Gestational Trophoblastic
Disease(GTD)
Dr D. T. Dambo
N.D.U.T.H.
INTRODUCTION
• Gestational Trophoblastic Disease is a term
commonly applied to a spectrum of inter-related
diseases origin...
INTRODUCTION
• Gestational Trophoblastic Disease are classified into`

-Hydatiform mole (Complete or Partial)
-Invasive mo...
INTRODUCTION
• These conditions represent a neoplastic spectrum
with moles at the benign end, and choriocarcinoma
at the m...
Incidence & Epidemiology
The incidence of GTD is higher in Asia and Latin America
than in western countries.
- South Asia ...
Risk Factors
• Racial –more common in Orients, blacks > Caucasians
• ABO group: Women with blood type A or AB are at
sligh...
Pathophysiology
• Complete hydatidiform mole –
• an abnormal conceptus, without an embryo.
• Characterised by generalized ...
Pathophysiology
Partial hydatidiform mole – an abnormal
conceptus with an embryo or fetus that tend to die
early.
• The pl...
Pathophysiology
• Invasive mole – this is a tumour invading the
•
•
•
•

myometrium .
Commonly results from complete hydat...
Pathophysiology
Placental site trophoblastic tumour –
• a tumour arising from the trophoblastic tissue of the
placental be...
Pathophysiology
• Gestational choriocarcinoma – it is a

carcinoma arising from trophoblastic epithelium that
shows both s...
Genetics
• Complete mole results when a haploid sperm (23x)
fertilizes an empty ova (nucleus is lost or inactivated)
and d...
Genetics
• A complete mole with 46yy chromosome
complement is never seen – b/c at least one xchromosome is essential for c...
genetics
Partial hydatidiform mole results from triploidy
(69xxx or 69xxy or 69xyy) with one maternal(23x)
and 2 paternal(...
Clinical Features
Complete Mole
1.Vaginal bleeding – most common 97%
2. Dislodged pieces of tumour that pass from
vagina, ...
.
Clinical Features
6. Lack of fetal movement.
7.Hyperthyroidism – 7%
8. Features of trophoblastic embolisation –
Respirator...
Clinical Features
Partial Moles
-Do not exhibit most of these dramatic features.
-Generally they have signs and symptoms o...
Clinical Features
• INVASIVE MOLE
Irregular vaginal bleeding
- Theca lutein cysts
- Uterine subinvolution
- Persistently e...
Clinical Features
• CHORIOCARCINOMA

Has a tendency toward early vascular invasion with wide spread
dissemination.
Most co...
Clinical Features
• Vagina

Suburethral nodule, fleshy mass

Hepatic

-

Irregular vaginal bleeding
Abnormal Vaginal disch...
Features of Complete and Partial mole
.
STAGING
• The official International Federation of Gynecology and
Obstetrics(FIGO) staging of gestational trophoblastic
ne...
•

RISK FACTORS AFFECTING STAGING
INCLUDE:
1. hCG > 100,000 IU / 24-hour urine
2. The detection of disease > 6 months from...
Prognostic scoring systems
The American National institute of health
(N.I.H ) system
Modified WHO Prognostic Scoring Sys...
Revised FIGO Scoring System
.
• The total score for a patient is obtained by adding the
individual scores for each prognostic factor.
Total score
•
-A s...
•

THE AMERICAN NATIONAL INSTITUTE OF HEALTH
(NIH)
Clinical criteria
- Non metastatic
- Metastatic (GTN)- disease outside ...
THE AMERICAN NATIONAL INSTITUTE OF HEALTH (NIH)
contd

1. Good- Prognosis metastatic disease (i.e.,absence of
high risk fa...
2. Poor-prognosis metastatic disease (i.e.,any
single high risk factor)
a. Long duration (>4 months).
b. Serum B-hCG >40,0...
SURVIVAL RATE
-Based on data from the new England
Trophoblastic disease center:
-The overall survival rate for stages I,II...
Differentials
•
•
•
•
•

