Section Outline
- Ch. 1. Objective Structured Clinical Examination (OSCE) in Gynecology
- A. General Gynecology
- Case 1: Polycystic Ovarian Syndrome (PCOS)
- Case 2: Endometriosis—A
- Case 3: Endometriosis—B
- Case 4: Pelvic Pain
- Case 5: Hydatidiform Mole
- Case 6: Cervical Fibroid
- Case 7: Menopause and Hormone Replacement Therapy (HRT)
- B. Adolescent Gynecology
- Case 8: Primary Amenorrhea
- C. Menstrual Abnormalities
- Case 9: Secondary Amenorrhea
- Case 10: Hematocolpos (Cryptomenorrhea)
- D. Infertility
- Case 11: Infertility—A
- Case 12: Infertility—B
- E. Oncology
- Case 13: Hysterectomy and Oophorectomy
- Case 14: Postmenopausal Bleeding
- Case 15: Carcinoma Cervix—A
- Case 16: Carcinoma Cervix—B
- Case 17: Carcinoma Cervix—C
- Case 18: Carcinoma Endometrium
- Case 19: Carcinoma of the Ovary
- Case 20: Inherited Cancers and the Management
A. GENERAL GYNECOLOGY
CASE 1: POLYCYSTIC OVARIAN SYNDROME (PCOS)
Q.1 What is the likely diagnosis?
Ans. Polycystic ovarian syndrome
Q.2 What is the current diagnostic criteria for PCOS?
Ans. According to ASRM/ESHRE, 2018 diagnosis of PCOS is based upon the presence of any two of the following three criteria:
- Oligo and/or anovulation
- Hyperandrogenism (clinical and/or biochemical)
- Polycystic ovaries.
Other causes of hyperandrogenic conditions (adrenal) are to be excluded.
Q.3 What are the symptoms of PCOS?
Ans.
- Obesity
- Infertility
- Menstrual abnormality: Oligomenorrhea, amenorrhea, abnormal uterine bleeding (AUB)
- Hirsutism
- Characteristic skin changes (acanthosis nigricans)
- Acne
- HAIR-AN syndrome (See Dutta's Textbook of Gynecology, 8th Edition, p. 385).
Q.4 What are the characteristic changes in the ovary of a woman with PCOS?
Ans. Ovaries are enlarged in volume. The capsule is thickened. On cut section multiple (≥ 2) follicular cysts measuring about 2–9 mm in diameter are seen peripherally (Fig. 1.2). There is stromal hyperthecosis. Transvaginal sonography (TVS) can demonstrate the enlarged ovarian volume with peripherally arranged cysts.
Q.5 What other investigations would be appropriate for her?
Ans.
- Ultrasound scan (TVS) (Figs. 1.3A and B)
- To detect polycystic ovarian changes
- Investigations for other factors for infertility, e.g., tubal patency test and husband's semen analysis.
Q.6 What is the basic underlying pathology in this condition of PCOS?
Ans. Hyperandrogenic state and chronic anovulation.
Q.7 What are the biochemical abnormalities seen in a case of PCOS?
Ans.
- Hyperandrogenemia [(↑) testosterone, DHEA, androstenedione)]
- Hyperinsulinemia (insulin resistance)
- Hypersecretion of luteinizing hormone (LH)
- (↑) Serum estrogen
- (↓) Sex hormone-binding globulin (SHBG)
- (↑) Lipids.
Figs. 1.3A and B: (A) Ultrasonography of the pelvis showing polycystic ovary (right); (B) Ultrasonography of the same patient showing polycystic ovary (left).Courtesy: Dr (Mrs) S Ghosh, Professor BN Chakravorty, IRM, Kolkata, India.
Q.8 How can obesity and hyperinsulinemia cause hyperandrogenism?
Ans.
- Obesity → increased insulin resistance and raised insulin level stimulate → ovary (theca cells) → androgens (↑) : Obesity → (↓) SHBG → (↑) androgens (free).
- Hyperinsulinemia → ovarian theca cells → (↑) androgens: increased insulin → (↓) hepatic synthesis of SHBG → more (↑) free androgens.
Q.9 What are the long-term consequences in a woman suffering from PCOS?
Ans.
- Risk of developing diabetes mellitus due to insulin resistance.
- Risk of endometrial carcinoma due to unopposed action of estrogen.
- Risk of developing hypertension and cardiovascular disease due to abnormal lipid profile (dyslipidemia).
Q.10 What is the aim of management of PCOS?
Ans. Aim of treatment is to individualize the patient for her presenting symptoms like infertility, obesity or menstrual abnormality. In obese patients, weight reduction is essential.
Q.11 How do you treat hyperandrogenemia?
Ans.
- Weight reduction
- Combined oral contraceptive pills
- GnRH agonists
- Cyproterone acetate
- Spironolactone
- Flutamide.
Q.12 What medical management will improve her fertility status?
Ans. Weight reduction and induction of ovulation. Adjuvant drugs may be needed (e.g., metformin, bromocriptine) depending upon the associated abnormalities.
Q.13 If the woman is desirous of pregnancy how can you help her?
Ans. Ovulation of induction is to be done as she suffers from chronic anovulation. However, other factors (male factor, tubal patency tests) should be normal.
Q.14 What drug is commonly used for induction of ovulation?
Ans.
- Clomiphene citrate
- However, clomiphene citrate is to be combined with other drugs when other biochemical abnormalities are associated.
- Clomiphene citrate + metformin → where there is obesity and hyperinsulinemia.
- Clomiphene citrate + bromocriptine → where there is associated hyperprolactinemia.
Q.15 What is the place of insulin sensitizers in the management of women with PCOS desiring for conception?
Ans. Women with PCOS with body mass index more than 25 are often found insulin resistant. Along with weight reduction, treatment with metformin (insulin sensitizer) is found to reduce hyperinsulinemia and hyperandrogenemia. Pioglitazone and rosiglitazone are also being used in cases, resistant to metformin. Metformin is given in a dose 500 mg thrice daily.
Q.16 What are the different surgical methods?
Ans. Laparoscopic ovarian drilling (LOD) or laser (CO2) vaporization of the cysts is usually done. LOD reduces systemic and intraovarian androgen levels. The woman ovulates spontaneously following LOD (See Ch 54).
Q.17 What is the likely diagnosis?
Ans. Pelvic endometriosis.
Q.18 What is endometriosis?
Ans. It is the presence of functioning endometrium (both glands and stroma) in sites other than the uterine mucosa.
Q.19 What are the common sites of endometriosis?
Ans.
- Ovary
- Uterosacral ligaments
- Rectovaginal septum
- Pouch of Douglas (POD)
- Sigmoid colon
- Abdominal scar.
Q.20 What are the other symptoms?
Ans. Abnormal menstruation like menorrhagia, dysmenorrhea (secondary), dyspareunia, pain during defecation, rectal bleeding. She may be asymptomatic.
Q.21 What is the naked eye appearance of pelvic endometriotic lesions?
Ans. Lesions may appear as:
- Small black dots (powder burns)
- Red flame shaped areas
- White patches
- Peritoneal windows
- Subovarian adhesions
- Puckering of peritoneum
- Ovaries may be involved—chocolate cysts
- White peritoneal areas.
Q.22 What are the important symptoms of pelvic endometriosis?
Ans.
- Some patients remain asymptomatic (25%)
- Dysmenorrhea (50%)
- Abnormal menstruation—menorrhagia, polymenorrhea
- Infertility (40–60%)
- Dyspareunia
- Pelvic pain
- Abdominal pain
- Bladder symptoms (dysuria)
- Bowel symptoms (rectal bleeding)
- Pain during defecation.
Q.23 How the diagnosis of pelvic endometriosis is confirmed?
Ans. It is commonly done by diagnostic laparoscopy.
Q.24 What is the place of serum CA-125 in the diagnosis of pelvic endometriosis?
Ans. Measurement of serum CA-125 levels is not a diagnostic tool because of its low sensitivity (< 50%). It may be used to predict the recurrence of endometriosis after therapy.
Q.25 What are the causes of infertility in a woman with pelvic endometriosis?
Ans. The possible cause of infertility are:
- Ovarian dysfunction: Anovulation, defective folliculogenesis or luteal phase defect.
- Tubal dysfunction: Pelvic adhesions, causing distorsion of normal tube ovary relationship.
- Others: Abnormal peritoneal fluid, implantation failure, miscarriage.
Q.26 What are the endocrine abnormalities associated with endometriosis?
Ans.
- Corpus luteum insufficiency
- Raised prolactin level
- Luteolysis due to increased PGF2α.
Q.27 What associated condition such a patient may present with?
Ans. Infertility.
Q.28 What are the complications of endometriosis?
Ans.
- Leakage or rupture of chocolate cyst
- Infection of chocolate cyst
- Infertility
- Obstructive features (ureteral obstruction).
Q.29 What are the different modalities of therapy for pelvic endometriosis?
Ans.
- Expectant
- Medical NSAIDs: Hormonal
- Surgery
- Conservative
- Definitive
- Assisted reproduction (See Ch 23).
Q.30 What are the factors that determine the type of treatment to a particular woman?
Ans. To an individual woman the determining factors are:
- Age of the woman
- Size and extent of lesion
- Severity of symptoms
- Desire for a child
- Stage of the disease [American Fertility Society (AFS) scoring system—See Dutta's Textbook of Gynecology, 8th Edition, p. 257]
- Results of previous therapy.
Q.31 What are the different hormones that can be used for the treatment of pelvic endometriosis?
Ans.
- Combined oral contraceptives (COCs)
- Progestogens
- Oral:
- Medroxyprogesterone acetate
- Dydrogesterone
- Dienogest
- Parenteral (IM): Medroxyprogesterone
- Intrauterine contraceptive device (IUCD): Levonorgestrel intrauterine system (LNG-IUS)
- Danazol
- Gestrinone
- GnRH analogs.
