Gynaeonc Flashcards
Endometrial hyperplasia without atypia:
Treatment with oral progestogens or the LNG-IUS should be for a minimum of 6 months in order to induce histological regression of endometrial hyperplasia without atypia.
Between 3 and 6 months the regression rates improved for the LNG-IUS from 84% to 100% and for oral medroxyprogesterone from 50% to 64%.
In women at higher risk of relapse, such as women with a BMI of 35 or greater orthose treated with oral progestogens, 6-monthly endometrial biopsies are recommended. Once two consecutive negative endometrial biopsies have been obtained then long-term follow-up should be considered with annual endometrial biopsies.
Hysterectomy is indicated in women not wanting to preserve their fertility when (i) progression to atypical hyperplasia occurs during follow-up, or (ii) there is no histological regression of hyperplasia despite 12 months of treatment, or (iii) there is relapse of endometrial hyperplasia after completing progestogen treatment, or (iv) there is persistence of bleeding symptoms, or (v) the woman declines to undergo endometrial surveillance or comply with medical treatment.
Endometrial hyperplasia with atypia:
Cumulative risk of cancer in 4 years was 8% (95% CI 1.31–14.6), which increased to 12.4% (95% CI 3.0–20.8) after 9 years and to 27.5% (95% CI 8.6–42.5) after 19 years. 33 Atypical hyperplasia has also been associated with a rate of concomitant carcinoma of up to 43% in women undergoing hysterectomy.
Due to the risk of underlying malignancy, bilateral salpingo-oophorectomy should be performed in all peri- and postmenopausal women undergoing hysterectomy for atypical hyperplasia.
Failure of atypical endometrial hyperplasia to regress is a worrying sign for underlying endometrial cancer.
Women with endometrial hyperplasia who wish to conceive should be followed up to ensure disease regression.
Endometrial cancer staging:
- Histology (pipelle or curettings)
- MRI pelvis abdomen and CXR (Grade 1 or 2 endometrioid/mucinous only)
- CT CAP (High grade only e.g. grade 3 endometrioid, serous, clear cell, LVSI, sarcoma etc)
Epithelial ovarian cancer histology:
Lifetime risk 1.2%. 3 times background if first degree relative has been diagnosed even without genetic mutation. Predominantly a disease of older post-menopausal women >80% diagnosed inw omen over 50 years old. Subtypes: • High grade serous carcinoma – 70% • Clear cell carcinoma – 10% • Endometrioid carcinoma – 10% • Mucinous - 3% • Low grade serous <5% • OTHER <5%
BRCA 1:
BRCA 1 gene on chromosome 17. It is a tumour suppressor gene that is involved in DNA repair. Loss of function of this gene to mutation leads to chromosomal instability which can lead to malignancies.
With BRCA 1 mutations, less than 2-3% of carriers will develop ovarian cancer prior to age 40, but this number increases to 10-21% by age 50.
RR BSO by age 40. 5% occult malignancy. Reduces ovarian cancer risk by 96%. Lifetime risk of developing ovarian cancer 44%.
Risk Reducing surgery for BRCA:
• For women at high risk of ovarian cancer due to BRCA1 gene mutation, risk reducing surgery should be recommended. This should include complete removal of the extra-uterine component of the fallopian tubes and ovaries bilaterally.
o Studies have demonstrated that a RRSO for BRCA1 carries has reduced the risk of ovarian cancer by 96% and breast cancer by 53%
o A RRSO should be considered around age 40. Optimal timing is between ages 35-40 or when childbearing is complete [3]. Ovarian cancer is rare in BRCA 1 carriers under the age of 40 and BRCA 2 carriers under the age of 50 – affecting 2-3% of women in these groups.
BRCA 2 carriers have a higher risk of breast cancer compared to BCRA 1 carriers in the group of women less than 50. Because a RRSO will also reduce the risk of breast cancer it is recommended that surgery is performed by age 40.
Lynch syndrome:
Lynch syndrome refers to individuals and families with a pathogenic germline autosomal dominant mutation in one of the DNA mismatch repair genes. People who have this mutation are at risk of several malignancies, particularly colorectal, endometrial and ovarian.