Abortion
Ectopic pregnancy
Pre-eclampsia
Hyperthyroidism
Cervical cancer
INVESTIGATIONS
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•

FBC, + differential
Bld culture,
ABO Bld grp
Urine - Urinalysis &m/c/s,
HV...
TREATMENT
Patients should be managed in a specialist unit.
• SURGICAL
• MEDICAL
• RADIOTHERAPY

• Choice of Tx modality is...
SURGICAL:

•

•
•
•
•
•

Suction evacuation.
Main surgical procedure esp. in H. mole.
In the theatre start with IV fluids,...
SURGICAL:

•
•

•
•

Suction evacuation contd.
After suction is completed, a gentle sharp
curettage is done to remove any ...
SURGICAL:

• Medical induction with
PG, Oxytocin, Hypertonic solutions
(saline,urea,glucose,) are no longer
acceptable met...
The risk of hydatidiform mole progressing to
choriocarcinoma increases
•
•
•
•
•

Pre-evacuation hCG level >100,000IU/l
Ut...
Follow-up for hydatidiform mole
• Choriocarcinoma occurs in 3% of cases of
complete hydatidiform mole, the risk is low
wit...
• The hCG measurement should continue for at least 6
months after it has become undetectable.
• The hCG must have been und...
Criteria for chemotherapy after
hydatidiform mole
• High hCG level more than 4 weeks after evacuation.
Serum level > 20,00...
Criteria for chemotherapy after
hydatidiform mole contd
• Raised hCG levels 6 months after evacuation
(even if falling).
•...
MEDICAL-CHEMOTHERAPY

Single agent therapy:

Methotrexate or actinomycin D
• MTX 30-60mg/m2 once a wk. For non-metastatic ...
Combination therapy for high risk group
MAC
Methotrexate 15mg IM
Actinomycin D 0.5mg IV
Cyclophosphamide 3.0mg/kg body wei...
EMA/CO
Day 1: Etoposide
Actinomycin D
MTX

Day 2: Etoposide
Actinomycin D
Folinic acid

100mg/m2 IV (in 200ml of N/S over ...
EMA/CE
Day 1: Etoposide
Actinomycin D
MTX

100mg/m2 IV (in 200ml of N/S over 30 minutes)
0.5mg IV bolus
100mg/m2 IV bolus
...
The side effects of chemotherapy
• Common side effects of chemotherapy drugs
include:
• · Alopecia
• · Mucositis
• · Loss ...
• Along with the effects listed above, some side effects
are specific to certain chemotherapy agents:
• Methotrexate can c...
• Etoposide and vincristine can cause
constipation, paralytic
ileus, neurotoxicity, peripheral neuropathy
and bladder aton...
Brain metastasis
• Increase the methotrexate dose in EMA-CO protocol
to 1g/m2, the urine should be alkalinized with iv
bic...
• Radiotherapy: used concomitantly with
combined chemotherapy in patients with liver
or brain metastasis.
• Cerebral metas...
FERTILITY
• Regular menses starts btw 2-6mths following
chemotherapy.
• Average age of menopause is reduced by 1yr
with Me...
ROLE OF SURGERY
The development of effective chemotherapeutic
agents has relegated surgery to a secondary
role in the mana...
Role of surgery in mgt of trophoblastic
diseases contd
• Suction-Evacuation
• Uterine perforation managed by local
resecti...
FOLLOW-UP
•
•
•
•
•

BhCG Titre wkly until 3 consecutive normal titres
Monthly for 12 months
3 monthly for 1 additional ye...
FOLLOW-UP CONTD
• Laboratory investigation follow-up =
FBC+DIFF, E&U+C, LFT, etc
• CXR repeated every 4wks for those that ...
COMPLICATIONS:

•
•
•
•
•
•
•
•
•

Anaesthetic complications
Uterine perforation
Injury to adjacent structures
Haemorrhage...
PROGNOSIS:

