomson has research interests in respiratory infection stay of treatment. A management plan is outlined and cystic ﬁbrosis.

Practice Points

UÊ 7 iiâiÊÃÊ>ÊÛiÀÞÊVÊÃÞ«ÌÊÊ«ÀiÃV ÊV `Ài° UÊ *ÀiÊÀÊ«ÃÌ>Ì>ÊÃ}ÊÃÊÌ iÊÃ}iÊÃÌÊ«ÀÌ>ÌÊÀÃÊv>VÌÀÊvÀÊÜ iiâiÊÊÌ ÃÊ>}iÊ}ÀÕ«° UÊ 6À>ÊviVÌÃÊ>ÀiÊÌ iÊViÃÌÊÌÀ}}iÀÃ° UÊ ÀV `>ÌÀÊÌ iÀ>«ÞÊÛ>Ê>ÊÃ«>ViÀÊÃ Õ`ÊLiÊÌ iÊwÀÃÌiÊÌÀi>ÌiÌÊvÀÊ>VÕÌiÊÃÞ«ÌÃ° UÊ iÕÌÀiiÊ>Ì>}ÃÌÃÊV>ÊLiÊivviVÌÛiÊ>`ÊÃ Õ`ÊLiÊÌÀi`ÊvÊ«À« Þ>ÝÃÊÃÊÜ>ÀÀ>Ìi`° UÊ >i`ÊVÀÌVÃÌiÀ`ÃÊÀ>ÀiÞÊ«ÀÛiÊÃÞ«ÌÃÊ>`Ê >ÛiÊÊ`Ãi>Ãi`vÞ}Ê«À«iÀÌiÃÊÊÌ iÊ}ÊÀÕ° UÊ Ê>ÊV>ÃiÃÊÜ iÀiÊ >i`ÊVÀÌVÃÌiÀ`ÃÊ>ÀiÊÃÌ>ÀÌi`]ÊÌÊÃÊ«ÀÌ>ÌÊÌÊÃÌ«ÊÌ iÀÊÕÃiÊ>vÌiÀÊÃiÛiÀ>ÊÌ ÃÊÌÊ ÊvÀÊiÛ`iViÊvÊÌ iÀÊivwV>VÞ°

REFERENCES

1. Martinez FD, Wright AL, Taussig LM, et al. allergen sensitization early in life and chronic analysis of prospective studies. J Pediatr postnatal glucocorticoids on early lung develop- Asthma and wheezing in the first six years of asthma in children: a birth cohort study. Lancet 2001;139:261–266. ment. J Appl Physiol 2005; 98:881–888. life. N Engl J Med 1995;332:133–138. 2006;368:763–770. 15. Debarry J, Garn H, Hanuszkiewicz A, et al. 21. Murray CS, Woodcock A, Langley SJ, et 2. Kuehni CE, Davis A, Brooke AM, et al. Are all 9. Ernst P, Cormier Y. Relative scarcity of asthma Acinetobacter Iwoffii and Lactococcus lactis al. Secondary prevention of asthma by the use wheezing disorders in very young (preschool) and atopy among rural adolescents raised on a strains isolated from farm cowsheds possess of Inhaled Fluticasone propionate in Wheezy children increasing in prevalence? Lancet farm. Am J Respir Crit Care Med 2000;161:1563– strong allergy-protective properties. J Allergy INfants (IFWIN): double-blind, randomised, 2001;357:1821–1825. 1566. Clin Immunol 2007;119:1514–1521. controlled study. Lancet 2006;368:754–762. 3. Stevens CA, Turner D, Kuehni CE, et al. The 10. Saglani S, McKenzie SA, Bush A, et al. A 16. Kummeling I, Stelma FF, Dagnelie PC, et 22. Oommen A, Lambert PC, Grigg J. Efficacy economic impact of preschool asthma and video questionnaire identifies upper airway al. Early life exposure to antibiotics and the of a short course of parent-initiated oral pred- wheeze. Eur Respir J 2003;21:1000–1006. abnormalities in preschool children with reported subsequent development of eczema, wheeze, nisolone for viral wheeze in children aged 4. Asthma UK. Out in the open: a true picture of wheeze. Arch Dis Child 2005;90:961–964. and allergic sensitization in the first 2 years of 1–5 years: randomised controlled trial. Lancet asthma in the United Kingdom today. Asthma J 11. Hogg C, Bush A. Childhood asthma—all that life: the KOALA Birth Cohort Study. Pediatrics 2003;362:1433–1438. 2001;6(suppl):3–14. wheezes is not inflammation. Clin Exp Allergy 2007;119:e225–e231. 23. Csonka P, Kaila M, Laippala P, et al. Oral 5. Morgan WJ, Stern DA, Sherrill DL, et al. 1997;27:991–994. 17. Chavasse R, Seddon P, Bara A, et al. Short prednisolone in the acute management of chil- Outcome of asthma and wheezing in the first 6 12. Stick SM, Burton PR, Gurrin L, et al. Effects acting beta agonists for recurrent wheeze in children aged 6 to 35 months with viral respiratory years of life: follow-up through adolescence. Am of maternal smoking during pregnancy and a dren under 2 years of age. Cochrane Database infection-induced lower airway disease: a J Respir Crit Care Med 2005;172:1253–1258. family history of asthma on respiratory function Syst Rev 2002;3:CD002873. randomised, placebo-controlled trial. J Pediatr 6. Stein RT, Sherrill D, Morgan WJ, et al. in newborn infants. Lancet 1996;348:1060–1064. 18. Wilson N, Sloper K, Silverman M. Effect of 2003;143:725–730. Respiratory syncitial virus in early life and risk 13. Tappin DM, Lumsden MA, Gilmour WH, et continuous treatment with topical corticosteroid 24. Bisgaard H, Zielen S, Garcia-Garcia ML, et al. of wheeze and allergy by age 13 years. Lancet al. Randomised controlled trial of home based on episodic viral wheeze in preschool children. Montelukast reduces asthma exacerbations in 2- 1999;354:541–545. motivational interviewing by midwives to Arch Dis Child 1995;72:317–320. to 5-year-old children with intermittent asthma. 7. Taussig LM, Wright AL, Holberg CJ, et al. help pregnant smokers quit or cut down. BMJ 19. Wilson NM, Silverman M. Treatment of Am J Respir Crit Care Med 2005;171:315–322. Tucson Children’s Respiratory Study: 1980 to 2005;331:373–377. acute, episodic asthma in preschool children 25. Robertson CF, Price D, Henry R, et al. Short- present. J Allergy Clin Immunol 2003;111:661– 14. Gdalevich M, Mimouni D, Mimouni M. using intermittent high dose inhaled steroids at course montelukast for intermittent asthma in 675. Breast-feeding and the risk of bronchial asthma home. Arch Dis Child 1990;65:407–410. children: a randomized controlled trial. Am J 8. Illi S, von Mutius E, Lau S, et al. Perennial in childhood: a systematic review with meta- 20. Kovar J, Willet KE, Hislop A, et al. Impact of Respir Crit Care Med 2007;175:323–329.

