Repro Cancers

Question 1

What type of cells/epithelium make up the cervix?

Answer 1

stratified squamous epithelium

Question 2

Age distribution of cervical cancer?

Answer 2

Bimodal - 30s and 80s.

Question 3

What cells make up cervical cancer?

Answer 3

Squamous cell carcinoma = 2/3rd (66%)
15% are adenocarcinoma

Question 4

1. Risk factors for cervical cancer?
2. High risk types of HPV that can lead to cervical cancer?
3. Presentation of cervical cancer?

Answer 4

1. HPV, young age of first intercourse, multiple sexual partners, exposure (no barrier protection), smoking, long use of COCP, immunosuppression/HIV, non-compliance to cervical screening programme, high parity, low socioeconomic status, co-infection with STIs, previosu cancer of vagina, vulva, kidneys and urinary tract
2. HPV 16 and 18
3. There are a few:
   * persistent unexplained abnormal bleeding = could be PCB, PMB (and not taking HRT), IMB, PMB with changes in heaviness/duration of bleeding if taking HRT.
   * Blood stained vaginal discharge
   * pelvic pain
   * abnormal appearance of cervix.
   * symptoms of advanced disease = fistula, renal failure, nerve root pain, lower limb odema.

Question 5

What are treatment options for cervical cancer?

Answer 5

• For very small cancers in stage IA treatment = conisation with free margins if aiming to spare fertility. Conisation is done using a scalpel (cold-knife conisation), laser, or electrosurgical loop, and is usually performed as an outpatient.
• Radical trachelectomy can be done for slightly more advanced, yet still early-stage cancers when the aim is to spare fertility. This involves removal of the cervix, the upper vagina and pelvic lymph nodes.
• Where remaining fertile is not an aim = a laparoscopic hysterectomy and lymphadenectomy is offered for women for early-stage cancer.
• For invasive, infiltrating and early metastatic cancer = a radical (Wertheim’s) hysterectomy can be performed which involves removal of the uterus, primary tumour, pelvic lymph nodes, and sometimes the upper third of the vagina and uterovesical and uterosacral ligaments.
• If the cancer has spread outside the cervix and uterus = treated with radiotherapy and/or chemotherapy.

Question 6

1. What are complications of surgically treating cervical cancer?
2. What are complications of treating cervical cancer with radiotherapy?

Answer 6

1. • Infection
   • VTE
   • haemorrhage
   • vesicovaginal fistula
   • bladder dysfunction
   • lymphocyst formation
   • short vagina
2. • vaginal dryness
   • vaginal stenosis
   • radiation cystitis
   • radiation proctitis
   • loss of ovarian function

Question 7

How does cervical cancer metastasise?

Answer 7

via lymphatic spread or hematogenous spread

Question 8

DDx for cervical cancer?

Answer 8

Question 9

Investigations for cervical cancer?

Answer 9

Bedside:
* cervical swab
* STI screen
* urine culture - rule out UTI
* Preg test

Bloods:
* Full blood count: anaemia (due to bleeding), raised white cell count (infection)
* CRP: infection
* Urea & electrolytes: baseline, organ dysfunction in metastatic disease and renal involvement or obstruction
* Liver function tests: elevated liver enzymes may suggest liver or bone involvement in metastatic disease
* Serology: rule out co-infection with HIV, syphilis

Imaging:
* Chest X-ray: exclude lung metastases (rare)
* CT chest, abdomen and pelvis: visualisation of metastatic lesions
* MRI pelvis: visualisation of metastatic lesions
* PET/CT whole body: detection of lymph node involvement and distant metastases

Question 10

What system is used to stage cervical cancer?

Answer 10

FIGO classification system

Question 11

In advanced or incurable cervical cancer, what are treatment goals?

Answer 11

• Pain: analgesia, nerve-blocking therapies or spinal therapy
• Renal failure: conservative management, percutaneous nephrostomy, retrograde stenting
• Bleeding and thrombosis
• Malodour
• Lymphoedema

Question 12

What is prognosis of patient with cervcial cancer?

Answer 12

• a good prognostic outlook is associated with an earlier stage of disease at diagnosis and earlier age of diagnosis.
• Around 90% of women aged 15-39 survive their diagnosis for five years or more, compared to 25% aged 80 and over.
• Early-stage diagnoses have a one-year survival rate of around 96%, compared to 50% in the latest stage.
• On average, over 80% of women survive their diagnosis for more than one year, over 60% survive for more than five years and over 50% survive for ten years or more.