Q.32 What are the important side effects of danazol and GnRH analogs?
Ans.
- Danazol: It causes symptoms due to pseudomenopause and it is less tolerated.
- GnRH analogs: It works by creating medical oophorectomy compared to danazol, GnRH analogs are well-tolerated.
Q.33 What are the indications of surgery for pelvic endometriosis?
Ans.
- Symptomatic endometriosis which is not responsive to hormone therapy.
- Severe endometriosis—to correct the distortion of pelvic anatomy or for improvement of symptoms.
- Chocolate cyst ≥ 4 cm needs ovarian cystectomy and adhesiolysis.
Q.34 What are the different types of surgery that can be done?
Ans. Either by laparotomy or laparoscopy.
Q.35 What is meant by conservative surgery?
Ans. Preservation of the reproductive organs and restoration of their anatomy for enhancement of fertility (function).
Q.36 What is meant by expectant treatment?
Ans. Expectant treatment means doing nothing actively. The woman is kept under observation.
Q.37 What is the place of expectant treatment?
Ans. Role of any treatment for minimal to mild endometriosis is controversial. Cumulative pregnancy rate is similar following expectant treatment and that after conservative surgery.
Q.38 Who are the cases for expectant treatment?
Ans. Minimal endometriosis when observed in
- Unmarried women
- Young married woman who is desirous of a baby
- Women approaching menopause.
Q.39 What type of laparoscopic surgery is commonly done?
Ans. Destruction of endometriotic implants over the peritoneal surface is commonly done. It is done by diathermy or by laser vaporization. Ovarian endometrioma (chocolate cyst) can be resected laparoscopically. Laparoscopic uterosacral nerve ablation (LUNA) is done when pain is very severe.
Division of adhesions (adhesiolysis) can also be done by laparoscopy.
Q.40 What are the treatment options for this woman?
Ans. Combined oral contraceptive pill for a period of 6–9 months would be most appropriate for her. Continuous therapy without the usual 7 days break would make her amenorrheic. This will help regression of the endometriotic deposits. This will also improve her symptoms. At the same time contraception is also provided.
Other options depending on the severity of endometriosis would be:
- Medical therapy: Continuous progestogen, dienogest or GnRH analogs.
- Surgical therapy: Laparoscopic laser or electrodiathermy to ablate the endometriotic implants.
Q.41 What would be the appropriate management when she desires to conceive?
Ans. Pregnancy itself provides remission to the problem. For this case, following the initial treatment, expectant management would be appropriate for next 6 months. About 60–70% women will become pregnant within a year provided there is no other factor for infertility.
Q.42 What is the optimum treatment for scar endometriosis?
Ans. Treatment is done by excision. Hormone therapy is ineffective.
Ans. Adenomyosis is a condition when there is ingrowth of endometrium (both the glands and stroma) directly within the myometrium (See Ch 12).
Q.44 How does a woman with adenomyosis present?
Ans. Usually the woman is parous, with age above 40 years.
Common symptoms are:
- Menorrhagia
- Dysmenorrhea.
Q.45 How can you differentiate a fibroid uterus from an adenomyosis?
Ans. See Ch 12.
Q.46 What should be the treatment of adenomyosis in a parous and elderly woman?
Ans.
- Treatment of adenomyosis (Figs. 1.5A and B) is predominantly surgical.
- Medical management (hormones) is often ineffective.
- Conservative surgery includes partial resection of adenomyomata.
- Total hysterectomy with or without bilateral salpingo-oophorectomy is the optimum treatment for a woman who is parous and aged.
- Currently, LNG-IUD is being used and found to be effective in improving the symptoms of menorrhagia and pelvic pain.
Figs. 1.5A and B: (A) Postoperative specimen of a uterus with tubes and ovaries. Mrs SE, a 46-year-old, parous lady, was admitted for menorrhagia and intractable dysmenorrhea. She did not respond to any medical therapy. She was investigated. She underwent hysterectomy and bilateral salpingo-oophorectomy. The uterus is seen uniformly enlarged; (B) The specimen of the same patient is cut opened to show myohyperplasia with hemorrhagic spots within the myometrium.
CASE 3: ENDOMETRIOSIS—B
Q.47 What more relevant questions you will ask her to make the provisional diagnosis?
Ans. Regarding the pain, e.g., character of pain, duration, exact relationship with the period, deep dyspareunia and fertility status.
Q.48 What clinical signs will help you to make the differential diagnosis?
Ans. Pelvic tenderness, nodularity in the pouch of Douglas, fixed retroversion of the uterus, adnexal mass, tenderness and bulky uterus. The differential diagnosis includes pelvic endometriosis, adenomyosis, chronic pelvic inflammatory disease.
Q.49 To confirm the diagnosis what single investigation would be most valuable?
Ans.
- Diagnostic laparoscopy by double puncture procedure.
- Laparoscopy revealed the diagnosis (Fig. 1.6).
Q.50 Is this pathology going to affect her future fertility?
Ans. There is an association of pelvic endometriosis and infertility. Amongst the infertile patients, 15% 8suffer from endometriosis. Whereas patients with endometriosis suffer from infertility in 40–60% cases. The possible explanations are—anovulation, luteal phase defect, luteinized unruptured follicle syndrome, pelvic adhesions, dyspareunia, increased macrophage activity, altered prostaglandin balance and altered immune response.
Q.51 Should a patient with mild endometriosis be treated?
Ans. There is no advantage of any therapy over expectant management in cases with minimal or mild endometriosis. The association of infertility and endometriosis is not absolute unless there is tubal obstruction or extensive pelvic adhesions.
Q.52 What would be the appropriate treatment for this patient?
Ans. The content of chocolate cysts can be drained and the cavity is to be lavaged with normal saline. The lining of the cyst wall is then separated from the ovarian tissue. This may be done either by laparoscopy or by laparotomy. The principle of surgery is similar to ovarian cystectomy. Bleeding points are electrocoagulated by bipolar diathermy. In a small size chocolate cyst, the contents are aspirated and the cavity is irrigated repeatedly. This may be done under TVS guidance or laparoscopically under anesthesia.
Q.53 What is the overall result of laparoscopic cystectomy for endometrioma?
Ans. It is effective in relieving pain in about 74% of cases of mild to moderate disease. Pregnancy rate is about 60% in cases with moderate disease. However, improved pregnancy rate is observed within the first 6 months of conservative surgery.
CASE 4: PELVIC PAIN
Q.54 What are the common causes of acute pelvic pain in gynecology?
Ans.
- Acute pelvic inflammatory disease (PID)
- Ruptured chocolate cyst
- Twisted ovarian cyst
- Ruptured corpus luteum cyst
- Disturbed tubal ectopic pregnancy
- Ovarian hyperstimulation syndrome.
Q.55 What are the common causes of chronic pelvic pain?
Ans.
- Dysmenorrhea
- Premenstrual tension syndrome
- Pelvic endometriosis
- Ovarian remnant syndrome—trapped or residual ovarian syndrome
- Psychosomatic
- Pelvic vericosities
- Uterine fibroid
- Adenomyosis
- Ovarian cyst
- Pelvic inflammatory disease (PID) (chronic)
- Retroversion or prolapse of the uterus
Q.56 What are the causes of dyspareunia?
Ans. Superficial
- Narrow introitus
- Tough hymen
- Tender perineal scar
- Vulval infection
- Vulvar vestibulitis syndrome
- Vaginal—septum, infection, agenesis.
Deep
- Pelvic endometriosis
- Chronic PID
- Prolapsed ovary in the polycystic ovarian disease (POD).
Q.57 Mention some of the important causes of postmenopausal bleeding.
Ans.
- Senile endometritis
- Senile vaginitis
- Dysfunctional uterine bleeding
- Decubitus ulcer
- Genital malignancy:
- Carcinoma of the cervix, endometrium, vagina, vulva, fallopian tube
- Uterine sarcoma.
- Retained foreign body—pessary, IUCD (Fig. 1.7)
- Urethral caruncle
Fig. 1.7: Lippes loop. This has been removed from a 65-year-old lady hysteroscopically. She presented with postmenopausal bleeding. She had this at her age of 27 years. It was embeded within the endometrium and became brittle (arrows).
CASE 5: HYDATIDIFORM MOLE
Q.58 What is the provisional diagnosis?
Ans. Hydatidiform mole.
Q.59 What investigations should be done for her?
Ans. Ultrasonography of the uterus (Fig. 1.8) and urine or serum for β-hCG. Once the diagnosis is confirmed, other investigations are complete hemogram, ABO and Rh-grouping, LFT and X-ray chest and thyroid profile.
Fig. 1.8: Ultrasonography—snowstorm appearance in hydatidiform mole.Courtesy: Dr (Mrs) S Ghosh, Professor BN Chakravorty, IRM Kolkata, India.
Q.60 What is the initial management for this problem?
Ans.
- Correction of anemia with blood transfusion
- To prevent infection
- Suction and evacuation of the uterus with or without oxytocin drip should be done. Tissue should be sent for histological examination.
Q.61 What are the common complications of this problem?
Ans.
- Hemorrhage
- Infection
- Pre-eclampsia
- Perforation of the uterus
- Respiratory distress due to pulmonary embolization of trophoblastic cells
- Coagulation failure
- Development of choriocarcinoma (2–10% cases).
Q.62 How should this patient be followed up and for how long?
Ans. Serial urinary β-hCG estimation weekly till negative. Usually, it becomes negative by 4–6 weeks time. Once negative, she is followed up at every month with serum hCG report for 6 months to 1 year.
Q.63 What precautionary measures she should be advised while on follow-up?
Ans. She should avoid pregnancy for at least 6 months to 1 year. For contraception, she can use barrier methods. Combined oral pills (low dose) may be used following normalization of β-hCG.
