Dr. Muhabat Salih Saeid MRCOG-London-UK
Definition : It is a clinical term used to indicate three closely related conditions characterized by active abnormal prol...
 These neoplasms retain certain characteristic of the normal placenta such as invasive tendencies and the ability to make...
 Pathological classification : Hydatidiform mole = 80 % of cases. Invasive mole =12-15% of cases. Choriocarcenoma=5-8%...
 The hydatidiform mole incidence ranges from 1  in 522 pregnancies in Japan To 1 in 1500 pregnancies in USA,and Sweden, ...
 The maternal age over 40 years found to have a 5.2-fold increased risk of trophoblastic disease in compression to the mo...
 Hydatidiform mole can be subdivided into:complete andpartial mole
 Based on:1.Genetic    and2.Histopathologicalfeatures
   Genetic features: One of the most remarkable  discoveries about hydatidiform mole has been the  demonstration that com...
•10
Aretriploid in originwith two sets ofpaternal haploid genesand one set of maternalhaploid genes
•12
 They   occur, in almost all  cases, following dispermic  fertilization of an ovum. There is usually evidence of  a fetu...
   In the partial moles ,the normal    finding is a triploid karyotype ,69    chromosomes instead of normal 46.    The mo...
Complete mole : there are numerous   edematous vesicles, which looks like a bunch of small clear grapes, usually no fet...
      microscopically: there are:    large oedematous enlarged villi ,   a vascular ,   with variable degree of tropho...
•Partial mole•Complete mole                                 •17
•Partial mole•Complete mole                                 •18
   Partial mole: Shows  a less clear -cut picture ,with  the formation of vesicles usually focal , fetus and membranes ...
 In general ,the more active  trophoblastic appearance the  greater the risk of malignancy. So the subsequent management...
Bleeding   : Bleeding in early pregnancy after variable period of amenorrhea is the most common clinical sign of the mole...
Hyperemesis    gravidarum : Occurs into 25% of cases of moles ,and appears more common when the uterus is much enlarged a...
 Uterine  enlargement: The uterus is  commonly “large for date”in 50% of case of  moles , although, in a small proportio...
Large  theca lutein cysts of the ovary are present in “20%”of moles , these may be exaggerated the clinical picture of la...
•25
   Pre-eclampsia :Occur in association    with the moles with range widely from    12-54%,these due to differing times of...
 Hyperthyrodism: Develop    in small proportion of women ,and this may be due to thyrotrophic effects of the human chorio...
History and examination : From the history of amenorrhea ,passage of vesicles vaginally with bleeding ;the size and consi...
The increasing use ofultrasound in earlypregnancy has probablyled to the earlierdiagnosis of molarpregnancy
By the U/S examination canbe diagnosed from very earlypregnancy ,characterized by“Snow-storm" appearance.
•31
By very high levels of serumhCG than the normal singletonpregnancy ,which is diagnosticand prognostic to the course ofthe...
The risks of hydatidiform mole are: Immediate hemorrhage ,sepsis, or pre-  eclampsia; the treatment of these  conditions ...
   Choriocarcinoma: The most important    danger association with the    hydatidiform mole is the development    of malig...
The aim of treatment is to eliminate all trophoblastic tissue from the maternal systems ; If the hydatidiform mole diagnos...
Suction & curettage(S&C): The method ofchoice even whenevacuation large mole
   Under GA.   Cervix dilation till 12mm.and S&C induced    to the uterine cavity.   I.V oxytocin infusion is started ....
Uterine   stimulation.
Medical termination of complete molar pregnancies including cervical preparation prior to suction evacuation, should be av...
 The contraction of the myometrium  may force tissue into the venous spaces  at the site of the placental bed. The disse...
Surgical   evacuation:
   Surgical evacuation: Hysterectomy has been    recommended as a suitable method of    treating hydatidiform mole in old...
 Inpartial molar pregnancies where the size of the fetal parts deters the use of suction curettage, medical termination c...
   After the uterus has been evacuated : About  90% of cases ,the trophoblastic tissue  die out completely. About 10% o...
So it is important that women who have had a hydatidiform mole: should have close follow-up by serum hCG levels after th...
 After a molar pregnancy ,the hCG  levels will usually have returned to non  pregnant levels by 4 to 6 weeks after  evacu...
 Serial quantitative measurement of serum hCG level at weekly intervals, after evacuation of moles till 4 to 5 weeks when...
 Indicationof chemotherapy after the evacuation of the hydatidiform mole in:Serum hCG >20000 i.u/L , at any time after e...
Evidence  of metastases ,hepatic,brain,and pulmonary.Persistent uterine hemorrhage after evacuation of mole with raised ...
   To achieve effective follow-up ,the    pregnancy is better to be avoided ,and also    the use of oral contraceptive pi...