• Excellent.
• Over 90% of patients have been able to
preserve reproductive functions.
HYPERGLYCOSYLATED HCG
• Hyperglycosylated hCG (hCG-H) is a glycosylation variant
of the hormone hCG.
• it is a very differ...
hCG-H CONTD
• hCG-H is an essential component for successful human
implantation to prevent early pregnancy loss and
sponta...
SUMMARY
• GTD forms a spectrum of illness, from borderline
malignancy of HM to Choriocarcinoma, which were
fatal in the pa...
SUMMARY CONTD
• As a result GTD is one of the modern day success
stories in oncology
THANK YOU
INTRODUCTION
INTRODUCTION
HYPERGLYCOSYLATED HCG
• Hyperglycosylated hCG (hCG-H) is a glycosylation variant of
the hormone hCG.
• it is a very differ...
SUMMARY CONTD
• Hyperglycosylated hCG is a biological variant of
BhCG still under research and is believed to enhance
the ...
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  1. 1. Gestational Trophoblastic Disease(GTD) Dr D. T. Dambo N.D.U.T.H.
  2. 2. INTRODUCTION • Gestational Trophoblastic Disease is a term commonly applied to a spectrum of inter-related diseases originating from the placental trophoblast. • It is a spectrum of a disease entity that worsens in prognosis with its progression from one entity to the other. • It is one of the rare human tumours that cure is achievable even in the presence of widespread dissemination.
  3. 3. INTRODUCTION • Gestational Trophoblastic Disease are classified into` -Hydatiform mole (Complete or Partial) -Invasive mole -Placental site trophoblastic tumour(PSTT) -Choriocarcinoma • They arise from fetal tissue within the maternal host and are composed of both syncytiotrophoblastic and cytotrophoblastic cells except PSTT, which is derived from intermediate trophoblastic cells.
  4. 4. INTRODUCTION • These conditions represent a neoplastic spectrum with moles at the benign end, and choriocarcinoma at the malignant extreme, and invasive mole being equivalent to a neoplasm of borderline malignancy.
  5. 5. Incidence & Epidemiology The incidence of GTD is higher in Asia and Latin America than in western countries. - South Asia – 3.2 to 9.9 per 1000 pregnancies. - In Europe/North America – 0.6 to 1.1 per 1000 pregnancies. - Mexico – 4.6 per 1000 pregnancies. - Japan – 2 per 1000 pregnancies. - Philippines – 5.0 per 1000 deliveries. - Nigeria – 2.6 per 1000 deliveries(highest in Yorubas). - NDUTH -- 3 cases in 2010. 6.2 per 1000 deliveries
  6. 6. Risk Factors • Racial –more common in Orients, blacks > Caucasians • ABO group: Women with blood type A or AB are at slightly higher risk than those with type B or O. • Age: < 20 and >40yrs • Consanguineous marriages • Previous molar pregnancy (2% after one, 25% after two) • Previous spontaneous abortion (2-3x after one abortion > nil) • Multiparity • Low social class • Diet – low protein, folic acid and vitamin A
  7. 7. Pathophysiology • Complete hydatidiform mole – • an abnormal conceptus, without an embryo. • Characterised by generalized swelling of the placental villi, with diffuse trophoblastic hyperplasia. • comprised of both cytotrophoblast and syncytial elements. • It is avascular • A classic mole resemble a bunch of grapes. • Serum and tissue HCG levels are markedly raised. • May either resolve or may progress to invasive mole or choriocarcinoma(15-20%).
  8. 8. Pathophysiology Partial hydatidiform mole – an abnormal conceptus with an embryo or fetus that tend to die early. • The placenta has focal villous swelling and focal trophoblastic hyperplasia with cistern formation. • The chorionic villi have characteristically marked scalloping and prominent stromal trophoblastic inclusions. • Less often progress to choriocarcinoma