Question 13

Where does cervical cancer metastasise to?

Answer 13

• lymph nodes
• pelvis
• abdomen
• liver
• lungs
• bones

Question 14

1. Describe pathophysiology of endometrial cancer?
2. what are endogenous causes?
3. what are exogenous causes?

Answer 14

1. Endometrial cancer develops due to the presence of unopposed oestrogen, this results from a lack of progesterone which can either be caused endogenously or exogenously.
2. Endogenous = PCOS, anovulatory menstrual cycles during menarche, perimenopause peripheral conversion of androstenedione to oestrone in adipose tissue, and granulosa cell tumours (which produce oestrogen).
3. Exogenous = hormone replacement therapy (HRT) containing only oestrogen and tamoxifen, an antioestrogen, which is often used for the treatment of breast cancer.

Question 15

Describe FIGO staging of endometrial cancer

Answer 15

Stage I = limited to body of uterus
Stage II = limited to body of uterus and cervix
Stage III = Extension to the uterine serosa, peritoneal cavity and/or lymph nodes
Stage IV = Extension to the vagina or parametrium

Question 16

What are RF for endometrial cancer?

Answer 16

• Obesity
• Conditions associated with obesity including type 2 diabetes mellitus, hypothyroidism, and hypertension
• Early menarche
• Late menopause
• Nulliparity
• Polycystic ovarian syndrome
• Lynch syndrome (hereditary nonpolyposis colorectal cancer (HNPCC) increases the risk of colorectal, endometrial, and ovarian tumours)
• Breast cancer (has similar risk factors as outlined above and is often treated with tamoxifen)

Question 17

What are protective factors against endometrial cancer?

Answer 17

• Parity (as there is a surge in progesterone during pregnancy)
• Combined oral contraceptive pills (COCP)
• Exercise
• Smoking
• Use of aspirin
• Drinking coffee

Question 18

What are clinical features of endometrial cancer?

Answer 18

• Abnormal uterine bleeding including post-menopausal bleeding, heavy menstrual bleeding, intermenstrual bleeding, irregular bleeding, or unscheduled bleeding while on HRT
• Increased vaginal discharge
• Pyometra which is a collection of pus in the uterine cavity
• Advanced disease may present as pelvic pain, oedema, rectal bleeding, weight loss, and fatigue
• Metastatic disease may present as cough, dyspnoea, haemoptysis, abdominal pain, jaundice, bone pain, hypercalcaemia, and pathological fractures

Question 19

What are clinical findings found on examination in endometrial cancer?

Answer 19

Uterine bleeding
Increased vaginal discharge
Pyometra
Oedema
In locally advanced disease the uterus may be enlarged or immobile on palpation
In advanced cases, there may be a palpable pelvic mass on examination of the abdomen

Question 20

What investiagtions would you do for endometrial cancer?

Answer 20

Bloods:
Full blood count: may show low haemoglobin and low platelets
CA-125: may be elevated but not usually performed for cases of suspected endometrial cancer

Imaging

Question 20

What investiagtions would you do for endometrial cancer?

Answer 20

Bloods:
* * Full blood count: may show low haemoglobin and low platelets
* CA-125: may be elevated but not usually performed for cases of suspected endometrial cancer

Imaging:
* Pelvic ultrasound: to visualise the uterus, ovaries, and fallopian tubes
* Transvaginal ultrasound: an endometrial thickness (ET) of ≥ 4mm would be an indication for further investigations such as endometrial biopsy
* CT scan of chest, abdomen, and pelvis: may be used for preoperative staging
* MRI pelvis: can be used to determine the local extent of the tumour and the presence of involved pelvic lymph nodes

Other inv:
* endometrial biopsy
* hysteroscopy

Question 21

Ddx for abnormal uterine bleeding?

Answer 21

PALM COEIN:

Polyp
Adenomyosis
Leiomyoma (fibroid)
Malignancy/hyperplasia
Coagulation disorder
Ovulatory dysfunction
Endometrial (primary disorder of mechanisms regulating haemostasis)
Infection/Iatrogenic (medications including HRT)
Not yet known

Question 22

1. Surgical management for endometrial cancer
2. Medical management for endometrial cancer?

Answer 22

1. Surgery = mainstay of treatment - allows surgical staging and removal of tumour.

The type of surgery offered is dependent on the stage of endometrial cancer:3,4

• Stage I: total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO)
• Stage II: exploratory laparotomy and surgical staging with radical hysterectomy, bilateral pelvic lymph node dissection (BPND) para-aortic lymph node clearance, pelvic and peritoneal washings for cytology and omental sampling
• Stage III/IV: exploratory laparotomy with maximal tumour debulking and full surgical staging
• Laparoscopic hysterectomy has gained popularity in recent years, and studies have shown better postoperative recovery in early disease.