Malignant trophoblastic disease can exist in two forms:Invasive mole = non-metastatic form.Choriocarcinoma = metastatic...
 Both treated with the chemotherapy  and monitored by hCG tumor marker. Choriocarcinoma subdivide into : good-prognosis...
 The diagnosis of invasive moles or  “chorioadenoma destruens” is applied to  the moles characterized by : Abnormal pene...
    The proliferative villi may invade the    myomatrum ,paramatrum or the vaginal    wall, although there is rarely evid...
 Choriocarcinoma subdivide into:good-prognosis (low risk).Poor- Prognosis (High risk).
•56
 The  incidence of choriocarcinoma  in the West: 1 :10000 and 1:70000  pregnancies; and In Asia between 1:250 and 1:6000...
 The antecedent pregnancy is :Hydatidiform mole in about 57% of cases.Normal pregnancy in about 26% of cases.Abortion ...
 The risk of Choriocarcinoma after a hydatidiform mole is about 2-4% which is 1000 times greater than after a normal preg...
 Choriocarcinoma     is more  likely to occur after complete  mole . The incidence is in excess in  maternal blood group...
 Site: In the uterus 90% of cases; 10 % of cases in the ovaries ,vagina, vulva, lung, liver, and brain.
 Macroscopically: Uterus: It may be localized in the form of hemorrhagic polyp or multiple hemorrhagic ,necrotic masses ...
Ovaries : May show stormal lutein hyperplasia, and theca-lutein cysts. And may be site of secondaries.
 Microscopically: Malignant hyperplasia of both  cytotrophoblasts,and syncytiotrophoblasts. Extensive hemorrhage. Abse...
   Direct : Through the myomatrum and    may end in uterine perforation    ,internal hemorrhage, and peritonitis    .Thro...
•66
 Blood : The main method of spread ,and  occurs to; Genital : Vagina, vulva, and ovary. Extra genital : Lung, liver, br...
 Lung Vagina Brain Liver           •68
 Vaginal bleeding. Haemoptysis. Intraperitoneal hemorrhage. Peritonitis. Metastasis to the vital organs  e.g,brain. ...
 Symptoms : Recent history of expulsion of vesicular  mole ,or abortion, or full term pregnancy. Persistent vaginal ble...
 PersistentGTD should be considered in any woman developing: acute respiratory or neurological symptoms after any pregnan...
 Signs: Marked deterioration of the general condition. An abdominal swelling may be felt.
 Vaginally :The uterus  symmetrically enlarged (less than 12 weeks).The ovaries may be enlarged.Hemorrhagic secondarie...
 Investigation: Serum hCG. Chest X-ray for pulmonary metastasis. L.F.T . Liver scan. CAT scan for the secondaries. ...
The clinical classification of gestational   trophoblastic disease:I.    Non-metastatic.II.   Metastatic:A.    Low risk: A...
B. High risk:1. B-hCG level higher than   100.000miu/ml.2. Associated pregnancy episode   more than 4 months before the   ...
3.   Following full-term pregnancy.4.   Liver or brain metastasis.5.   Failure of previous chemotherapy.6.   Symptoms of m...
    Prophylaxis: After care of vesicular     mole;    D&C after one week of the     evacuation.    Monitored for the si...
II.   Diagnostic D&C is done if :     The hCG levels remains high.     The hCG levels rises after gets negative.     Ut...
I.   Non metastatic GTD:o    Methotrexate (antimetabolite) +folinic     acid.o    The cytotoxic therapy is controlled by  ...
   Women scoring: Non metastatic    GTD,and(low risk) GTD receive    intramuscular methotrexate on alternate    days, fol...
o   Physical examination, chest x-    ray, and LFT.o   Total abdominal hysterectomy ,if the    patient does not desire to ...
II.   Low metastatic GTD:o     Methotraxate , or Actinomycin D      ,if there is resistance ,change to      triple chemoth...
o   The criteria for initiation, and    continuation of each methotraxate    treatment ;   Platelet count more than 100.0...
III.   High risk metastatic GTD :o      Triple chemotherapy :       Methotraxate, Actinomycin D,       and Cytoxan.
o Surgery: TAH may    be done in patients not  desirous of further reproduction. Surgical extirpation of isolated  metas...
o Irradiation: Whole brain irradiation for cerebral metastases , The whole organ irradiation for hepatic metastases
 After successful therapy ,the hCG  levels are obtained : every 2weeks for 3 months, every month for 3months, every 2m...
 If at any time hCG levels rises, repeat  the evaluation , staging ,and  chemotherapy. Physical examination, and chest x...
 Pregnancy is not allowed except after  one year of negative follow up but with  danger of : Molar pregnancy (4-5 times ...