Q.64 What are the reasons that the patient needs to be followed up following initial treatment?
Ans.
- Detection of cases with persistent trophoblastic disease.
- Early detection of choriocarcinoma.
Q.65 What is her prospect of future pregnancy and chance of recurrence of the problem?
Ans. Prospect of future successful pregnancy is high, provided she is followed up. The risk of recurrence is less than 5%.
Q.66 What is the karyotype pattern of a complete hydatidiform mole and that of a partial mole?
Ans. In complete moles—karyotype pattern in majority is normal—46XX (90%). There is fertilization of ‘an empty ovum’ by a single sperm carrying 23 chromosomes. The usual 46XX chromosome pattern is the result of doubling of the paternal set of chromosomes (Fig. 1.9).
In about 10% cases, an empty ovum is fertilized by two sperm (dispermy), one carrying X and the other carrying Y chromosome. The chromosomal pattern is 46XY. All the chromosomes are derived paternally.10
Partial moles (Fig. 1.10) consist of both the placenta and the fetus. Partial moles usually (90%) have triploid karyotype (Fig. 1.11). A normal ovum is fertilized by double sperm (dispermy), resulting in 69 chromosomes with sex chromosome configuration of 69XXX, 69XXY and 69XYY. The extra haploid set of chromosomes usually is derived from the father. The fetus is usually triploid, dies in the first trimester or is growth retarded with multiple malformations (syndactyly, hydrocephaly).
Fig. 1.10: Partial mole with a stillborn baby.Courtesy: Dr S Mitra, Professor, Department of G and O, KPC Medical College, Kolkata.
Fig. 1.11: Triploid chromosomal pattern of a partial mole. Genome is both paternal and maternal in origin.
CASE 6: CERVICAL FIBROID
Q.67 What is the diagnosis?
Ans. Posterior cervical fibroid.
Q.68 With what signs and symptoms she may have presented?
Ans. Vaginal discharge, pressure symptoms:
- Bowel: Constipation, incomplete evacuation.
- Urinary: Frequency, retention.
- Lateral pelvic wall pressure to cause leg pain or edema.
Q.69 What surgery had been done for her?
Ans. Total abdominal hysterectomy with bilateral salpingo-oophorectomy.
Q.70 What are the dangers of this operation?
Ans. Hemorrhage, injury to bladder, rectum and the ureter.
Q.71 How the dangers could be minimized?
Ans.
- Delineation of the course as well as the proximity of the ureters to the fibroid could be done preoperatively by intravenous urography.
- Ureteric catheterization may be done preoperatively as a precautionary measure.
- Enucleation of the myoma first followed by hysterectomy.
- Preoperative GnRH analog therapy for 3 months may facilitate surgery.
Q.72 What are the common causes of postmenopausal bleeding?
Ans. Senile vaginitis, senile endometritis, cervical carcinoma, endometrial carcinoma.
Q.73 What investigations should you organize for her?
Ans. Ultrasonography to assess endometrial thickness and/or any of the biopsy methods as:
- Pipelle endometrial biopsy
- Hysteroscopy and endometrial biopsy
- Fractional curettage and endometrial biopsy.
Q.74 What abnormality will guide her to go for hysterectomy?
Ans. Significant endometrial pathology and risks of endometrial carcinoma are as follows:
Type of endometrial hyperplasia and the risk of endometrial carcinoma.
Typical
- Simple (cystic without atypia): 1%
- Complex (adenomatous without atypia): 3%.
Atypical
- Simple (cystic with atypia): 8%
- Complex (adenomatous with atypia): 29%The risk of malignancy with atypical hyperplasia is high. This may necessitate hysterectomy.
She is aware of menopause and osteoporosis. She wants to know the following.
Q.75 Has she got any of the risk factors for osteoporosis?
Ans. Risk factors are:
- Family history
- Early menopause
- Low body weight
- Excess caffeine intake
- Smoking
- Sedentary habit or use of some drugs (corticosteroids).
Q.76 What preventive measures can she take to prevent osteoporosis?
Ans. Exercise, adequate dietary intake of calcium, vitamin D and nonhormonal treatment (biphosphonate) or HRT.
Q.77 What HRT would be appropriate for her?
Ans. If the uterus is intact, combined estrogen and progestin cyclically. Progestin is added for last 12–14 days of each month or she can have low dose estrogen and progestin combined and continuous. Otherwise, following hysterectomy she should take estrogen only. There is reduction in the risk of osteoporosis, coronary heart disease and colon cancer.
Q.78 What other benefits can she have with HRT?
Ans.
- Improvement of vasomotor symptoms (hot flushes, night sweats)
- Prevention of atrophic changes in the skin, genital and urinary tract epithelium
- Protection against cardiovascular disease
- Reduction in the problems of anxiety, insomnia, irritability and depression.
Q.79 Is there any risk for continuing HRT?
Ans. In a well-selected case, risks are generally less compared to the benefits. In most of the studies (WHO 2003, Million Women Study 2003), there is no increased risk of breast cancer when estrogen is only used (in a hysterectomized woman). Currently low dose estrogen (conjugated equine estrogen 0.3 mg or ethinyl estradiol 1 mg) is recommended. However, the woman needs to be counseled.
But regular breast self-examination (BSE) monthly, clinical breast examination (CBE) yearly and mammography yearly (ACOG-2000) should be carried out as a part of breast screening.
There is an increased risk of deep vein thrombosis (DVT) from 10 to 30 per 10,000 users.
Q.80 What are the contraindications of HRT?
Ans. Contraindications are:
- Undiagnosed genital tract bleeding
- Estrogen-dependent cancer in the body
- Active liver disease
- History of venous thromboembolism
- Gallbladder disease.
Q.81 What are different routes through which HRT can be administered?
Ans. HRT can be administered orally, through the skin as patches, gel, subcutaneous implant or nasal spray. It can also be administered by vaginal route as creams or pessaries. Use of oral route and the first pass liver metabolism has its beneficial effects on the lipoproteins.
Q.82 How long can HRT be taken?
Ans. The optimal duration of use for HRT is currently debatable. Small dose and short-term use for a period of 3–5 years has been recommended for bone protection.
CASE 8: PRIMARY AMENORRHEA
Q.83 What is most likely the diagnosis?
Ans. A case of vaginal agenesis.
Q.84 How do you define primary amenorrhea?
Ans. A young girl who has not menstruated by 16 years of age is defined as primary amenorrhea.
Q.85 When do you start investigations for primary amenorrhea?
Ans.
- No menstruation by the age of 16 years, when other secondary sex characters are normal.
- No menstruation by the age of 14 years when there is absence of growth and/or development of secondary sex characters.
Q.86 What are the factors essential for the onset and continuation of normal menstruation?
Ans.
- Normal female chromosomal pattern (46XX).
- Coordinated function of the hypothalamopituitary ovarian axis.
- Anatomical presence and patency of the outflow tract.
- Responsive endometrium.
- Active support of thyroid and adrenal gland.
Q.87 What is cryptomenorrhea?
Ans. It is a condition where the menstrual blood fails to come out from the genital tract due to an obstruction present in the passage.
Q.88 What are the common causes of cryptomenorrhea?
Ans.
- Congenital
- Imperforate hymen
- Transverse vaginal septum.
- Acquired
- Cervical stenosis following amputation
- Vaginal stricture following traumatic (instrumental delivery).
Q.89 What are the common causes of primary amenorrhea?
Ans.
- Hypogonadotrophic hypogonadism
- Delayed puberty
- Hypothalamic and pituitary dysfunction (stress, weight loss, anorexia nervosa)
- Kallmann syndrome
- CNS tumors—craniopharyngioma.
- Hypergonadotrophic hypogonadism
- Primary ovarian failure
- Galactosemia.
- Abnormal chromosomal pattern
- Turner's syndrome (45X)
- Various mosaic states (45X/46XX)
- Testicular feminization (46XY).
- Developmental defect of genital tract
- Müllerian agenesis (MRKH syndrome)
- Imperforate hymen
- Transverse vaginal septum
- Vaginal agenesis (Fig. 1.13).
- Thyroid and adrenal disorders
- Metabolic disorders (juvenile diabetes)
- Systemic illness (tuberculosis)
- Others: Uterine synechiae, unresponsive endometrium (receptor defect).
Q.90 What are the characteristic features of Mayer-Rokitansky-Kuster-Hauser syndrome?
Ans.
- Stature—average
- Breasts—normal
- Sexual hair—normal
- External genitalia—normal
- Internal genitalia:
- Vagina—absent
- Uterus—absent/rudimentary
- Ovaries—normal
- Karyotype—normal (46XX)
- IVP—Urinary tract abnormalities (30%)
- Primary amenorrhea.
Q.91 What are the characteristic features of Turner's syndrome?
Ans.
- Stature—short.
- Secondary sex character—poorly developed
- Shield chest
- Wide apart nipples
- Cubitus valgus
- Coarctation of aorta
- ‘Streak’ gonads
- Serum gonadotropins—high
- Karyotype: 45XO or 45XO/46XX (Fig. 1.14)
- Primary amenorrhea.
Q.92 What are the characteristic features of androgen insensitivity syndrome [testicular feminization syndrome (Fig. 1.15)]?
Ans.
- Stature—average
- Scanty pubic and axillary hair
- Breast development—normal
- Vagina—short and blind
- Uterus and tubes—absent
- Gonads—at labia or intra-abdominal or at inguinal region
- Gonadal biopsy—testicular tissue
- Serum testosterone—equal to normal males
- Karyotype: 46XY
- Primary amenorrhea.
Q.93 What are the characteristic features of adrenogenital syndrome? (Fig. 1.16)
Ans.