JPOG NOVEMBER 2012 • 399 ININ PRACTICEPRACTICE

Case of the Month Women with Cyst Formation in Right Breast Prabhu Prakash, Asha Mathur, Sneha Ambwani, Seema Surana, PC Gupta

ANSWER

TRICHINOSIS PRESENTING AS BREAST CYST

INTRODUCTION reports of trichinosis (caused by dogs and Indian mole rat (Bandicota bengalensis). But, India is the seventh-largest country in the pigs respectively).4 Trichinosis generally pres- in India, very few outbreaks are reported in world; an unimaginable disparity exists in ents as muscle cyst with or without eosino- swines and very few case reports of human the geography, ethnicity, religion, food and philia5,6,7 but presentation as a breast cyst is trichinosis is available from Punjab, West personal habits, level of education and stan- a rarity. Bengal and Maharastra.4,8 Case reports of dards of living within the country.1 Livestock Psoas muscle5 and other skeletal muscleS plays a pivotal role in the socioeconomic life DISCUSSION involvement are reported but presenting of India. Parasitic Zoonoses affect human In Western-Rajasthan, trichinosis is rarely as breast cyst is a rarity and very important and animal health directly, and consequently reported, even this may be the ﬁ rst case differential diagnostic clue for surgeons. affect livestock production. Zoonoses of para- report, though cysticercous, toxoplamosis Internationally, cases of trichinosis are sitic origin are prevalent throughout India and other Zoonotic parasitic diseases are reported, specially in areas where pork or at varying rates.2 Factors such as poverty, frequently reported,2,4 it may be due to undercooked pork is consumed or policy lack of personal hygiene, defecating in open misdiagnosis or under-reporting as all muscle regarding inspection of slaughter houses spaces, scarcity of potable water, abundance cysts are not sent for biopsy, non-availability and their hygienic conditions are not good of stray animals, high population density, and of serological test and rare case reports of T. (as epidemic of trichinosis is reported in certain culinary habits are responsible for spiralis cyst. In India, Trichinella spp. infec- swines).3,6 the rising prevalence of Zoonoses in India.3 tion has been documented rarely.9,10 Few Trichinosis is acquired through the Among protozoa, Cryptosporidium parvum, reports showed the presence of capsulated consumption of raw or insufﬁ ciently cooked Toxoplasma gondii, Leishmania spp., Giardia larvae of Trichinella spp. in domestic cats, meat harbouring infectious nurse cell larva duodenalis, Sarcocystis spp. and Entamoeba in a wild toddy cat (Paradoxurus hermaphro- complex.7 The usual incubation period is 5–15 histolytica are the major examples and the ditus), in a wild civet cat (Viverricula indica), days. The clinical course of trichinosis has 2 main helminth zoonoses include echinococ- and in domestic pigs. The non-encapsulated phases: An enteral (gastrointestinal) phase cosis, cysticercosis and rarely few case species, pseudospiralis was detected in an and a parenteral (systemic) phase. During the

JPOG November 2012 • 400 IN PRACTICE

enteral phase larvae are released by digestive with sporadic cases being the exceptions. A References enzymes in the stomach and passed into the 1. BB Singh, R Sharma, JK Sharma & PD Juyal: Parasitic single detected case of trichinosis implies zoonoses in India: an overview Rev. sci. tech. Off. int. small intestine. Following the invasion of the that other people may be infected.10 Anti- Epiz., 2010;29 (3):629-637. 2. Parija SC- Emerging parasitic zoonoses in India. intestinal mucosa, parasite moults become Trichinella antibodies confi rmed by the pres- InProc. 5th All India Annual Conference of the Asso- sexually mature. The mature female begins ence of larvae of Trichinella in the digested ciation of Public Health Veterinarians, 21-23 December, AndhraPradesh, 2002;103-121. to expel newborn larvae following copulation. muscle tissue. Usually the encapsulated 3. Alipuria S, Sangha HK, Singh G & Pandhi S. Trichino- This invasion of the small intestine can cause larvae in the muscle biopsy can easily be sis: a case report. Indian J. Pathol. Microbiol., 1996;39: 231-232. gastrointestinal symptoms which clinically seen by histopathological staining methods, 4. Ahuja A, Gahlot AK, Purohit SK, Bumb RA & Mehta manifest as nausea, upper abdominal pain, RD- Zoonotic signifi cance of cutaneous leishmaniosis:an but non-encapsulated ones, e.g., T. pseudo- important zoonosis of western Rajasthan. Intas. Polivet., vomiting, diarrhoea, etc. The subsequent spiralis, are diffi cult to detect.10 2006;7 (2):437-443. parenteral phase begins when the larvae 5. Mohan H, Aggarwal R, Nanda R, Punia RPS, Ahluwa- In present case as cyst was present in lia M. Trichinosis of psoas muscle. JAPI 2002;50:729-30. enter the blood circulation and migrate to breast, it was involving chest muscle, was 6. Niphadkar S.M., Pardhan M.H. & Deshpande V.S.– striated muscles where they encyst. This can Rediscovery of Trichinella spiralis (Owen, 1835) in tender and gradually increasing in size, biopsy domesticpigs in India. Curr. Sci., 1979;48 (8):372-373. cause infl ammatory reactions and local tissue 7. Dubey ML ,KhuranaS, SinghalL ,Dogra S ,Singh S; was sent for histopathology and diagnosis was necrosis. According to the criteria defi ned by Atypical trichinellosis without Eosinophilia associ- confi rmed. There was no other cyst in body. On ated with osteomyelitis. TROPICAL DOCTOR 2011;41: the Centers for Disease Control and Preven- 244–246. direct questioning, patient admitted that she tion, a confi rmed case of trichinosis is defi ned 8. Parmeter S.N., Schad G.A. & Chowdhury A.B. Another is non-vegetarian and used to have pork in the record of Trichinella spiralis in Calcutta. Wiadom.Para- as illness with at least 3 clinically compatible zytol., 1968;14:239. past. Patient was given antihelminthic drug manifestations of trichinosis (which includes 9. Schad GA & Chowdhury AB (1967). – Trichinella spira- (albendazole), antibiotics and analgesics. lis inIndia. I. Its history in India, rediscovery in Calcutta, gastrointestinal symptoms, eosinophilia, and theecology of its maintenance in nature. Trans. roy. Soc. trop. Med.Hyg., 1967;61:244-248. fever, periorbital oedema, myalgia, subcon- 10. Gottstein B, Pozio E, Nockler K. Epidemiology, diag- juctival haemorrhages, etc.) and a laboratory Conclusion nosis, treatmentand control of trichinellosis. Clin Micro- confi rmed trichinella infection. Laboratory Attention is drawn to the unusual clinical biol Rev 2009;22:127–45. confi rmation of infection is made either by a presentation of trichinosis in this patient that About the Authors positive serological test for trichinella-specifi c presented as breast cyst. All surgeons must Dr Prabhu Prakash is an Associate Professor, Department be aware of trichinosis and should include it Microbiology, Dr Asha Mathur is a Professor, Department antibody or by the identifi cation of trichinella Pathology, Dr Sneha Ambwani is a Professor, Department larvae in tissue obtained by a muscle biopsy. in their differential diagnosis when examin- Pharmacology, Dr Seema Surana is an Assistant Profes- Most cases occur as outbreaks which is ing patients with any type of cyst (specially sor, Department Microbiology, SNMC Jodhpur and Dr PC Gupta is a Junior Specialist, General Surgery, District suggestive of a common source of infection, involving muscle) in body. Hospital, Jodhpur.