2. Medical = used alongside surgery in advanced disease
   * Radiotherapy: post-operative external beam irradiation and/or intracavity brachytherapy are given to those diagnosed with stage Ib grade 3 and stage II-IV of any grade. Radical radiotherapy can also be used for local recurrences and in patients unsuitable for major surgery.
   * Chemotherapy: doxorubicin, paclitaxel and carboplatin/cisplatin can be used in stage III and IV disease though the response rates tend to be poor.
   * Hormonal therapies: tamoxifen and progestogen can be used in recurrent or advanced disease.

Advanced metastatic cancer = palliative treatment

Question 23

Complications of endometrial cancer?
Complications related to the treatment for endometrial cancer?

Answer 23

If endometrial cancer is not diagnosed and treated promptly, complications due to advanced disease can occur:6

Anaemia due to excessive blood loss from the uterus can present with symptoms including fatigue, weakness, and palpitations
Symptoms of weight loss, shortness of breath, and bone pain if there is metastasis to the bladder, rectum, vagina, or distant organs

Complications related to treatment:
* Bleeding
* Infection
* Damage to local structures (bladder, bowel, and/or vasculature)
* Lymphoedema
* Vaginal stenosis
* Vaginal atrophy
* Bowel or bladder fistula post-irradiation
* Bladder instability
* Sexual dysfunction

Question 24

Epidemiology of ovarian cancer?

Answer 24

* ovarian cancer accounts for 4% of cancers in UK women (about 7000 cases per year) * it is the fifth most common cancer and causes 5.6% of cancer deaths (about 4000 per year) * there is a lifetime risk of 2.0%, or 1 in 51, for women in the UK * it has a peak incidence in women in their 60s and 70s; is rare under the age of 40 * incidence has decreased over the past 10 years, possibly due to increased use of the OCP * ovarian cancer is almost twice as common in developed countries than in the developing world

Question 25

Risk factors for ovarian cancer?

Answer 25

* damage to ovarian surface epithelium during ovulation * incessant ovulation RF - early menarche, late menopause, delayed childbearing, nulliparity, use of HRT for >5 years, use of fertility drugs such as clomiphene to stimulate ovulation, and increasing age\ * previous ovarian disease, such as ovarian cysts (2-9x risk) or endometriosis (1.5x risk), can increase risk, probably through similar mechanisms * pelvic radiotherapy for previous gynaecological cancers or lymphoma (1-2x risk) * previous breast cancer (2-4x risk) or ovarian cancer (obviously) * smoking is a proven risk factor for some types of ovarian cancer * obesity, diabetes and sedentary lifestyle can also increase risk, especially in younger women * occupational carcinogen exposure – asbestos is a known ovarian carcinogen (3-5x risk) * family history is important as several inherited genetic traits can significantly increase risk, for example, BRCA1 (46% risk by age 70), BRCA2 (12% risk by age 70) and HNPCC (12% lifetime risk

Question 26

Protective factors for ovarian cancer?

Answer 26

* multiparity (>3 pregnancies), * breastfeeding * OCP use * hysterectomy * tubal ligation * exercise * aspirin

Question 27

Presentation of ovarian cancer? 1. Symptoms 2. Signs

Answer 27

Symptoms of ovarian cancer can include: * its insidious onset * non-specific GI symptoms such as bloating or indigestion (often misdiagnosed as IBS) * gradually increasing abdominal distension (often misdiagnosed as “middle-aged spread”) * increasing tumour size results in pressure effects causing chronic abdominal, pelvic or back pain, urinary frequency/urgency (pressure on the bladder), constipation/altered bowel habit/bowel obstruction (pressure on bowel), leg swelling and DVT/PE (pressure on pelvic veins) * abnormal vaginal bleeding can also be a symptom * symptoms of metastatic disease include pleural effusion, ascites, weight loss and fatigue * less commonly, sudden torsion, rupture or infection of the tumour in early disease can present with acute abdominal or pelvic pain – this is a blessing in disguise as it can lead to early diagnosis. Clinical signs associated with ovarian cancer include: * general examination – cachexia, lymphadenopathy, signs of pleural effusion * abdominal examination – distension, ascites, palpable pelvic mass, “omental cake” metastasis * Cusco speculum examination – usually normal * bimanual palpation – palpable adnexal/pelvic mass which may be fixed and immobile

Question 28

DDx for a pelvic mass?

