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Part 1 book “Jeffcoate’s principles of gynaecology” has contents: A clinical approach to gynaecology, anatomy, ovarian functions, menstruation and other cyclical phenomena, clinical aspects of menstruation and ovulation, puberty and adolescent gynaecology, spontaneous abortions,… and other contents.
Jeffcoate’s PRINCIPLES OF GYNAECOLOGY Website: www.gynecologyblog.blogspot.com Website: www.gynecologyblog.blogspot.com Website: www.gynecologyblog.blogspot.com Jeffcoate’s PRINCIPLES OF GYNAECOLOGY Eighth International Edition Revised and updated from the Seventh Edition by Narendra Malhotra MD FICOG FRCOG (Honoris Causa) Professor, Dubrovnik International University, Croatia FOGSI Representative to FIGO Consultant and Director, Global Rainbow Healthcare Agra, Uttar Pradesh, India Pratap Kumar MD DGO FICOG Professor and Head, Department of Obstetrics and Gynaecology Kasturba Medical College, Manipal, Karnataka, India Past Vice President, The Federation of Obstetric and Gynaecological Societies of India (FOGSI) Jaideep Malhotra MD FICOG Professor, Dubrovnik International University, Croatia Honorary General Secretary, Indian College of Obstetrics and Gynaecology President The Asia Pacific Initiative on Reproduction (ASPIRE) Consultant and Director, ART Rainbow-IVF Agra, Uttar Pradesh, India Neharika Malhotra Bora MD Assistant Professor, Department of Obstetrics and Gynaecology Bharati Vidyapeeth Medical College, Pune, Maharashtra, India Parul Mittal MD Consultant Global Rainbow Healthcare Agra, Uttar Pradesh, India ® JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD New Delhi • London • Philadelphia Panama Website: www.gynecologyblog.blogspot.com đ Jaypee Brothers Medical Publishers (P) Ltd Headquarters Jaypee Brothers Medical Publishers (P) Ltd 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 Email: jaypee@jaypeebrothers.com Overseas Offices J.P Medical Ltd 83, Victoria Street, London SW1H 0HW (UK) Phone: +44-2031708910 Fax: +02-03-0086180 Email: info@jpmedpub.com Jaypee-Highlights Medical Publishers Inc City of Knowledge, Bld 237, Clayton Panama City, Panama Phone: +1 507-301-0496 Fax: +1 507-301-0499 Email: cservice@jphmedical.com Jaypee Brothers Medical Publishers (P) Ltd 17/1-B, Babar Road, Block-B, Shaymali Mohammadpur, Dhaka-1207 Bangladesh Mobile: +08801912003485 Email: jaypeedhaka@gmail.com Jaypee Medical Inc The Bourse 111, South Independence Mall East Suite 835, Philadelphia, PA 19106, USA Phone: +1 267-519-9789 Email: jpmed.us@gmail.com Jaypee Brothers Medical Publishers (P) Ltd Bhotahity, Kathmandu, Nepal Phone: +977-9741283608 Email: kathmandu@jaypeebrothers.com Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2014, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and not necessarily represent those of editor(s) of the book All rights reserved No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners The publisher is not associated with any product or vendor mentioned in this book Medical knowledge and practice change constantly This book is designed to provide accurate, authoritative information about the subject matter in question However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications It is the responsibility of the practitioner to take all appropriate safety precautions Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book This book is sold on the understanding that the publisher is not engaged in providing professional medical services If such advice or services are required, the services of a competent medical professional should be sought Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com Jeffcoate’s Principles of Gynaecology First Edition Fifth Edition Sixth Edition Seventh Edition Eighth Edition : 1957 : 1987 : 2001 : 2008 : 2014 ISBN: 978-93-5152-149-5 Printed at vip.persianss.ir Website: www.gynecologyblog.blogspot.com Dedicated to The teachers of gynaecology and the students vip.persianss.ir Website: www.gynecologyblog.blogspot.com vip.persianss.ir Website: www.gynecologyblog.blogspot.com Preface to the Eighth International Edition We, Narendra Malhotra and Pratap Kumar, feel very honoured for being asked to revise again the best textbook on gynaecology by Sir Norman Jeffcoate Dr Jaideep Malhotra (ART specialists) has especially added inputs in infertility, assisted reproductive technology and other chapters In the rapidly advancing age of technology and rapidly changing trends in management, diagnosis, drugs and procedures, it is of paramount importance to update books and manuals periodically This book was earlier updated and edited (2008) by us as an international edition (Seventh edition), but soon the publishers felt the need for revising it within a span of five years Professor Norman had expressed in 1974 that he had endeavoured to preserve his personal approach We have added many new chapters and rewritten a few chapters, all together trying to maintain Sir Jeffcoate’s style We have retained the description of Professor Jeffcoate’s original case discussions, photographs and pictures New additions have been made on the feedback from postgraduate students Dr Neharika Malhotra Bora, Assistant Professor, Bharati Vidyapeeth Medical College, Pune, Maharashtra, India, and Dr Parul Mittal, Consultant, Global Rainbow Healthcare, Agra, Uttar Pradesh, India, have been instrumental in adding a lot of inputs Dr Nidhi Gupta, Dr Pranay Shah, Dr Maninder Ahuja, Dr Kanta Singh, and Dr Narayan M Patel have painstakenly revised and edited and updated many chapters We hope that the undergraduate and the postgraduate students will appreciate our efforts to update this Bible of Gynaecology Narendra Malhotra Pratap Kumar Jaideep Malhotra Neharika Malhotra Bora Parul Mittal vip.persianss.ir vip.persianss.ir Preface to the Fifth Edition It was inevitable that following Professor Sir Norman Jeffcoate’s retirement, there would be pressure to continue to publish the Principles of Gynaecology In the last revision in 1974, Sir Norman emphasised that he had endeavoured to preserve his personal approach, bearing in mind the objectives and principles outlined in the preface to the First Edition In addition, some of Sir Norman’s comments in the preface to his Fourth Edition are included to emphasise the guidelines the present author has taken in an attempt to maintain the format of the Principles of Gynaecology Much of the material presented is retained from the last edition, since it also reflects the gynaecological training of the author under Professor Jeffcoate in Liverpool The views expressed are therefore personal ones from a pupil of Sir Norman Jeffcoate against the background of all the information available Once given, the views expressed mean that references are excluded for the special reasons given in the preface to the First Edition In the process of being taught Obstetrics and Gynaecology by Sir Norman, one was encouraged to consider all the facts about a case, to come to a conclusion and to be able to justify it Even though a critical approach to each case was expected, we were never allowed to forget that we were dealing with a woman, mother or child with a personal problem Indeed, Professor Jeffcoate’s personal approach was such that in a clinic with many students and postgraduates present, it was obvious that as far as the patient was concerned Sir Norman was the only person there I have never been able to achieve the same effect, but I hope that my efforts in revising this book will be acceptable to an outstanding teacher, guide and friend If so, then I am sure it will benefit all those who read it Victor Tindall vip.persianss.ir Tumours of the Cervix Uteri Fig 29.6: An endocervical adenocarcinoma which has spread to the corpus and also to the external os and glassy cell carcinomas the worst prognosis among the variants of adenocarcinoma Clear cell adenocarcinoma may be associated with exposure to diethylstilboestrol (DES) Fig 29.7: A hypertrophic squamous cell carcinoma of the cervix fungating into the vaginal vault There is a leiomyoma in the uterus Squamous Cell Carcinoma Squamous cell carcinoma usually starts in the area of the squamo-columnar junction (transformation zone) as described above Occasionally, however, it arises in the endocervix, sometimes deep to the lining Even if not all squamous cell growths begin in reserve cells, those developing in the endocervix almost certainly Squamous cell carcinoma of the cervix is seen in the microinvasive and invasive forms Some invasive cancers of the cervix are hypertrophic or exophytic, producing a cauliflower-like mass; others are mainly eroding and ulcerative or infiltrative (Figs 29.7 and 29.8) An early growth can simulate an erosion The squamous cell carcinoma has histological