The cervix This is the part of the uterus below the internal os. The endocervical canal is lined with mucous columnar epithelium, the vaginal cervix with squamous epithelium. The tra nsition zone between them \200\224the squamo \200\223columnar junc- tion \200\224is the are a which is predisposed to malignant change. Cervical ectropion/erosion (see \201 g 1; an alarm- ing term for a normal phenomenon). There is a red ring around the os because the end ocervical epithelium has extended its territory over the paler epithelium of the ectocervix . Ectropions extend temporarily under hormonal in \202 uence during puberty, with the comb ined Pill, and dur- ing pregnancy. As columnar epithelium is soft and glandular, ectropion is prone to bleeding, to excess mucus production, and to infection. Treat- ment: Cryocauter y will treat these if they are a nuisance; otherwise no treatment is required. Nabothian cy sts These mucus retention cysts found on the cervix are harmless. Treatment: Cryocautery if they are discharging. Cervical polyps These pedunculated benign tumors of endocervical epi the- lium may cause increased mucus discharge or postcoital bleeding. Treatment: In young w omen they may be simply avulsed, but in older women treatment usually includes D&C to exclu de intrauterine pathology. Cervicitis This may be follicular or mucopuru- lent, presenting with discharge. Causes: Chla- mydia (up to 50%), gonococci, or herpes (look for vesicles). Chronic cervicitis (see \201 g 2) is usually a mixed infection and may respond to antibac terial cream. Cervicitis may mask neoplasia on a smear. Cervical screening Cervical cancer has a pre- invasive phase: cervical intra-epithelial neoplasia (CIN \200\224not to be prono unced \200\230sin \200\231). CIN 1 aff ects the lower basal third of cervical epithelium. Associat- ed with oncogenic human papilloma viruses (HPV) 6 and 11, it commonly regresses ( 57%). CIN 11 and CIN 111 aff ect < \205\224 and > \205\224 or full thickness of epithe- liu m respectively, are associated with the more oncogenic HPV viruses types eg 16, 18, (p272) are less likely to regress (43%, 32% respectively) and a signi \201 cant number develop in to invasive squamous carcinoma of the cervix. Papanicolaou smears collect cervical cells fo r microscopy for dyskaryosis (ab- normalities which re \202 ect CIN). A smear therefore id enti \201 es women who need cervical biopsy. The degree of dyskaryosis approximates to the severity of CIN (Table, p273). CIN III lesions tend to progress to invasive carcinoma. Thi s may take 10yrs, but may happen much faster in young women. 270 \200 Fig 1. Cervical ectropion. y g o o c e a n y G Courtesy of Mike Hughey. l Fig 2. Chronic cervicitis. Courtesy of Mike Hughey. In the UK the 1st smear is taken at aged 25, then 3-yearly until 49, 5-yearly from 50 to 64 (only screen after 65 if one of the last 3 was abnormal). HIV +ve women should have annual smears. Those most at risk are the hardest to trace and persuade to have screening, eg old er women, smokers, and those in inner cities. 83% of the eligible UK population is now scre ened, and mortality is 50% that of 1988 (the year screening started); this depends critical ly on being able to retain skilled lab staff . 271 Taking a smear \200 Explain the nature and purpose of the test, and how results will be c on- veyed. Warn that results are not always unequivocal. The cervix is visualized with a speculum (p242). Are there any suspicious areas? If so, car ry on with the smear and indicate this on the referral form, but do not wait for its result s before arranging further care. Cells are scraped from the squamo-columnar transformation zone with a special spatula or brush, then transferred to a slide and \201 xed at once. \200 Liquid -based cytology (LBC) 82 involves rinsing the sampler or detaching its head into a vial of liquid creating a cell suspension from which slides are prepared which are quicker and easi er to screen than conventional smears. \200 Suspensions can also be tested for human papi lloma virus (see p273) and y g o o c e a n y G chlamydia. Inadequate smear rates are reduced with LBC. l Ensure regular training and supervision, and audit of numbers of \200\230inad- equate samp le \200\231 reports. Don \200\231t do smears on a one-off basis (in the UK NHS, professiona lism mandates formal methods of quality control, and speci \201 es an acceptable number of smears per year, etc). Automatic analysers can identify areas of slides likely to be of interest to cytologists. 8 3 Good technique is needed (make sure that all 4 quadrants of the cervix are sampled): \200\207learn by instruction from an expert at the couch. Cervical carcinoma Aim to detect pre-invasive disease. 