- Stature: Average
- Phenotypically: Normal female
- Labial fusion
- Enlargement of clitoris
- Uterus: Normal
- Ovaries: Normal
- Vagina: Normal
- Karyotype: 46XX
- Serum 17-OHP: Elevated
- Urinary pregnanetriol: Elevated
- Primary amenorrhea.
Fig. 1.15: Testicular feminization syndrome showing short and blind vagina, scanty pubic hair, clitoromegaly and labial gonads (arrows).
Fig. 1.16: A 14-month-old girl with adrenogenital syndrome showing labial fusion and enlarged clitoris. Congenital adrenal hyperplasia is commonly due to 21-hydroxylase deficiency.
CASE 9: SECONDARY AMENORRHEA
Q.94 What is her present problem?
Ans. Secondary amenorrhea.
Q.95 How do you define secondary amenorrhea?
Ans. It is the absence of menstruation for 6 months or more in a woman who has menstruated normally in the past.
Q.96 What are the common ‘uterine factors’ that may cause secondary amenorrhea?
Ans.
- Tubercular endometritis
- Synechiae
- Surgical removal (hysterectomy)
- Transcervical resection of endometrium (TCRE).
Q.97 What are the ‘ovarian factors’ that may cause secondary amenorrhea?
Ans.
- Polycystic ovarian syndrome
- Premature ovarian failure
- Surgical removal
- Radiation.
Q.98 Dysgenetic gonads are the common ‘hypothalamic factors’ that may cause secondary amenorrhea?
Ans.
- Stress
- Anorexia nervosa
- Strenuous exercise
- Trauma
- Infection (tuberculosis)
- Psychogenic drugs (phenothiazine)
- Tumors (craniopharyngioma, meningioma).
Q.99 What are the common causes of secondary amenorrhea?
Ans.
- Stress
- Polycystic ovary syndrome (PCOS)
- Premature ovarian failure
- Synechiae (Asherman's syndrome)
- Drugs (phenothiazine)
- Postpill amenorrhea.
Q.100 What is PCOS?
Ans. See Ch 8.
CASE 10: HEMATOCOLPOS (CRYPTOMENORRHEA)
Q.101 What is the diagnosis?
Ans. Imperforate hymen with hematocolpos.
Q.102 What other symptoms she might have?
Ans. Urinary retention, dysuria, lower abdominal heaviness and cyclical lower abdominal pain.
Q.103 What investigation you may do for her?
Ans. Ultrasonography of the lower abdomen to ascertain the extent of pathology, e.g., hematocolpos, hematometra, hematosalpinx.
Q.104 What would be the appropriate treatment for her?
Ans. Incision (cruciate) and drainage under general anesthesia, antibiotic coverage.
Q.105 What is the prospect of her future reproductive career?
Ans. Normal.
Ans. It is due to failure of disintegration of the central cells of the Müllerian eminence that projects into the urogenital sinus. Depending upon the amount of blood so collected, it may present with hematocolpos (blood in the vagina), hematometra (blood in the uterus) or hematosalpinx (blood within the fallopian tubes).
Q.107 What is crypyomenorrhea?
Ans. There is periodic shedding of the endometrium and bleeding but the menstrual blood fails to come out from the genital tract due to obstruction in the passage.
Q.108 What are the common causes?
Ans.
- Congenital:
- Imperforate hymen
- Transverse vaginal septum
- Vaginal atresia in the upper part
- Acquired:
- Stenosis of the cervix following amputation, conization
- Secondary vaginal atresia following difficult vaginal delivery.
CASE 11: INFERTILITY—A
Q.109 According to WHO, how the ovulatory disorders are classified?
Ans. Group I: Hypothalamic-pituitary failure (hypogonadotrophic hypogonadism).
Group II: Hypothalamic pituitary dysfunction (normogonadotrophic normogonadism).
Group III: Ovarian failure (hypergonadotropic hypogonadism).
Q.110 How the problems of anovulatory infertility is treated?
Ans. Induction of ovulation is done. Different drugs are used depending upon the response. Clomiphene citrate is the commonly used drug. It is usually prescribed 50 mg twice daily from D-3 to D-7 (5 days) of the cycle. Ovulation usually occurs 5–7 days after the last day of therapy.
Q.111 What are the indications of gonadotrophin therapy for induction of ovulation?
Ans. Women with infertility due to:
- Hypogonadotrophic hypogonadism (WHO group I)
- Women who have either failed or are resistant to clomiphene citrate (WHO group II)
- Women with unexplained infertility.
Q.112 When are GnRH analogs used for induction of ovulation?
Ans.
- Patients who are refractory to gonadotropins.
- Patients with elevated LH.
- Patients with premature ovulation due to premature LH surge.
- Patients with premature follicular luteinization.
Q.113 How do you manage the woman with WHO groups I, II or III ovulatory disorders?
Ans. WHO group I
- Gonadotropins: Follicle-stimulating hormone (FSH), LH.
- GnRH (pulsatile).
WHO group II
- Clomiphene citrate
- FSH
- For premature LH surges—GnRH agonist/antagonist
- For insulin resistance—insulin sensitizer
- Adrenal androgens—glucocorticoids.
WHO group III
- Cyclic hormone replacement therapy
- Gonadotropins—high dose
- Chance of spontaneous pregnancy—occasional
- Assisted reproductive technology (ART) (See Ch 23)
- Oocyte donation.
Q.114 What are the different types of surgery done for the management of infertility?
Ans. Surgery may be needed both for female as well as male factors for infertility.
For female
- Laparoscopic ovarian diathermy (drilling) (LOD).
- Wedge resection of ovary in cases with PCOS (not commonly done) (See Ch 54).
- Surgery for pituitary prolactinomas.
- Salpingo-ovariolysis—laparoscopically.
- Proximal tubal block: Cannulation and balloon tuboplasty: This is done under hysteroscopic guidance.
- Midtubal block: Recanalization procedure (reversal of tubal ligation).
- Distal tubal block:
- Fimbrioplasty
- Neosalpingostomy
- Tubal reconstruction (tuboplasty) following sterilization operation.
Q.115 What is assisted reproductive technology (ART)? What are the different methods of ART?
Ans. ART encompasses all procedures that involve manipulation of gametes and embryos for the treatment of infertility. For the rest (See Ch 23).
Q.116 What are the indications of in vitro fertilization-embryo transfer (IVF-ET)?
Ans.
- Tubal disease
- Unexplained infertility
- Endometriosis
- Male factor infertility
- Cervical hostility
- Failed ovulation induction.
Q.117 What are the indications of intrauterine insemination (IUI)?
Ans.
- Cervical stenosis
- Immunological factors for infertility (male and female)
- Oligospermia or asthenospermia
- Unexplained infertility.
Ans.
- Down regulation using GnRH analog
- Controlled ovarian stimulation (COS)
- Monitoring of follicular growth
- Oocyte retrieval
- Fertilization in vitro [IVF, intracytoplasmic sperm injection (ICSI)]
- Transfer of gametes or embryos
- Luteal support with progesterone.
Q.119 How is the monitoring of follicular growth done?
Ans. It is done by:
- Sonographic (TVS) measurement of follicular diameter
- Serum estradiol level 3 or more follicles > 18 mm in diameter and serum E2 levels: 100–150 pg/mL/follicle is optimum. Injection hCG 5000–10,000 IU is given IM. Oocytes are retrieved 36 hours after hCG administration.
Q.120 What is the procedure for embryo transfer?
Ans. Transfer is done at 4–8 cell stage (48–72 hours later) transcervically. Usually two embryos are transferred.
Q.121 What is ovarian hyperstimulation syndrome (OHSS)?
Ans. It is characterized by multiple follicular development and ovarian enlargement following hCG stimulation. It may be a serious complication.
It is clinically manifested by bilateral ovarian enlargement, abdominal pain, nausea, vomiting, ascites, hypotension, hemoconcentration, oliguria, disseminated intravascular coagulation (DIC), thrombosis and sometimes adult respiratory distress syndrome.
Q.122 How can OHSS be prevented and managed?
Ans. See Dutta's Textbook of Gynecology, 8th Edition, p. 444.
Q.123 How endometrial receptivity could be improved in an IVF cycle?
Ans. Exact understanding of endometrial receptivity is lacking. Importance of many adhesion molecules (integrins) have been considered. However supplemental progesterone therapy is started after oocyte retrieval in all IVF programs as a routine. This is mainly because GnRH analog use and oocyte aspiration impair the secretion of endogenous progesterone from the ovary (corpus luteum).
Q.124 How is egg retrieval done in an IVF cycle?
Ans. Ultrasound-guided needle aspiration of oocyte through the vagina is done. This is done under IV sedation. The complications may be injury to bowel, bladder or infection.
Q.125 How can a man without any sperm to ejaculate, father children?
Ans. ICSI is the optimum procedure for this man, if he can produce sperm on testicular biopsy. ICSI is also helpful to men with congenital absence of vas deferens.
Q.126 Should a woman with hydrosalpinx be considered for IVF-ET?
Ans. IVF is considered to bypass the function of the blocked tubes. But presence of hydrosalpinges causes implantation failure with reduced pregnancy rate in IVF cycles. So, it is recommended to remove the tubes (prophylactic salpingectomy) prior to IVF in these women. The tubes may be clipped laparoscopically to get the same benefits.
CASE 12: INFERTILITY—B
Q.127 What is this investigation?
Ans. Hysterosalpingography.
Q.128 What is the pathology revealed by the procedure?
Ans. Bilateral hydrosalpinx without any spillage of dye.
Q.129 What is the basic pathology for this abnormality?
Ans. In majority, it is the sequelae of ascending infection from the lower genital tract. Chlamydia trachomatis (85%), N. gonorrhoeae and other pyogenic infections (E. coli) are responsible. Mixed infections (aerobic and anaerobic) are more common. Infection and inflammation cause destruction of tubal epithelium and pus formation known as pyosalpinx. There is 18peritubal adhesion formation and agglutination of the fimbriae. Gradually when the inflammation subsides, the pus settles down and the tube is filled with a clear fluid called hydrosalpinx. The tube is dilated, retort-shaped with closed abdominal ostium.
