Date post: | 11-Nov-2014 |
Category: |
Health & Medicine |
Upload: | lee-jhung |
View: | 947 times |
Download: | 1 times |
Common Gynaecological
Carcinoma
Top killers of the female genderAll Females, All Ages Percent*
1) Heart disease 25.1
2) Cancer 22.1
3) Stroke 6.7
4) Chronic lower respiratory diseases 5.5
5) Alzheimer's disease 4.3
6) Unintentional injuries 3.6
7) Diabetes 2.9
8) Influenza and pneumonia 2.3
9) Kidney disease 2.0
10) Septicemia 1.6
: 10 Principle Cause of Deaths in Ministry of Health, Malaysia (MOH)Hospitals, 2006
1. Septicaemia 16.872. Heart Diseases & Diseases of Pulmonary Circulation 15.703. Malignant Neoplasms 10.594. Cerebrovascular Diseases 8.495. Pneumonia 5.816. Accidents 5.597. Diseases of the Digestive System 4.478. Certain Conditions Originating in The Perinatal Period 4.209. Nephritis, Nephrotic Syndrome & Nephrosis 3.8310. Ill-defined conditions 3.03All causes 100.0
Prevalence of various types of cancer amongst Malaysian ladies of all agesBREAST 3525 29.9
COLORECTAL 1247 10.6
CERVIX UTERI 1074 9.1
OVARY 685 5.8
THYROID GLAND 670 5.7
LUNG 603 5.1
CORPUS UTERI 372 3.2
STOMACH 324 2.7
BRAIN, OTHERNS 303 2.6LYMPHOMA 279 2.4
Taken from the Malaysian Cancer Statistics 2006
CERVICAL ENDOMETRIAL OVARIAN
The squamo-columnar junction and the Transformation zone
Common site for HPV infection
-Most commonly Adenocarcinoma-90%: Endometriod adenoCA-10%:Serious papillary AdenoCA
-Rarely: Clear cell
80% from Ovarian Epithelium20% others: Germ cell, sex-cord stromal, mixed mullerian,
HPV infection persists in certain individuals, eventually triggering oncogenic processes within the TZ
Mechanism poorly understoodTwo main theories
Cell metaplasia occurs:Immortalization of the basal cells leading to rapid turnover and subsequent immature cells
1. Incessant ovulationrepeated trauma to ovarian epithelium
These immature cells picked up on PAP smear as Cervical Intraepithelial Neoplasia CIN
2. Excess gonadotrophin secretionhigher level of estrogenEpithelial proliferation
PATHOPHYSIOLOGY
CERVICAL ENDOMETRIAL OVARIAN
Infection by HPV16,18,31,33
Conditions that lead to high levels of estrogen-Tamoxifen-Unopposed estrogen therapy as HRT
Endometriosis
Immunosupressed state leading to increased risk of HPV infection:-RVD-Immunosupressive drugs
Family history (debatable)-endometrial cancer-colorectal/ovarian cancer-HNPCC
Family history-increased risk from 1.4% in general populace to 5%50% if 2 first degree relatives
Nulliparity Nulliparity
Late menopause >52 years
Obesity Obesity
Smoking-theory: immunosupressive effects of nicotine within the cx
Diabetes
AETIOLOGY & RISK FACTORS
Mnemonic of risk factors for endometrial cancer
• O=ObesityL=Late menopauseD=Diabetes mellitus
A=cAncer: ovarian, breast, colonU=Unopposed estrogen: PCOS, anovulation, HRTN=NulliparityT=Tamoxifen, chronic use.
RMI score for ovarian CAFeature RMI 1 Score RMI 2 Score
Ultrasound features: • multilocular cyst • solid areas • bilateral lesions • scites • intra-abdominal
metastases
0= none1= one abnormality3= two or more abnormalities
0= none1= one abnormality4= two or more abnormalities
Premenopausal 1 1
Postmenopausal 3 4
CA125 U/ml U/ml
RMI score = ultrasound score x menopausal score x CA125 level in U/ml.
The RMI scoring system is the method of choice for predicting whether or not an ovarian mass is likely to be malignant.