  9. 9. Pathophysiology • Invasive mole – this is a tumour invading the • • • • myometrium . Commonly results from complete hydatidiform mole. Usually does not progress to choriocarcinoma. If untreated it invades the uterine wall and , resulting in perforation and haemorrhage. May resolve spontaneously
  10. 10. Pathophysiology Placental site trophoblastic tumour – • a tumour arising from the trophoblastic tissue of the placental bed. • Composed mainly of cytotrophoblastic cells and produces low levels of hCG relative to its mass. • Produces abundant human placental lactogen(HPL). • Though locally invasive, many are self limiting and subject to cure by hysterectomy or surgical excision. • This condition is much more resistant to standard chemotherapy than other forms of GTB.
  11. 11. Pathophysiology • Gestational choriocarcinoma – it is a carcinoma arising from trophoblastic epithelium that shows both syncytiotrophoblastic and cytotrophoblastic elements. • Preceding conception could result in a live birth, stillbirth, abortion at any stage, ectopic pregnancy or hydatidiform mole. • Antecedent pregnancy – -50% - complete mole - 25% - abortion - 22% - normal pregnancy - 3% - ectopic pregnancy
  12. 12. Genetics • Complete mole results when a haploid sperm (23x) fertilizes an empty ova (nucleus is lost or inactivated) and duplicate itself to form a 46xx complement – paternal chromosomes. • A small percentage of complete mole results from dispermy – 2 haploid sperm (23x) fertilizing an empty egg. • The karyotype of complete mole is usually 46xx(homozygous) and only in minority is it 46xy(heterozygous).
  13. 13. Genetics • A complete mole with 46yy chromosome complement is never seen – b/c at least one xchromosome is essential for cell survival.
  14. 14. genetics Partial hydatidiform mole results from triploidy (69xxx or 69xxy or 69xyy) with one maternal(23x) and 2 paternal(23x,23y) chromosome sets. – About 90-93% of partial mole have been reported to be triploid. – some may have tetraploid karyotype.
  15. 15. Clinical Features Complete Mole 1.Vaginal bleeding – most common 97% 2. Dislodged pieces of tumour that pass from vagina, resembling a bunch of grapes(vessicles). 3.Pre-eclampsia/PIH - 27% of patients with complete moles. May occur as early as 16Wks 4. Hyperemesis gravidarum – 8% 5. Changes in uterine size – 28%. a)Uterus larger than dates in 50% of cases’ b)Uterus corresponds with dates in 25% c)Uterus smaller than dates in 25%
  16. 16. .
  17. 17. Clinical Features 6. Lack of fetal movement. 7.Hyperthyroidism – 7% 8. Features of trophoblastic embolisation – Respiratory distress 9. Theca Lutein ovarian cysts. Abdominal pain due ovarian accidents. Disappear in 4 months following evacuation. 10. DIC
  18. 18. Clinical Features Partial Moles -Do not exhibit most of these dramatic features. -Generally they have signs and symptoms of incomplete or missed abortion
  19. 19. Clinical Features • INVASIVE MOLE Irregular vaginal bleeding - Theca lutein cysts - Uterine subinvolution - Persistently elevated serum hCG levels - Intra peritoneal bleeding (perforation through myometrial wall) - Abnormal Vaginal discharge/acute pelvic pain when there is associated sepsis −
  20. 20. Clinical Features • CHORIOCARCINOMA Has a tendency toward early vascular invasion with wide spread dissemination. Most common sites are - lungs Vagina Pelvis Liver Brain -80% -30% - 20% - 10% - 10% . Symptoms Relating to metastasis are due to spontaneous bleeding at metastatic site. Lungs - Chest pain Cough, haemoptysis, dyspnoea
  21. 21. Clinical Features • Vagina Suburethral nodule, fleshy mass Hepatic - Irregular vaginal bleeding Abnormal Vaginal discharge - - CNS- Epigastric or Right upper quadrant pain May cause hepatic rupture/intra peritoneal bleeding when the lesion is Haemorrhagic. Focal Neurologic deficit following spontaneous haemorrhage in the brain.