features similar to those of an epithelioma in any site except that pearl formation is unusual About 20% of the tumours are of the well-differentiated type (often known as “large cell keratinising tumours”) Moderately differentiated tumours (large cell nonkeratinising tumours) constitute about 60% of the total The remaining 20% are poorly differentiated (small cell nonkeratinising tumours) However, biopsies taken from different areas of the same tumour often show different degrees of differentiation and different predominant cell types Two distinctive histological variants of cervical squamous cell carcinoma merit mention; some, usually of the welldifferentiated type, have cells which contain abundant glycogen and thus appear as “clear” cells, whilst occasionally the poorly differentiated tumours assume a spindle-shaped cell form and so resemble a sarcoma Fig 29.8: An early eroding squamous cell carcinoma of the cervix Spread Direct Extension By this mechanism the growth spreads to the body of the uterus, the vaginal wall, the bladder, and the cellular tissues of the broad and uterosacral ligaments Direct invasion of the rectum is rare because the pouch of Douglas intervenes In the broad ligament the growth surrounds and constricts the lower ends of the ureters but does not invade them Similarly, when it reaches the pelvic wall and the sacral plexus, it causes sciatic pain but the nerves and their sheaths are never demonstrably penetrated vip.persianss.ir 437 438 Jeffcoate’s Principles of Gynaecology When the disease is established the patient’s general state is usually good but the cervix may be enlarged, misshapen, ulcerated and excavated, completely destroyed or replaced by a hypertrophic mass The cardinal signs are hardness, friability, fixation and bleeding on examination Whenever cancer is suspected, vaginal examination should be gentle lest it precipitate the most violent haemorrhage If this should happen, the vagina should be packed tight with gauze and the woman kept lying flat with the foot of the couch raised The diagnosis is difficult if the growth is entirely intracervical The external os then looks normal but the cervix as a whole feels big, broad and barrel-shaped Fixation occurs relatively early but bleeding on examination is not a prominent sign in such cases In most cases a rectal examination is more useful in determining the extent of spread within the pelvis Lymphatic Permeation and Embolism Spread by the lymphatics in the bases of the broad ligaments and in the uterosacral ligaments is an early feature, the nodes most commonly involved being the obturator, external iliac and those at the bifurcation of the common iliac vessels Others are the internal iliac, common iliac, sacral and ultimately the para-aortic nodes Bloodstream This route is much less frequently used but embolic metastases are occasionally seen in the ovary, brain, bones and lungs The occurrence of distant metastases without simultaneous involvement of the lungs is explained by the transfer of cancer cells by the vertebral venous plexus (See Chapter 2) Complications • Pyometra—The cancer obstructs the cervical canal and is also a focus of infection; pyometra is therefore common • Vesicovaginal and vesicocervical fistulas • Rectovaginal fistula—This is rare in untreated cases • Hydronephrosis and pyonephrosis caused by ureteric obstruction • Uraemia—This is caused by renal failure due to a combination of infection and ureteric obstruction The ultimate causes of death in their order of frequency and importance used to be: uraemia; cachexia associated with recurrent haemorrhage; infection and interference with nutrition; complications of treatment; and remote metastases in vital organs (rare) With improved radio therapy, uraemia is less common in developed countries as the main cause of death In its very early stage, invasive carcinoma of the cervix causes no symptoms and is only discovered accidentally or as a result of routine search (see below) Symptoms come with surface ulceration and consist only of irregular uterine bleeding or discharge or both, these being perior postmenopausal in half the cases The first episode of bleeding commonly follows coitus, straining at stool, or any circumstance which exposes the cervix to trauma, and may be slight Later the losses can be alarmingly heavy The discharge is at first creamy or white but subsequently resembles dirty brown water; it has a particularly offensive and characteristic odour The odour is caused by an infection of necrotic tissue with saprophytes Any other symptoms usually occur so late that they are to be regarded as evidence of advanced (late-stage) cancer They include frequency of micturition, dysuria, urinary incontinence, rectal pain, deep pelvic ache, low backache, sciatica, ureteric colic, oedema of the legs, loss of weight, anorexia and malaise Liver metastases may present as right upper quadrant pain and fullness; lung metastases as haemoptysis and a persistent, racking cough A remarkable feature of carcinoma of the cervix is that most of those who suffer from it not present early for treatment, and this despite propaganda and health education This is partly explained by the fact that the irregular bleeding or discharge is dismissed as being insignificant Even those women who report symptoms immediately not necessarily have the consolation of knowing that their growth is amenable to treatment because the duration of symptoms is not proportional to the extent of the disease Symptoms Cervical Screening Data from many countries have shown that screening with cervical cytology reduces the incidence and mortality from cervical cancer Principles • The purpose of a cervical screening programme is to reduce the incidence and mortality of cervical cancer • Cervical screening should be population based with wide coverage (aim for at least 80% coverage of the population • Cervical cytology is the most used method of screening Screening Guidelines Age Group to be Screened Physical Signs In the early stages the cervix may appear normal, eroded or chronically infected Suggestive signs are hardness, irregularity and bleeding on examination; any cervix which bleeds when touched is suspect This depends on the particular age distribution of deaths from cervical cancer and may be “country specific” Deaths from cervical cancer are rare before age of 25 years Women can be discharged from the screening programme at the age of 65 if they have had two negative smears in the previous 10 years vip.persianss.ir 439 Tumours of the Cervix Uteri The diagnosis and prognosis of carcinoma of the cervix is not always easy, as the following cases show A married nulliparous woman, aged 35 years, complained of cyclical menorrhagia for year without any irregular bleeding or discharge Examination revealed a normal nulliparous cervix with a tumour above which had all the signs of a uterine leiomyoma the size of a 10-week pregnancy She was opposed to having children and it was decided to carry out hysterectomy At operation the mass proved to be in the supravaginal cervix and, as hysterectomy proceeded, it was clear that the dissection was being carried out through malignant tissue which was infiltrating the outer coat of the bladder Examination of this specimen showed a squamous cell carcinoma arising in the substance of the cervix and nowhere nearer than cm to the endocervix or to the portio vaginalis The patient was subsequently treated with what now would be regarded as inadequate radiotherapy and, as expected, she was admitted months later with bleeding and discharge from the growth which had then ulcerated through the vaginal vault Her husband was informed that the situation was hopeless and a box of radium needles was packed into the vaginal vault for 48 hours with the object merely of controlling the bleeding and discharge during what remained of her life Thirty years later this woman was alive and well and free from any sign of growth! A multiparous woman aged 44 years, a chronic attender at hospitals, was seen on account of menorrhagia for which no gross abnormality could be found A small cervical polyp was removed and curettage carried out; all tissues showed nothing remarkable on histological examination The menorrhagia persisted and months later curettage was repeated and a menopausal dose of radium was inserted into the uterus Thereafter the patient continued with minor complaints and attended a general physician for recurrent anaemia When she developed lower abdominal discomfort she was again seen by a gynaecologist and no pelvic abnormality was noted A smear taken from the cervix was negative then, and again months later when for the first time she complained of slight vaginal discharge A mass was then noted to the