1900 women die yearly of cervical c ancer in the UK. The main cause is human papilloma virus (eg HPV 16, 18, 31, 33, 35, 39, 45 , 51, 52, 56, 58, 59, 68). Vaccines work only against a subset, eg Gardasil 1 covers HPV 1 6 & 18, the cause in 70% of cases. (99.7% of cervical cancers contain HPV DNA.) 272 \200 Prolonged Pill use may be an important co-factor (may \200\200risk 4-fold in those +ve for HPV DNA). 84 Other risk factors: high parity; many (>4) sexual partners or a partner with many other partners (especially if that male is uncircum- cised); 85 early \201 rst coitu s; HIV; other STDs; smoking. Management of abnormal smears (See p273) the histology of cerv ical intra- epithelial neoplasia (CIN) is explained there.) Either a repeat smear or colpos - copy and biopsy are needed, depending on likelihood of the smear re \202 ecting CIN III or small-volume invasive disease (<3mm). \200\207Abnormal smears may cause anxiety and gui lt. Explain. Give support. Treating pre-invasive cancer Examine the cervix by colposcope ( \211\21010 bin- ocular microscope). Abnormal epithelium has characteristic blood vessel pat - terns and stains white with acetic acid. Take punch biopsies for histology. CIN is destro yed by cryotherapy, laser, cold coagulation, or large loop excision of transformation zone (LLETZ). These give 90% cure rates with one treatment. She needs annual smears for at leas t 10yrs. If the squamo \200\223columnar junction cannot be seen, or if small-volume invasiv e carcinoma is found on histology, the abnormal tissue is removed by cone biopsy, which may be curative. Colposcopy does not detect adenocarcinoma (it usually lies within endocervica l canal). Invasive disease Most are squamous cancers. 15 \200\22330% are adenocarcinomas (f rom endocervical epithelium), especially aff ecting women under 40. Spread is local and lym phatic. Stage I tumors are con \201 ned to the cervix. Stage II have extended locally to u pper \205\224 of the vagina; IIb if to parametria. Stage III have spread to lower \205 \223 of vagina IIIa; or pelvic wall IIIb. Stage IV have spread to bladder or rectum. IVb if spread to distant organs. Most present in stages I or II. Diagnosis \200\207Overt carcino ma is rarely detected on a smear. Non-menstrual bleeding is the classic symptom. The early tumor is \201 rm. It grows as a friable mass which bleeds on contact. Use CT/MRI to stage ; positron emission tomog- raphy if unsuitable for surgery detects para-aortic node metasta ses and may modify treatment regimes. 19 Treating invasive cancers 86 Stage Ia1 (microscopi c lesions, invasion <3mm) may be treated by cervical conization in those wishing to preserv e fertility, extrafascial hysterectomy for those with completed families. Radical hyster- e ctomy with pelvic lymphadenectomy or radiotherapy is used for stage Ia2 (microscopic, invas ion 3 \200\2235mm depth <7mm horizontally) disease and some stage Ib1 (macroscopic, tumor < 4cm). Chemoradiation is the \200\230gold standard \200\231 for most stage Ib, II or bulky stage II disease. It is also used for stage III and IV disease. Use of chemotherapy in adva nced and recurrent disease is palliative. The main chemotherapy agent is cisplatin. Adding topotecan for recurrent, resistant or metastatic disease increases survival time, but with increased toxicity. 87 Pelvic exenteration (p309) is sometimes used in stage IVa disease. C ure rates for stages I (80% 5-yr survival) and II (60%). Radiotherapy causes vaginal stenos is, so encourage intercourse within 2 months of treat- ment (+lubricant). Follow-up: annual smears. Smears are of no value after rad- ical radiotherapy. Terminal problems are pain, \201 stulae, and GI/GU obstruction. y g o o c e a n y G l 1 Gardasil targets HPV6, 11, 16 & 18. 3 IM does, 0.5mL (deltoid/lateral thigh). Age range : 9 \200\22318yrs (9 \200\22326 ). Dose 2 is \211 1 month after dose 1, and dose 3 \211 4 months after dose 1. CI: pregnancy, bleeding disorders. Cervarix (bivalent; HPV16 & 18). Unanswered questions: How long does protection last? Should boys be vaccinated too? Will t he ecospace created be populated by new carcinogenic strains of HPV?88 \200\22390 273 Histology of cervical pre-malignant disease CIN=cervical intra-epithelial neoplasia Papanic olaou class I Action Repeat in 3 years (Unless clinical suspicion) Take swab; treat infection Repeat in 6 months (Colposcopy after 3 abnormal) Repeat in 4 months (Colposcopy after 2 abnormal) HPV test Colposcopy Histology 0.1% CIN II \200\223III Normal II In \202 ammatory 6% CIN II \200\223III Mild atypia 20 \200\22337% CIN II \200\223III III Mild dyskaryosis 20 \200\22330% CIN II \200\223III 50 \200\22375% CIN II \200\223III 80 \200\22390% CIN II \200\223III 5% invasion y g o o c e a n y G Moderate dyskaryosis Colposcopy Colposcopy IV Severe dyskaryosis l \200\230Positive \200\231 \200\230Malignant cells \200\231 Invasion suspected Abnormal gl andular cells V Urgent colposcopy Urgent colposcopy 50% invasion ?Adenoca cervix or endometrial ca CIN I =mild dysplasia; CIN II=moderate dysplasia; CIN III=severe dysplasia/ carcinoma-in-si tu. The table above shows comparative terms and the recommended action. The third column, h eaded histology, shows the percentage of smears in each Pap- anicolaou (cytological) class which have more serious lesions (CIN II or III) on histology. With in \202 ammatory smears , swabs should be taken and any infec- tion treated. 