  22. 22. Features of Complete and Partial mole .
  23. 23. STAGING • The official International Federation of Gynecology and Obstetrics(FIGO) staging of gestational trophoblastic neoplasia is as follows: • Stage I – Confined to the uterus • Stage II – Limited to the genital structures (ovary, tube, vagina, broad ligament) • Stage III – Lung metastases with or without known genital tract involvement. • Stage IV – Other metastases Substage • A – No risk factor • B – One risk factor • C – Two risk factors
  24. 24. • RISK FACTORS AFFECTING STAGING INCLUDE: 1. hCG > 100,000 IU / 24-hour urine 2. The detection of disease > 6 months from termination of the antecedent pregnancy to diagnosis.
  25. 25. Prognostic scoring systems The American National institute of health (N.I.H ) system Modified WHO Prognostic Scoring System as Adapted by FIGO. Based on Bagshawe`s analysis of the prognostic factors.
  26. 26. Revised FIGO Scoring System .
  27. 27. • The total score for a patient is obtained by adding the individual scores for each prognostic factor. Total score • -A score of 6 or less – low risk disease treatable by single agent chemotherapy • -A score of 7 or greater – high risk disease that requires combination chemotherapy. • - Minimum score = 0, maximum sore = 25 • -Medium risk categorization no more in use
  28. 28. • THE AMERICAN NATIONAL INSTITUTE OF HEALTH (NIH) Clinical criteria - Non metastatic - Metastatic (GTN)- disease outside the uterus a) Good prognosis b) Poor prognosis
  29. 29. THE AMERICAN NATIONAL INSTITUTE OF HEALTH (NIH) contd 1. Good- Prognosis metastatic disease (i.e.,absence of high risk factor) a. Short duration(<4 months). b. Serum B-hCG < 40,000mIU/ml (PRETREATMENT) c. No metastasis to brain or liver d. No prior unsuccessful chemotherapy e. No malignant GTN following term pregnancy
  30. 30. 2. Poor-prognosis metastatic disease (i.e.,any single high risk factor) a. Long duration (>4 months). b. Serum B-hCG >40,000mIU/ml c. Metastasis to brain or liver d. Prior unsuccessful chemotherapy e. Gestational trophoblastic neoplasia following term pregnancy.
  31. 31. SURVIVAL RATE -Based on data from the new England Trophoblastic disease center: -The overall survival rate for stages I,II & III ( OR NON-METASTATIC AND LOW RISK METASTATIC) is virtually 100%. -Stage IV ( OR HIGH RISK METASTATIC) dx Survival rate - 70-73%
  32. 32. Differentials • • • • • Abortion Ectopic pregnancy Pre-eclampsia Hyperthyroidism Cervical cancer
  33. 33. INVESTIGATIONS • • • • • • • • • • • • • • • • FBC, + differential Bld culture, ABO Bld grp Urine - Urinalysis &m/c/s, HVS m/c/s, Retroviral screening HBsAg screening E/U/Cr BhCG [csf:bld ratio=1/60]. Normal serum level <2IU/L. TFT LFT CXR USS(Theca lutein cyst) CT scan (bm) MRI (sm) Histology (RPC)
  34. 34. TREATMENT Patients should be managed in a specialist unit. • SURGICAL • MEDICAL • RADIOTHERAPY • Choice of Tx modality is to a great extent dependent on -the spectrum of the disease, - the stage, -the prognostic indices.
  35. 35. SURGICAL: • • • • • • Suction evacuation. Main surgical procedure esp. in H. mole. In the theatre start with IV fluids, usually with crystalloids Select the most appropriate cannula to use, usually the largest. Oxytocin used when moderate amount has been evacuated and is maintained for 24hrs post evacuation Pulmonary trophoblastic embolization may occur especially if the oxytocin drip is started before the suction evacuation begins. This is to help the uterus to contract