left of and behind the uterus, and laparotomy revealed this to be an inoperable squamous cell carcinoma of the cervix which had already reached the pelvic wall Even then the cervix looked normal and the cervical canal was not invaded Another weeks passed before a doubtfully positive smear was obtained It was years and months after the first investigation before the diagnosis was made—despite repeated examinations by three different gynaecologists and despite full observance of the standard practices These cases illustrate the most dangerous type of cancer of the cervix; one which commences deep in the cervical tissue and which spreads eccentrically without breaking the surface of the genital canal Such growths presumably commence in a gland whose epithelium has undergone squamous cell metaplasia Recommendations for management after a cervical smear: • Routine recall: For a reportedly normal smear • Repeat smear: – If smear is inadequate, repeat in months – For mild dyskaryosis or borderline nuclear changes, repeat in 6–12 months, depending on national protocol The recommended repeat interval allows for possible resolution of changes If the abnor mality persists on repeat cytology, colposcopy is recommended An alternative apporach is to perform high risk HPV typing in patients with borderline cytology Colposcopy should then be performed if high risk HPV types are found If high risk HPV types are not found, cytology should be repeated in 12 months • Refer for colposcopy: For moderate or severe dyskaryosis, query invasive disease or query glandular neoplasia Cervical Biopsy The diagnosis can only be made for certain by microscopic examination of cervical tissue; biopsy is essential in every case where signs or symptoms raise the slightest suspicion, and this irrespective of whether cervical smears or not contain malignant cells The site of biopsy is usually clear when the disease is clinically evident and in most cases a biopsy can be obtained without the necessity for an anaesthetic Unless a cone biopsy is taken, curettage of the endocervix is also essential to exclude an endocervical tumour Cytodiagnosis Although the findings on routine cytodiagnosis can be a means of stimulating the investigation which reveals an early symptomless invasive carcinoma, cytology is not a diagnostic method Indeed, in 10–15% of cases of clinically evident cancer of the cervix, smears remain persistently negative This is because the actively malignant cells are deep seated or the exfoliated ones are degenerated and contaminated by inflammatory cells or blood Colposcopy and Colpomicroscopy Diagnosis Management of Cervical Cytology Results There is higher incidence of women developing an interval cancer if the time from the previous smear is extended beyond years Frequency of Screening These techniques can, in the hands of experts, reveal cancer which is not apparent to the naked eye The diagnosis, however, still has to be confirmed by biopsy, so their chief value is to indicate the sites from which tissue can most profitably be taken for histological examination vip.persianss.ir 440 Jeffcoate’s Principles of Gynaecology Clinical Staging of Disease TABLE 29.1 Rules for Classification FIGO stages Postsurgical treatment—Pathologic staging: In cases treated by surgical procedures, the pathologist’s findings in the removed tissues can be the basis for extremely accurate statements on the extent of disease The findings should not be allowed to change the clinical staging, but should be recorded in the manner described for the pathologic staging of disease The TNM nomenclature is appropriate for this purpose Infrequently it happens that hysterectomy is carried out in the presence of unsuspected extensive invasive cervical carcinoma Such cases cannot be clinically staged or included in therapeutic statistics, but it is desirable that they be reported separately Staging is determined at the time of the primary diagnosis and cannot be altered, even at recurrence Only if the rules for clinical staging are strictly observed it is possible to compare results among clinics and by differing modes of therapy The FIGO staging (1995) has been devised to allow comparison of results of therapy from various centres (Table 29.1) (Fig 29.9) The staging procedures are shown in Table 29.2 Regional Lymph Nodes (N) • NX — Regional lymph nodes cannot be assessed • N0 — No regional lymph node metastasis • N1 — Regional lymph node metastasis TNM categories Primary tumour cannot be assessed No evidence of primary tumour TX T0 Carcinoma in situ (preinvasive carcinoma) Tis I Cervical carcinoma confined to uterus (extension to corpus should be disregarded T1 IA Invasive carcinoma diagnosed only by microscopy All macroscopically visible lesions—even with superficial invasion—are stage IB/T1b T1a IAI Stromal invasion no greater than 3.0 mm in depth and 7.0 mm or less in horizontal spread T1a1 IA2 Stromal invasion more than 3.0 mm and not more than 5.0 mm with a horizontal spread 7.0 mm or less T1a2 IB Clinically visible lesion confined to the cervix or microscopic lesion greater than IA2/T1 T1b IB1 Clinically visible lesion 4.0 cm or less in greatest dimension T1b1 IB2 Clinically visible lesion more than cm in greatest dimension T1b2 II Tumour invades beyond the uterus but not to pelvic wall or to lower third of the vagina T2 IIA Without parametrial invasion T2a IIB With parametrial invasion T2b III Tumour extends to pelvic wall and/or involves lower third or vagina and/or causes hydronephrosis or nonfunctioning kidney T3 IIIA Tumour involves lower third of vagina no extension to pelvic wall T3a IIIB Tumour extends to pelvic wall and/or cause hydronephrosis or non-functioning kidney T3b IVA Tumour invades mucosa of bladder or rectum and/or extends beyond true pelvis T4 IVB Distant metastasis M1 Clinical-diagnosis staging: Staging of cervical cancer is based on clinical evaluation; therefore, careful clinical examination should be performed in all cases, preferably by an experienced examiner and under anaesthesia The clincal staging must not be changed because of subsequent findings When there is doubt as to which stage a particular cancer should be allocated, the earlier stage is mandatory The following examinations are permitted: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray exmination of the lungs and skeleton, suspected bladder or rectal involvement should be confirmed by biopsy and histologic evidence Conisation or amputation of the cervix is regarded as a clinical examination Invasive cancers so identified are to be included in the reports Findings of optional examinations, e.g laparoscopy, ultrasound, CT scan, MRI, and PET scan are of value for planning therapy but, because there are not generally available and the interpretation of results is variable, the findings of such studies should not be the basis for changing the clinical staging Fine needle aspiration (FNA) of scan detected suspicious lymph nodes may be helpful in treatment planning FIGO staging FIGO stage IA1 IA2 IB1 IB2 IIA IIB IIIA IIIB IVA IVB vip.persianss.ir UICC T N M Tis T1a1 T1a2 T1a1 T1b2 T2a T2b T3a T1 T2 T3a T3b T4 Any T N0 N0 N0 N0 N0 N0 N0 N0 N1 N1 N1 Any N Any N Any N M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1 Tumours of the Cervix Uteri Fig 29.9: The clinical staging of carcinoma of the cervix as agreed by the International Federation of Gynaecology and Obstetrics (FIGO) Carcinoma in situ (previously Stage 0) is excluded Distant Metastasis (M) Site • MX — Distant metastasis cannot be assessed • M0 — No distant metastasis • M1 — Distant metastasis An endocervical growth is potentially more dangerous than one which grows on the vaginal surface because it is diagnosed relatively late, and it spreads to the broad ligaments and to lymph nodes relatively early Prognosis Irrespective of the type of treatment the prognosis depends on the following: Naked-Eye Appearance The Extent of Growth at the Time of Treatment The hypertrophic, florid, massive growth filling the upper vagina generally carries a bad prognosis—even if it does not appear to have spread much beyond the cervix This is the single most important factor vip.persianss.ir 441 442 Jeffcoate’s Principles of Gynaecology TABLE 29.2 Staging procedures • Palpate lymph nodes • Examine vagina • Bimanual rectovaginal examination (under anaesthesia recommended) Radiological studiesa • • • • Intravenous pyelogram Barium enema Chest X-ray Skeletal X-ray • • • • • • • Biopsy Conisation Hysteroscopy Colposcopy Endocervical curettage Cystoscopy Proctoscopy Management of invasive cancer of cervix Stage la1 (< mm depth) < mm invasion, no LVSI Conisation or type I hysterectomy (no lymphadenectomy) < mm invasion, w/LVSI Radical trachelectomy or type II