Gestational tropoblastic disease.prof presentation,

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Gestational tropoblastic disease.prof presentation,

  1. 1. K H A L I D S A I T C H A I R M A N O F S C I E N T I F I C C H A I R O F P R O F . A B D U L L A H H U S S A I N B A S A L A M A H F O R G Y N E C O L O G Y O N C O L O G Y D I R E C T O R O F G Y N E C O L O G Y O N C O L O G Y U N I T P R O F E S S O R F A C U L T Y O F M E D I C I N E K I N G A B D U L A Z I Z U N I V E R S I T Y GESTATIONAL   TROPHOBLASTIC  DISEASE  
  2. 2. DEFINITION   •  It is an abnormal condition of the ovum where there are partly degeneration and partly hyperplastic changes in the young chorionic villi, these result in the formation of small cysts of varying size. •  Because of its superficial resemblance to a hydatid cyst, it is named as hydatidiform mole. •  It is best regarded as a benign neoplasia of the chorion with malignant potential.
  3. 3. • H Y D AT I D I F O R M M O L E • P E R S I S T E N T / I N VA S I V E • C H O R I O C A R C I N O M A • P L A C E N TA L S I T E T R O P H O B L A S T I C T U M O R S GESTATIONAL   TROPHOBLASTIC  DISEASE  
  4. 4. INCIDENCE   •  In Western countries, 1 per 1000-1500 pregnancies •  1/20-30000 pregnancies in Canada. •  Latin American nations often have high rates (1 per 12 to 500 pregnancies). •  Twofold increased risk in Saudi Arabia and Japan compared to other population •  In Saudi Arabia, 1.2 per 1000 pregnancies •  Japan has 2 per 1000 pregnacies. •  In the Far east, 1 per 120 pregnancies. ( Indonesia 1:85)
  5. 5. RISK  FACTORS  FOR  MOLER  PREGNANCY   •  Extremes of reproductive years( maternal age ) •  Prior moler mole •  Prior spontaneous abortion •  Vit A deficiency •  Smooking •  Infertility •  Nulliparity •  OCP •  Race
  6. 6. CLINICAL  PATHOLOGY  OF  GESTATIONAL   TROPHOBLASTIC  DISEASE   •  1- Cytotrophoblast and syncytiotrophoblast cells proliferation Moler pregnancy ( complete – partial ) Invasive mole Choriocarcinoma •  2- Intermediate trophoblastic cells derivative Placental – site tumor
  7. 7. ETIOLOGY   •  The cause is not definitely known, but it appers to be related to the ovular defect as it sometimes affect 1 ovum of a twin pregnancy. Suggested hypothesis are: ü Its prevalence is highest in teenage pregnancies and in those women > 35yrs. ü Faulty nutrition caused by inadequate intake of high class protein could partly explain its prevalence in the oriental countries low dietary intake of carotene is associated with increase risk
  8. 8. ETIOLOGY   ü Disturbed maternal immune mechanism suggested by: Ø Rise in gamma globulin level in absence of hepatic disease Ø Increased association of of AB blood group which posses no ABO antibody. ü Cytogenic abnormality
  9. 9. Diandric diploidy •  5 % result from dispermic fertilization of empty egg which can result into either 46 xx or 46 xy •  Infrequently the chromosomal pattern maybe 46xx or 45x
  10. 10. Diandric triploidy
  11. 11. HISTOLOGIC  FEATURES   •  COMPLETE MOLE •  No fetal tissue •  Diffuse chorionic villi swelling with trophoblastic hyperplasia •  46XX(90%) or 46XY entirely of paternal origin •  PARTIAL H.MOLE •  Fetal tissue present •  Focal chorionic villi swelling with trophoblastic hyperplasia •  Triploid(90%) 69 XXY, 69 XXX, 69 XYY).
  12. 12. HISTOLOGICAL  FINDINGS   •  Complete Mole( triad): Fetal tissue is absent, severe trophoblastic proliferation, hydropic villi. Additionally, complete moles show over expression of several growth factors, including c-myc, epidermal growth factor, and c-erb B-2, compared to normal placenta.
  13. 13. •  Partial Mole: Fetal tissue is often present as well as amnion and fetal red blood cells. Hydropic villi and trophoblastic proliferation are not alot.