  36. 36. SURGICAL: • • • • Suction evacuation contd. After suction is completed, a gentle sharp curettage is done to remove any molar tissue that may be left behind. All specimens taken should be sent for histology. Post operative ultrasound is done to verify the emptiness of the uterus. If uterus is not empty repeat the curettage in 2 weeks or when bleeding occurs.
  37. 37. SURGICAL: • Medical induction with PG, Oxytocin, Hypertonic solutions (saline,urea,glucose,) are no longer acceptable methods for evacuation of a molar pregnancy. • Hysterectomy • Craniotomy(borehole), Thoracotomy, Angio graphic embolization, Hepatic resection
  38. 38. The risk of hydatidiform mole progressing to choriocarcinoma increases • • • • • Pre-evacuation hCG level >100,000IU/l Uterine size greater than gestational age Large (>6cm) theca lutein cyst Maternal age >40yrs Use of oral contraceptive pill before hCG level falls to undetectable level • Medical induction
  39. 39. Follow-up for hydatidiform mole • Choriocarcinoma occurs in 3% of cases of complete hydatidiform mole, the risk is low with partial mole. • Follow-up is necessary to detect those who require chemotherapy for invasive mole or choriocarcinoma. • The serum hCG is assayed weekly until it becomes undetectable (< 2IU/l) 3 normal values, then monthly in the 1st year after evacuation and every 3 months in the 2nd year after evacuation.
  40. 40. • The hCG measurement should continue for at least 6 months after it has become undetectable. • The hCG must have been undetectable for 6months before starting another pregnancy. • After all subsequent pregnancy monitor hCG – due to risk of hydatidiform mole and choriocarcinoma. • Post chemotherapy – hCG follow-up is for life.
  41. 41. Criteria for chemotherapy after hydatidiform mole • High hCG level more than 4 weeks after evacuation. Serum level > 20,000IU/l or urine level > 30,000IU/l • Progressively rising hCG levels at anytime after evacuation. • Beta-hCG levels rising for 2 successive weeks. • Beta-hCG constant(plateau) for 3 successive weeks. • Beta-hCG levels elevated at 15 weeks postevacuation. • Rising Beta-hCG titer after reaching normal levels.
  42. 42. Criteria for chemotherapy after hydatidiform mole contd • Raised hCG levels 6 months after evacuation (even if falling). • Persistent uterine bleeding and positive hCG levels • Histological diagnosis of choriocarcinoma • Evidence of CNS, renal, hepatic, GIT or pulmonary metastasis > 2cm in diameter or >3 in number.
  43. 43. MEDICAL-CHEMOTHERAPY Single agent therapy: Methotrexate or actinomycin D • MTX 30-60mg/m2 once a wk. For non-metastatic only. • MTX 0.4mg/kg/day IV or IM x5/7, repeat every 14/7. • MTX 1 mg/kg IM on days 1,3,5,and 7 and folinic acid 0.1mg/kg IM on days 2,4,6,and 8, repeat every 15-18 days. • Actinomycin – D 12µg/kg/day IV for 5 days • Actinomycin – D 1.25mg/m2 IV every 2 weeks • This drug may be especially useful in patients with liver problems, because it is less toxic to the liver than methotrexate is. This regimen is for low risk groups
  44. 44. Combination therapy for high risk group MAC Methotrexate 15mg IM Actinomycin D 0.5mg IV Cyclophosphamide 3.0mg/kg body weight. PO or Chlorambucil 6-10mg PO All daily for 5 days and repeat after 2 or 3 weeks.
  45. 45. EMA/CO Day 1: Etoposide Actinomycin D MTX Day 2: Etoposide Actinomycin D Folinic acid 100mg/m2 IV (in 200ml of N/S over 30 minutes) 0.5mg IV bolus 100mg/m2 IV bolus 200mg/m2 IV (infused over 12hrs) `100mg/m2 IV (in 200ml of N/S over 30minutes) 0.5mg IV bolus 15mg IM or orally every 12hrs for 4 doses beginning 24hrs after start of MTX. Day 8: Cyclophosphamide 600mg/m2 IV in saline Oncovin( Vincristine) 1mg/m2 IV bolus.