Women with an RMI score >200 should be referred to a centre with experience in ovarian cancer surgery. Evidence grade 2+
CERVICAL ENDOMETRIAL OVARIAN
Abnormal PV bleeding Abnormal PV bleeding Persistent pelvic-abdominal pain
1. Post-coital bleeding*The cervical cancer is a
friable vascular mass on the cervix: Mechanical irritation during coitus: Post-coital bleed
1. Post-Menopausal Bleedddx: Cervical, endometrial polyps,
cervical erosion, vaginal atrophy
10% of PMB turns out to be Endometrial CA
Increased abdominal size and bloating
2. Irregular Vaginal bleeding
3. Advanced stage:-constitutional sx-lungs mets: Recurrent bilateral pleural effusion
3. Advanced stage:-constitutional sx-lungs mets: Recurrent bilateral pleural effusion
3. Advanced stage:-constitutional sx-lungs mets: Recurrent bilateral pleural effusion
Incontinence Change in bowel habits
Anemia Sx Urinary sx
Renal failure Back ache
CLINICAL FEATURES
CERVICAL ENDOMETRIAL OVARIAN
Aim of diagnostics: To provide histopathological evidence of malignant cancer tissue.To provide sufficient information to properly stage the tumourTo confirm the malignancy1. Colposcopy : outpatient
examination of the magnified cervix using a light source
Additional Lugol’s Iodine/ 5% acetic acid are used to highlight the presence of abnormal cells
2. Cervical Biopsy: To confirm the malignancy and type of tumour
To confirm the malignancy1. Sampling by Pipelle:
Outapatient procedure, results operator dependant, difficult to do if nulliparous, retroverted uterus, presence of fibroids
2. Hysteroscopic DD+C: done if unable to obtain good sample by Pipelle / Contraindicated for Pipelle
To confirm the malignancy and for staging1.TAHBSO2.CT-scan/MRI3.PET-scan
* In some patients (esp those unfit for a major surgery such as TAHBSO, laparascopic examination and biopsy is done instead
To assess stage1.CT-scan abdomen-pelvis2.EUA : Vaginal and rectal
To assess stage1.TAHBSO2.CT-scan/MRI3.PET-scan
INVESTIGATIONS AND SUSPICIONS
Tumuor markers1. Not used for diagnosis for cancer. Diagnosis of cancer is strictly based histopathological
evidence2. Tumour markers can be useful for:
- Monitoring the response of the malignancy to anti-cancer therapies - Monitoring patients on a regular basis to assess for reoccurance
Tumour marker Cancer1 Ca-125 Endometrial, ovarian2 CEA Pancreas, colon3 a-FP Liver (HCC)4 Ca 19-9 Pancreas
CERVIX ENDOMETRIAL OVARIAN
I: Cervical cancer confined to cervixIa1: < 3mmIa2: > 3mm
Ib1: < 4cm1b2:> 4cm
IA: Endometrium only
IB: <1/2 of myometrium
IC: >1/2 of myometrium
I: Ovaries onlyIA: One ovaryIB: Two ovariesIC: Ruptured ovary/+ve peritoneal wash/ascites
II: Cervical cancer extending beyond the cervix, but not invading pelvic wallIIA: No obvious parametric invasionIIB: Obvious parametric invasion + upper 2/3 of vagina
IIA: Endocervical glandular involvementIIB: Cervical stroma invasion
II: Ovaries + pelvic involvementIIA: Uterus + TubesIIB: Pelvic/parametrial tissueIIC: Rupture/+ve peritoneal wash/ascites
III: Cervical ca extending to pelvic wallIIIa: Invasion of lower 1/3 vaginaIIIb: Extention to pelvic wall with hydronephrosis
IIIA: Serosa/Adnexa/+ve peritoneal washIIIB: Invasion of vaginaIIIC: Invasion of pelvic/ Paraaortic LN
III: Ovaries + peritoneumIIIA: Microscopic seedlingsIIIB: < 2cm seedlingIIIC: > 2cm seedling
IVa: Growth to adjacent organsIVb: Distant metastasis
IVA: Invasion to bladder/rectumIVB: Distant metastasis
IV: Distant metastasisPleural effusion
CERVICAL CANCER FIGO
STAGING
ENDOMETRIAL CANCER FIGO STAGING
Cervical Cancer
STAGE TREATMENT PROTOCOL
Stage 1a Surgery: TAH, PLND Modified radical trachelectomy (fertility sparing): remove 80% of cervix, parametrial tissues, pelvic LN ~ 40% miscarriageFertility sparing therapy seldom done Radiation therapy: Brachytherapy(internal radiotherapy)
Stage 1b Wertheim’s hysterectomyTAHBSO+Parametrial tissue excision+PLND+upper 1/3 vaginaRadiation therapy has similar success rates, and considered who are unfit for surgery
Stage 2-4 Chemotherapy : Carboplatin + PaclitaxelRadiotherapy: External beam: Teletherapy Internal radiotherapy: Brachytherapy *Surgery seldom done at this stage:-High rates of surgical complications esp: Bleeding-Unlikely chance of achieving complete clearance of tumour-Requiring post op radiotherapy, and this combined treatment can lead to high complication rates
Remember: No tumour markers for Cervical Cancer
Endometrial Carcinoma
Surgery*Generally surgery indicated in all patients diagnosed with Endometrial CAC/I: Unfit for surgery, metastasised cancer (Stage IV)
Stage 1A, 1BTAHBSO (PLND also commonly done as there is a high chance of spread to LN at this stage)
Stage 1C, 2A, 2BTAHBSO + PLND (50% risk of LN dissemination at these stages)
Stage 2C, 3, 4/Papillary serous/Clear cell
TAHBSO + PLNDAdjuvant Chemotherapy