  14. 14. CASE PRESENTATION •  36 y.o P4 + 0 •  She had H/o amenorrhea for 16 wks , presented with mild PV bleeding and lower abdominal pain •  Examination pulse 100/min BP120/80 •  Abd/ soft, not tender - 24 weeks uterus •  V/E minimal bleeding, cervix normal and close , uterus 20 weeks size and no adnexial masses •  HCG= 200,000 •  u/s
  15. 15. CLINICAL  FEATURES   COMPLETE  MOLE       •  Large for date 50 % •  Hyper emesis 20 % •  Early PIH 5% •  Absent FH ( except in partial mole or twin pregnancy) •  Hyperthyroidism symptom and sign 5% •  Rarely presented with metastasis symptom and sign •  Theca Lutein Cysts regress after treatment •  3 % asymptomatic of cases
  16. 16. •  Twinning with complete mole and a fetus with normal placenta has been reported. Cases of healthy infant in these circumstances have been reported.
  17. 17. PARTIAL  MOLE   •  - Uterine enlargement and pre eclamsia is reported in only 3% of patients. - Theca lutein cyst, hyperemesis and hyperthyroidism are rare.
  18. 18. Ø Very rarely, women can present with acute respiratory failure or neurological symptoms such as seizures; these are likely to be due to metastatic disease.
  19. 19. LABARATORY  STUDIES   •  Quantitative beta-HCG levels greater than 100,000mlu/ml indicate exuberant trophoblastic growth and raise suspicion •  A molar pregnancy may also have a normal HCG level.
  20. 20. IMAGING  STUDIES   •  The classic image is of a snowstorm pattern
  21. 21. MANAGEMENT  OF  MOLER  PREGNANCY  
  22. 22. PATIENT  COUNSELLING   •  Explain •  Consent •  preoperative preparation
  23. 23. PRIOR  TO  EVACUATION       v CBC v Type and screen v Quantitative BhCG v TSH,LFT,RFT v CXR
  24. 24. MANAGEMENT Ø Suction curettage. Ø when the size of the fetal parts deters the use of suction curettage and then medical evacuation can be used.
  25. 25. MANAGEMENT Ø Preparation of the cervix immediately prior to evacuation is safe. Ø a senior surgeon directly supervising surgical evacuation is advised Ø The use of oxytocic infusion prior to the evacuation is not recommended.
  26. 26. FOLLOW  UP  POST  EVACUATION   •  Serum level ,within 48 hours of evacuation •  Weekly untill hCG become normal for three weeks •  Monthly for 6-12 months •  Reliable contraception recommended during hCG surveillance. •  The histological assessment of material obtained
  27. 27. GTN  RISK Ø The need for chemotherapy following a complete mole is 15%( 10 % LOCALIZED DISEASE AND 5 % METS) and 1 % after a partial mole. Ø The development of postpartum GTN requiring chemotherapy occurs at a rate of 1/50 000 births
  28. 28. FACTORS THAT PREDICT THAT PATIENT WITH MOLAR PREGNANCY MAY REQUIRE CHEMOTHERAPY:     1- Age more than 35 2- Uterine size more than 20 weeks 3- Initial B HCG more than 100,000 miu/ml 4- Presence of bilateral theca luteal ovarian cyst
  29. 29. •  Prophylactic chemotherapy for hydatidiform mole?
  30. 30. FIGO  CRITERIA  FOR  THE  DIAGNOSIS  OF   POST  MOLAR  GTN     •  ■A serum hCG concentration that plateaus (decline of less than 10 percent for over three weeks) •  ■A serum hCG concentration that rises (increase more than 10 percent of three values over two consecutive weeks eg, day 1, 7, 14) •  ■Persistence of detectable serum hCG for more than six months after molar evacuation * Presence of choriocarcinoma histopathology J Reprod Med 2002; 47:445.
  31. 31.            PERSISTENT  GTD     •  90 % invasive mole •  <10 percent are choriocarcinomas •  PSTTs are rare.
  32. 32. GTN   •  Malignant transformation of trophoblastic tissue is probably related to activation of oncogenes and inactivation of tumor suppressor genes •  The presence of metastatic disease usually implies the presence of choriocarcinoma rather than invasive mole
  33. 33. CASE  PRESENTATION   •  A patient diagnosed with complete mole after evacuation and during the follow up her HCG were not decrease ( 14000. 13800.13850)over three weeks period.