6% of in \202 ammatory smears have se rious pathology, hence the recommendation for colposcopy if in \202 ammation persists. Bor derline nuclear abnormality (BNA) implies doubt as to the neoplastic na- ture of any change . Human papilloma virus (HPV) test From 2012 UK screening tests smears with borderline nucl ear change and mild dyskaryosis for presence of oncogenic hu- man papilloma viruses (HPV) T his is referred to as HPV triage. The 20% that are HPV positive are then referred for colpo scopy. Those negative for HPV return to normal screening (p270). For those having colposcop y, if CIN1 not requir- ing treatment is found, they will be resmeared ( colposcopy) after 1 year. If that smear has borderline nuclear change or mild dyskaryosis the sample will ag ain be HPV triaged, and further colposcopy arranged if it is HPV positive; if that smear is HPV negative women return to routine follow-up. Women with CIN1, CIN2 or CIN3 requiring tr eatment are resmeared 6 months after treatment, and if the result is normal, or has borderl ine nuclear change and mild dys- karyosis, that sample is also HPV tested (this stage is re ferred to as test of cure). If HPV positive, further colposcopy is arranged and follow-up w ill follow national guidelines (eg annual smears for 10 years); if HPV negative, women will have a recall after 3 years. If that one is normal women over 50 years return to 5-year re call. In the UK, 6 \211\210106 smears are done per year on women up to 65yrs old, and cervical ca ncer deaths have fallen by 15% in recent years to <1900/yr. The inci- dence of cervical can cer in England and Wales fell by 42% between 1988 and 1997. Cervical screening is thought t o prevent 2000 deaths/year in the UK. \200\22591 2.4% of smears show mild dyskaryosis, and 2.2% have BNA. Terminology used in reporting smears changed in the 1980s, and diff erent countries use diff erent nomenclature \200\224eg the Bethesda system. The uterus Endometritis Uterine infection is uncommon unless the barrier to ascending infec tion (acid vaginal pH and cervical mucus) is broken, eg after miscarriage, ToP and childbir th, IUCD insertion, or surgery. Infection may involve Fallopian tubes and ovaries. Presenta tion: Lower abdominal pain and fever; uterine tenderness on bi- manual palpation. Low-grade infection is often due to chlamydia. Tests: Do cervical swabs and blood cultures. Treatmen t: Give antibiotics (eg doxycyline 100mg/12h PO with metronidazole 500mg/8h PO, eg for 7 da ys). Endometrial proliferation Estrogen stimulates endometrial proliferation in the \201 rst half of the menstrual cycle; it is then in \202 uenced by progesterone and is shed at menstruation. A particularly exuberant proliferation is associated with heavy menstrual ble eding and polyps. 274 Continuous high estrogen levels (eg anovulatory cycles) make the endome- trium hyperplastic ( \200\230cystic glandular hyperplasia \200\231 \200\224a histological diagnosis af- ter D &C). It eventually breaks down, causing irregular bleeding (dysfunctional uterine bleeding) . Treatment: Cyclical progestogens (p253). In older women proliferation may contain foci of atypical cells which may y g o o c e a n y G lead to endometrial carcinoma (p278). Pyometra This is a uterus distended by pus eg associa ted with salpingitis or secondary to out \202 ow blockage. Treatment: Drain the uterus, tr eat the cause. Haematometra This is a uterus \201 lled with blood due to out \202 ow obs truction. It is rare. The blockage may be an imperforate hymen in the young (p246); carcino ma; or iatrogenic cervical stenosis, eg after cone biopsy. Endometrial tuberculosis Genital tract tuberculosis is rare in Britain, except among high-risk groups (eg immigrants). It i s blood-borne and usually aff ects \201 rst the Fallopian tubes, then the endometrium. l It may present with acute salpingitis if disease is very active, or with subfer- tility, pe lvic pain, and menstrual disorders (40%) eg amenorrhoea, oligomen- orrhoea. There may be py osalpinx. Send peritoneal \202 uid at laparoscopy, and/ or endometrial curettings for cul ture and histology. Exclude lung disease by CXR. Treatment is medical with antituberculous therapy (OHCM p398 \200\2239). Re- peat endometrial histology after 1 year. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is treatment of choice if there are adne xal masses and the woman is >40yrs. 92 Uterine ultrasound 93 Transvaginal ultrasound gives better resolution than transabdominal. Homogeneity, echoes of low intensity and presence of a lin- ear central shadow are associated with absence of endometrial abnormality. Normal c ycle thickness: <5mm early cycle, 11mm in proliferative phase; 7 \200\22316mm late cycle. E ndometrial cancer is suggested by endometrial thickness >20mm (>5mm if postmenopausal not o n hormones), heterogeneous appear- ance, and hypoechoic areas. Polyps have cystic appearanc e (also with hyper- echoic endometrium) and are most clearly seen in the early days of the cycle. If postmenopausal and not on HRT, double-layer endometrial thickness should be <5mm (if per imenopausal <5mm on day 5 of cycle). Sequential hormone replacement \200\200endometrial th ickness (average 5 \200\2238.5mm); if on continuous combined replacement HRT thicknesses ar e 4.5 \200\2237mm; tibolone treated endometrium <5mm; but tamoxifen thickens it to 13mm ( also associ- ated with endometrial polyps, often large, usually benign). It thins down by 6 months after stopping tamoxifen, then stays thin. 94 Ultrasound is useful for detecting \201 broids and assessing cystic change in rapidly growing \201 broids to assess risk of malignant change. 275 Vaginal carcinoma These tumors are usually squamous. They are commonest in the upper third of the vagina. Presentation is usually with bleeding. Clear cell adeno- carcinoma is associ ated with intrauterine exposure to diethylstilboestrol before 18 weeks \200\231 gestation b ut risk is low (0.1 \200\2231 : 1000). (Note: risk of invasive cervical carcinoma is also i ncreased 3-fold, and structural abnormalities of the genital tract \200\224uterine 69% and cervical 44% \200\224are problems following past exposure). \200\22595 Spread is local and by lymphatics. Treatment is usually ra- diotherapy. Prognosis is poor eg 58% 5-yr survival for squamous vaginal carci- noma; 34% for adenocarcinoma. 96 y g o o c e a n y G l Fibroids (uterine leiomyomata) Fibroids are benign smooth muscle tumors of the uterus (leio myomas) ( \201 g 1. p240). They are often multiple, and vary in size from seedling size to tumors occupying a large part of the abdomen. They start as lumps in the wall of the uteru s but may grow to bulge out of the wall so that they lie under the peritoneum (subserosal, 20%) or under the endometrium (submucosal, 5%), or become pedunculated. Fibroids are common (20% of women have \201 broids), increasing in frequency with age and in non-Caucasians. Associations Mutation in the gene for fumarate hydratase can cause \201 broids and a rar e association with skin & uterine leiomyomata, and renal cell cancer.1 97 Natural history F ibroids are estrogen-dependent. Consequently they en- large in pregnancy and on the combine d Pill and atrophy after the menopause. They may degenerate gradually or suddenly (red dege neration). Occasionally they calcify ( \200\230womb stones \200\231). Rarely, they undergo sarcomatous change \200\224usu- ally causing pain, malaise, bleeding, and increase in size in a postmenopausal woman. Presentation Many are asymptomatic. \200 Menorrhagia: Fibroids often produce heavy and prolonged periods ( anae- mia, eg dyspnoea etc. They do not gene rally cause intermenstrual or post- menopausal bleeding. 276 \200 y g o o c e a n y G l Fertility problems: Submucosal \201 broids may interfere with implantation ( \200\230natu ral IUCD \200\231). Large or multiple tumors which distort the uterine cavity may cause mis carriage should pregnancy occur. Pain: This may be due to torsion of a pedunculated \201 broid, producing symp- toms simil ar to that of a torted ovarian cyst. \200\230Red degeneration \200\231 following thrombosi s of the \201 broid blood supply: see OPPOSITE. Mass: Large \201 broids may be felt abdominally. They may press on the blad- der, causing frequency, or on the veins, causing oedematous legs and vari- cose veins. Pelvic \201 br oids may obstruct labor or cause retention of urine. Treatment In many women, no treatment is needed. Menorrhagia due to \201 broids tends to respond poorly to anti-prostaglandins, progestogens, or danazol. If the uterine cavity is n ot too distorted a Mirena intrauterine device can be used and may decrease \201 broid s ize. Women who have completed their families may opt for hysterectomy. In younger women, a reversible menopausal state may be induced with analogs of LHRH (lutein- izing hormone rele asing hormone), eg goserelin (better than buserelin 2). A single dose of 10.8mg SC reduces bulk by \211 50%. 98 Bone demineralization can occur, but is ameliorated by concurrent ral oxifene 99 or tibolone. 100 They may be used pre-op to reduce \201 broid bulk; in those u n \201 t for surgery; or those de- siring later pregnancy. Side eff ects are menopausal sy mptoms. Fertility (and \201 broids) return when drugs are stopped. Alternatively, \201 broids may be surgically shelled out (myomectomy). Com- plications: t orrential bleeding needing hysterectomy; post-op adhesions. Pregnancy rates can be 50% pos t-op. 101 Laparoscopic surgery laser use is possible but needs much patience. Myomectomy is the treatment of choice in subfertility. Embolizing \201 broids (interventional radio logy) can shrink them, so resolving menorrhagia. This involves only a short hospital stay, but it is not widely available. It can be very painful. Fibroid bulk reduces by 30 \200\223 46%. 