Figs. 1.19A and B: (A) Laparoscopic fimbrioplasty by introducing the closed forceps within the closed ostium; (B) The phimotic ostium is opened up and the fimbrial folds are released by opening up the forceps blades.
Q.130 Is there any other method of evaluation?
Ans. Diagnostic laparoscopy and chromopertubation under general anesthesia. It may reveal tubal edema, hyperemia, dilated tubes (hydrosalpinx), fimbrial adhesion and/or peritubal adhesions.
Q.131 What are the treatment options that may resolve her problem of infertility?
Ans. Tubal reconstructive surgery (tuboplasty) may be attempted. This may be in the form of releasing the peritubal adhesions (adhesiolysis) and/or opening up the fimbrial end (fimbrioplasty or salpingostomy). As the tubal epithelium is often destroyed, the results of such operations are not always successful. Pregnancy rate following laparoscopic fimbrioplasty is 30–35%. Ectopic pregnancy rate is 5–10% (Figs. 1.19A and B).
Q.132 What other options are left to her?
Ans. Assisted reproduction—IVF-ET.
Q.133 What are the different methods of assisted reproductive technology that you know?
Ans.
IVF–ET: In vitro fertilization and embryo transfer GIFT: Gamete intrafallopian transfer ICSI: Intracytoplasmic sperm injection TESE: Testicular sperm extraction MESA: Microsurgical epididymal sperm aspiration PESA: Percutaneous epididymal sperm aspiration |
CASE 13: HYSTERECTOMY AND OOPHORECTOMY
Q.134 What are the risks of bilateral oophorectomy during hysterectomy?
Ans. Risks are mainly due to loss of endocrine function of the ovaries. Loss of estradiol function is significant. Moreover, ovarian stroma secretes androgen precursors which are converted to estrogen in adipose tissue (peripheral endocrine organs). Major health hazards following oophorectomy are osteoporosis, fracture and cardiovascular risk. Additional morbidities are due to atrophy of the genital and urinary organs (dyspareunia, dysuria), vasomotor instability (hot flushes) and psychological disturbances (irritability, insomnia, mood swing).
Q.135 What are the benefits of doing bilateral oophorectomy during hysterectomy?
Ans. Bilateral oophorectomy protects the woman against the risks of developing ovarian cancer (100%) and peritoneal cancer (95%). It reduces residual ovarian syndrome (3–5%) and risks of relaparotomy (5–10%) for any benign or malignant ovarian lesions. It also reduces the risk of breast cancer by 50%. It eliminates the problems of chronic pelvic pain and dyspareunia.
Q.136 What is the risk of age (46 years in this case) in developing ovarian cancer?
Ans. Yes, this age has its own independent risk. The current information about the age and the risk of ovarian cancer as follows:
Age < 40 years = infrequent; age 40–45 years = 15–16/100,000; age 60–70 years = 57/100,000 and the median age for ovarian cancer is 63 years.
Q.137 What are the benefits and risks of hysterectomy alone in relation to ovarian cancer and menopause problems?
Ans. The current information in this regard is, a woman who had undergone hysterectomy alone had a long-term reduced risk of epithelial ovarian cancer. However, hysterectomy is associated with earlier onset of menopause (3.7–4.4 years) even if the ovaries are preserved.
Q.138 What is familial ovarian cancer and how common it is?
Ans. Mutations of certain genes (BRCA1 and BRCA2) are associated with higher risk of ovarian and breast cancers. However, of all the epithelial ovarian cancers 1 out of 10 is hereditary. Familial ovarian cancer has an earlier onset of disease.
Q.139 Is there any current guidelines for prophylaxis of oophorectomy during hysterectomy?
Ans. Nothing is specifically recommended till date. It should be based on individual woman's risk and the family history. However, prophylactic oophorectomy during hysterectomy is performed at a median age of 48 years or 5 years before the index case with the family history of ovarian cancer whichever is earlier. Once oophorectomy is done, management of surgical menopause with nonhormonal or hormonal method should be considered.
All these needs informed consent of the individual concerned.
CASE 14: POSTMENOPAUSAL BLEEDING
Q.140 What are the common causes of PMB?
Ans. In the developing countries including India genital malignancy particularly carcinoma cervix is the most common cause of PMB. Other causes are:
- Atrophic endometritis
- Endometrial hyperplasia
- Endometrial polyps
- Dysfunctional uterine bleeding (DUB)
- Decubitus ulcer
- Retained (forgotten) pessary or IUCD (Fig. 1.20)
- Endometrial carcinoma.
Q.141 Who are the high-risk women to develop endometrial carcinoma?
Ans.
- Unopposed estrogen stimulation
- Delayed menopause
- Hypertension
- Diabetes
- Overweight (50 pounds overweight increases the risk by 10 times)
- Nulliparity
- Tamoxifen therapy
- Family history of endometrial, breast, ovary or colon carcinoma.
Fig. 1.20: Rubber ring pessary. This had been removed from a 70-year-old woman. She presented with postmenopausal bleeding. She had been using this for last 20 years. This forgotten pessary caused ulceration and infection in the vagina. Crust had been formed on its surface due to its prolonged stay in the vagina.
Q.142 What is the significance of family history?
Ans. Lynch II syndrome is observed in about 2% of all such cases of hereditary cancers. Such families display high incidence of hereditary nonpolyposis colorectal cancer (HNPCC), adenocarcinoma of ovary, endometrium, stomach, small bowel and the urinary tract. It is associated with mutations in the DNA mismatch repair (MMR) genes (MSH2, MLH1, PMS1 or MSH6).
Q.143 What is the current change in the trends of diagnosis of endometrial cancer?
Ans. Most gynecologists recommend outpatient endometrial biopsy to confirm the diagnosis. Diagnostic accuracy of outpatient endometrial biopsy using pipelle endometrial sampler is 90–98%. Besides pipelle endometrial sampler, Sherman curette, transvaginal ultrasonography, sonohysterography, hysteroscopy and directed biopsy are also used.
Q.144 What is the place of different procedures in the diagnosis of endometrial carcinoma?
Ans. Fractional curettage is a definite diagnostic procedure for endometrial cancer but it is invasive. Role of hysteroscopy in the diagnosis has certain advantages. To date, there is no universal agreement to the cut-off measurement of endometrial thickness to diagnose endometrial cancer. Endometrial thickness less than or equal to mm in a postmenopausal woman is commonly due to atrophy.
- Hysteroscopy is more accurate in detecting polyps or submucous fibroids. It helps to see the pathologic lesion as to take direct biopsy. It also helps to evaluate the endocervical canal.
- Saline infusion sonography (SIS) is helpful in differentiating patients with minimal endometrial tissue from patients with thickened endometrium or polyps.
- Fractional curettage is mandatory if endometrial sampling procedures fail to provide sufficient material for diagnostic evaluation or when the symptoms are persistent in spite of negative endometrial sampling.
- Considering the benefits most clinics prefer to do outpatient (office) endometrial biopsy as a first diagnostic step. When biopsy result is negative and further evaluation is needed, hysteroscopy and biopsy is done.
Q.145 What are the characteristics of type I and type II endometrial carcinoma?
Ans. Differentiating features of type I and II endometrial carcinoma
Clinical characters | Type I | Type II |
|---|---|---|
Risk factor | Unopposed estrogen | Age |
Occurrence | Common (85%) | Less common |
Predisposing factor | Hyperestrogenic state | No such |
Precursor endometrium | Atypical hyperplasia | May be atrophic |
Age | Young (perimenopause) | Older (postmenopause) |
Endometrial hyperplasia | Present | Absent |
Tissue differentiation | Well | Poor |
Myometrial invasion | Minimal | Deep |
Histology | Endometrioid | Serous, clear |
Molecular characters | ||
Ploidy | Polyploid | Aneuploid |
HER2/neu overexpression | No | Yes |
P-53 | No | Yes |
PTEN mutations | Yes | No |
Prognosis | Favorable | Not favorable |
Q.146 Are all endometrial cancers due to estrogenic stimulation?
Ans. Currently, two pathogenic types of endometrial carcinoma are being observed.
21Type I: The majority (75–85%) belong to this group. Women having a persistent stimulation of endometrium with unopposed estrogen either endogenous or exogenous, run the risk of developing type I endometrial carcinoma.
Type II: Women with type II develop endometrial carcinoma without any estrogenic stimulation. Carcinoma develops not from the background of endometrial hyperplasia but may arise from an atrophic endometrium.
Estrogen dependent tumors develop in relatively younger perimenopausal women as opposed to the estrogen independent tumors that occur in older postmenopausal women. Tumors that are estrogen dependent have favorable prognosis compared to estrogen independent tumors. Based on molecular genetic studies, these two types of tumors have different pathogenetic pathways.
Q.147 What is the current situation of TVS, CT and MRI in the evaluation of endometrial cancer?
Ans. MRI is found to be superior to conventional CT in the assessment of depth of myometrial invasion. Studies have shown diagnostic accuracy of TVS is about the same (68–69%) compared to T2-weighted MRI (68–74%) in evaluating myometrial invasion. However, contrast enhanced MRI is always superior to TVS and is found to be better when compared to CT even.
The accuracy of MRI in staging endometrial carcinoma has been reported to be 85% overall. Gadolinium enhanced images significantly improve accuracy.
There are certain clinical situations where assessment of endometrial carcinoma may be difficult (e.g., obesity) or may not be possible (e.g., contraindications for surgical staging or because of tumor spread). In such situations MRI has got distinct advantages to evaluate the disease.
Suggested Reading
- Walker JL, Piedmonte MR, Spirots NM, et. al. Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2. JClin Oncol. 2009;27:5331–6.