  34. 34. CHOICES     •  Repeat D and C •  Start chemotherapy •  Do work up then decide
  35. 35. •  To diagnose metastases: •  CXR or CT Scan shows lung lesions will be acceptable, CXR to count the lung lesions •  CT Scan or U/S to document liver metastases will be acceptable •  For brain metastases MRI is superior to CT even with cuts <1cm
  36. 36. INVESTIGATIVE  TOOLS  TO  DIAGNOSE   METASTASES   •  High-risk sites of metastases rarely occur without pulmonary metastases. Cancer 1990 •  Cerebral metastases are rare unless there are concurrent lung or vaginal metastases. •  Therefore CT or MRI brain scans may be omitted in those patients without vaginal or lung metastases on chest X-ray. Best Practice & Research Clinical Obstetrics and Gynaecology 2003
  37. 37. CASE  PRESENTATION     •  40 year Indian patient G7 P5 +1 •  Referred from Makah as case of GTN •  She is five months post evacuation of complete mole •  follow up ?? •  Quantitative BhCG 200.000 •  CT abdomen showed multiple liver mets
  38. 38. SECOND  UTERINE  EVACUATION Ø No clinical indication for the routine use of second uterine evacuation Ø Some case series have found that there may be a role for second evacuation in selected cases when the hCG is less than 5000 units/lit. and patient severely bleeding
  39. 39. HYSTERECTOMY   • 
  40. 40. MANAGEMENT OF MOLAR PREGNANCY Risk of Persistent GTT Procedure 20 %Suction Evacuation 5%Hysterectomy
  41. 41. MALIGNANT  GTD(  GTN)   •  Invasive mole •  Choriocarcinoma •  PSTT
  42. 42. INVASIVE  MOLE   •  Typically appears as one or more poorly defined masses in the uterus with anechoic areas. •  Color Doppler of the anechoic areas reveals high vascular flow. •  Invasion into the myometrium may be visualized •  Rarely metastasis
  43. 43. PLACENTA  SITE  TROPHOBLASTIC     (TUMORS(  PSTT     Slowly-growing malignant tumors , can metastasis •  derived from intermediate cytotrophoblast cells •  <0.2 %   •   30 percent of patients already have metastases at presentation •  Lymph node metastases occur in 6 %   •  IF persist after evacuation will required hysterectomy because it is highly resistant to chemotherapy. •  Mets disease mortality up to 50 % •  PSTT generally present months to years after a term gestation. •  Irregular vaginal bleeding and an enlarged uterus are common, a mass in the uterus ( myometrium involvement) . •  virilization may occur, and nephrotic syndrome has been reported •  The serum hCG concentration in PSTT is relatively low relative to the tumor volume ( less than 100) •  Secrete HPL
  44. 44. CHORIOCARCINOMA   • 50% of choriocarcinoma cases follow a hyatidiform mole •  25% form after an aborted pregnancy • 25% form after a term pregnancy. Klatt, et al. Cancer 3-15-1990;65:1456-9.
  45. 45. DISCUSSION   KLATT,  ET  AL.  CANCER  3-­‐15-­‐1990;65:1456-­‐9.   •  Metastasis from choriocarcinoma is common: •  80% have lung lesions •  30% have vaginal lesions •  20% have pelvic lesions •  10% have brain lesions •  10% have liver lesions and bowel •  kidney and spleen are affected in less than 5%. •  Intracardiac tumors are very occasionally identified as Metastatic choriocarcinoma.
  46. 46. MANAGEMENT  OF  PERSISTANT  GTD   •  Hysterectomy •  D and C •  Give oral methoraxate •  Do risk assessment and start chemotherapy accordingly
  47. 47. MODIFIED WHO PROGNOSTIC SCORING SYSTEM AS ADOPTED BY FIGO   score 0 1 2 4 Age < 40 ≥ 40 - - Antecedent pregnancy H-mole abortion Term pregnancy - Interval (mo) from index pregnancy <4 4 - 6 7 - 12 >12 hCG level <103 103 - 104 >104 - 105 >105 Largest tumor size (including uterus) - 3 - 4 cm ≥5 cm - Site of metastases - kidney, spleen GI tract brain, liver Number of metastases - 1 - 4 5 – 8 >8 Previous failed chemotherapy - - Single drug two or more drugs •  low-risk group (score ≤ 6) •  High-risk group (score ≥7)
  48. 48. REMINDER  
  49. 49. THE  CHEMOTHERAPY Ø Women with scores ≤ 6 are at low risk and are treated with single-agent chemotherapy. Ø Women with scores ≥ 7 are at high risk and are treated with intravenous multi-agent chemotherapy
  50. 50. SINGLE AGENT CHEMOTHERAPY 1)  Methorexate 1gm/kg on day 1,2,3 and 7 Folinic acid 0,1mg/kg IM on day 2,4,6 and 8 ( repeat every 7 days if possible) 3)  Methotraxate 30-50 mg/m2 IM weekly 2)  Dactinomycin 1,25 mg/m2 iv Q 2 w max 2 mg 3)  Etoposide 200mg/m2 po Q12 days
  51. 51. •  If hCG values have not decreased by 10%, treatment should be changed to alternative single-agent regimen. •  In case of failure, the patient should be referred to specialized center.