JPOG JPOG November AUGUST 20122012 •• 401401 CASE STUDY

Study of Serum Homocysteine and

Vitamin B12 Levels in Eclampsia, Pre-Eclampsia, and the Effectiveness of

Treatment with Inj. Vitamin B12 on the Outcome of these Patients

Radha Yegnanarayan, GS Shekhawat, Hemand S Damle

INTRODUCTION wide, because of complications such as Pre-eclampsia.3,4 Moreover, determinants eclampsia, foetal growth retardation, of hyperhomocysteinaemia, such as low Pregnancy-induced hypertension may premature birth or abruption placentae.1,2 concentrations of folic acid and vitamin 1 occur in about 3–10% of all pregnancies. An increased concentration of total circu- B12 involved in homocysteine metabolism It remains a major cause of perinatal and lating homocysteine in serum is recog- are also associated with increased risk maternal morbidity and mortality world- nised as an independent risk factor for of vascular damage and pre-eclampsia.5

Table 1. Demographic data in controls

Parameters Eclampsia Pre-eclampsia Past History Control group p value group (n=10) group of PET/ without any past (n=10) eclampsia group history or PET/ (n=10) eclampsia in present pregnancy (n = 10) Age (years) 21.6±2.3 22.1±3.1 25.5±3.3 25.1±2.4 <0.05 Gestation age (weeks) 32 36 36 36 Parity P1=02 P1=06 Eclampsia=02 P1=04 P2=06 P2=02 Pre eclampsia=06 P2=4 P3=02 P3=02 P3=02 SBP (mm of Hg) 158.7±7.1 144.3±4.6 118.1±8.2 120.3±6.1 <0.05 DBP (mm of Hg) 108.1±5.2 96.3±3.1 90.6±2.9 84.0±3.9 <0.05 Proteinuria mg/24 hour Signifi cant Signifi cant Not Signifi cant Absent <0.05

Th e results were compared between pre-eclampsia/eclampsia groups and control group. Th e values are presented as mean ± S.D.

JPOG NOVEMBER 2012 • 402 CASE STUDY CASE STUDY

Table 2. Baseline Serum total homocysteine and vitamin B12 levels in four groups

Parameters Eclampsia Pre-eclampsia Past history Control group p value group (n=10) group of PET/ (n=10) (n=10) eclampsia group (n=10) Homocysteine (μmol/l) 34.1±6.2 22.3±4.8 10.97±1.61 8.8±3.2 <0.01

Vitamin B12 (pg/ml) 131.9±20.5 157.4±44.8 411.4±8.3 624.6±11.9 <0.05 Hb% 9.28±2.5 9.39±3.2 9.22±3.8 9.65±1.9 >0.05

Th e results were compared between pre-eclampsia/eclampsia groups and control. Th e values are presented as mean ± SEM.

It is uncertain whether hyperhomocyste- examined in all 40 cases for the pres- were subjected to special investigation inaemia per se or low concentrations of ence of megaloblasts. In all those cases including renal, liver and coagulation vitamin B12 and folic acid are atherogenic where homocysteine concentrations were function tests for pre-eclampsia/eclamp- 6 factors that trigger pre-eclampsia. The high and vitamin B12 levels were low, we sia patients. present study was undertaken to deter- administered Inj. B12, 1500 µgm I/M in 3 mine the levels of serum homocysteine, divided doses. Exclusion Criteria and vitamin B12 and their correlationship Patients having use of medications (ther- in patients with pre-eclampsia. We also Inclusion Criteria apy involving S-adenosyl-methionine, studied the effectiveness of treatment This prospective study was conducted carbamazepine, phenytoin, 6-azauridine, with Inj. B12 in patients who showed low among 40 patients, who were divided in xanthopterin, antifolic acids, anticonvul- levels of vitamin B12. 4 groups. Ten patients with eclampsia, 10 sant agents, tamoxifen, and theophylline) patients with pre-eclampsia, 10 patients for cancer, severe anaemia, systemic Material and Methods with past history of pre-eclampsia/ illness and those with major illness were This study was carried out at Depart- eclampsia and another 10 normotensive excluded from study.7 ment of Pharmacology and Department of patients as control without any sign, Obstetrics and Gynaecology, Smt Kashibai symptoms, lab test suggestive of pre- Blood Sample Collection Navale Medical College and General eclampsia were included. Besides routine Venous blood samples were collected Hospital, Pune, after obtaining Institu- baseline ANC investigations, all patients in test tube with aseptic precautions. tional Ethics Committee approval. All Table 3. Number of patients treated with Inj. of B12 in each group participants completed a medical history form and provided informed consent. Forty Drug Eclampsia Pre- Past p value patients in the age group of 18–35 years group eclampsia history were studied for estimation of serum (n=10) group of PET/ (n=10) eclamp- total homocysteine, and vitamin B12 over sia a period of 18 months. Detailed dietary group (n=02) history with reference to vegetarian or non-vegetarian status and consumption Vitamin B12 10 10 02 <0.05 of folate rich foods were recorded in all (pg/ml) cases. Peripheral blood smears were

JPOG NOVEMBER 2012 • 403 CASE STUDY

After 2 hours of collection, sample was Table 4. Serum homocysteine and Vitamin B12 levels after Inj. B12 treatment in each group. Th e values are presented as mean ± SEM centrifuged at 3000 rpm for 5 min. Serum was separated and collected in polythene Drug Eclampsia group Pre-eclampsia p value tube with cork. The sera with no sign of (n=10) group (n=10) haemolysis was coded and used for the Homocystein(µmol/l) 14.51±7.14 11.03±2.34 <0.001 analysis of total circulating homocysteine Vitamin B12 (pg/ml) 1239.1±755.7 1412.4±615.1 <0.01 and vitamin B12. The investigator carrying the estimation was unaware of the clini- Results cal history and treatment status of the were compared, decrease and normalisa- patients. Demographic data of pre-eclamptic tion of homocysteine levels and increase

patients such as mean age of patients and normalisation in vitamin B12 levels

Biochemical Analysis showed significant fall (p<0.05). Systolic were seen after Inj. B12 treatment in both Serum homocysteine concentration was blood pressure (SBP) and diastolic eclampsia and pre-eclampsia patients blood pressure (DBP) were significantly (Table 4). This improvement was statis- measured by competitive chemilumi- increased (p<0.05) in pre-eclamptic/ tically highly significant (p<0.001). A nescent enzyme immunoassay method.6 eclamptic group as compared with control negative and statistically significant Serum vitamin B12 concentration was group (Table 1). Table 2 depicts changes correlation (r=-0.335 and p<0.05) was evaluated by solid phase, competitive in serum profile when control group found between serum homocysteine and chemiluminescent assay method. We was compared with study group of pre- vitamin B in pre-eclampsia (Table 5). used fully automated enzyme amplified 12 eclampsia. As can be seen, significant Final outcome of these patients after Inj. chemiluminescent immuno assay based increase (p<0.05) were observed in serum Vitamin B12 therapy has improved at par immulite 1000 analyzer. Hyperhomo- homocysteine whereas, vitamin B12 levels with control group without any neonatal cysteinaemia was defined as a serum showed significant decrease (p<0.05). A or maternal mortality in all four groups; homocysteine concentration greater than negative and significant correlation was however, maternal and perinatal morbid- 15 µmoles/l. Vitamin B deficiency was 12 observed between serum homocysteine ity was much higher among pre-eclamptic defined as Vitamin B12 level lower than when compared with vitamin B12 (Table and eclamptic group because of pre-exist- 223 pg/ml. 2 and 3). All patients of eclampsia and ing pathology (Table 6). pre-eclampsia were treated with vitamin Statistical Analysis B12 whereas only 02 patients with past DISCUSSION Numerical variables were reported in history of pre-eclampsia needed vita- terms of mean and standard deviation or min B12 treatment as their homocysteine Our findings suggest that levels of serum standard error of mean. Statistical analy- levels were above normal (Table 3). homocysteine and vitamin B12 are altered sis of results was done by dtudent’s t test When pre and post vitamin B12 levels in pre-eclampsia and eclampsia patients with correction and Yates corrected chi Table 5. Correlation of total homocysteine and vitamin B12 in preeclampsia patients square test wherever applicable. In this analysis, variables showing p value less Parameters ‘r’ value p value than 0.05 and 0.001 were considered to Homocysteine -0.71 <0.0001 be statistically significant and highly Vitamin B12 (pg/ml) -0.52 <0.01 significant, respectively. Pearson correla- r = Correlation coeffi cient tion test was used to test correlation.