Endometrial cancer is typically diagnosed at a younger age in women with Lynch syndrome – mean age 47 to 55years compared to a mean age of 60 in those without Lynch Syndrome. A large portion of endometrial cancers under the age of 40 are women with Lynch syndrome. Ovarian cancer risk is typically diagnosed at a younger age in women with Lynch syndrome – mean age 43 to 48 years compared to a mean age of 60 in those without Lynch Syndrome.
Would also recommend a hysterectomy + BSO between ages 40-50. Lifetime risk of ovarian cancer 17%.
Breast cancer history
Further enquiry regarding number of family members affected and at what age to determine whether suitable for testing/genetic referral
Criteria
• Triple neg breast ca < 50
• Triple neg breast ca and family member of same
• More than one primary cancer
• Family history of known BRCA in first degree relative
• BRCA on tumour testing
• Affected and > 10% risk on score and > 20% risk
• High grade non mucinous ca of ovary < 70 years
How to perform RR BSO for genetic cancer risk
• Recommended to have this performed laparoscopically as less surgical morbidity
• Tubes and ovaries to be removed in their entirety
• Washings should be taken at the time of the procedure
A Cochrane review in 2018 demonstrated at 6% of specimens for risk reducing surgery had evidence of occult malignancy present.
• Consider omental and peritoneal biopsies
Still a small residual risk of primary peritoneal cancer 1-2%.
Discussion about menopausal symptoms:
• It is recommended that if a prophylactic BSO is performed prior to age 45 that HRT should be given
• In those that do not receive HRT they have a significantly higher cardiovascular mortality compared to those who did receive oestrogen
Systematic reviews have not shown an increased risk of breast cancer in women who have BCRA1/2 (who have not had a history of breast cancer themselves), when used in the short term up to age 51 (average age of menopause).
Discussion about the psychological wellbeing post risk reducing surgery.
Radical Trachlectomy
Lithotomy position.
Grasp vaginal mucosa 1-2cm from cervix with straight clamps. Inject dilute adrenaline solution. Make a circumferential incision around the vaginal mucosa
Grasp anterior and posterior edges of vaginal mucosa/cervix. Enter posterior cul-de-sac. Paracolpos excised, pararectal space entered, uterosacral ligaments divided and tied.
Enter vesicouterine space anteriorly and dissect out paravesical spaces.
Localise and mobilise the ureters by dissecting bladder pillars off the cardinal ligament. Mark ureters for ongoing identification
Descending branch of uterine artery is identified, secured and transected
Cervix transected approximately 1cm BELOW the internal cervical os
Prophylactic Shirodkar cerclage placed with Mersilene tape at the level of the isthmus
Rubber catheter is inserted into the new uterine outlet to keep it patent
Vaginal mucosa reapproximated to new ectocervix
Pelvic lymph node dissection
Laparoscopy routine entry by Hassan or Veress needle entry. Additional ports placed under direct vision. Pelvic side wall carefully dissected out. Obturator, external and internal iliac nodes are removed to the level of the lower common iliac vessels. Frozen section analysis. If negative, proceed to radical vaginal trachelectomy.
Ovarian cancer follow up
Follow up surveillance -
• 3 monthly ROS, examination, Ca 125 for two years
• 6 monthly ROS, examination, Ca 125 to five years
• Annually thereafter
• Imaging reserved if any suspicion of recurrence
Endometrial cancer follow up
Majority of recurrence in first 2-3y • ~80% by 3y • Majority will have symptoms • Early stage – 2-15% recur • Advanced stage – up to 50% recur • ~50% of recurrence is local only • Many local recurrences are curable • No evidence for routine smears or imaging • If subtotal hysterectomy done – needs cervical smears as per screening programme/risk of recurrence See 2 weeks post op for diagnosis All patients discussed at MDM Pelvic exam at each appointment Follow up 6 monthly for 2-3 years Estrogen replacement after total hysterectomy and bilateral oophorectomy for women aged <50 and no current breast cancer is important to counteract increased cardiovascular risk and reductions in bone density
Laparotomy for suspected ovarian cancer
- Anaesthetic referral and pre operative medical optimisation
- Patient consent
- Theatre team sign in with anaethestic, nursing, and surgical teams
- Position in supine position on table
- Insertion IDC
- Application of pneumostatic stockings
- Administration antibiotic prophylaxis
- Surgical prep and drape in aseptic fashion
- Surgical technique
• Midline incision
• Ascitic fluid or perineal washings to cytology
• Systematic review of pelvis and abdomen looking for any evidence of disease spread (including liver, bowel, spleen, diaphragmatic surfaces, pelvic peritoneum, appendix)
• TAH + BSO
• Omentectomy
• Peritoneal biopsies
• Excision or biopsy of any other areas within the pelvis suspicious for malignancy.