102 20 \200\22344% will require further surgery. Chance of successful pregnancy is bet ter after myomectomy. 103 Red degeneration requires only analgesia until symptoms settle. T orsion may resemble an acute abdomen, requiring urgent surgery. 1 Gene location: 1q42.3 \200\223q43. 2 Buserelin nasal spray 100 g/4h is expensive and int ermittent use may cause \201 broid size to increase. 277 Fibroids in pregnancy 5 : 1000 Caucasian women have \201 broids in pregnancy. They are co mmoner in Afro-Caribbean women. They may cause miscarriage. They increase in size in pregna ncy \200\224especially in the 2nd trimester. Ultrasound aids diagnosis. Col- our \202 ow Doppler distinguishes \201 broids from myometrium. 104 If pedunculat- ed they may tort. R ed degeneration is when thrombosis of capsular vessels is followed by venous engorgement an d in \202 ammation, causing abdominal pain ( vomiting & low-grade fever), and localized peritoneal tenderness \200\224 usually in the last half of pregnancy or the puerperium. \200\230Here, a certain fe- verishness leads them to their \201 nal degeneration \200\231 , and imitating the course of all grand passions, \200\230they grow big and tender, and th en die \200\231.D.H. Lawrence Treatment is expectant (bed rest, analgesia) with resolution over 4 \200\2237 days. Most \201 broids arise from the body of the uterus and do not ther efore obstruct labor, as they tend to rise away from the pelvis throughout pregnancy. If la rge pelvic masses of \201 broids are noted prior to labor, cesarean section should be pla nned. Obstruction of labor also needs cesarean section. Sons & Lovers p324 y g o o c e a n y G l Endometrial carcinoma \200\207Investigate postmenopausal vaginal bleeding promptly as the cause may be endometrial cancer. Cancer of the uterine body is less common than cancer of t he cervix. It usually presents after the menopause. Most are adenocarcinomas, and are relat ed to excessive exposure to estrogen unop- posed by progesterone. There is marked geograph- ical variation: North American:Chinese ratio \211\2107 : 1. Presentation This is usually as postmenopausal bleeding (PMB). A woman with a history of PMB has a 10 \200\22320% risk o f genital cancer. It is initially scanty and occasional ( watery discharge). Then bleedin g gets heavy and frequent. Premenopausal women may have intermenstrual bleeding, but 30% ha ve only menorrhagia. Diagnosis Postmenopausal bleeding is an early sign, and generally lead s a woman to see her doctor, but examination is usually normal. Endometrial carcinoma can s ometimes be seen on a smear. Uterine ultrasound may be sug- gestive (p274). The diagnosis i s made by uterine sampling (p279) or curettage. All parts of the uterine cavity must be sam pled; send all material for histol- ogy. Hysteroscopy enables visualization of abnormal end ometrium to improve accuracy of sampling. Skeptics claim it may cause spread through the Fa l- lopian tubes to the peritoneum. NB: hysteroscopy requires dilatation of the os which may prove impossible (misoprostol 1mg PV self-administered the night before surgery helps, but occasionally causes severe pelvic pain). 107 Pathology Most tumors start in the fun- dus, and spread slowly to the uterine mus- cle, cervix and/or peritoneum. They may metastasize t o the vagina (5%), ovary (5%), or any of the pelvic lymph nodes (7%). Staging ( \201 g 1) The tumor is \200 278 \200 Risk factors \200 Obesity1 \200 Unopposed estrogen \200\224 \200 Functioning ovarian tumor FH of breast, ovary, or colon cancer Nulliparity \200 Late menopause \200 Diabetes mellitus \200 Tamoxifen,2 tibolone 105 \200 Pelvic irradiation \200 Polycystic ovaries 106 y g o o c e a n y G l I in the body of the uterus only II in the body and cervix only III advancing beyond the uterus, but not beyond the pelvis IV extending outside the pelvis (eg to bowel and bladder). Fig 1. Uterine cancer ( \211 stage II). Treatment Stages I and II may be cured by total hysterectomy with bilateral sal- pingo-ooph orectomy and/or radiotherapy if un \201 t for surgery (5-yr survival: stage I \211\210 72 %, stage II \211\210 56%). Post-operative vault irradiation reduces vault recurrence.3 In advanced disease consider radiotherapy and/or high-dose progestogens, eg medroxyprogesteron e acetate 200mg/24h PO, which shrinks the tumor (SE: \202 uid retention). Radiotherapy ma y be given either pre-opera- tively (caesium or radium rods inserted into the uterus and up per vagina) or post-operatively (external radiation). Courtesy of Prof. J. Carter. Recurrent disease usually presents in the 1st 2 \200\2233yrs; common sites: pelvic (in non- irradiated patients), lung, bone, inguinal/supraclavicular nodes, vagina, liver, peritoneal cavity. Medroxyprogesterone, surgical exenteration radio- therapy may be tried. Cytotox ics may be used if unresponsive to the above. 