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Table 6. Obstetric and perinatal outcome among all 04 groups

Parameters Eclampsia Pre-eclampsia Past history Control group p value group (n=10) group of PET/ (n=10) (n=10) eclampsia group (n=10) Perinatal outcome Low Birth weight 100% 40% 20% 10% <0.001 IUGR 60% 30% 20% 10% <0.001 IUD 10% 0% 0% 0% - Abruptio Placentae 10% 0% 0% 0% - Need for NICU 80% 60% 20% 20% <0.001 Need for Resuscitation 60% 40% 10% 10% <0.001 1 Min APGAR<7 40% 30% 20% 10% <0.001 Maternal outcome Normal delivery 40% 60% 70% 80% <0.001 Cesarean Section 40% 40% 30% 10% <0.001 Instrumental Delivery 20% 0% 0% 10% - (Forceps/ Vacuum) DIC 2% 0% 0% 0% as compared in age-matched normoten- lism, which corroborates with the work of pooled normal and pre-eclamptic groups, sive pregnant control subjects. The pres- Walker et al., Hogg et al., Vollset et al. but these levels were significantly lower ent study shows that there was significant Several studies have demonstrated serum in patients with the 677 CT mutation of hyper homocystinaemia and deficiency of concentrations of elevated homocysteine MTHFR.13 The serum homocysteine was 11 vitamin B12 in patients with pre-eclampsia in pre-eclampsia. These studies support found to have negative and insignificant and eclampsia. Several prospective stud- our results. In our study, the levels of correlation with serum folic acid in pre- ies with rather small cohorts of patients vitamin B12 were also significantly lower eclamptic patients. In our study negative with pre-eclampsia have shown an inde- in the pre-eclamptic and eclamptic group and statistically significant correlation (r= pendent association between elevated as compared to control groups, suggest- -0.335 and p<0.05) was found between serum homocysteine level and untoward ing raised homocysteine was due to serum homocysteine and vitamin B12 in 7,8 obstetric outcome. Several factors may vitamin B12 deficiency. Carmel R found pre-eclampsia. There are two pathways increase homocysteine levels in women differences in folic acid concentrations by which homocysteine is metabolised:- with pre-eclampsia.9 Metabolism in the between pre-eclamptic and normal preg- remethylation and trans-sulfuration. Folic kidney is the major route by which homo- nant women. Similarly, in a systematic acid and vitamin B12 are required for the cysteine is cleared from plasma and this review by Mignini et al., folic acid and remethylation of homocysteine to methio- route of elimination may be affected by vitamin B12 concentrations were lower nine; vitamin B6 is required for the trans- preeclamptic changes in the kidney.10 in pre-eclamptic women when compared sulfuration of homocysteine to cysteine. Hyperhomocysteinaemia in pre-eclamptic with those of normotensive women.12 In A good correlation between serum homo- patients found in our study might be due another study, there was no difference in cysteine, and vitamin B12 levels observed to modulation in homocysteine metabo- folic acid and vitamin B12 levels between in our study support this view. It is

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15 justifiable to administer Inj. vitamin B12, associated with metabolic disturbances morbidity. Further studies should help 1500 µgm to all patients developing pre- in pre-eclampsia can contribute to obstet- define the role of genetic polymorphism eclampsia as prophylactic dose to prevent ric complications.14 On the other hand, in enzymes of homocysteine, folic acid, further complications of PIH. there is an absolute need for large stud- vitamin B12 metabolism and their role in From the above discussion, we can ies designed to answer the question as pre-eclampsia.16 assume that biochemical screening such to whether hyper homocysteinaemia and as homocysteine, vitamin B12 are of para- vitamin B12 deficiency are associated About the Authors Dr Radha Yegnanarayan, GS Shekhawat are Professors mount importance in pre-eclampsia. The with increased risk for pre eclampsia and Head of Department Pharmacology, and Dr Hemant inverse relation between homocysteine, and whether therapy of these disorders S Damle is an Associate Professor, Department Obstetrics and Gynaecology, Smt Kashibai Navale Medical College, and vitamin B12 indicates that severity might influence maternal mortality and Pune, Maharashtra.

REFERENCES

1. Hogg BB, Tamura T, Johnston KE, 5. Barron WM, Murphy MB, Lindheimer J, Lakka TA, Salonen JT. Low dietary folic teinemia in end-stage renal disease: DuBard MB, Goldenberg MA, Goldenberg MD. Management of hypertension during acid intake is associated with an excess prevalence, etiology, and potential rela- RL. Second-trimester plasma homocyste- pregnancy. In: Laragh GH, Brenner BM, incidence of acute coronary events: the tionship to arteriosclerotic outcomes. ine levels and pregnancy-induced hyper- editors. Hypertension: pathophysiology, Kuopio ischemic heart disease risk factor Kidney Int. 1997;52:10–20. tension, preeclampsia, and intrauterine diagnosis and management. Raven: New study. Circulation. 2001;103:2674–80. 14. Mignini L, Latthe P, Villar J, Kilby M, growth restriction. Am J Obstet Gynecol. York; 1990. p.1809–27. 10. Klerk M, Verhoef P, Clarke R. MTHFR Carroli G, Khan K. Mapping the theories 2000;183:805–9. 6. Desouza C, Keebler M, McNamara D studies collaboration group. MTHFR 2. Vollset SE, Refsum H, Irgens LM, M & Fonseca V(2002)- Drugs affecting 677C T polymorphism and risk of coro- of preeclampsia: the role of homocyste- Emblem BM, Tverdal A, Gjessing HK, et homocysteine metabolism; Drugs 62(4) nary heart disease: a meta-analysis. J ine. Obstet Gynecol. 2005;105: 411–25. al. Plasma total homocysteine, pregnancy 605-606. Am Med Assoc. 2002; 288:2023–31. 15. Lachmeijer AM, Arnigrimsson R, complications, and adverse pregnancy 7. Clarke R, Daly L, Robinson K, Naugh- 11. Ueland PM, Refsum H, Stabler SP, Bastiaans EJ, Pals G, ten Kate LP, de outcomes: the Hordaland homocysteine ten E Cabalane S, et al (1991) Hyper- Malinow MR, Andersson A, Allen RH. Vries JIP. Mutation in the gene for meth- study. Am J Clin Nutr. 2000;71:962–8. chromocystenemia; an independent risk Total homocysteine in plasma or serum: ylenetetrahydrofolate reductase, homo- 3. Gambhir D S, Gambhir J K (2000) factor in vascular disease, New England methods and clinical applications. Clin cysteine levels and vitamin status in Homocysteine metabolism in health & Journal of Medicine 324 (17) 1149-1155. Chem. 1993; 39:1764–79. women with history of preeclampsia. Am disease, Indian Heart Journal 52(suppl) 8. Wald DS, Law M, Morris JK. Homo- 12. Walker MC, Smith GN, Perkins SL, 59-515 . cysteine and cardiovascular disease: Keely EJ, Garner PR. Changes in homo- J Obstet Gynecol. 2001;184:394–402. 4. Hankey G L, Eikelboom J W(2000) evidence on causality from a meta-analy- cysteine levels during normal pregnancy. 16. Finkelstein JD. Methionine metabo- Homocysteine and vascular disease. sis. Br Med J. 2002; 325:1202–6. Am J Obstet Gynecol. 1999; 180:660–4. lism in mammals. J Nutr Biochem. Indian Heart Journal, 52 (suppl) 518-526. 9. Voutilainen S, Rissanen TH, Virtanen 13. Bostom AG, Lathrop L. Homocys- 1990;1:228–37.