• Leave drain in pelvis if any free fluid or haemostatic concerns
• Close rectus sheath en masse with delayed absorbable (Looped PDS)
• Interrupted skin closure - Post operatively
• Thromboprophylaxis - cleaxane / teds / pneumostatic
• Early mobilisation
• Allow E&D
• Chest physiotherapy
Differentials for ovarian mass
Malignant: Ovarian: Tumour: germ cell; sex cord stromal, EOC Tubal: Serous tubal intraepithelial
Benign:
Ovarian: ovarian torsion, functional cyst, endometrioma, benign germ cells or sex cord stromal tumour.
Tubal: ectopic pregnancy, hydrosalpinx,
Non-gynaecological: Constipation Appendiceal mass Bowel malignancy Retroperitoneal sarcoma
Borderline ovarian tumour explanation
A borderline serous tumour has low malignant potential i.e. there is a low risk of recurrence and survival prognosis is good. 10 year survival following treatment for this tumour is 95-100%. If there was no spread to the peritoneum/outside of the ovary seen which is associated with a more favourable prognosis.
If a cystectomy rather than an oophorectomy was performed there is a recurrence rate of 15-50% associated with this; this does not change her survival prognosis. Advise to report symptoms such as: abdominal pain, abdominal bloating, early satiety, unintentional weight loss.
Follow-up involves: Every 6 months. From fifth year: annually. Annual TVUSS surveillance Not for routine CA-125 monitoring if not elevated at initial presentation.
Usual type VIN
- Warty type
- Basaloid type
- Mixed type
HPV mediated VIN - Usually HPV 16
Tends to be in younger patients (than differentiated VIN)
differentiated VIN
<5% of preneoplastic lesions of the vulva
Usually occurs in postmenopausal women
Often associated with lichen sclerosis (not HPV)
Treatment of VIN
Wide local excision:
Preferred treatment for dVIN as it is unifocal in nature and has higher malignant potential
Can identify occult invasive SCC in women, especially common in those >50y
Laser ablation:
Useful in multifocal disease, especially when there are multiple small lesions
Improved cosmesis
Useful in areas where tissue conservation is important
Imiquoimod: Aimed at preserving anatomy Useful in younger patients Avoids surgery Avoids distortion of anatomy and disruption of sexual function
Vulval cancer treatment
Surgical treatment is first-line / main stay of Rx for vulval cancer
This is in the form of a wide local excision
- Radical WLE is as effective as radical vulvectomy in preventing local recurrence, but substantially decreases the psychosocial morbidity of the treatment
Groin lymph node surgery is the single most important factor in decreasing mortality
- Options of sentinel LN vs. lymphadectomy
- Sentinel LN recommended as associated with lower morbidity
Criteria for sentinel nodes:
- Unifocal tumour confined to the vulva
- <4cm in diameter
- Stromal invasion >1mm
- Clinically negative groin nodes
If sentinel LN positive, then bilateral inguinofemoral lymphadenectomy is recommended
Radiation can be considered:
- adjuvant to treat pelvic lymph nodes or evidence of extracapsular spread post surgery
- post-surgery for inadequate margins to help prevent local recurrence. This can improve overall 5 year survival
Vulval SCC
Photo/diagram CT CAP Gynae Onc MDM Counsel on treatment expectations: - Radical excision - Groin node assessment - Surgery mainstay of treatment - RT in some instances - Chemo occasionally - High rate of recurrence
Lichen sclerosis
Chronic inflammatory condition, likely autoimmune, perform thyroid screen
2-5% chance of vulval malignancy
Risk of sclerosing skin changes and deformation of anatomy
Reduce risk of sclerosis and malignancy by suppressive therapy = high strength topical corticosteroid eg clobetasone proprionate 0.05% BD for 4 weeks then attempt to taper if skin texture normalised. Can then tailor maintenance steroid to lowest needed to maintain normal skin appearance
Continue vulval care regime as above
Refer to vulval clinic for follow up initially 3 monthly until stable, then long term 6-12 monthly
Histology: Hyperkeratosis, significant thinning with loss of the normal rete ridge pattern.