radical hysterectomy with pelvic lymph node dissection la2 (3–5 mm depth mm long) > 3–5 mm invasion Radical trachelectomy or type II radical hysterectomy with pelvic lymphadenectomy lb1 (< cm) > mm invasion, < cm Radical trachelectomy or type III radical hysterectomy with pelvic lymphadenectomy > mm invasion, > cm Type III radical hysterectomy with pelvic lymphadenectomy Proceduresa Physical examinationa TABLE 29.3 • Computerised axial tomography—97% specific • Lymphangiography • Ultrasonography—99% specific • Magnetic resonance imaging — more sensitive • Positron emission tomography • Radionucleotide scanning • Laparoscopy lb2 Type III radical hysterectomy with pelvic and para-aortic lymphadenectomy or primary chemoradiation Stage lla Type III radical hysterectomy with pelvic and para-aortic lymphadenectomy or primary chemoradiation llb, llla, lllb Primary chemoradiation Stage IVa Primary chemoradiation or primary exenteration IVb Primary chemotherapy ± radiation Optional studiesb a Allowed by the International Federation of Gynaecology and Obstetrics (FIGO) b Information that is not allowed by FIGO to change the clinical stage Abbreviation: LVSI, lymphovascular space invasion Histology Age The younger the patient the more likely is the growth to be poorly differentiated in type and the worse the outlook Ureteric Obstruction If, at the outset of managing a case, pyelography reveals unilateral or bilateral ureteric obstruction, the ultimate outlook is poor Treatment of Invasive Cancer Treatment is by radiotherapy, surgery or chemotherapy, or by combinations of these (Table 29.3) It is now highly specialised, and the best results can only be obtained when there is good teamwork between gynaecologists, radiotherapists, physicists and others with a particular interest and experience Moreover, these require complicated and expensive equipment as well as trained nursing and technical staff, so centralisation of the facilities in any one area becomes more and more desirable This inevitably means the congre gation of most patients into special units, an arrangement which, despite its many disadvantages from the standpoint of patient happiness and radiation hazards, generally gives the best results in terms of patient survival The tendency to follow a fixed plan of treatment for all cases has an advantage when it comes to assessing results An adenocarcinoma offers relatively unfavourable prospects, not because it is less radiosensitive than a squamous cell growth as was once believed Groups of cases of adenocarci noma certainly show a much inferior salvage rate but this is because they include cancers in young women and more cancers in an advanced stage Since adenocarcinoma is usually endocervical in site, it is discovered and treated relatively late If the results of treatment are properly controlled by matching cases by age of patient, stage of growth and other factors, there is no difference between those of the two cell types The same applies to mixed adenosquamous growths in older women but not in women under 40 years of age Among the squamous cell growths, the well-differen tiated are to be preferred because they grow slowly and metastasise late It is sometimes suggested that they are more radiosensitive but the widely accepted view is that the anaplastic tumours have the advantage in this respect The presence of lymphovascular space invasion (LVSI) is associated with a poorer prognosis vip.persianss.ir 443 Tumours of the Cervix Uteri It is not, however, in the interests of the individual patient, and the aim should be to choose and to modify treatment to suit the circumstances of each case It may even be necessary to change treatment if the initial response is not satisfactory If it is concluded that radiotherapy is not effective, it can be abandoned in favour of surgery Unfortunately, the evidence suggests that poor responders to radiotherapy equally badly with surgery Table 29.4 shows management of advanced disease Assessment of the Case Before Treatment Magnetic Resonance Imaging Magnetic resonance imaging is the best method of imaging to determine the size and extent of a tumour, especially if an endovaginal receiver is used However, even with MRI, small metastatic deposits in the lymph nodes are likely to be missed Radiotherapy This is the treatment of choice in the majority of cases and is applicable at all stages of the disease It aims at giving a cancericidal dose of gamma rays to all areas where there is growth or there is likely to be growth The goal is to deliver a dose of 70–80 Gy at point A, this being situated cm above the mucosa of the lateral vaginal fornices and cm lateral to the central uterine canal This objective is generally achieved by intracavitary therapy (see below) Point B lies cm lateral to point A, i.e the outer part of the broad ligament This is exposed to 60 Gy by cobalt units or linear acceleration external beam radiotherapy In certain cases, especially advanced ones, the last is used to cover the whole field When Computed Tomography This can be used to demonstrate tumour spread It can visualise enlarged lymph nodes (although it cannot TABLE 29.4 Preliminary pelvic examination under anaesthesia may be necessary in order to estimate the extent of the disease, the size of the uterus and vaginal fornices, and to obtain material for histological study Cystoscopy, intravenous pyelography and an estimation of the blood urea level are essential The presence of remote metastases should be excluded as far as possible Anaemia and malnutrition should be corrected, even at the expense of delaying treatment A normal blood picture improves the results of radiotherapy considerably, possibly because it means better oxygenation of the malignant tissues; it is a prerequisite for safe surgery differentiate enlargement due to tumour from that caused by infection) and distortion of tissue spaces or planes by tumour or surgery It is helpful for assessing recurrence of disease after surgical treatment of carcinoma of the cervix (Fig 29.10) It provides more information about involvement outside the pelvis (See Chapter 1) Management of advanced cervical cancer Stages Stages IIB-IVA Staging Examination under general anaesthesia Chest X-ray Renal imaging Optional CT/MRI scan of abdomen and pelvis PET scan Radiation technique A B Primary target dose External irradiation 50 Gy/5-6 weeks + LDR intracavitary boost 30–35 Gy point A (for IIB - IVA, 35–40 Gy) Secondary target External irradiation 50 Gy/5 weeks Total treatment time: 6–7 weeks Concurrent chemotherapy Cisplatine 40 mg/m2 every week during external irradiation Primary target Tumour + uterus Secondary target Pelvic lymph nodes and common iliac lymph nodes Field technique: fields Field borders for external irradiation A Tumour determined by palpation and CT scan (if available) + cm margin B A-P fields: Lateral: cm lateral to the bony margin of the pelvic Superior: Between L5 and S1 Inferior: cm below the obturator foramen (or cm below lower extent of clinical tumour) C Lateral fields: Anterior: Individually determined by tumour Posterior: Individually determined by tumour vip.persianss.ir 444 Jeffcoate’s Principles of Gynaecology external beam therapy can be varied according to the stage of the disease but it should be arranged to cover the direct extension of the tumour and the anticipated area of lymphatic spread In general, the area covered extends from just above the urethral orifice to the lower border of the fourth lumbar vertebra and laterally to cover the whole of the pelvis, with the femoral heads protected and related to the patient’s physical characteristics Intracavitary Radiotherapy (ICRT) combinations are used, the dose of one agent is adjusted to that of the other to ensure that the total dose is not excessive, using time-dose fractionation (TDF) and linear-quadratic (LQ) models Despite all technical advances, however, intracavitary treatment centrally in the uterus and adjacent to the cervix in the vagina takes precedence over other forms of radiation Intracavitary treatment is usually given at the end of the external therapy because it is more effective following reduction in tumour size Gamma rays act by damaging the nuclear structures in actively dividing cells and by inducing a fibrous tissue and protective reaction in the host tissue Radiosensitivity depends to a large extent on whether the tumour receives a good blood supply from its bed This may mean that a high oxygen concentration is the determining factor In favourable cases the tumour disappears within weeks Overdosage not only causes adverse reactions and permanent ill-effects but is less likely to cure the carcinoma because it interferes with the host response If the initial course of treatment offers a