- Commence adjuvant chemotherapy- 1st Line: 6 cycles of Carboplatin + Paclitaxel- 2nd Line: 9 cycles (A+B) of Gemcitabine
Chemotherapy
Follow-up: Ca-125, CT-Scan
Ovarian Cancer
Surgery*Studies show that the most important prognostic factor is no residual disease following laparatomy
Non fertility sparing-Vertical insicion done to gain visual access to ALL areas of the abdomen-Ascites and peritoneal washing samples are obtained-TAHBSO + Omentectomy KIV further debulking if required- PLND
Fertility sparing (rarely done)-Vertical insicion done to gain visual access to ALL areas of the abdomen-Unilateral SO, Omentectomy, Peritoneal biopsies- PLND+ Endometrial sampling to exclude concerrent tumour
MDT meeting between Oncogynae with pathologist, radiologist
Stage 1A- Chemotherapy withheld in some cases
Stage IB, IC , II, III, IV- Commence adjuvant chemotherapy- 1st Line: 6 cycles of Carboplatin + Paclitaxel- 2nd Line: 9 cycles (A+B) of Gemcitabine
Chemotherapy
Follow-up: Ca-125, CT-Scan
Drug Mech of action AECisplatin Platinum based drug
Acts by binding and cross-linking DNA leading to cell apoptosis
Nephrotoxic (check RP before giving)GIT: N+VOtotoxicityElectrolyte imbalances
Carboplatin Neurotoxicity: peripheral neuropathyMyelosupression Aneamia,neutropenia,TCPLess GIT effects compared to CisplatinNo nephrotoxic effect
Gemcitabine Neucloside analogue.Kills cells in the S-phase of mitosis: Cell phase specific
Flu-like symptomsGIT: Mild N+VHair ossMyelosupression
5-FU Pyrimidine analogueInhibits Thymidine synthase: Cell phase specific (S-phase)
MyelosupressionMucositis, dermatitisDiarrhoea
Paclitaxel Stabilizes the microtubules preventing the Interphase thus interrupting mitosis: Cell phase specific
MyelosupressionNeurotoxicity: Peripheral neuropathyElevated LFTN+V, hair loss, arthritis
Gestational Throphoblastic Disease
Hydatidiform Mole Invasive Mole Choriocarcinoma Placental site throphoblastic tumour (PSTT)
Hydatidiform Mole
Complete Incomplete
Risk factors Extremes of age (<15, >40) – risk of complete molesPrevious molar pregnancy X 10Ethnicity (East Asians: x 2)
Presentation Irregular first-trimester bleeding >90%Uterus large for dates~ 25%Abdominal pain (from hyperstimulation of theca lutien cysts)Exxaggerated early pergnancy symptoms (hyperemesis gravidarum) ~ 10%
Diagnosis ClinicalBiochemical – excessively raised serum bHCG levels (may be normal in partial moles)Scan findings – classic snowstorm appearanceHistological – post evacuation
Management Complete mole – surgical evacuation (higher risk of uterine perforation and significant bleeding)Incomplete mole – Surgical or medical evacuation
Follow-up Review HPE of evacauted mole – determine for sure complete or incompleteRecommended follow-up plan-Fortnightly bHCG until levels normal < 4-4 weekly intervals urine bHCG levels for one year, then 3-monthly in 2nd year-Contraception until bHCG normal for 6 monthsThe purpose of this follow up is to detect malignancy early
When to suspect malignancy?
The International Federation of Gynecology and Obstetrics considers an elevated serum hCG level 6 or more months after evacuation of a hydatidiform mole to be diagnostic of malignancy (ie, GTN). *However, serum hCG levels spontaneously return to normal without chemotherapy in most patients with elevated but still declining serum hCG levels 6 months after diagnosis of a hydatidiform mole.
Indication for chemotherapy
1. Serum bHCG levels >20000 4 weeks after uterine evacuation2. Static or rising bHCG levels post evacuation3. Histological evidence of choriocarcinoma4. Metastatic disease5. Persistent symptoms
ChoriocarcinomaIncidence Rare : Amongst Orientals 1:11000 (1:30000 amongst Caucasians)
20% of complete hydatidiform moles become ChorioCAPresentation Similar to hydatidiform mole
-First trimester vaginal bleeding, abdominal painSymptoms pointing to possibility of chorioCA-Dyspnoea and hemoptysis (lung mets), hematuria, neurological sx-Jaundiced, abdominal tenderness, rebound
Investigations Biochemical – Persistantly raised / pleateau or increasing trend of bHCG even after surgical evacuation of GTDScan findingsCXR (lung is most frequent site of mets) CT abdomen and chest
Treatment CHEMOTHERAPY-Regime based on prognostic scoring assestmentLow Risk : MTX + Folinic Acid / Actinomycin DMed Risk: MTX + EtoposideHigh Risk: Intensive weekly EMA (Etoposide,MTX,Dactinomycin) alternating with CE (Cyclophosphamide and Vincristin) – the EMA-CE regiment
Prognosis Overall survival > 90% - it is one of the most curable forms of malignant cancerPoorer prognosis if -Age >40-Time interval between antecedent pregnancy and start of chemotherapy > 4months-After 12 months of normal hCG levels, less than 1% of patients with GTN have recurrences.
Next pregnancy
Fertility not impaired by chemoNo increased risk of fetal anomalies