Upper dermis exhibits homogenisation of collagen overlying a lymphocyte band.
Vulval SCC
Lesions >1mm depth of invasion have a greater than 10% chance of undiagnosed lymph node involvement
If stage 1 then 80% 5 years survival, but if upstaged to stage 3 by positive lymoh nodes then survival falls to 40%
Will refer to MDM to discuss final treatment plan by subspecialists but will likely involve a double surgical procedure – a lymph node dissection can likely be performed unilaterally, not suitable for SNB as has had previous wide local excision, and would then need vulvectomy.
May need post operative radiotherapy if microscopically positive nodes are found to reduce recurrence risk
Morbidity related to vulval surgery includes wound breakdown, infection, VTE, pressure sores, vaginal stenosis, urinary or faecal incontinence, lymphoedema, hernia, and psychosexual dysfunction.
Recurrence risk depends on nodal status. If positive nodes then high risk of recurrence. Groin recurrence is <6 months and is very poor prognosis, vulval recurrence is usually 3-4 years later and is usually treated with chemorad
Written information and access to support groups and cancer nurse specialist, and arrange follow up in clinic after MDM consensus
STUMP
Not cancer – does not meet criteria for LMS, but not clearly benign
Potential to recur
Path review via GONC MDM
Requires follow-up (clinical/USS)
Return precautions
Consider hysterectomy +/- BO when family complete (no evidence)
Significant history for genetic referral
Further enquiry regarding number of family members affected and at what age to determine whether suitable for testing/genetic referral
Criteria
Triple neg breast ca < 50
Triple neg breast ca and family member of same
More than one primary cancer
Family history of known BRCA in first degree relative
BRCA on tumour testing
Affected and > 10% risk on score and > 20% risk
High grade non mucinous ca of ovary < 70 years
AIS
HPV associated precancerous lesion of glandular cells of the endocervix and precursor to endocervical adenoma carcinoma
Difficulty with detection, screening and colp and biopsy due to endocervical nature and skip lesions.
Prognosis:
Cone +ve margins - recurrence 52% Cancer 6%
Cone -ve margins - Recurrence 20% cancer 1.5%
TAH <1.5% cancer risk
Follow up:
- With histology
- 6 monthly colposcopy and biopsy
- Repeat Cytology and HPV 12 months
- Annual cytology until TAH + BS and routine screening till 70
Investigation of carcinoma of cervix
Biopsy
CXR
FBC, U&E, LFT and HIV
MRI vs EUA
PET-CT Stage 1B2+
CT-CAP if curative treatment is not being considered
Clinical staging EUA, cystoscopy and proctoscopy
Cervical cancer: Stage 1A1 and 1B2 extent and treatment
Stage 1A1 cervical cancer
Cervical carcinoma confined to uterus stromal invasion <3mm depth and <7mm horizontal spread
Treatment: Cone/simple hysterectomy + BS +/- Oophrectomy risk lymph node involvement 1%
Stage 1A2
Confined to uterus stromal invasion 3-5mm with horizontal spread <7mm
Radical trachelectomy and pelvic lymph node (7-8% risk of involvement) dissection
Cervical cancer: Stage 1B1 to 2A extent and treatment
Clinically visible disease without parametrial involvement
Radical hysterectomy and pelvic lymph node dissection
What is a radical hysterectomy
Removal of uterus, cervix, parametrium and upper 1/3 vagina.