full cancericidal dose, radiotherapy can never be used again, even if the growth recurs Intracavitary (uterine and vaginal) therapy is very effective in cervical cancer because high doses can be given centrally within the tolerance level of adjacent normal tissues Fig 29.10: CT scan displays a cervical mass posterior to the urinary bladder with air pockets within it suggestive of ulceration (Courtesy: Dr Shashi Paul) Since the first volume of this book was published there have been considerable changes in radiotherapeutic techniques Radium has now been replaced by cheaper and more readily available artificially produced isotopes such as caesium and cobalt 60 The traditional method of treatment was to place radium in applicators in the uterus and vaginal fornices for a given period of time (27–30 hours), and then remove it and give a similar course of treatment either on three occasions at intervals of weeks (Stockholm technique), or for 72 hours on two occasions, repeating the first course after an interval of week (Manchester technique) (Table 29.5) The dose and duration of each treatment can be varied according to the size of the uterus and vagina in an individual patient but the time intervals between treatments remain constant for the chosen technique To reduce the dose of radiation to the adjacent bladder and rectum, vaginal packing is used to increase the distance between them and the source of radiation The use of radioactive sources involves the exposure to radiation of medical and nursing staff while the sources are in theatre and while in situ in the patient, hence the development of afterloading techniques which are based on the traditional method described above but deliver much higher doses of radiation over a much shorter period of time (15–30 minutes compared with 24–48 hours) The more rigid applicators are inserted under general anaesthesia and the source introduced later with the staff protected (Fig 29.11) Low-dose rate (LDR) therapy is the older system and requires fewer sessions but needs hospitalisation High-dose rate (HDR) treatment can be done on an outpatient basis; it has less morbidity and is more cost-effective, though the equipment is more expensive Cathetron is the oldest cobalt 60-based HDR unit Selectron was introduced as a LDR system but now an HDR system is also available Recently, heavy particle radiation using Californium-252 has been used which has a low oxygen enhancement ratio and can be used in bulky, poorly vascularised tumours containing a high proportion of hypoxic cells Techniques of Radiotherapy External Irradiation External beam radiotherapy (EBRT) preferably from a linear accelerator using cobalt 60 is given in short daily treatments over a period of 3–6 weeks (usually on a Monday-to-Friday basis) This “fractionation” of the total dose required is much more effective than a single total dose The area covered by Interstitial Brachytherapy In patients with advanced parametrial disease, distorted anatomy or postoperative/postirradiation recurrences, the interstitial perineal implant (with or without the ICRT) can vip.persianss.ir Tumours of the Cervix Uteri TABLE 29.5 Techniques of radiotherapy Amount and type of radiation Number of application Duration Stockholm Intrauterine tube 50 mg one vaginal ovoid 50–60 mg Three 48 hours each with gap of week between first and second and gap of weeks between second and third Paris Intrauterine tube One 33.3 mg and two vaginal ovoids 13.3 mg For five days, (each day, radium removed, cleaned and replaced) Manchester Intrauterine Two tube 50 mg Vaginal colpostat 30–50 mg For 72 hours at interval of week Fig 29.11: The afterloading Fletcher-Suit applicator for low-dose rate intracavitary brachytherapy (Courtesy: Dr BK Mohanty) deliver supplementary dose following EBRT more optimally Parametrial implants using radium needles were used earlier Currently, afterloading transperineal perforated templates with iridium-192 and iodine-125 are used (Figs 29.12 and 29.13) The highest dose of radiation is given to tissues adjacent to the radioactive source and the dose then falls off rapidly, in an inverse fashion related to the distance The fall-off in dose related to distance also explains why intracavitary treatment alone does not give a cancericidal dose to the lymph nodes on the pelvic side walls and why additional therapy is required for advanced lesions Fig 29.12: Syed-Neblett perineal template brachytherapy with iridium-192 source for advanced stage cancer of the cervix Fig 29.13: X-ray showing interstitial brachytherapy template with parametrial needles in situ (Courtesy: Dr BK Mohanty) Complications of Radiotherapy The morbidity resulting from properly conducted radiotherapy is minimal but major complications are sometimes caused by overdosage or technical errors Perforation of the uterus may occur at the time of insertion of the uterine tandem, especially in patients with previous conisation or advanced disease Pelvic inflammatory disease (PID), diverticulitis and previous surgery are associated with an increased morbidity Since there is a fairly high incidence of PID in women with carcinoma of the cervix, a flare-up may occur during radiotherapy usually 2–6 hours after insertion of the tandem; surgery may be required before any further irradiation, or is vip.persianss.ir 445 446 Jeffcoate’s Principles of Gynaecology These are related to the continued arteritis and fibrosis which is a consequence of radiation therapy In the area treated, the small and large bowel are the most radiosensitive and late complications occur in 5–10% of patients Blood loss from the pelvic colon or rectum may be a problem with radiation proctitis, but it usually resolves with measures to keep faeces soft and the use of prednisolone suppositories or enemas More serious complications are the fibrotic and vascular changes which lead to impaired function and narrowing of the bowel with subacute or acute obstruction Some of these patients may require surgery Occasionally, necrosis leads to perforation of the bowel and fistula formation Once recurrent disease has been excluded, these can be managed surgically The bladder is more resistant to radiation and, although there may be characteristic changes noted on cystoscopy, episodes of haematuria which can occur are more often due to superimposed infection The incidence of vesicovaginal and of rectovaginal fistulas following radiotherapy carried out in the best of centres is 1–2% of each type, excluding cases due to recurrent tumour Successful closure of these fistulas using flaps has been attempted Vesicovaginal fistulas usually require urinary diversion The risk of inducing tumours by modern radiotherapeutic techniques is low and at the most is almost one-and-a-half times the normal The loss of ovarian function is associated with menopausal symptoms but except in young women it does not appear to cause many problems There is narrowing and shortening of the vagina and this is aggravated by the associated loss of ovarian function and the general fixation of tissues following treatment Coital Late Effects Surgery can be carried out as a primary procedure, in Stages I and IIA, especially in young women to conserve ovarian function, or when carcinoma of the cervix shows a poor response to radiotherapy, or if it recurs after such treatment For advanced and failed radiotherapy cases, ultraradical surgery such as exenteration is sometimes practised Exenteration is more appropriate for patients with recurrent central disease occurring at least years after radiotherapy Rutledge classification clasifies varies hysterectomy procedures into five classes (Table 29.6) In Stage IA1, where invasion is mm, if there is no LVSI, conisation or an extrafascial total abdominal hysterectomy (Type I hysterectomy) may be sufficient My policy is to try and individualise the treatment based on a proper assessment of all the factors Conisation allows preservation of fertility in younger patients If the lesion is within the limits defined above, surgical margins are free of disease and the patient desires a pregnancy, conservative management is possible, provided adequate and regular follow-up by cytology and colposcopy have been carried out If there is any departure from the normal, or the family is complete, then Type I hysterectomy should be carried out Even in Stage IA1, pelvic lymph node metastases are reported although the incidence is less than 1% If confluent areas or LVSI are present, or the disease is in Stage is IA2, a Type II (modified radical) hysterectomy is recommended and pelvic node dissection is advisable This involves the removal of the whole uterus, the upper third of the vagina, the fallopian tubes and sometimes the ovaries, the broad ligaments