1 BMI >25 doubles risk; BMI >30 trebles risk. 2 Note: tamoxifen 20mg daily \200\201annual risk of breast cancer recurrence by 27%. Risk of endometrial cancer from taking tamoxifen i s 1.2 per 1000 person-yrs. Counsel to report abnormal vaginal bleeding. 3 NNT=16.8 to preve nt 1 local recurrence; not needed if low risk type of stage 1 disease. Cochrane.108 279 Endometrial sampling in outpatients This bedside investigation is used for postmenopausal b leeding, perimeno- pausal irregular bleeding, and unexpected bleeding patterns in women on hormone replacement therapy because it is cheap, reliable, and gives quick results without the need for anesthesia. If transvaginal uterine ultrasound precedes the procedure, sample if endometrium >5mm thick. It is less useful in menorrhagia in women with regular cycles, a s pathology is less common. It is not indicated if <35 years old. A sample is obtained using a side-opening plastic cannula in which a vac- uum is created by withdrawal of a stopped central plunger mechanism. As the cannula is withdrawn and rotated in each quadrant of the uterine cav- ity, endometrial tissue is sucked into its interior, through the hole in its side ( \201 g 1). Successful insertion is possible in 90 \200\2239 9% of women (D&C possible in 99%). Adequate samples will be obtained in 91% of these, and i n 84% of those for whom postmenopausal bleeding (PMB) was the indication. Abandon the proce dure if it is impossible to enter the uterus, or if it causes too much pain. Technique 1 Bi manual examination to assess size and position of uterus (p242). 2 Bend cervical cannula to follow the curve of the uterus. 3 Insert device, watching the centimeter scale on the side ; observe resist- ance on entering the internal os (at 3 \200\2234cm) and then as the tip r eaches the fundus (eg at 6cm if postmenopausal or 8cm in an oestrogenized uterus). 4 When t he tip is in the fundus, create a vacuum by withdrawing plunger until the stopper prevents further withdrawal. Then move sampler up and down in the uterus, rotate and repeat to sampl e whole cavity. y g o o c e a n y G l 5 Remove cannula, and expel tissue into formalin. Send for histology. Vabra vacuum aspirati on samples a greater area of tissue, and has higher cancer detection rates, but is more unc omfortable. 109 Management Reassure those in whom the results show normal or atrophic endometrium and those in whom tissue was suffi cient for diagnosis. If those with PMB re-bleed refer for hystero scopy (polyps or a \201 broid will be present in 20%). Those with simple hyperplasia on h istology can be treated with cy- clical progesterones (but refer if >55yrs to search for ex ogenous estrogen source). Refer those with polyps or necrotic tissue on histology for hyste r- oscopy and curettage, and those with atypical hyperplasia or carcinoma for hysterectomy and bilateral salpingo-oophorectomy. If transvaginal uterine ultrasound is not already done , perform in those on whom the procedure was impossible or abandoned to establish endometri al thickness (<5mm normal in the postmenopausal; refer if >5mm thick or if polyps seen, for hysteroscopy and curettage). Fig 1. Endometrial sampling. 82 Redrawn from information supplied by Genesis Medical. Ovarian tumors Any of the ovary \200\231s many tissue types may become neoplastic. Benign t umors (94%). They are usually cystic. 24% of all ovarian tumors are functional cysts. Other s: endometriotic cysts (5% \200\224p288); theca-lutein cysts (p264); epithelial cell tumors (serous and mucinous cystadenomas \200\22440%); mature teratomas (from germ cells \200\224 20%); \201 bromas (solid \200\2245%). Malignant tumors (6%). 5% are cystadenomas which ha ve become malig- nant. 0.5% are a group of rare germ cell or sex cord malignancies (p281). 0.5% are secondaries, eg from the uterus or the stomach (Krukenberg tumors \200\224in which spread is transcoelomic, ie in the case of the abdomen, via the peritone- um). Risk marker s of ovarian malignancy: Nulliparity (risk \200\200 \211\210 1.5); subfertil- ity; early m enarche; +ve family history (p283); no past use of the Pill (by 50%). Presentations are var ied, depending on size, form, and histological type: Asymptomatic \200\224chance \201 ndi ng (eg on doing a bimanual for a smear test). Swollen abdomen \200\224with palpable mass ar ising out of the pelvis which is dull to percussion (and does not disappear if the bladder is catheterized). Pressure effects (eg on bladder, causing urinary frequency). Infarction/h emorrhage \200\224this mimics torsion (see below). Rupture local peritonism. Rupture of a large cyst may cause peritonitis and shock. Rupture of a malignant cyst may disseminate m alignant cells through- out the abdomen. Rupture of mucinous cystadenomas may disseminate c ells which continue to secrete mucin and cause death by binding up the viscera (pseudomyxom a peritonei). See p281. Pseudomyxoma peritonei is treated by surgical debulking. 