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AMELIA – A Rare Case

Varsha Deshmukh, KA Yelikar, VY Kalyankar, Neha Golechha, PS Deshmukh

INTRODUCTION history, exposure to teratogens or history of postpartum haemorrhage or any tears. of fever with rash during pregnancy. She Baby was female 2.2 kg by weight, Amelia is an extremely rare birth defect had USG done in a private hospital at 30 fresh still birth. Evidence of tetramelia, marked by absence of one or more weeks of gestation. USG showed single (Figure 2), cleft lip and cleft palate. Figure limbs.1 Its incidence is 1.5-1lakh live live intrauterine pregnancy of gestation 1, spine was normal, external genitalia birth and 7.9/10000 still birth.2 Teramelia age 30 weeks+1 day ± 3 weeks. Evidence was normal figure 3, placental weight means absence of all four limbs (Amelia of Amelia (upper and lower limbs not 500 gms normal in morphology. Umbili- Marranne). We report a very rare case of appreciated) with evidence of paramedian cal cord had a single umbilical artery. tetramelia with cleft lip and cleft palate. cleft lip. Liquor is adequate, placenta situ- The aetiological factor for Amelia are ated left laterally, effective foetal weight thalidomide use, amniotic band syndrome, 2160 gms. diabetes, autosomal recessive mutation The relatives were counselled and consanguineous marriages.3 Consan- about poor prognosis of baby. Patient guineous marriage is causative agent in progressed well and delivered a female our case. baby by face presentation. No evidence

Case A 25 year old primigravida presented to emergency ward at GMCH, Aurangabad with a USG report showing “foetus with absent limbs,” she was 38 weeks by date. She was in early labour with face presentation. On detail examination, it was found that there is an evidence of consanguineous marriage. She had married with her Figure 1: Shows cleft lip Figure 2: Shows tetramelia first cousin. There was no relevant past

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Embyologically, the limb buds appear during 3rd week of gestation, upper limb buds appear few days before lower limb bud. Complete absecnce of limbs occurs prior to 8th week of gestation. Failure to formation of limb buds during early embyogenesis may be secondary to vascular, mechanical stress or teratogenic Figure 3: Showing anus and ext exposure. It may also be due to genetic genitalia mutation.4 Autopsy did not reveal any internal organ In this case, there is history of dysmorphism. A babygram was performed consanguineous marriage (2nd degree). after birth figure 4. Mother’s blood sugar About 20% of Amelia cases can now were within normal limits. Parents were be traced with probable genetic causes counselled about low recurrence rate and including recessive or dominant mutation, advised to have an early anomaly scan in chromosomal aberrations. Where entire future pregnancy. set of chromosomes deleted, duplicated Figure 4: Showing babygram or exchanged. Prenatal diagnosis includ- Discussion ing detailed anomaly scan and amnio- Amelia is very rare congenital anomaly. scentesis in doubtful cases play a major scan and genetic counselling are impor- Usually, Amelia is associated with role in this cases tant to make informed decisions regard- multiple organ systems defects including ing terminations cardiovascular, gastrointestinal, urogeni- CONCLUSION tal, neural tube and respiratory defects4 About the Authors 2 Dr Varsha Deshmukh, Dr VY Kalyankar is a Associ- like lung hypoplasia, absent kidney. The Amelia is an isolated abnormality, when ate Professor, Dr KA Yelikar is a Professor and Head of prognosis is very poor in these babies. it is associated with other abnormalities Department, Dr Neha Golechha and Dr PS Deshmukh is a Resident, Department Obstetrics and Gynaecology, 5 Most of them die in first year of their life. prognosis is poor. Antenatal anomaly Government Medical College, Aurangabad.

REFERENCES

1. Journal of Obs. And gynec. Of india. 4. Frostarisleliousug, BairdPA,Amelia.. 2011;61(4):441-442. incidence and associated defects in 2. Amelia..Marianee FO connor MT large population. Tetralogy 1990;41;23- (ASCP),MPH Thompsone,Gale. 31. 3. Kumar, Abbas & Fausto eds. Robbins 5. FetalAmelia..a case report Nihal and cotrans pathological basis of disese a’s riyami, Ashfhaq Ahemad Shahilla 7 th edition page no 473. Tanzeem, mohammadabdul.

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Robotic Surgery in Gynaecology

Yuen Pong Mo, MBChB (CUHK), FHKAM(O&G), FHKCOG (HK), FRCOG (UK)

INTRODUCTION carry out surgical procedures over a dis- ued following the acquisition of Computer tance. With the involvement of the Stanford Motion by Intuitive Surgical in March 2003. Laparoscopy offers advantages of better Research Institute (subsequently named Intuitive Surgical had developed the cosmesis, less blood loss, less post-oper- SRI International), the robotic telemanipu- da Vinci® Surgical System based upon the ative pain, shorter hospitalization time and lating system was combined with virtual original telepresence concept and intro- quicker recovery. Though basic laparoscopic reality (telepresence) systems to provide a duced the product in 1999. FDA approval procedures are widely practiced, relatively tele-robotic surgical system. Two companies was received for use in general surgical few gynaecologists possess the skills in began commercializing the robotic surgi- procedures in July 2000, in urology in June performing advanced procedures like hys- cal systems in the early 1990s, Computer 2001 and in gynaecology in April 2005. terectomy and myomectomy, not to mention Motion, Inc., and Intuitive Surgical, Inc. the more complex procedures such as radi- Computer Motion’s system, ZEUS®, USING THE DA VINCI® cal hysterectomy and pelvic reconstructive was developed from the very beginning SURGICAL SYSTEM procedure. This is because laparoscopy is as an integrated robotic surgical system. It hampered by its two-dimensional visuali- used the same type of robotic arm as that The da Vinci® Surgical System (Figure 1) con- zation, counterintuitive hand movements, which was designed to hold a laparoscopic sists of an ergonomically designed surgeon limited degrees of instrument motion and camera (AESOP) and an integrated operat- console, a patient-side cart with four inter- inferior ergonomic surgeon position. The ing-room control system (HERMES) to cre- active robotic arms, the high-performance steep learning curve and longer operating ate a suite of systems that provided a com- InSite® Vision System and the proprietary time are major obstacles to the more wide- plete surgical environment. The system was EndoWrist® instruments. spread applications of this minimally inva- designed for laparoscopic surgery, and in The mobile surgeon console consists sive technique. The introduction of robotic September 2001, the first transatlantic tele- of a stereoscopic viewer, two handles and technology into surgical practice overcomes surgery (laparoscopic cholecystectomy) was five foot-pedals. The console is operated by the limitations of conventional laparoscopy successfully performed using the ZEUS® the surgeon in a sitting position and controls and facilitates the application of these Robotic Surgical System and high-speed fi- the four (or in the previous model, three) minimally invasive techniques for more ad- bre optic networking.1 The system received mobile arms of the robot for intra-abdomi- vanced and complex procedures. regulatory clearance from the US Food and nal manipulations, camera movements and Drug Administration (FDA) in October 2001. electrosurgical coagulation. The surgeon A BRIEF HISTORY OF By February 2003, the world’s first tele- SURGICAL ROBOTICS robotic surgical service had been established in Ontario, Canada, between St Joseph’s The concept of surgical robotics was first Healthcare Hamilton, a teaching hospital developed in the late 1980s at the National affiliated with McMaster University, and Aeronautics and Space Administration North Bay General Hospital, a community © 2009 Intuitive Surgical, Inc. (NASA) as a means of performing battle- hospital 400 km away.2 However, manufac- Figure 1. da Vinci S Surgical System, field surgery, enabling surgeons to remotely turing of the ZEUS® system was discontin- components