CASE 15: CARCINOMA CERVIX—A
Q.148 Clinically, what are the different types of the lesion?
Ans. (i) Exophytic, (ii) Ulcerative, and (iii) Infiltrative.
Q.149 Histopathologically, what are the different types of carcinoma cervix?
Ans. (i) Squamous cell carcinoma (75–80%), (ii) Adenocarcinoma (20–25%), (iii) Adenosquamous carcinoma, (iv) Neuroendocrine tumors, and (v) Others: Lymphomas.
Q.150 What are the different modes of spread in carcinoma cervix?
Ans.
- Direct extension (parametrium, endocervix, vagina, bladder)
- Lymphatics (pelvic and para-aortic)
- Direct implantation
- Bloodstream (lung, mediastinum, bone, liver).
Q.151 What are the complications that may arise in a case with carcinoma cervix?
Ans.
- Hemorrhage
- Pain in the loin due to pyelitis, pyelonephritis
- Vesicovaginal fistula
- Rectovaginal fistula
- Uremia
- Sepsis.
Q.152 What are the advantages of radiotherapy as a primary modality of therapy?
Ans.
- Wider applicability in all stages of carcinoma cervix.
- Survival rate of radiotherapy (85%) is comparable to that of surgery in early stages.
- Less primary mortality or morbidity.
22Q.153 Mention the different types of hysterectomy that can be done for the management of microinvasive and early invasive carcinoma cervix?
Ans. Classification of extended hysterectomy (ACOG–1974).
Rutledge's classification of extended hysterectomy (1974)
Class | Description | Indication |
|---|---|---|
I | Extrafascial hysterectomy; pubocervical ligament is incised, allowing lateral deflection of the ureter | CIN, early stromal invasion |
II | Removal of the medial half of the cardinal and uterosacral ligaments; upper third of the vagina | Microcarcinoma post-irradiation |
III | Removal of the entire cardinal and uterosacral ligaments; upper third of the vagina removed | Stage IB and stage IIA tumors |
IV | Removal of all periureteral tissue, superior vesical artery and three-fourths of the vagina | Anteriorly occurring central recurrences |
V | Removal of portions of the distal ureter and bladder | Central recurrent cancer involving bladder and ureter |
Q.154 What are the preventive measures against carcinoma cervix?
Ans. Primary prevention
- Identifying and preventing the high-risk factors: Preventing human papillomavirus (HPV) infection with HPV vaccine to all school girls (9–15 years).
Other risk factors (cofactors) to avoid are:
- Early sexual intercourse
- Early age of first pregnancy
- Multiple partners
- Too many births and too frequent births
- Poor local hygiene.
Secondary prevention:
- Screening against carcinoma cervix: cytology (liquid-based cytology), HPV testing (hybrid capture II), visual inspection with acetic acid (VIA), colposcopy and biopsy.
- ‘Down staging screening’ by WHO—intends to diagnose the disease early and to minimize cancer death.
Q.155 What is the role of HPV in the pathogenesis of carcinoma cervix?
Ans. HPV is a DNA virus which is epitheliotropic. High oncogenic risk HPV (types 16, 18, 31, 33, 35, 45, 56) types are responsible in the etiopathogenesis of cancer cervix (Fig. 1.22).
Fig. 1.22: Pathogenesis of HPV infection showing normal stratified squamous epithelium on the left and its progression to CIN/CIS and invasive on the right. The grades of CIN (I to III), CIS and the invasive carcinoma are shown.
Over 99.7% of patients with CIN and invasive cancer are found to be positive with HPV-DNA. Infection always starts at the transformation zone (TZ) of the squamocolumnar junction (SCJ). Once the high-risk oncogenic HPV-DNA integration occurs within human (host) genome (infection), there is overexpression of E6 and E7 oncoproteins. These oncoproteins suppress the tumor suppressor genes [P-53 and retinoblastoma (Rb)]. This results in neoplastic transformation of the mitotically active metaplastic epithelium of the ‘transformation zone’ at 23the level of SCJ (See Dutta's Textbook of Gynecology, 8th Edition, p. 269). Normally the tumor suppressor gene P-53 will cause infected cell death by apoptosis and thus halting the viral multiplication. But these oncoproteins cause proteolytic degradation of P-53, resulting in cell immortalization and viral multiplication. Currently, HPV vaccines are available. Vaccines are very effective in preventing infection with HPV. Vaccines (Cervarix, Gardasil) are approved to all school girls (9–15 years) and women (16–26 years). Immunity persists for about 5–7.5 years. Vaccines are type specific and effective only when used prophylactically. Currently nonvalent vaccines are available. Single dose vaccine may be used and is found to be effective (61.6%).
Q.156 What are the advantages of surgery in the management of carcinoma cervix, over radiotherapy?
Ans.
- Thorough surgicopathological staging during surgery.
- Accurate prediction of survival rate by para-aortic and pelvic node assessment surgically.
- Preservation of ovarian function when desired.
- Retention of more functional and pliable vagina.
- Transposition of ovaries when needed for consideration of future radiotherapy.
- Psychological benefit of the woman.
Q.157 What is neoadjuvant chemotherapy and what are the benefits?
Ans. Platinum-based combination chemotherapy is given for three cycles. This is followed by radical hyterectomy and pelvic lymphadenectomy. Neoadjuvant chemotherapy improves the resectibility of bulky (4 cm) disease (stage IB2 and stage IIA).
Q.158 What is concurrent chemoradiation?
Ans. It is the combined therapy with radiation and weekly cisplatin-based combination chemotherapy. This therapy is found helpful as a primary treatment for stage IB, IIA or advanced stage (IIB to IVA) disease.
Q.159 How the radiation dose is calculated in the management of cancer cervix?
Ans. Radiation dose is calculated with respect of radiation received at two arbitary points—point A and point B.
- Point A is 2 cm cephalic and 2 cm lateral to the external os. It is the point of crossing of the uterine artery and ureter.
- Point B is 2 cm cephalic and 5 cm lateral at the same plane. It is approximately the site of obturator node.
- Point A gets about 7000–8000 cGy and point B 2000 cgy from radium (brachytherapy). Cancerolytic dose is approximately 7000–75000 cGy. The rest of the dose at point B is supplemented by external beam radiation.
Q.160 What is the overall 5 years survival rate following therapy in a woman with carcinoma cervix?
Ans.
STAGES | 5 years survival rate (%) (International Federation of Gynecology and Obstetrics) | |
|---|---|---|
IA1 IA2 | 98.7 95.9 | The overall 5 years survival for all the stages is 1.9% Important prognostic factors are: tumor volume, lymph node metastasis, parametrial invasion and lymphovasular space invasion |
IB1 IB2 | 88.0 78.8 | |
IIA IIB | 68.8 64.7 | |
IIIA IIIB | 40.4 43.3 | |
IVA IVB | 19.5 15 | |
Q.161 How cervical cancer screening could be organized in a low-resource setting?
Ans. Cytology based cervical cancer screening program (India, Pacific islands) could not be successful, in many countries of the world, as it requires a number of procedures. Alternative cervical cancer screening strategies in low resource settings can have a consistent and significant impact to improve upon the burden of cancer deaths.
Recommendations (ACOG-2015): The following are the acceptable alternatives where cytology based screening is not feasible or practical.
- HPV testing and follow-up treatment for woman with positive test results.
- In settings where HPV-DNA is not available, visual inspection with acetic acid followed by treatment with cryotherapy to be done. Cryotherapy should not be done in women where squamocolumnar junction is not entirely visualized. It has been established with a prospective randomized study in rural India that a single life time HPV-DNA screening test can reduce cervical cancer mortality and late stage disease by about 50%.
Q.162 Discuss the sensitivity of different screening procedures to detect CIN2+.
Ans. Sensitivity of screening to detect CIN2+
Test | Sensitivity (%) |
|---|---|
1. Conventional pap | 55–82 (63) |
2. Liquid-based cytology | 57–90 (74) |
3. VIA | 41–79 (60) |
4. HPV | 94–98 (96) |
5. HPV + Pap test | 99–100 (99+) |
Ans.
ROAD TO ‘ELIMINATE’ CERVICAL CANCER | |||
|---|---|---|---|
THRESHOLD: All countries to reach < 4 cases 100,000 women-years | |||
2030 control targets | |||
90% of girls fully vaccinated with HPV vaccine by 15 years of age | 70% of women screened with an high precision test at 35 and 45 years of age | 90% of women identified with cervical disease receive treatment and care | 30% reduction in mortality from cervical cancer |
SDG 2030: Target 30% reduction in mortality from cervical cancer | |||
The 2030 targets and elimination threshold are subject to revision depending on the outcomes of the modeling and the WHO approval process. | |||
Q.164 What are the aims of palliative treatment? What different palliative treatments can be given to a woman with carcinoma cervix?
Ans. Palliative treatment is aimed to provide comprehensive care for relief of symptoms along with treatment of the cancer, in the advanced stage.
Palliative treatment is given:
- To control vaginal discharge
- To control hemorrhage
- To relief pain.
Discussion continued: Case 16.
Suggested Reading
- Clavel C, Masure M, Bory JP, Putaud I, Mangeonjean C, Lorenzato M, et al. Human papillomavirus testing in primary screening for the detection of high-grade cervical lesions: a study of 7932 women. BJC. 2001;89:616.
- Cuzick J, Clavel C, Petry KU, et al. Overview of the European and North American studies on HPV testing in primary cervical cancer screening. IJC. 2006;119:1095-101.
- Ronco G, Segnan N, Giorgi-Rossi P, et al. Human papillomavirus testing and liquid-based cytology: results at recruitment from the new technologies for cervical cancer randomized controlled trial. JNCL. 2006;98:765-74.