10-year su rvival is 30 \200\22350%. Ascites \200\224shifting dullness suggests malignancy or Meigs \200\231 syndrome (see BOX). If tense, ascites may be hard to distinguish from a mass. Tors ion \200\224to twist, a tumor must be on a pedicle. Twisting occludes the venous return but the arterial supply continues to engorge the tumor, and causes great pain (with a high WBC ). Tumors may twist and untwist, giving a history of intermittent pain. If the pain is not too severe, a \201 rm tender adnexal swelling may be felt. Endocrine or metastatic effect s \200\224Hormone-secreting tumors may cause virilization, menstrual irregularities, or pos tmenopausal bleeding. Management Ultrasound may con \201 rm the presence of a mass and may show whether it is cystic or solid. Laparoscopy may distinguish a cyst from an ectopic pre gnancy or appendici- tis. Note: laparoscopy is not advised if malignancy is possible, due t o seeding along the surgical tract. Fine-needle aspiration may be used to con \201 rm the impression that a cyst is benign. Urgent laparotomy is required when a cyst problem present s as an acute abdomen. 280 \200 y g o o c e a n y G l Any cyst not positively identi \201 ed as non-neoplastic should be removed, as seemingly b enign tumors may be malignant. In younger women cystectomy may be preferable to oophorectom y. In postmenopausal women, if one ovary is pathological both ovaries and the uterus are re moved. For guidelines for investigation and treatment of tumors in postmenopausal women see p282. For management in pregnancy see p282. 281 Ovarian tumors: pathology Functional cysts These are enlarged or persistent follicular or corpus lu- teum cysts. They are so common that they may be considered normal if they are small (<5cm). They may cause pain by rupture, failing to rupture at ovu- lation, or bleeding. If <5cm they usually resol ve over 2 \200\2233 cycles. Serous cystadenomas These develop papillary growths that may be so pro- li \201 c that the cyst appears solid. They are commonest in women aged 30 \200 \22340 years. About 30% are bilateral and about 30% are malignant. Mucinous cystadenomas Th e commonest large ovarian tumors; these may become enormous. They are \201 lled with muci nous material and rupture may rarely cause pseudomyxoma peritonei (p280). They may be multi locu- lar. They are commonest in the 30 \200\22350 age group. About 5% will be malig- nant. Remove the appendix at operation in those with suspected mucinous cystadenoma and send for histology. (Interestingly men can get pseudo- myxoma from intestinal or appendicular neopl asms; most women with pseu- domyxoma peritonei do not have overt rupture of ovarian tumors and 90% have concurrent intestinal or appendicular tumors and it is now thought that the ov arian tumors may be secondary to GI tumors.) Fibromas These are small, solid, benign, \201 brous tissue tumors. They are as- sociated with Meigs \200\231 syndrome: pleural eff u sion, often right sided + benign ovarian \201 broma (or thecoma, cystadenoma, granulosa c ell tumor) + ascites. Teratomas These arise from primitive germ cells. A benign mature tera to- ma (dermoid cyst) may contain well-diff erentiated tissue, eg hair, teeth. 20% are bila teral. They are most common in young women. Poorly diff erentiated malignant teratomas are rare. Other germ cell tumors (all malignant and all rare) Non-gestational cho- riocarcinoma s (secrete HCG); ectodermal sinus tumors (yolk sac tumors \200\224 secrete \200 -fetoprote in); dysgerminomas. Sex-cord tumors (rare; usually of low-grade malignancy) These arise fro m cortical mesenchyme. Granulosa-cell and theca-cell tumors produce oes- trogen and may pre sent with precocious puberty, menstrual problems, or postmenopausal bleeding. Arrhenoblasto mas secrete androgens. y g o o c e a n y G l Symptoms suggestive of ovarian cancer \200 100 \200 \200\230Bloating \200\231, abdomina l distension \200 Early satiety \200 Loss of appetite \200 Unexplained weight loss \200 Change of bowel habit \200 Fatigue \200 Onset of \200\230irritable bowel \200 \231 symptoms age >50 years \200 Urinary frequency or urgency \200 Abdominal or pelvic pain Examine: if pelvic mass or ascites refer under 2-week rule to gynecology. Check CA-125 (cancer antigen 125), (and \200 -fetoprotein ( \200 FP), \200 -human chori- onic gonadot rophin ( \200 HCG) if <40yrs to identify women who may not have ovarian epithelial cancer). See above. Ovarian epithelial cancers are ad- enocarcinomas. If CA-125 is >35 IU/mL arrang e urgent abdominal and pelvic ultrasound. If ultrasound