JPOG NOVEMBER 2012 • 409 operates the master controls naturally un- through a binocular three-dimensional (3D) is like operating with the human hand, to- der the display with hands and wrists sup- viewing monitor with optimal hand-eye gether with the capability of grasping, reported by the resting panel (Figure 2), and alignment. The image is displayed above tracting, dissecting, cutting, coagulating the movements are seamlessly translated the hands of the surgeon so that it gives and suturing. into precise, real-time movements of surgi- the surgeon the illusion that the tips of the The da Vinci® Surgical System is a cal instruments inside the patient. There is instruments are an extension of the control stand-alone, dexterity-enhancing system no tactile sensation, so the surgeon has to grips, thus giving the impression of being with a fully articulated ‘wrist’. The surgeon rely on visual feedback. The console can be immersed at the surgical site. The high-def- feels ‘immersed’ in a full 3D experience, positioned anywhere inside or outside the inition image provides improved clarity and operating as if the surgical field is imme- operating theatre. However, the FDA regu- detail of tissue planes. diately in front of him/her. (Figure 5) The lations require that except in telesurgery, The patient-side cart provides four robot- hand motions used for the surgical console the console be placed in the same room as ic arms (three in the previous model)—three exactly replicate the motions of open sur- the operative table. instrument arms and one camera arm—that gery, even though they are converted into The two hand controls operate either execute the surgeon’s commands. The move- laparoscopic fulcrum-effect motions. There the camera or the robotic instruments arms, ments of the surgeon are digitalized, scaled is essentially no learning curve in using the 1 1 1 but not both at the same time. Only two at ⁄1, ⁄3 or ⁄5, and transmitted by computer system; the surgeon simply begins using of the three robotic instrument arms can to the intra-abdominal instruments without the handles as if performing open surgery. be used at any one time; the third arm is noticeable delay. Normal physiological hand inactive and can only be used for tissue tremor is also filtered, making it possible to APPLICATIONS OF ROBOTICS holding and retraction. The four foot-pedals perform very fine and precise tasks. Attached IN GYNAECOLOGY are separated in the middle by an addi- to the robotic arms are a full range of propri- tional long and narrow pedal that adjusts etary EndoWrist® instruments. (Figure 4) The The world’s first robot-assisted gynaecologi- the focus of the camera. The outer left foot extra-abdominal movements of the instru- cal surgical procedure reported in a human pedal uses the clutch mechanism to allow ments controlled by the robotic arms have was a tubal re-anastomosis using the ZEUS® repositioning of the hand controls without 4 degrees of freedom. The intra-abdominal Robotic System in 1999.3 The first gynaeco- moving the robotic arms, similar to raising articulations of the microinstruments at 2 logical use of the da Vinci® Surgical System a computer mouse to reposition the mouse cm from the tip mimic those of the human was also for a tubal re-anastomosis in without moving the onscreen pointer. The hand and wrist. They possess 7 degrees of 2000,4 and the first series of robot-assisted inner left foot pedal provides a navigation freedom—and, therefore, function more laparoscopic hysterectomies were reported control of the camera movement by moving instinctively—and overcome the fulcrum ef- in 2002.5 Currently, the da Vinci® system both hand controls in and out, right and left, fects seen with conventional laparoscopy. is the only commercially available surgical up and down. The instrument arms remain The patient-side cart is wheeled in robotic system. The number of reports on still while adjusting the camera position. between the patient’s legs, and the robotic robot-assisted gynaecological procedures The two pedals on the right control the mo- arms are attached to the metal robotic tro- has increased dramatically following the nopolar and bipolar diathermy. cars so that they are integrated together. FDA clearance in 2005, and the technique The image is provided by the Insite® The robotic instrument is then put through has been applied to virtually all abdominal Vision System (Figure 3) through a 12 mm the trocar and mounted onto the robotic and laparoscopic gynaecological procedures. endoscope (0 or 30 degrees) comprising arm so that the multiarticulated instrument Besides the common gynaecological proce- two laparoscopes fused together. The sur- tips can be operated by the hand controls. dures, other procedures reported include geon operates in a sitting position and looks The manipulation of the robotic instruments ovarian transposition,6 abdominal cerclage,7, 8

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repair of vesico-vaginal fistula9,10 and trache- robot-assisted laparoscopic hyster- lectomy after subtotal hysterectomy.11 ectomy in 16 patients. The operating time was long, ranging from 270 Tubal Re-anastomosis min to 600 min. Average blood loss Degueldre et al reported the first series of was 300 mL, and the average hos- laparoscopic tubal re-anastomoses using pital stay was 2 days. Conversion the da Vinci® Surgical System in eight pa- was required in one patient because tients and achieved a patency rate of 93.8%, of bleeding. Beste et al 14 reported Figure 2. A surgeon operating the hand controls 4 with two pregnancies within 4 months. 11 robot-assisted total laparo- in a natural and comfortable position The mean operating time was 181.5 min. In scopic hysterectomies (TLH) with a retrospective case-control study, Rodgers a mean operating time of 192 min et al 12 compared 26 cases of robot-assisted and a mean hospital stay of 1 day. tubal anastomosis with 41 cases by outpa- There was one conversion because tient minilaparotomy. Median surgical time of uncontrolled bleeding and one for the robot was significantly longer than cystotomy. Similarly, Fiorentino et al 15 by minilaparotomy (229 min vs 181 min). reported 20 cases of robot-assisted There were no differences in the hospi- TLH with a mean operating time of © 2009 Intuitive Surgical, Inc. talization time, pregnancy rate and ectopic 200 min and a mean hospital stay Figure 3. InSite® Vision and the endoscope pregnancy rate. The time to return to work of 2 days. Conversion was required was significantly shorter in the robotic group in two cases because of severe adhesions. was 2.95 min, and the mean console time by approximately 1 week. Marchal et al 16 reported 30 cases of robot- (surgeon’s time dedicated exclusively to the Dharia Patel et al13 compared 18 pa- assisted laparoscopic hysterectomy; the performance of the surgery) was 73 min. tients undergoing robot-assisted tubal re- mean operating time was 186 min, excluding The total operating time was 122 min—14 versal with 10 historical cohorts using open the 30 min of robotic setup time. One patient min shorter when compared to conventional microscopic technique. The mean operating required conversion because of obesity, and laparoscopic hysterectomy in their institu- time for robotic anastomoses was signifi- there were five minor post-operative compli- tion. There was one enterotomy and six cantly longer (201 min vs 155 min), but the cations. Reynolds and Advincula17 reported post-operative complications. Nezhat et al19 hospitalization time was significantly short- 12 cases of TLH and four cases of laparo- reported 27 hysterectomies out of 87 patients er (4 h vs 34.7 h) and the recovery time was scopic supracervical hysterectomy. The mean undergoing robot-assisted gynaecological quicker (11.1 days vs 28.1 days). There was operating time (including docking time) was surgery. The removal of ovaries at the time no difference in the pregnancy rates (62.5% 242 min. There was no conversion and four of hysterectomy increased the mean operat- vs 50%), but the rate of abnormal pregnan- complications, including one case of bowel ing time from 192 min to 236 min. cy was higher in the robotic group. and bladder injury. The only comparative study reported The results of robotic tubal re-anas- According to unpublished data from was published by Payne et al.20 They com- tomosis are similar to the open approach, the University of Michigan, robot-assisted pared 100 patients undergoing total laparo- with a longer operating time but a shorter laparoscopic hysterectomy took an addi- scopic hysterectomy with 100 patients un- recovery period. tional 60 min more than conventional laparo- dergoing robotic hysterectomy. Overall, the scopic hysterectomy.17 Kho et al 18 published robotic cohort experienced a longer operat- Hysterectomy the largest series of robotic hysterectomies ing time by an average of 27 min. However, Diaz-Arrastia et al 5 were the first to report involving 91 patients. The mean docking time the last 25 robotic cases had a shorter oper-