together with their cellular tissue, the medial half of the cardinal and uterosacral ligaments and the pelvic nodes (Wertheim’s original operation included selective removal of enlarged lymph nodes only) The uterine vessels are ligated medial to the ureter In Stages IB and IlA radical (Type III) hysterectomy as advocated by Meigs is recommended This is a modification of Wertheim’s hysterectomy Complete pelvic lymph node dissection is done; the lymph nodes are removed starting from the common iliac and proceeding caudally to the groups around the internal and external iliac vessels up to the obturator fossa Most of the uterosacral and cardinal ligaments are removed with the clamps being placed nearer The majority of, if not all, patients will have some symptoms caused by the effects of ionizing radiation on the bowel mucosa These are usually seen after a dose of 20–30 Gy has been administered Diarrhoea, abdominal cramps, nausea, and occasionally bleeding from the bowel are the symptoms seen in these patients A low-gluten, low-lactose, low-protein diet should be prescribed The bowel symptoms usually settle down with appropriate treatment within a few weeks of completion of treatment but the majority of women will have some permanent minor change in bowel habit Symptoms related to the bladder are uncommon unless there is a urinary infection Occasionally, haematuria may occur Surgery Morbidity during Treatment difficulties are often underestimated, even though advice may be given initially regarding vaginal dilators and the resumption of coitus an alternative method of treatment Indeed, sometimes it may be wiser to carry out a bilateral salpingectomy or salpingooophorectomy before radiotherapy The small intestine (which has a much lower tolerance to radiation) is mobile, thus preventing too high a dose being given to any particular portion or loop of small bowel The presence of adhesions prevents this and explains the development in some cases of the acknowledged late complications of intracavitary treatment TABLE 29.6 Rutledge classification of extended hysterectomy Class I — All cervical tissue (Extrafascial) Class II — Modified radical Class III — Radical classical hysterectomy Class IV — Extended radical Class V — Pelvic exenteration vip.persianss.ir 447 Tumours of the Cervix Uteri This operation should not be performed unless the patient recognises the risk of recurrence of the disease Indications Primary surgery is only applicable to Stage I and early Stage II cases, that is, to 30–40% of all cases For these, its place in preference to radiotherapy is largely a matter of personal opinion Nevertheless, it may have advantages in certain cases, namely: when cervical cancer is associated with pregnancy, chronic salpingo-oophoritis, or other local disease of the pelvic organs; when narrowing or other anatomical errors of the vagina make it difficult to apply radium efficiently; possibly for endocervical tumours of the columnar celled type; and in the younger woman when it is decided that ovarian function should be conserved In favour of surgery, it is argued that it permits the removal of affected lymph nodes, which are invaded with cancer in approximately 15% of Stage I growths and which may not receive a cancericidal dose of radiotherapy Moreover, some women are happier with the thought that the disease has been removed rather than “treated” Nevertheless, radical surgery is one which requires special skill and experience, and one which even the expert avoids when the cancer sufferer is obese, in poor general health, or has associated medical disorders Complications The primary mortality of radical surgery is 1–2%, except in very skilled hands when it can be as low as 0.1–0.5% The immediate dangers are haemorrhage, shock, peritonitis, paralytic ileus, intestinal obstruction and thromboembolism An average blood loss of 800 mL is reported The operation involves considerable risk of direct injury to the bladder, ureters and rectum Ureteric fistula, previously a major complication, is now relatively uncommon as a result of improved operative technique especially in selected centres where experienced gynaecologists these operations regularly Febrile morbidity is a common complication Atony of the bladder, incomplete emptying, cystitis and pyelitis complicate 20% of operations and there is generally a need for postoperative bladder drainage Minor degrees of hydronephrosis and hydroureter occur in some cases but these changes usually disappear within year Nevertheless, ureteric incompetence, with reflux of urine from the bladder, persists in some cases and troublesome stress incontinence can be a problem Late sequelae include stenosis of the ureter by surrounding fibrosis and lymphocyst formation The latter, which occurs in 1–5% of cases if lymphadenectomy is routinely carried out, can be mistaken for recurrent cancer; it is a cystic dilatation of the remaining but interrupted lymph channels and can be left untreated if small, aspirated under ultrasonic control or marsupialised into the abdominal cavity if large Secondary infection requires drainage vip.persianss.ir the attachments of the ligaments to the sacrum after opening the rectovaginal space The ureteric tunnels are dissected and the uterine vessels divided laterally The more radical the resection of the parametrium, the higher is the incidence of postoperative bowel dysfunction The ovaries are involved in less than 1% of patients with squamous cell carcinoma of the cervix, so they may be conserved in women younger than 40 years of age if they appear grossly normal However, they should be transposed above the pelvic brim into the paracolic gutters and anchored there with a permanent suture, so that they can be spared the effect of radiotherapy should it be required subsequently (see below) The discovery at laparotomy that the para-aortic lymph nodes are positive for cancer may prompt the operator to discontinue the operation and to opt for radiotherapy instead Tumour extension into the bladder base which cannot be detected cystoscopically may prevent adequate mobilisation of the bladder flap, leading to the procedure being abandoned For this reason, this part of the operation is undertaken early on opening the abdomen Okabayashi described his technique of radical hysterectomy in 1921 This technique aimed at improving the operability rate even in those patients with advanced disease, with a more radical dissection of the parametrial and paracervical tissue Sakamoto and colleagues further modified this (Tokyo method) They attempted to preserve the base of the cardinal ligaments which contain the pelvic nerve bundles and also treated the ureters differently, leaving a protective sheath Both these technical differences resulted in a decreased incidence of bladder dysfunction which is the main advantage of the Tokyo method Several other modifications in the Wertheim’s procedure have been reported from time to time; most of these have been attempts to decrease the rate of ureteric fistula formation A rather less extensive operation (so far as node dissection is concerned) can be carried out by the vaginal route (Schauta’s or Schauta-Amreich’s operation) but is only popular in a few centres Mitra from India modified the operation and added bilateral extraperitoneal lymphadenectomy through two separate abdominal incisions to correct this deficiency Nowadays, the Schauta’s procedure can be combined with laparoscopic lymphadenectomy to decrease the morbidity of the procedure In selected young women with early Stage I disease confined to the ectocervix, who desire to preserve fertility, radical trachelectomy has been described recently, in which the cervix is removed along with the cardinal and uterosacral ligaments, and paracervical tissue, followed by suturing of the uterus to the vagina Lymphadenectomy is either done pre viously at a separate sitting or the lymph nodes are assessed by frozen section to be free of disease The lymphadenectomy can be performed laparoscopically Subsequent pregnancy has also been reported in almost half of these patients, but there is a risk of mid-trimester abortion or preterm delivery 448 Jeffcoate’s Principles of Gynaecology Intraoperative radiotherapy (IORT) is now being tried in recurrent cervical cancer The bowel is retracted out of the field and EBRT and ICRT administered Combined Radiotherapy and Surgery Chemotherapy Chemotherapy has not been shown to cure cervical cancer but it can cause significant tumour regression Single agents used are cisplatinum, bleomycin, ifosfamide and methotrexate The best response rates have been observed with cisplatinbased combinations Neoadjuvant chemotherapy has been used in cases with bulky tumours preoperatively and in com