  52. 52. MULTI AGENT CHEMOTHERAPY - MAC - CHAMOMA( Bagshawe 1970) met/cyclo/ doxoru/hydroxyurea and vincrestin - Modified CHAMOMA(Surwit) melphalan - EMA-CO ( Charing Cross Hospital in London)
  53. 53. REMISSION  OF  GTN     Disease 5 year survival •  Low risk 100% •  High risk 86%
  54. 54. FOLLOW-­‐UP  POST  TREATMENT   •  Low Risk (Treated): HCG’s weekly until 3 (neg), then monthly for 12 months, then q 3 months X 1 yr. (for an additional year of follow up). Pregnancy allowed after 12 months of normal titres and US is recommended to confirm the pregnancy. At the completion of pregnancy, the placenta/currettings must be examined histological with a report sent to the registry, Beta HCG 6 weeks after pregnancy, irrespective of outcome. •  High Risk (Treated): HCG’s weekly until 3 (neg), then monthly for 2 years, q 3 months for the 3rd year, q 6 months for the 4th year, then yearly thereafter. Pregnancy allowed after 24 months of normal titres and US is recommended to confirm the pregnancy.  Beta HCG 6 weeks after pregnancy, irrespective of outcome. 
  55. 55. •  Successful pregnancy has been reported even in patient who survived after chemotherapy for high risk metastatic disease
  56. 56. TREATMENT FAILURE FACTORS 1) Extensive disease 2) Inadequate initial treatment: 3) Interruption of treatment cycles
  57. 57. RECURRENCE OF GTN DISEASE RECURRENCE Moler pregnancy 2 % Low rish GTD 5 % High risk GTD 15 % The mean time to recurrence from the last non-detectable hCG level was 6 months
  58. 58. POST  CHEMO Ø Women who receive chemotherapy for GTN are likely to have an earlier menopause Ø Women with high-risk GTN who require multi-agent chemotherapy which includes etoposide should be advised that they may be at increased risk of developing secondary cancers.
  59. 59. THE  MOST  IMPORTANT  FACTORS   TO  ASSURE  SUCCESSFUL  THERAPY     •  Experience with gestational trophoblastic disease •  Experience with chemotherapy •  Patient’s compliance
  60. 60. WE  DO  HAVE  PROBLEM…..   •  No Proper initial treatment of initial of diagnosis of moler pregnancy •  No Proper follow up with HCG •  No good Interpretation of the HCG drop •  Tendency of repeating D and C ???? •  Thinking that Hysterectomy is the answer for persistent GTD ?????? •  Improper selection of chemotherapy •  Improper management of patient during and after chemotherapy
  61. 61. SAUDI  GTD  REGISTRY     Gynecology oncology unit
  62. 62. SAUDI  GTD  REGISTRY     Objective •  To get exact incidence of GTD in Saudi Arabia •  If GTN diagnosed treatment is coordinated with gynecology oncology
  63. 63. WHO  SHOULD  REGISTERED  ?     •  All cases of molar pregnancy or GTN ie partial ,complete mole and choriocarcinoma •  Patient with unexplained elevation of hCG titer can also be registered •  The registry provides services to women and physician in western region in Saudi Arabia and well accept registration from all region in Saudi Arabia
  64. 64. SAUDI  GTD  REGISTRY     How to get registered? •  Registration is accepted fro all sources v Gynecology v General practitioner v Pathologist •  Registration form fax to gynecology oncology unit at KAUH Fax 026401000 ext 11480 E-mil gou_kauh@yahoo.com •  Follow up recommendation is then made to the responsible physician
  65. 65. CASE  PRESENTATION   •  40 years old was diagnosed with low risk GTD received single agent methoraxate •  Hcg was reched 80 •  A week after was 75 •  A week later was 78 •  What to do ?
  66. 66. PHANTOM  HCG   •  Falsely elevated hCG can occur due to heterophilic antibodies in the assay. This is due to human anti-mouse Ab (HAMA), reacting with mouse Ab used in assays. •  It does not pass into urine so hCG should be negative. •  Another way to rule out this lab error is to retest with another type of assay that uses serial dilutions(competitive RIA. (HCG REFERANCE CENTER IN USA) •  Unnecessary chemotherapy or surgical intervention can be avoided
  67. 67. KEY  WORDS   •  Group of disease with wide range of neoplastic potential •  Create a lot of challenge for us in term of diagnosis and treatment •  Diagnosis and management will depends on the history, HCG level and metastasis work up •  Women with metastatic GTD should be referred to specialized with experience treating the disease •  GTD IS A RARE ENTITY THAT IS HIGHLY CURABLE , EVEN IN THE PRESENCE OF WIDESPREAD METASTASES
  68. 68. THANK YOU

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