- Sangrajrang S, Laowahutanont P, Wongsena M, Muwonge R, Karalak A, et al. Comparative accuracy of Pap smear and HPV screening in Ubon Ratchathani in Thailand. Papillomavirus Res. 2017;3:30-35.
- Sankaranarayanan R, Gaffikin L, Jacob M, Sellors J, Robles S. A critical assessment of screening methods for cervical neoplasia. Int J Gynaecol Obstet. 2005;89(Suppl 2):S4-S12.
- Sankaranarayan R, Nene BM, Shastri SS, et al. HPV screening for cervical cancer in rural India. N Engl J Med. 2009;360:1385-94.
- Srivastava AN, Misra JS, Srivastava S, Das BC, Gupta S. Cervical cancer screening in rural India: Status and current concepts. IJMR. 2018;148(6):687-96.
CASE 16: CARCINOMA CERVIX—B
Q.165 What is the stage IIA carcinoma cervix?
Ans. Carcinoma of the cervix extending downwards up to upper two-third of the vagina but not laterally (without parametrial invasion).
It is subdivided into:
IIA1: Clinically visible lesion less than or equal to 4.0 cm in greatest dimension.
IIA2: Clinically visible lesion greater than 4 cm in greatest dimension.
Fig. 1.23: Carcinoma cervix—radical hysterectomy done. Tied ends of uterine arteries are seen as they were dissected out and severed from the origin.
Q.166 What does this radical hysterectomy mean?
Ans. Removal of the uterus, cervix, upper vagina, parametrium, pelvic lymph nodes. Para-aortic node sampling is also done.
Q.167 What are the important complications of the operation?
Ans. Anesthetic complications and complications due to surgery: hemorrhage, injury to bladder, bowel, ureters, infection, intestinal obstruction and lately fistula and lymphocyst formation.
Ans. Progression of the disease and the problems of bleeding, sepsis, metastases, cachexia and renal failure (uremia).
Q.169 What is the long-term outcome following the operation?
Ans. If the nodes are not involved, 5-year survival rate is about 80%. On the other hand 5-year survival rate is about 50% if nodes are involved.
Q.170 Is there any alternative method of treatment?
Ans. Radiotherapy (combined teletherapy and brachytherapy) has got equal survival rate for this stage. Chemoradiation therapy is also effective. (See Dutta's Textbook of Gynecology, 8th Edition, p. 295).
Q.171 What is the place of fertility sparing surgery for carcinoma cervix?
Ans. Fertility-preserving surgery for carcinoma cervix is done in highly selected women (See Ch 39).
Indication: Woman keen to preserve her fertility and has no other factor for infertility.
Case selection criteria
- Early stage disease (See Dutta's Textbook of Gynecology, 8th Edition, p. 295)
- Woman is strongly motivated for follow-up
- Invasive disease has been excluded on thorough examination
- Tumor is not a highly aggressive histologic subtype (neuroendocrine tumor).
Stage (FIGO) of the disease and the type of operation
Stage (FIGO) | Operation (fertility preservation) |
|---|---|
|
|
Q.172 What are the serum tumor markers of carcinoma cervix?
Ans. Serum tumor markers are valuable for predicting the prognosis, the response to treatment and also the risk of recurrence. In carcinoma cervix, the role of serum tumor markers in predicting 5-year survival rate is limited.
The most commonly studied tumor markers are:
- Squamus cell carcinoma antigen (SCCA)
- Cancer antigen 125 (CA 125)
- Cytokeratin fragment 19 (CYFRA 21.1).
- Raised levels of SCCA, CYFRA 21.1 and CA 125 have been observed in 20–88% of women with cervical cancer. Raised levels are correlated with tumor stage, tumor volume, cervical stromal invasion, lymphovascular space invasion, parametrial involvement and lymph node metastasis.
Q.173 What is the role of radiographic studies in tumor evaluation?
Ans. According to FIGO, radiographical studies such as CT, PET, combined PET/CT and MRI may be used to determine the extent of the disease within the pelvis, lymph nodes, for evaluation of prognosis and risk of recurrence following of initial treatment. However, imaging and pathology can be used, where available. In that case, adding notation of r (imaging) and p (pathology) has to be made.
- MRI is more accurate to determine tumor diameter, uterine extension and parametrial involvement compared to CT or clinical examination.
- PET/CT is more valuable to evaluate nodal metastases.
- Dynamic contrast-enhanced MRI can evaluate tumor vascularity and perfusion. [18F] fluorodeoxyglucose PET: PET/CT can evaluate intratumoral metabolic actively. All these can predict response to therapy. Discussion continued: Case 17.
CASE 17: CARCINOMA CERVIX—C
Q.174 What is stage IA carcinoma cervix?
Ans. Carcinoma strictly confined to the cervix and that is in the preclinical stage. It is diagnosed by biopsy only.
Q.175 Is there any subdivisions of the stage?
Ans. Yes, stage IA1: When there is minimal microscopically evident stromal invasion < 3.0 mm in depth.
Stage IA2: Microscopically measured stromal invasion > 3 mm but < 5 mm.
Ans. It is entirely related to spread of the disease and hence directly related to the prognosis and survival outcome.
Q.177 What is the approximate rate of lymph node involvement in this stage and 5-year survival rate?
Ans. Pelvic nodes involvement for stage IA1 (< 3 mm) is 0–0.5% and for stage IA2 (3–5 mm) is 5–6%. The risk of para-aortic nodes involvement is 0 and 1%, respectively. 5-year survival rate for stage IA1 is 98.7% and for stage IA2 is 95.9% respectively. (See Dutta's Textbook of Gynecology, 8th Edition, p. 296).
Q.178 What are the treatment options for this woman?
Ans. Either extrafascial hysterectomy (type I) or modified radical hysterectomy (type II) should be optimum for her depending on whether she belongs to stage IA1 or stage IA2.
Q.179 What is meant by type I and type II hysterectomy?
Ans. Type I: Extrafascial hysterectomy; the pubocervical ligament is incised allowing lateral deflection of the ureter.
Type II (modified radical): Here medial half of the Mackenrodt's and uterosacral ligaments along with selective (clinically enlarged and palpable) lymph nodes are removed. Upper third of vagina is also removed.
Q.180 Can she have any surgery preserving her fertility status?
Ans. Yes, such treatment can be provided in exceptional circumstances only. Therapeutic conization is the option that she can have. In that case, she must realize the need of long-term follow-up. She should be followed up with cytology and colposcopy regularly.
Laparoscopic-assisted radical vaginal trachelectomy with pelvic and aortic lymphadenectomy (LARVT) is also recommended currently for early stage (IA2 and IB1) disease. This is done only for a strongly motivated woman who wants to preserve her fertility (See Dutta's Textbook of Gynecology, 8th Edition, p. 295).
In either of the above treatment options, the surgical margin must be free of disease.
Q.181 What is radical trachelectomy?
Ans. It involves removing the cervix, parametria and cuff of vagina. Body of the uterus is preserved for fertility. This procedure is combined with either extraperitoneal or laparoscopic pelvic lymphadenectomy.
Q.182 What is concurrent chemoradiation?
Ans. Cisplatin-based concurrent chemoradiation is currently recommended as a treatment option of carcinoma cervix. It acts as a radiosensitizer and reduces disease progression. The appropriate cases for this treatment are: (i) Early stage (stages IA2, IB, IIA) disease after radical hysterectomy, (ii) Locally advanced (stages IIB to IVA) disease as a primary therapy.
CASE 18: CARCINOMA ENDOMETRIUM
Q.183 What are the important etiological factors for endometrial carcinoma?
Ans.
- Unapposed estrogen stimulation
- Age: 50–60 years
- Parity—nulliparity
- Late menopause
- Corpus cancer syndrome (obesity, hypertension and diabetes)
- Overweight (21–50 pounds overweight increases the risk 3 times)
- Tamoxifen therapy
- Positive family history
- Endometrial hyperplasia.
Fig. 1.24: Following surgery, uterus of the same woman is cut open to show a diffused and ulcerated growth at the fundus. The growth is seen to invade the myometrium. Histology confirmed adenocarcinoma
Q.184 What is the common histological type of endometrial carcinoma?
Ans. Adenocarcinoma.
Q.185 What are the high-risk factors for endometrial carcinoma?
- Persistent and unopposed estrogen stimulation of endometrium
- Corpus cancer syndrome—obesity, hypertension and diabetes
- Endometrial hyperplasia
- Family history of colon, ovarian or breast cancer.
Q.186 How can be endometrial carcinoma diagnosed?
Ans.
- History and clinical examination: A case of postmenopausal bleeding is considered due to endometrial carcinoma unless proved otherwise.
- Endometrial biopsy (pipelle) diagnostic accuracy is 90–98%.
- Papanicolaou smear (unreliable) as diagnosis accuracy is only 30%.
- Ultrasonography (TVS) including color Doppler, endometrial thickness > 4 mm with increased vascularity is suggestive.
- Endometrial thickness ≥ 13 mm is strongly suggestive.
- Hysteroscopy helps in detecting polyps or submucous myomas.
- Fractional curettage is the definitive method of diagnosis in case where adequate evaluation is not possible with pipelle biopsy specimen or where bleeding recurs after a negative endometrial biopsy.
- CT and MRI, both can detect myometrial invasion, lymph node involvement and also the spread of the disease. MRI is superior to CT (Figs. 1.25A and B).
Figs. 1.25A and B: (A) Magnetic resonance image (MRI) in the sagittal plane of a 55-year-old woman with endometrial carcinoma. Sagittal T1-weighted image shows endometrial tumor with invasion to the myometrium, more than 50%. There is extension of the cancer to the cervix (see arrows); (B) Magnetic resonance image (MRI) in the axial view of the same woman with endometrial carcinoma. Invasion to the myometrium, more than 50% is seen.Courtesy: Department of Obstetrics and Gynecology and Department of Radiology, Assam Medical College, Dibrugarh, Assam, India.