JPOG NOVEMBER 2012 • 411 ating time compared with the laparoscopy In a recent retrospective case-control cohort (78 min vs 92 min). The mean blood study, Advincula et al 23 compared 29 cases loss was significantly less, and the mean of robot-assisted laparoscopic myomectomy length of hospital stay was significantly with 29 cases of abdominal myomectomy. shorter in the robotic cohort. The number of The robotic group had a longer operating exploratory laparotomies (0% vs 11%) and time (231 min vs 154 min), less blood loss rate of intraoperative conversions (4% vs (195 mL vs 364 mL), a lower transfusion 9%) were both lower in the robotic cohort. rate (0% vs 6.9%), shorter length of hos- Early experience suggested that pital stay (1.5 days vs 3.6 days) and lower robot-assisted laparoscopic hysterectomy complication rate (13.8% vs 41.4%). In takes longer than conventional laparoscop- another retrospective study, comparing 15 ic hysterectomy, partly because of the extra robotic-assisted laparoscopic myomecto- time required for docking. With experience, my with 35 matched-control laparoscopic © 2009 Intuitive Surgical, Inc. et al both the docking time and console time can myomectomy, Nezhat also reported a Figure 4. EndoWrist® instruments be reduced, but it may take up to 75 cases significantly longer operating time with the before an operating time similar to conven- robotic assistance (234 min vs 203 min).24 colpopexy or sacrouteropexy in 15 patients tional laparoscopic hysterectomy can be However, there were no differences in blood with symptomatic stages 3 and 4 pelvic or- achieved. Also, the robotic assistance al- loss, hospitalization time and post-operative gan prolapse. The mean operating time was lows more hysterectomy to be performed complications. 317 min, the mean blood loss was 814 mL, using the laparoscopic approach. Published data on robot-assisted myo- and the mean hospital stay was 2.4 days. At mectomy are limited. Despite the advantage a mean follow-up of 3 months, all patients Myomectomy of ease in suturing, robot-assisted myomec- had their prolapse resolved. Senapati and Advincula21 recently de- tomy requires significantly longer operating In a retrospective review of open scribed their technique in robot-assisted time compared with both the conventional laparoscopic and robot-assisted sacrocol- laparoscopic myomectomy as a means to open and laparoscopic approaches. popexy involving five patients in each group, overcome the difficulties encountered with the robot-assisted group had the shortest hysterotomy enucleation repair and ex- Sacrocolpopexy operating time (robot, 358 min; open, 418 traction during conventional laparoscopy. Robot-assisted laparoscopic sacrocolpopexy min; laparoscopy, 510 min) and hospital stay Advincula et al reported the first series of was first reported by Di Marco et al in (robot, 2 days; open, 3 days; laparoscopic, robot-assisted laparoscopic myomectomies 2004.25 The same authors recently reported 3 days).28 Geller et al 29 retrospectively com- in 35 patients; there were three conversions the accumulated series of 42 cases with a pared 73 robotic and 105 abdominal sacro- and one patient was excluded because of mean follow-up of 36 months.26 The mean colpopexy. When compared with abdominal adenomyosis.22 Of the 31 completed cases, operating time was 3.1 h. All but one patient sacrocolpopexy, the robotic approach was the mean number of myomas removed was were discharged from the hospital after an associated with less blood loss (103 mL vs 1.6 and the mean diameter was 7.9 cm. The overnight stay. Two patients were converted 255 mL), a longer operating time (328 min vs mean estimated blood loss was 169 mL, to an open procedure secondary to dense 225 min), shorter length of stay (1.3 days vs the mean operating time was 230 min and adhesions. There were two cases of recur- 2.7 days) and higher incidence of post-oper- the median length of hospital stay was 1 rence and two cases of vaginal extrusion ative fever (4.1% vs 0%). Short-term vaginal day. Two patients developed post-operative of mesh. Daneshgari et al 27 reported 12 vault support at 6 weeks post-operation was complications. successful robot-assisted abdominal sacro- similar between the two groups.

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Robot-assisted laparoscopic sacro- gynaecological malignancies, 21 for cervical major perioperative complication rate was colpopexy accomplishes a repair identical cancer, seven for endometrial cancer, one also lower in the robotic group (3.6% vs to that of the open technique, but with a for ovarian cancer and three for cervical dys- 20.8%). There was no difference in the to- longer operating time, while preserving the plasia. Surgical procedures included total tal lymph node count (19 vs 18). Seamon et benefits of reduced morbidity and hospital hysterectomy, bilateral oophorectomy, and al 34 reported the outcomes of their first 105 stay of the laparoscopic approach. Clearly, a pelvic and/or lomboaortic lymphadenecto- patients with early-stage endometrial carci- longer follow-up is needed. my. The median operating time was 180 min, noma who underwent robotic hysterectomy and the median blood loss was 110 mL. No and pelvic-aortic lymphadenectomy for com- Gynaecological Oncology Surgery perioperative complications were observed, prehensive staging; 13 (12.4%) were con- Despite the well-accepted benefits of lapa- and the median hospital stay was 3 days. verted. Conversion risk increased with body roscopic surgery for benign gynaecological Early experience suggests that robotic mass index. The average operating time was pathologies, the use of laparoscopy in gy- assistance can be safely applied to gynae- 242 min, and the mean blood loss was 99 naecological malignancy is still the excep- cological oncology surgery with encouraging mL. The median number of lymph nodes re- tion. However, the application of robotics in short-term outcomes. covered was 29 (median of 21 pelvic nodes gynaecology focuses mostly on oncological and nine aortic nodes). The median length of procedures, and most of the publications so Endometrial Carcinoma Staging hospital stay was 1 night. far are in these area. Boggess compared 43 patients undergoing Boggess et al compared the outcomes Marchal et al 16 evaluated 12 malignant endometrial staging robotically with 101 pa- of 322 women undergoing endometrial can- cases (five endometrial adenocarcinomas tients staged laparoscopically.32 None of the cer staging by different surgical techniques: and seven cervical carcinomas) undergoing robotic patients were converted to laparot- 138 by laparotomy, 81 by laparoscopy and robot-assisted laparoscopic hysterectomy in omy compared to 3% in the laparoscopy 103 by robotic technique.35 The robotic co- 2005. Radical hysterectomy was performed group. Significantly more lymph nodes were hort had the highest lymph node yield, the in some patients, and bilateral pelvic lym- retrieved (30 vs 23), less blood was lost (63 shortest length of hospital stay and the phadenectomy was performed in nine cas- mL vs 142 mL), a shorter operating time was least blood loss. Operating time was long- es. The mean operating time was 181 min, required (163 min vs 213 min), and a shorter est for laparoscopy (213 min), followed by and the mean number of pelvic lymph nodes hospitalization period was necessary (1 day robotic technique (191 min) and laparotomy removed was 11. No port-site metastasis or vs 1.2 days) with the robotic cohort com- (147 min). Post-operative complication rates recurrences were found with a mean follow- pared with the laparoscopy cohort. DeNardis were lowest for robotic technique (5.9%), up of 10 months. In the same year, Reynolds et al 33 compared the first 56 robot-assisted followed by laparoscopy (13.6%) and et al 30 reported seven robot-assisted laparo- laparoscopic hysterectomies with 106 total laparotomy (29.7%). Conversion rates for scopic staging procedures: four for endome- abdominal hysterectomies with aortic and/ the robotic and laparoscopic groups were trial cancer, two for ovarian cancer and one or pelvic lymphadenectomy for endometrial comparable. Similarly, Bell et al 36 compared for fallopian tube cancer. Six patients under- carcinoma. Three robotic cases (5.4%) were 110 patients who underwent hysterectomy went pelvic and para-aortic lymphadenecto- converted to open procedure secondary with bilateral salpingo-oophorectomy pelvic my, and one patient underwent pelvic lymph to intra-operative factors. Compared with and para-aortic lymphadenectomy via robot- node sampling. The median number of lymph laparotomy, the robotic group had a longer ic assistance (n=40), laparotomy (n=40) and nodes removed was 15. The mean operating mean operating time (177 min vs 79 min), laparoscopy (n=30) for endometrial cancer time was 257 min, mean blood loss was 50 less blood loss (105 mL vs 241 mL), a lower staging. All cases were performed by a sin- mL and median hospital stay was 2 days. transfusion rate (0% vs 8.5%) and shorter gle surgeon at a single institution. The oper- Lambaudie et al 31 reported 28 patients with length of stay (1 days vs 3.2 days). The ating time was longer in the robotic cohort