  46. 46. EMA/CE Day 1: Etoposide Actinomycin D MTX 100mg/m2 IV (in 200ml of N/S over 30 minutes) 0.5mg IV bolus 100mg/m2 IV bolus 1000mg/m2 IV (infused over 12hrs) Day 2: Ectoposide Actinomycin D Folinic acid 100mg/m2 IV (in 200ml of N/S over 30 minutes) 0.5mg IV bolus 30mg IM or orally every 12hrs for 6 doses beginning 32hrs after start of MTX. Day 8: Cisplatin Etoposide 60mg/m2 IV with prehydration 100mg/m2 IV (in 200ml of N/S over 30 minutes) PVB : Cisplatin, Vinblastine, Bleomycin Cisplatin Vinblastine Bleomycin
  47. 47. The side effects of chemotherapy • Common side effects of chemotherapy drugs include: • · Alopecia • · Mucositis • · Loss of appetite • · Nausea and vomiting • · Myelosupression • Most of these side effects are short-term and tend to go away after treatment is finished.
  48. 48. • Along with the effects listed above, some side effects are specific to certain chemotherapy agents: • Methotrexate can cause stomatitis, hepatitis, nephrotoxicity, dermatatis and hepatocellular damage. • Actinomycin-D can cause diarrhea & cardiomyopathy • Bleomycin can cause pulmonary fibrosis. • Cyclophosphamide can cause nephrotoxicity, ototoxicity, haemorrhagic cystitis, decrease sperm production, cessation of menstruation, infertility and secondary cancers.
  49. 49. • Etoposide and vincristine can cause constipation, paralytic ileus, neurotoxicity, peripheral neuropathy and bladder atony. • Cisplatin can cause ototoxicity, nephrotoxicity and neurotoxicity..
  50. 50. Brain metastasis • Increase the methotrexate dose in EMA-CO protocol to 1g/m2, the urine should be alkalinized with iv bicarbonate • Depending on tumour size there might be need for irradiation of whole brain or excisional surgery. • The irradiation is to prevent catastrophic haemorrhage rather than controlling the trophoblastic disease. • Irradiation may also be needed for liver metastasis.
  51. 51. • Radiotherapy: used concomitantly with combined chemotherapy in patients with liver or brain metastasis. • Cerebral metastasis Rx over 2 wks with 300 rads daily, 5 days a week, to a total organ dose of 3000 rads. • Whole liver irradiation Rx over 10 days with 200 rads daily, 5 days a week, to a total organ dose of 2000 rads • Pelvic artery embolization is used in cases of intractable haemorrhage.
  52. 52. FERTILITY • Regular menses starts btw 2-6mths following chemotherapy. • Average age of menopause is reduced by 1yr with Methotrexate & 3yrs with EMACO • Patient should avoid pregnancy for 1yr(following chemotherapy) to reduce risk of teratogenicity from chemotherapeutic agents & confusion from rising HCG levels. • 83% of patients have been able to achieve a live birth following chemotherapy
  53. 53. ROLE OF SURGERY The development of effective chemotherapeutic agents has relegated surgery to a secondary role in the management of trophoblastic tumour. Surgery has been limited to the treatment of :- resistant cases to chemotherapy, - uncontrollable haemorrhage from the uterus - Tumour perforation of the uterus - Infected uterine tumour not responding to antibiotics, thus delaying chemotherapy..
  54. 54. Role of surgery in mgt of trophoblastic diseases contd • Suction-Evacuation • Uterine perforation managed by local resection of tumour and uterine repair. • Hysterectomy may be required for persistent heavy bleeding – but usually responds to chemotherapy • Surgical removal of drug-resistant disease in resectable site. (lungs or brain)).
  55. 55. FOLLOW-UP • • • • • BhCG Titre wkly until 3 consecutive normal titres Monthly for 12 months 3 monthly for 1 additional year 6 monthly indefinitely Contraception for at least 1yr after remission(OCP, Condom) • Gynaecologic examination started 1 week post evacuation – assess Ut size, adnexal masses, check for metastases on the vulva, vagina, urethra, and cervix. If no complication repeat exam 4 wkly throughout period of surveillance.