Q.187 Describe orderly the steps of fractional curettage.
Ans.
- Endocervical curettage
- Dilatation of internal os
- Introduction of a polyp forceps to remove any polyp
- Uterine curettage (1) Uterine fundus, and (2) body of the uterus
- Specimens, so obtained are sent for histology separately.
Q.188 Mention the important surgical procedures for the management of a case of endometrial carcinoma.
Ans. In stage I: Extrafascial hysterectomy, bilateral salpingo-oophorectomy.
Procedures
- Incision—longitudinal
- Peritoneal washings for cytology
- Thorough exploration of pelvic and abdominal organs including the pelvic and para-aortic lymph nodes
- Extrafascial hysterectomy (TAH and BSO) is done
- Uterus is cut open in the theater for tumor evaluation (gross examination or frozen section)
- Lymph node sampling—pelvic and para-aortic nodes are done when there is myometrial invasion (See Ch 33 and 34).
CASE 19: CARCINOMA OF THE OVARY
Q.189 What are the reasons for failure to improve the outcome of ovarian cancer?
Ans.
- No high-risk factor is known
- Deep-seated organs—diagnosis is often late
- No effective preventive measures
- No preinvasive stage of the disease
- No effective screening procedure for early detection
- Spread of the disease is unrelated to the size of the mass and or symptoms of the woman
- Limitations of cytoreductive surgery, chemotherapy and radiation therapy.
Figs. 1.26A and B: (A) Gross photograph of a surgical specimen showing the uterus with a huge ovarian tumor. The other tube and the ovary are seen. Stretched fallopian tube over the tumor is seen; (B) The cut section of the same ovarian tumor to show the solid areas (see arrows). Histology revealed serous cyst adenocarcinoma.
Q.190 What is the place of screening for ovarian cancer?
Ans. Unfortunately, till date no specific method of screening for early detection of epithelial ovarian cancer is available.
- Clinical methods—bimanual pelvic examination is neither specific nor helpful.
- Tumor markers CA-125 and HE4 are being done. These are useful but nonspecific (See Ch 17).
- Ultrasound imaging TVS color Doppler imaging has been used to differentiate a benign from a malignant mass. However, it is not specific also.
- Risk of malignancy index (RMI) is calculated by U × M × CA 125. The risk of cancer is 75% when the RMI value is greater than 250. When RMI is less than 25 the woman is in the low-risk group. RMI: 25–250 is in the moderate-risk category.
- Risk of ovarian malignancy algorithm (ROMA): ROMA is a quantitative test using CA-125, HE4 concentration and menopausal status to calculate the risk of ovarian cancer (see below).
- No screening procedure is effective for early detection of ovarian cancer.
Tumor Marker (HE4)
Human epididymis 4 (HE4) protein is derived from the distal epithelium of the epididymis. It is essential for sperm maturation as it is a protease inhibitor.
Levels of serum HE4 is found high in women with serous epithelial ovarian cancer. Unlike serum CA-125, serum levels of HE4 are less affected by other benign pelvic conditions like endometriosis. The sensitivity and specificity of detecting ovarian malignancy with HE4 is high in premenopausal women. This is especially beneficial for early stage ovarian cancer.
The use in combination of serum CA-125 and HE4 was found superior when compared with any other marker alone.
Risk of ovarian malignancy algorithm (ROMA): ROMA calculation is based on the combined results of the CA-125 and the HE4. This algorithm classifies women either as low-risk or high-risk for malignant disease. A cut-off value of 2.27 representing a high-risk of malignancy. Overall, it has a sensitivity of 89% and a specificity of 75%. Both the tumor markers are related to tumor stage and histological type of serous epithelial ovarian cancer.
Q.191 What are the other tumor markers?
Ans. CEA, CDX2, CA 72-4, CA19-9, Alpha FP, LDH and beta-hCG. There is not enough evidence to do the panels of multiple markers as there is no added advantage. All these markers have low sensitivity and wide variation in specificity. The routine use of any of these markers is not recommended (RCOG-2016).
Q.192 What are the epidemiology and risk factors for epithelial ovarian cancer?
Ans.
- Women of North America and most of the industrialized countries of Europe have high incidence.
- Pregnancy, breastfeeding reduce the risk.
- Use of combined oral contraceptives are associated with reduced risk.
- Pregnancy in a women after the age of 35 years is more protective against ovarian cancer.
- Use of long-acting progestin only contraceptive (DMPA, Provera) has protective effects similar to COCs.
- Prophylactic/risk reducing salpingectomy in high-risk women is protective (See Ch 53).
Q.193 What is the place of imaging studies in the management of ovarian cancer?
Ans. Computed tomography (CT)/positron emission tomography (PET) scan has been integrated for the diagnosis of ovarian cancer and evaluation of disease recurrence. PET scan has very high sensitivity but low specificity. There are false positive results due to increased FDG uptake in benign but metabolically active tissues and with inflammatory changes. Combined CT/PET scan had high sensitivity of 100% and specificity of 92%. It can detect recurrent disease which is superior to CA 125 or CT/MRI scans used alone.
Magnetic resonance imaging (MRI) is a nonradioactive imaging modality. It has excellent soft tissue contrast resolution. MRI is better than CT or ultrasonography in the diagnosis of small peritoneal metastases. CT imaging is better in identifying omental metastasis in ovarian cancer.
Q.194 What is the place of lymph node dissection in the managment of ovarian cancer?
Ans. Lymph node dissection in early ovarian cancer: Both pelvic and para-aortic lymph nodes should be removed. Lymph node dissection provides important prognostic and staging information for patients with suspected early stage ovarian cancer. This is helpful for the decision of about adjuvant chemotherapy. However, there is no convincing evidence that lymphadenectomy has got any therapeutic survival benefit in advanced ovarian cancer. Enlarged nodes may be removed as a part of debulking procedure.
Q.195 What is the place of neoadjuvant chemotherapy?
Ans. Neoadjuvant chemotherapy: Women with FIGO IIIC or IV ovarian cancers were treated with neoadjuvant platinum-based chemotherapy followed by primary debulking surgery. Subsequently, they were treated with platinum-based chemotherapy. The blood loss during surgery was less. The largest residual tumor could be reduced to less than 1 cm. The operative time was also shorter. For patients with huge tumor burden, ascites and several comorbidities, neoadjuvant chemotherapy is a very reasonable choice. Surgical debulking procedure is the single most important component in the management of ovarian cancer.
Suggested Reading
- Moore RG, Brown AK, Miller MC, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008;108(2):402-8.
- Rafael Malina, Jose M, Jose Auge, et al. HE4 a novel tumor marker for ovarian cancer: Comparison with CA125 and ROMA algorithm in patients with gynecological diseases. International Society of Oncology and Biomarkers 2011.
CASE 20: INHERITED CANCERS AND THE MANAGEMENT
Q.196 Ms RT is keen to know what is inherited or familial cancers. How it could be prevented?
Ans. Familial or inherited cancers are well known. They are more common in relation to ovarian, endometrial, breast and colon cancers. Unfortunately, as regard the diagnosis and prevention, no such specific guidelines are there as yet.
Q.197 What are the diagnostic criteria for familial cancers?
Ans. Till date no such specific guidelines are there. Amsterdam criteria (1999) has considered the following:
- At least three relations with breast, ovarian cancer and hereditary nonpolyposis colorectal cancer must be there.
- One affected person is a first-degree relative of the other two.
- At least two successive generations are affected.
- At least one person was diagnosed before the age of 50 years.
- Familial adenomatous polyposis had been excluded.
- Tumors have been verified by histopathological examination.
Q.198 How do BRCA-1, BRCA-2 and mismatch repair genes protect us?
Ans. BRCA-1 and BRCA-2 are the tumor suppressor genes. Others: MLH-1, MSH-2 and MSH-6 are the mismatch repair genes. These genes repair the single base pair 30mismatches that occur during DNA replication. Mutations in these genes cause cell immortalization, neoplastic proliferation and ultimately cancers.
Q.199 How familial cancers could be prevented?
Ans. At the moment there are no such guidelines. But following measures could be adopted:
- Family history must be enquired and recorded in all positive cases.
- Clinical geneticist must be consulted and family tree should be drawn in a positive case (Amsterdam criteria).
- Molecular screening for detection of gene mutation is not possible at the moment. This is very expensive, time consuming and also labor intensive.
- Screening procedure may be initiated wherever available (e.g., breast cancer, colon cancer).
- Combined oral contraceptives are chemopreventive against ovarian cancer and endometrial cancer. Tamoxifen is chemopreventive against breast cancer.
- Place of prophylactic surgery may be considered. Prophylactic salpingo-oophorectomy/salpingectomy may be done especially while doing hysterectomy for some other reason. This is an alternative in the high-risk group of women for ovarian cancer.
- Human fertilization and embryology authority (HFEA), UK, has recommended preimplantation genetic diagnosis in cases with familial cancers. Affected blastocysts are removed from the transfer in ART. This may be one way to eliminate the risk of inherited cancers.
- As a prophylaxis to endometrial cancer, LNG-IUS is currently being used. Long-term reports are awaited.
- Resequencing chips are being tried, once available molecular diagnosis of gene mutation would be helpful.
Q.200 Who are the women that may be considered for molecular screening?
Ans. At the moment there is no such established criteria. However, women fulfilling the following criteria are the high-risk group for consideration:
- Positive family history following Amsterdam criteria.
- Risk scoring more than 10 (Manchester scoring system).
- Tumors positive for microsatellite instability by immunohistochemistry method.
Q.201 What is the significance of family history?
Ans. This is often observed in early age onset (around 45 years).
Lifetime risk of endometrial cancer in women with Lynch II syndrome is 32–60% and that of ovarian cancer is 10–12%.