bination with radiotherapy However, it has not been shown to improve survival rates Concurrent chemotherapy and radiotherapy are now being tried with bulky and advanced cancer of the cervix Preliminary results suggest that this may become the new standard of care in these patients Ultraradical Surgery and Palliation Results Care is necessary in the appraisal of published results Standards of diagnosis vary and a high cure rate may mean the inclusion of cases of carcinoma in situ, and of cervical conditions which not all would accept as malignant The staging of growths is also inevitably a matter of opinion despite the guidelines laid down by FIGO There is, nevertheless, clear evidence that, in developed countries with good medical services, the overall results have improved considerably in the last 35 years According to figures collected from many centres throughout the world, and covering treatments of all kinds—radiotherapy, surgery, and combinations of these—the 5-year apparent cure rate for women treated during the period 1941–1945 was 36.9% For the period 1976–1978 it was 55.0% The change was due in large measure to earlier diagnosis and treatment, and to technical advances In recent years the annual rate of improvement in results has slowed down considerably The results obtained anywhere depend mostly on the staging of the growth at the outset The worldwide figures for treatments of all kinds indicate 5-year apparent cure rates as follows: Stage I: Eighty-five percent of patients treated (Stage IB about 82%: 87–91% if node-negative and 51–67% if node-positive) Stage II: Sixty percent of patients treated Stage III: Thirty-three percent of patients treated Stage IV: Ten percent of patients treated In developing countries with poor medical services (often no facilities for radiotherapy of any kind), and where women rarely present for treatment before their cancers are in Stage III or IV, the overall results are still extremely depressing, relatively few cures being obtainable Here we are concerned with combined therapy as a planned primary procedure, not with the resort to one when the other has failed or appears to be failing Radiotherapy may follow surgery and the usual indication for this is the unexpected discovery of an occult invasive cancer in the cervix of a uterus removed by simple total hysterectomy alone or the finding of more extensive disease than expected, i.e metastases to the pelvic lymph nodes, deep cervical invasion, invasion of paracervical tissue or positive surgical margins Of these high-risk factors, only the last-mentioned is universally agreed on as being benefited by postoperative radiotherapy In the case of positive pelvic nodes, radiotherapy has been shown to decrease the incidence of recurrence but there is no benefit in terms of survival unless there are at least three positive nodes Stage IB2 disease has been shown to have a higher risk of metastatic disease and postoperative radiotherapy is recommended in these patients In young patients in whom invasive cervical cancer was found after simple hysterectomy, reoperation has been described Pelvic node dissection, radical excision of parametrial tissue, cardinal ligaments and vaginal stump are done Survival is reported to be similar to primary radical hysterectomy However, as the anatomy is distorted after surgery, this procedure is technically more difficult and the usual practice is to give radiotherapy Sometimes, preoperative irradiation can make surgery possible when it would not have been otherwise It is generally accepted that preoperative radiotherapy makes the surgery easier for the barrel-shaped endocervical carcinoma There is considerable debate as to whether the dose of intracavitary treatment should be similar to that used normally or whether it should only be about one-half to twothirds of the dose Surgery is carried out within 10 days of radiotherapy, before reactions occur, or about weeks later, when the immediate radiation reactions will have settled and the tumour regressed before the late changes in blood vessels occur The disadvantages of combined surgery and radiotherapy are as follows: • The operation can be more difficult technically because of radiation reaction, if not carried out at the optimal time • Healing, especially of the vaginal vault, is delayed • Exposure of tissues to two risks increases the chance of fistula formation although this is not the experience of all those who adopt this method These disadvantages are minimised by not giving more than two-thirds of the standard dose of radium, and by not dissecting the ureters too cleanly • If the surgeon fails to operate or cannot, for one reason or another, the patient’s treatment is compromised because curative radiotherapy depends on a combination of the most appropriate dose and its timing vip.persianss.ir 449 Tumours of the Cervix Uteri The results vary with the circumstances and with the equipment available in any one centre Given good, or exceptionally good (for these, take the figures at the tops of the ranges) facilities, the 5-year survival rates to be expected are 80–90% for Stage I, 55–70% for Stage II, 30–35% for Stage III, 10% for Stage IV, and an overall figure of 55–58% Guidelines—Locally recurrent cervical cancer following surgery: • Radiation therapy is indicated in patients with locally recurrent cervical cancer following radical surgery • Concurrent chemotherapy with either 5-fluorouracil and/or cisplatin with radiation should be considered and may improve outcome • Pelvic exenteration may be an alternative (particularly if a fistula is present) to radical radiotherapy and concurrent chemotherapy is selected patients without pelvic sidewall involvement Radiotherapy Surgery Radiation dose and volume should be tailored to the extent of disease Fifty Gray in 180 cGy fractions should be delivered to microscopic disease and using field reductions 64 to 66 Gy should be delievered to the gross tumour volume Where disease is metastatic or recurrent in the pelvic after failure of primary therapy and not curable, a trial of chemotherapy with palliative intent or symptomatic care is indicated Cisplatin is the single most active agent for the treatment of cervical cancer The expected median time to progression or death is 3–7 months Local recurrence following definitive (radical) radiation: Guideline—Local recurrence following prior radiotherapy • Selected patients with small disease (< cm) confined to the cervix may be suitable for radical hysterectomy • Patients with a central recurrence and no evidence of metastatic disease should be considered for pelvic exenteration Radical hysterectomy may be used for patients with small disease (< cm) in diameter confined to the cervix The morbidity is high, but some patients can be cured without need for a stoma Patients with a central recurrence that involves the bladder and/or rectum, without evidence of intraperitoneal or extra pelvic spread, and who have a tumour-free space along the pelvic sidewall, are potentially suitable for pelvic exenteration The triad of unilateral leg oedema, sciatic pain and ureteral obstruction almost always indicates unresectable disease on the pelvic sidewall, and palliative measures are indicated The prognosis is better for patients with a disease-free interval greater than months, a recurrence 3 cm or less in diameter, and no sidewall fixation The year survival for patients selected for treatment with pelvic exenteration is in RELAPSE Management of Patients who Relapse after Primary Treatment Treatment decisions should be based on the performance status of the patient, the site of recurrence and/or metastases, the extent of metastatic disease and the prior treatment Locally recurrent cervical cancer following: Radical surgery Reported experience suggests that a full or modified course of radiotherapy followed by radical surgery gives slightly better results than are generally obtained by surgery or radiotherapy alone This is particularly true for Stage II cases, in which 5-year survival rates of 60–80% are recorded, and in bulky disease From the above it would appear that, for Stage I and certain Stage II cases, there is little to choose between the different methods of treatment as practised by experts Nevertheless, assuming an average standard of skill on the part of the gynaecologist and radiotherapist, there is no doubt that treatment based primarily on radiotherapy offers the best chance in most cases of invasive cancer, early as well as advanced Relapse in the pelvis following primary surgery may be treated by either radical radiation or pelvic exenteration Radical irradiation (± concurrent chemotherapy) may cure a substantial proportion of those with isolated pelvic failure after primary