suggests ovarian cancer refer under 2-week rule to gynecology. If ultrasound has suggested cancer arrange staging CT of abdome n ( chest) in secondary care. Ovarian tumors in pregnancy These are found in 1/1000 pregnancies. It is easier to disting uish them (lying as they do in the rectovaginal pouch) with an anteverted uterus than with a gravid retroverted uterus. Suspicion of presence of a tumor can be con- \201 rmed by ul trasound. Torsion of ovarian cysts is more common in pregnancy and the puerperium than at o ther times. Cyst rupture and hemorrhage into cysts may also occur, but not more commonly th an at other times. Torsion may present with abdominal pain, nausea, vomiting, shock, local tenderness (usually at 8 \200\22316 weeks). 2 \200\2235% of tumors are malignant. Suspect m alignancy with ruptures (then biopsy other ovary). 25% of malignant tumors will be dysgerm inomas. 282 Tumors can become necrotic due to pressure on them in labor. Tumors lying in the pelvis can obstruct labor so cesarean section will be needed unless they are cysts which can be aspir ated under ultrasound control before labor. Asymptomatic simple cysts <5cm across can be left until after delivery if watched by ultras ound. Those 5 \200\22310cm may be aspirated under ultrasound control (and the aspirate exam ined cytologically). Other tumors (those that are complex multilocular or with solid portio ns on ultrasound) should be removed at about 16 weeks \200\231 gestation (by which time the pregnancy is not dependent on the corpus luteum and miscarriage is less likely) to exclude car- cinoma and prevent complications developing. If the diagnosis is made late in pregnan cy and the tumor is not obstructing the pelvis, it is usual to let labor progress normally, and to remove the tumor in the early puerperium because of the risk of torsion then. y g o o c e a n y G l Postmenopausal ovarian tumors The aim is to identify those with high risk of cancer for tre atment at special cancer centers. 21% of postmenopausal women have cysts on screening ul- t rasound. Ultrasound is 89% sensitive and 73% speci \201 c for detecting cancer. CA-125 (p2 83) estimations 81% and 75% respectively. A CA-125 >30u/mL is +ve in 80% of malignancies (b ut in only 50% stage I). Risk of malignancy (RMI) can be calculated with the formula below. RMI <25 has a cancer risk <3%, risk is 75% if RMI > 250 (manage these high-risk women at a cancer center). RMI=U \211\210 M \211\210 CA-125 (M=3; CA-125 is the number for U/mL; U is 1 if ultrasound score=1, and 3 if ultrasound score 2 \200\2235.) To calculate ultrasound score add 1 for each of the following ultrasound features: multilocular cyst; solid area i n cyst; bilateral lesions; evidence of metastases; ascites present. \200\225111 Unilocular cysts <5cm with a normal CA-125 can be managed conservatively (ultrasound every 4 months for 1 year). Low-risk cysts may be removed at bilateral laparoscopic oophorectomy (if suitable for laparoscopic treatment). Postmenopausal cysts should not be aspirated. Hig h-risk cysts need optimal surgical staging ie total abdominal hysterectomy + bilateral salp ingo-oopho- rectomy + infracolic omentectomy at a cancer center with cytology of ascites an d washings, + biopsy of suspicious (eg peritoneal) areas/adhesions (random biopsy if none s uspicious), + retroperitoneal lymph node assessment, (biopsy palpably abnormal para-aortic or pelvic wall nodes or random samples if none palpable). 283 Ovarian carcinoma This is rare, but more women die from it (it is the 5th commonest cause o f cancer-related death in UK women) than from carcinoma of the cervix and uterine body comb ined because in 80% it causes few symptoms until it has metastasized, often to the pelvis with omental and peritoneal seedlings ( lymphatic spread via the para-aortic nodes). Over all 5-yr survival <35%. Incidence 1 in 2500 women >55yrs; 1 in 3800 if >25yrs. If 2 close r elatives aff ected lifetime ovarian cancer risk is 40% (liaise with a gynecologist; see bel ow). 10% of aff ected North American women carry mutations in BRCA1 or BRCA2 genes. Carrier risk of developing carcinoma is 40% for women with BRCA1 mutation, 25% if BRCA2. It is com moner in those with many ovulations (late menopause, nullipara) and, possibly, after subfer tility treatment (p294). Combined oral contraceptive Pill use (p300), breastfeeding, hyster ectomy and tubal ligation reduce risk. Current HRT use increases risk.1 Presentation Sympto ms are often vague. See page 281. Screening & prevention There is really no good screening test. Transvaginal ultrasound with tumor blood \202 ow measurement can diff erentiate bet ween benign and malignant neoplasms at an early stage but does not seem to re- duce mortali ty in high-risk women. 112 Plasma levels of cancer-associated anti- gen (CA-125) lack suffi cient sensitivity or speci \201 city for population screening. y g o o c e a n y G l