Parametrium is round, broad, cardinal and uterosacral ligaments.
Cervical cancer: Stage 2B +
Stage 2: Invades beyond the uterus but not to pelvic wall of lower third of vagina
Stage 3: Extends to pelvic wall and/or lower third of vagina and/or causes hydro-nephrosis or non-functioning kidney
Stage 4: Extend beyond the true pelvis or has involved the mucosa of the bladder or rectum.
Treat combined chemo with cisplatin and radiotherapy.
When to offer adjuvent radio and chemo
Positive or close surgical margins
+ve lymph nodes
Microscopic parametrial involvement
Better 4 year survival 81% and progression free survival
Cervical cancer follow up
>75%recurrence occur in first 2-3 years Early stage 1A1 surgery only follow up 6months, 1year and 2 year for smear + HrHPV once 2 negative HrHPV discharge to GP for routine screening 1A2 to 1B1 3 monthly for 1 year 6 monthly for 1 year Year 3 + Year 5 Annual smear if no radiation
Germ cell tumour follow up
Highest risk of relapse being in first 2 years 1 year monthly 2nd year 2 monthly 3rd year 3 monthly 4th year 4 monthly 5-10 years 6 monthly Pelvic USS, tumour markers, CXR + CT-AP Women wishing to concieve not to do so within first 2 years Can have HRT +/- hormonal contraception
sex-cord stromal tumuor follow up
Relapse tends to occur late so follow up starts in the third year and continued indefinitely
History exam and tumour markers 6 monthly
Virilisation may suggest recurrence in sertoli-leidig tumours
If fertility sparing surgery 6 monthly uss
HRT not safe
HPV vaccine
Made from virus like proteins that do not contain live virus they induce an antibody response. Contains 9 strains HPV 6, 11, 16, 18, 33, 45, 52 & 58
Prevents 90% cervical cancers
Could also prevent anal and oropharynx cancer
Since programme has started there has been a reduction in high grade and cancerous lesions in under 30s by 75%
If under 15 2 doses 6 monthly
If over 15 3 doses (0,2+6months)
It is not a treatment so only effective against strains a woman has not been exposed to
59% reduction in genital warts
BRCA 2
Higher risk breast cancer by age 45
RR BSO by age 45
1:5 chance of ovarian cancer
Occult cancer risk in RRBSO 5%
Lynch
Endometrial, colorectal and ovarian
RR Hysterectomy BSO by age 40-50
HRT after RRBSO
Offer to all those under 45 to manage symptoms and prevent osteoporosis and fracture. Continue till 50. Contraindications to HRT: - Personal history of breast cancer - High risk of thromboembolism - Abnormal uterine bleeding - Uncontrolled hypertension - Existing CVD
Non hormonal Menopausal treatments
CBT and hypnosis SSRIs SNRIs Gabapentin Clonidine
Radical trachlectomy
Removal of upper third of vagina and the cervix leaving behind a uterus intact, allowing you to become pregnant. The lymph nodes are also removed through keyhole surgery - if cancer is found we would recommend a radical hysterectomy.
Surgery for EOC
Laparotomy extrafasicial hysterectomy with BSO, omentectomy and washings. Assess upper abdomen peritoneal biopsies, large and small bowel mesentery with possible biopsy.
Adjuvent chemo in EOC
6 cycles of platinum and taxane recommended for all FIGO stage II-IV post surgery as risks of recurrence for disease spread beyond the ovaries is significant
Staging work up in Ovarian CA
RMI CT-CAP (if under 35 consider MRI + CXR) CA125, CEA Ca19-9 IF under 40 AFP, HCG, LDH + INhibin U&Es, LFTs and albumin
Calculating RMI
RMI = UxMxCA125 U = mutilocular solid areas bilateral lesions Ascites Intra-abdominal masses M= menopause pre 1 menopause post 3 >250 ~75% risk of cancer