Answer 28

* ovarian pathology – ovarian cyst/benign tumour, ovarian cancer * tubal pathology – tubo-ovarian abscess, tubal malignancy (treat as ovarian) * uterine pathology – pregnancy, fibroids/benign tumour, uterine cancer * urological pathology – distended bladder, pelvic kidney, transplanted kidney * GI pathology – the 6 Fs: fat, fluid, flatus, faeces, fetus, filthy big tumour * other abdominal pathology – primary peritoneal cancer, retroperitoneal sarcoma.

Question 29

Investigations for ovarian cancer?

Answer 29

* preg test for women of reproductive age * tumour markers - CA-125, CA19-9, beta-hCG, placental ALP, AFP, inhibin, LDH * transabdominal +/ - transvaginal USS Calculate risk of malignancy: menopausal status score x ultrasound assessment score x CA-125 result * a score of > 200 - 75% risk of cancer so need prompt referral to a specialist gynae-oncology centre.

Question 30

What staging investigations would you do for patients with high RMI score (over 200)?

Answer 30

* blood tests – FBC (for anaemia), U+E (for renal function), LFTs (for metastases) * imaging – CXR to check for pleural effusion or lung metastases, CT +/- MRI abdomen and pelvis to assess mass, pelvic nodes and any metastases; a PET scan may be required in advanced disease * invasive tests – pleural or ascitic tap may be required if effusion/ascites present * laparoscopy and biopsy is indicated for large cystic lesions or adnexal masses to inform further management * formal surgical staging = part of definitive managament

Question 31

What is surgical management for ovarian cancer?

Answer 31

* exploratory laparotomy = for tumour debulking and formal surgical staging. A major procedure -involves total abdo hysterectomy and bilateral salpingo-oophrectomy, infracolic omentectomy, pelvic and para-aortic LN sampling etc. * maximal cytoreduction (largest residual tumour deposit < 2cm) can be achieved in up to 80% of patients and significantly improves survival * a second “interval” debulking can be carried out after chemotherapy in some cases

Question 32

What is medical therapy used in treating ovarian cancer?

Answer 32

* adjuvant chemo * intraperitoneal chemo * radiotherapy * biological immunotherapy * advanced metastatic cancer = palliative.

Question 33

Prognosis for ovarian cancer? Monitoring needed in follow up?

Answer 33

Poor - 43% have 5 year survival. Follow up = by a specialist gynae-oncology centre, with regular pelvic examinations and CA-125 levels

Question 34

Histopathological types of ovarian cancer?

Answer 34

90% = epithelial ovarian tumours * derived from surface coelomic epithelium, generally affect the over 50s * 50-80% serous adenocarcinoma * 10% endometrioid adenocarcinoma (like endometrial cancer) * 3-8% mucinous adenocarcinoma * 4-5% clear cell adenocarcinoma * 2% other rare types: squamous cell, transitional cell, mixed mesodermal tumour, carcinosarcoma, undifferentiated sarcoma 10% = are other tumour types * derived from other parts of the ovary, generally affect younger women and progress more quickly and aggressively * 1% sex cord stromal tumours – granulosa-theca cell, Sertoli-Leydig, gynandroblastoma, lipid cell * 1.5% germ cell tumours – dysgerminoma, endodermal sinus (yolk sac) tumour, embryonal carcinoma, teratoma, choriocarcinoma, polyembronoma, gonadoblastoma * 7% metastases from other sites – gastric (Krukenberg tumour), colorectal, breast, endometrial, cervical, lymphoma, leukaemia

Question 35

How does vaginal cancer present?

Answer 35

Vaginal cancer is believed to usually present with a mass or ulceration within the vagina.

Question 36

What is definitive diagnosis of vaginal cancer?

Answer 36

Definitive diagnosis requires biopsy, performed in secondary care.

Question 37

Prevelance of vaginal cancer?

Answer 37

Over 250 new vaginal cancers are diagnosed each year in the UK, meaning most GPs will not encounter a woman with the disease during their career

Question 38

Prognosis of vaginal cancer?

Answer 38

5-year survival varies considerably with stage.

Question 39

When should I refer a person with suspected vaginal cancer?

Answer 39

Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for vaginal cancer in women with an unexplained palpable mass in or at the entrance to the vagina.