surgery Combined Radiotherapy and Radical Surgery Therapeutic Options for Local Relapse after Primary Surgery It must be reckoned that only Stage I and certain selected Stage II cases are usually treated by radical hysterectomy Given average to good surgical skill, the 5-year apparent cure rate is 70% for Stage I, 45–50% for Stage II, or 55–60% for both stages combined Nevertheless, there are a few gynaecologists throughout the world who, having specialised in this operation and acquired particular skill and experience, report 5-year survival rates of 85% for Stage I, and 70% for Stage II, cases Amongst those patients whose lymph nodes prove positive for malignant cells, the 5-year apparent cure rate is as high as 30–35% A 5-year survival rate of at least 50% of patients treated is claimed for the schauta operation combined with extraperitoneal lymphadenectomy Indeed, a few gynaecologists with experience of both operations say that the radical vaginal approach gives results equal to those of the radical abdominal operation and is attended by fewer complications such as fistula formation vip.persianss.ir 450 Jeffcoate’s Principles of Gynaecology Further Observation Often invasive carcinoma is found after hysterectomy for what was considered benign or preinvasive disease If the original lesion was a small Stage IB tumour, a 5-year survival rate of 82% may be achieved with radical parametrectomy, upper vaginectomy and pelvic lymphadenectomy The other option with equivalent results is radiotherapy A dose of 45 Gy is given over weeks, followed by vault irradiation Carcinoma of the Cervix Complicated by Other Pelvic Conditions Carcinoma of the Cervix and Pregnancy Cases of invasive cancer of the cervix discovered during pregnancy are usually Stage I or Stage II The prognosis for those with advanced disease is relatively unfavourable because: the patient is relatively young; the hormonal and vascular changes in pregnancy encourage rapid growth and early dissemination; and the presence of the pregnancy hinders treatment Diagnosis is usually made by a colposcopy-directed biopsy if the Pap test is positive However, if this is not possible a diagnostic conisation may be necessary and this should be done in the second trimester only if the Pap smear is strongly suggestive of invasive cancer, as the procedure carries a high risk of abortion Treatment depends on the stage of disease, the period of gestation, and the wishes of the patient In Stage IA with no LVSI, patients may be delivered vaginally at term followed by hysterectomy weeks later if no further childbearing is required or a conisation if further child bearing is required In Stage IA1 with LVSI and in Stage IA2, delivery is at term but by caesarean section and modified radical hysterectomy with pelvic node dissection is carried out at the same time The tissue planes separate easily during pregnancy so dissection is facilitated, but there may be troublesome haemorrhage from engorged veins around the vagina In Stage IB, delivery can be delayed for a maximum of weeks in the interests of improving foetal lung maturity In tertiary care institutions, the foetus can be delivered after 32 weeks by classical caesarean section and radical hysterectomy with pelvic lymph node dissection In Stages II through IV, radiotherapy is the treatment of choice In the first trimester, treatment is started with EBRT; spontaneous abortion may occur after the first sitting and usually results before the delivery of 40 Gy In the second trimester, the patient’s wishes and the available facilities need to be taken into consideration before deciding the timing In the third trimester, treatment is by classical caesarean section after foetal maturity is attained This is followed by external irradiation and intracavitary therapy The treatment is usually commenced 4–21 days after delivery of the child The overall 5-year survival rate is slightly better for patients with carcinoma cervix in pregnancy because they are usually in an early stage of the disease The possible development of cancer in the cervical stump after subtotal hysterectomy is one of the reasons why this operation had virtually disappeared from gynaecological practice Sometimes the malignancy represents a recurrence of carcinoma of the corpus (or even of the cervix) which was present at the time of operation and passed unrecognised Otherwise the carcinoma (usually squamous cell) develops de novo, and is especially likely when the hysterectomy has been performed for pelvic infection The incidence naturally varies with the standards of gynaecology in any area Where subtotal hysterectomy is carried out exceptionally, and then only after a negative cervical smear, stump carcinoma is rare The tumour behaves like any cancer of the cervix but carries a less favourable prognosis because the peritoneal cavity, the bladder and the rectum are all at the top of the stump So they become invaded early, and not allow the vital high intrauterine dose of radiotherapy Radical surgery is more difficult and less complete in these cases because of the disturbed anatomy The 5-year survival rate for all cases of stump carcinoma after any method of treatment was formerly only 20–30%, but the prospects have improved with modern radio therapeutic apparatus and combinations of radiotherapy and radical surgery Five-year survival rates of up to 60% are obtained in the most advanced clinics Stump Carcinoma Whatever the method of treatment, the patient treated for invasive cancer of the cervix should thereafter be examined routinely every months in the first years, 6-monthly for the next years, and yearly thereafter At each visit, assessment of the situation is made by analysis of symptoms and physical signs, by cytology, renal function tests and sometimes, with large central tumours, by endocervical curettage A chest X-ray may be done annually in patients with advanced disease Intravenous pyelography is indicated if a pelvic mass is detected or if there are urinary symptoms CT scan may be done at 6–12 months in surgically treated patients with a high risk of recurrence to allow for early institution of radio therapy It is sometimes difficult to distinguish recurrence of cancer from later radiation reaction in the parametrium on cytology As a general rule, however, it is wise to assume that any woman who, after a period of complete freedom after treatment, has a return of symptoms, or develops symptoms referable to the pelvic organs, has a return of growth Most recurrences occur within the first two years after therapy Premenopausal patients may require counselling for sexual dysfunction and can be given hormone replacement therapy Carcinoma after Simple Hysterectomy the order of 30–60% and the operative mortality should be less than 10% vip.persianss.ir 451 Tumours of the Cervix Uteri in the adnexa, even a quiescent one, is a contraindication for radiotherapy Radical surgery is preferable if it is technically possible If it is not, it may be necessary to operate on the tubal disease first (bilateral salpingectomy or salpingooophorectomy) and to follow this by radiotherapy 4–6 weeks later Carcinoma of the Cervix Associated with Uterine Leiomyomas and Ovarian Cysts An ovarian cyst can be removed first, radiotherapy being given 2–4 weeks later If large uterine leiomyomas interfere with adequate irradiation, a radical hysterectomy, or a combination of this with radiotherapy, is clearly indicated In some cases it may be possible to carry out radiotherapy in full, leaving the removal of the second tumour until later; the disadvantage is that the cyst or myoma may undergo necrosis Carcinoma of the Cervix Associated with Salpingo-Oophoritis Because of probable exacerbations with peritonitis and abscess formation, the presence of an inflammatory lesion OTHER MALIGNANT TUMOURS OF THE CERVIX These include growths which have spread or metastasised from elsewhere, usually from the body of the uterus or from the vagina Rare primary tumours include the melanoma Sarcoma and mixed Müllerian tumours are considered with similar tumours arising in the body of the uterus vip.persianss.ir ... Menorrhagia 10 9 Conception 11 1 Fertilisation of the Ovum 11 1; Early Development of the Ovum 11 3; Implantation of the Ovum into the Uterus 11 3; Formation of Foetus and Membranes 11 6; Hormonal Control of. .. Delhi 11 0 002, India Phone: + 91- 11- 43574357 Fax: + 91- 11- 43574 314 Email: jaypee@jaypeebrothers.com Overseas Offices J.P Medical Ltd 83, Victoria Street, London SW1H 0HW (UK) Phone: +44-20 317 08 910 ... Urethra 18 0; Development of the Vulva 18 1 13 Malformations and Maldevelopments of the Genital Tract 18 2 Müllerian Duct Anomalies 18 2; Ovary 19 3; Fallopian Tube 19 4; Uterus 19 4; Vagina 19 5; Vulva 19 7;