JPOG NOVEMBER 2012 • 413 patients are alive and disease free. Magrina compared a total of 27 patients undergoing robotic radical hysterectomy with 31 patients and 35 patients operated by laparoscopy and laparotomy, respectively.41 The mean operating time for patients undergoing robotic, laparoscopy and laparotomy radical hysterectomy were 190 min, 220 min and 167 min, respectively;

Figure 5. The immersive feeling of doing open surgery in an ergonomic sitting position the mean blood loss was 133 mL, 208 mL and 444 mL, respectively; the mean number than in the laparotomy cohort but similar to laparoscopic radical hysterectomies and bi- of removed lymph nodes was 25.9, 25.9 and the laparoscopic cohort (184 min, 109 min lateral pelvic lymph node dissection for early 27.7, respectively; and the mean length of and 171 min, respectively). Estimated blood cervical carcinoma compared with seven hospital stay was 1.7 days, 2.4 days and 3.6 loss was significantly reduced in the robotic total laparoscopic radical hysterectomies.38 days, respectively. There were no significant cohort (robotic, 166 mL; laparotomy, 316 No conversions were observed in the robotic differences in intra- or post-operative com- mL; laparoscopic, 253 mL). The complica- group. The median operating time was 241 plications among the three groups, and no tion rate was lowest in the robotic cohort min (console time) in the robotic group and conversions were required in the robotic or (7.5%) relative to the laparotomy (27.5%) 300 min in the conventional laparoscopic laparoscopic group. None of the patients and laparoscopic cohorts (20%). Return to group. Docking time for the robotic system had experienced recurrence at a mean fol- normal activity for the robotic patients was was 25 min. The number of lymph nodes, low-up of 31.1 months. significantly shorter (24.1 days) than those the parametrial tissue and vaginal cuff size Boggess et al 42 compared the out- undergoing laparotomy (52 days) and lapar- were similar in both groups. Less bleeding come of 51 consecutive robot-assisted type oscopy (31.6 days). Lymph node retrieval did (71 mL vs 160 mL) and a shorter hospital 3 radical hysterectomies with 49 historical not differ between the three groups (robotic, stay (4 days vs 8 days) were observed in the abdominal radical hysterectomies for early- 17; laparotomy, 14; laparoscopic, 17). robotic group. Kim et al 39 reported 10 suc- stage cervical cancer. All of the robotic The quality of lymph node staging us- cessful robotic radical hysterectomies with procedures were completed successfully ing robotic assistance may be significantly pelvic lymphadenectomy for stage 1 cervical without any conversion to laparotomy. There more extensive than laparotomy and lapar- carcinoma with no complications. The mean were significantly more lymph nodes re- oscopy. Though operating time seems to operating time was 207 min, the mean dock- covered robotically than abdominally (33.8 be longer for robotic assistance than for ing time was 26 min, and the mean blood vs 23.3) with a shorter operating time (211 laparotomy, it is equivalent or shorter than loss was 355 mL. The average number of min vs 248 min), less blood loss (97 mL vs for conventional laparoscopy. pelvic lymph nodes removed was 27.6. 417 mL) and a lower transfusion rate (0% Fanning et al 40 described 20 consecutive vs 8%). The mean hospital stay was 1 day Radical Hysterectomy robot-assisted type 3 radical hysterectomies in the robot-treated patients and 3.2 days The first robot-assisted radical hysterectomy for stage 1B–2A cervical carcinoma. The for the abdominal group. There were no dif- (Piver type 3) with bilateral pelvic lymph node median operating time was 6.5 h, and the ferences in the incidence of post-operative dissection was reported by Sert and Abeler median blood loss was 300 mL. All patients complications (7.8% vs 16.3%). Ko et al 43 in 2006.37 One year later, the same authors were discharged on the first post-operative compared the short-term surgical outcome reported the result of seven robot-assisted day. At median follow-up of 2 years, 90% of of 16 patients undergoing robotic radical

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hysterectomy with 32 open radical hysterec- Blood loss was less than 200 mL in all cases. robotic system and its instruments almost tomies for the treatment of early-stage cer- There were no complications reported, and prohibit its widespread and routine use. The vical cancer. The mean operating time was all patients had their period return after the system is large in size, and the robotic arms significantly longer for the robotic group (4.8 operation. The follow-up period was short, are relatively cumbersome, which, in pelvic h vs 3.7 h), while the mean blood loss was and no pregnancy has yet been reported. surgery, limits the surgical assistants’ access significantly less (82 mL vs 666 mL). There to the surgical field. A large operating room, was no difference in the mean number of CONCLUSION therefore, is required to house both the sur- lymph nodes resected (15.6 vs 17.1). There gical team and the robot. There is no tactile were no intraoperative complications in the Laparoscopic surgery has revolutionized the feedback from the system, and the surgeon robotic group and one ureteral transection concept of minimally invasive surgery for the has to rely on visual cues to assess the ten- in the open group. No differences were ob- last 3 decades. Robot-assisted surgery is sile strength of tissue and sutures. served in the post-operative complication one of the latest innovations in the field of Despite these limitations, robotic rate (18.8% vs 21.9%). The mean length of minimally invasive surgery, and studies on dif- surgery has a shorter learning curve than hospital stay was significantly shorter for ferent surgical procedures have confirmed its conventional laparoscopy. It is envisaged the robotic group (1.7 days vs. 4.9 days). feasibility and potential benefits. The surgi- that surgical robots will make minimally Robot-assisted radical hysterectomy cal robotic system is an enabling technology invasive surgery easier and more efficient. appears to be better than the conventional that allows surgeons the ability to perform Difficult laparoscopic interventions may be- laparoscopic approach, with a shorter op- laparoscopic procedures in an open surgery come easier and safer to perform, with de- erating time and higher lymph node count. environment. Robotic-assisted surgery es- creased fatigue for the surgeon. As stated The results are probably similar, if not bet- tablishes a straight foot-hand-eye axis that by Ahlering et al,47 the great advantage of ter, than the open approach. However, the does not exist in either open or laparoscopic robot-assisted laparoscopy is the success- real benefits of this technique have to be surgeries and restores the 3D view that is ful transfer of open surgery to a laparo- established in a prospective randomized lost in laparoscopic surgery. With the da scopic environment, even for laparoscopi- manner. Vinci® system, the surgeon is completely cally ‘naive’ surgeons, with a significantly immersed in the operative field without pe- shortened learning curve. Radical Trachelectomy ripheral stimulations. The system seems to be A total of four cases of robot-assisted to- most beneficial for complex and prolonged About the Author tal laparoscopic radical trachelectomy for procedures, especially when intra-abdominal Dr Yuen is Director of Minimally Invasive Gynaecology, Hong Kong Sanatorium and Hospital; Honorary Clinical Associate early cervical cancer have been reported microsurgery or manipulations in a narrow or Professor, Department of Obstetrics and Gynaecology, The so far.44,45,46 Operating time ranged from 172 difficult-to-access space are required. Chinese University of Hong Kong; and Honorary Consultant, Department of Obstetrics and Gynaecology, Kwong Wah min to 387 min, with a mean of 315.5 min. However, the extremely high cost of the Hospital, all in Hong Kong SAR, China.

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