  56. 56. FOLLOW-UP CONTD • Laboratory investigation follow-up = FBC+DIFF, E&U+C, LFT, etc • CXR repeated every 4wks for those that had pulmonary metastasis prior to evacuation, until remission, thereafter every 3 months for period of surveillance. • Switch to alternate drug in an event of BhCG titre rises 10x or more, plateaus at elevated levels, histological identification of ca cells, persistent uterine bleeding • CMT continues for 2 courses after –ve BhCG titre.
  57. 57. COMPLICATIONS: • • • • • • • • • Anaesthetic complications Uterine perforation Injury to adjacent structures Haemorrhage Sepsis Infertility Convulsion Coma Death
  58. 58. PROGNOSIS: • Excellent. • Over 90% of patients have been able to preserve reproductive functions.
  59. 59. HYPERGLYCOSYLATED HCG • Hyperglycosylated hCG (hCG-H) is a glycosylation variant of the hormone hCG. • it is a very different molecule to the hormone hCG. • hCG-H is produced by cytotrophoblast cells while regular hCG is made in syncytiotrophoblast cell. • it is an autocrine acting directly on the cells which produce it, while regular hCG is an endocrine acting on maternal corpus luteal cells. • hCG-H has minimal biological activity in promoting progesterone production compared to regular hCG. • hCG-H functions unlike regular hCG as an invasion promoter, whether invasion as in choriocarcinoma and testicular germ cell malignancies, or as in implantation of pregnancy.
  60. 60. hCG-H CONTD • hCG-H is an essential component for successful human implantation to prevent early pregnancy loss and spontaneous abortion. • hCG-H is critical for promoting the midtrimester hemochorial implantation, and for preventing pre-eclampsia. • measurements of hCG-H have advantages over measurements of regular hCG or total hCG, in detecting pregnancy, pregnancy outcome (failing or term pregnancy), predicting pre-eclampsia in pregnancy, or as a tumor marker for gestational trophoblastic diseases. • PMID: 17346790 [PubMed - indexed for MEDLINE]
  61. 61. SUMMARY • GTD forms a spectrum of illness, from borderline malignancy of HM to Choriocarcinoma, which were fatal in the past. • However in the last 55yrs a lot has been learnt about the biology, pathology and natural history of GTD. • Furthermore, accurate diagnostic and monitoring methods have been developed, together with effective treatment regimens.
  62. 62. SUMMARY CONTD • As a result GTD is one of the modern day success stories in oncology
  63. 63. THANK YOU
  64. 64. INTRODUCTION
  65. 65. INTRODUCTION
  66. 66. HYPERGLYCOSYLATED HCG • Hyperglycosylated hCG (hCG-H) is a glycosylation variant of the hormone hCG. • it is a very different molecule to the hormone hCG. • hCG-H is produced by cytotrophoblast cells while regular hCG is made in syncytiotrophoblast cell. • it is an autocrine acting directly on the cells which produce it, while regular hCG is an endocrine acting on maternal corpus luteal cells. • hCG-H has minimal biological activity in promoting progesterone production compared to regular hCG. • hCG-H functions unlike regular hCG as an invasion promoter, whether invasion as in choriocarcinoma and testicular germ cell malignancies, or as in implantation of pregnancy. These functions seemingly occur through action on cytotrophoblast cell TGFbeta receptors.
  67. 67. SUMMARY CONTD • Hyperglycosylated hCG is a biological variant of BhCG still under research and is believed to enhance the management of GTD because it has been found to be more sensitive than BhCG in detecting quiescent variant of GTD as against the invasive variety. • As a result GTD is one of the modern day success stories in oncology
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