If a further molar pregnancy does occur, in 68–80% of cases it will be of the same histological type
 Women  who undergochemotherapy are advisednot to concieve for one yearafter completion oftreatment
THIS IS THE END OF THE LECTURE .  HOPE YOU ENJOYED IT !     THANK YOU ! ! !
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Gestational trophoblastic disease 2

  1. 1. Dr. Muhabat Salih Saeid MRCOG-London-UK
  2. 2. Definition : It is a clinical term used to indicate three closely related conditions characterized by active abnormal proliferation of trophoblastic cells : :hydatidiform mole ,invasive hydatidiform mole andChoriocarcinoma
  3. 3.  These neoplasms retain certain characteristic of the normal placenta such as invasive tendencies and the ability to make hCG hormone
  4. 4.  Pathological classification : Hydatidiform mole = 80 % of cases. Invasive mole =12-15% of cases. Choriocarcenoma=5-8% of cases. Clinical classification : The course, and prognosis of the disease accurately reflected by hCG hormone Benign = 80% Malignant=20%
  5. 5.  The hydatidiform mole incidence ranges from 1 in 522 pregnancies in Japan To 1 in 1500 pregnancies in USA,and Sweden, this variation is not understood, but ethnic factors have been suggested . The incidence is higher in the poorest socioeconomic classes than the semiprivate(4 times), and (8 times) than the privet , and these mostly related to diet especially protein deficiency .
  6. 6.  The maternal age over 40 years found to have a 5.2-fold increased risk of trophoblastic disease in compression to the mothers below the age of 35 years.
  7. 7.  Hydatidiform mole can be subdivided into:complete andpartial mole
  8. 8.  Based on:1.Genetic and2.Histopathologicalfeatures
  9. 9.  Genetic features: One of the most remarkable discoveries about hydatidiform mole has been the demonstration that complete moles have chromosomes exclusively from the paternal side ,and the karyotype is nearly always 46,xx and only rarely is 46,XY observed. The normal mechanism is for a haploid sperm,23X,to fertilize an empty egg, and to duplicate itself to form a 46,XX complement. Much less commonly ,two spermatozoa, one being 23,X, and the other,23,Y, can fertilize an empty egg, to give karyotype a 46,XY.
  10. 10. •10
  11. 11. Aretriploid in originwith two sets ofpaternal haploid genesand one set of maternalhaploid genes
  12. 12. •12
  13. 13.  They occur, in almost all cases, following dispermic fertilization of an ovum. There is usually evidence of a fetus or fetal red blood cells
  14. 14.  In the partial moles ,the normal finding is a triploid karyotype ,69 chromosomes instead of normal 46. The most common mechanism appears to be fertilization of normal egg by two sperm, giving a complement of 69,XXY.
  15. 15. Complete mole : there are numerous edematous vesicles, which looks like a bunch of small clear grapes, usually no fetus, or membranes.,
  16. 16.  microscopically: there are: large oedematous enlarged villi , a vascular , with variable degree of trophoblastic hyperplasia. carries greater risk of malignancy and requires longer follow up than the partial mole.
  17. 17. •Partial mole•Complete mole •17
  18. 18. •Partial mole•Complete mole •18
  19. 19.  Partial mole: Shows a less clear -cut picture ,with the formation of vesicles usually focal , fetus and membranes may present, the vesicles have degree of vascularity.
  20. 20.  In general ,the more active trophoblastic appearance the greater the risk of malignancy. So the subsequent management depends more on the hCG results than the histological reports.
  21. 21. Bleeding : Bleeding in early pregnancy after variable period of amenorrhea is the most common clinical sign of the mole (occurs in 90% of cases), with the passage of the vesicles.
  22. 22. Hyperemesis gravidarum : Occurs into 25% of cases of moles ,and appears more common when the uterus is much enlarged and hCG levels are very high.
  23. 23.  Uterine enlargement: The uterus is commonly “large for date”in 50% of case of moles , although, in a small proportion of cases the uterus corresponding to the gestational age or smaller than date. The uterus having a doughy consistency. The fetal parts are not palpable, and fetal heart is absent.
  24. 24. Large theca lutein cysts of the ovary are present in “20%”of moles , these may be exaggerated the clinical picture of large for date uterus. These cysts are manifestation of excessive hCG.
  25. 25. •25
  26. 26.  Pre-eclampsia :Occur in association with the moles with range widely from 12-54%,these due to differing times of diagnosis, the longer pregnancy progresses ,the greater chance to developing pre-eclampsia. If the signs of pre-eclampsia appears early in pregnancy , the possibility of hydatidiform mole should be looked for with out delay.
  27. 27.  Hyperthyrodism: Develop in small proportion of women ,and this may be due to thyrotrophic effects of the human chorionic thyrotrophin , which may lead to goitre,fine tremor ,supra-ventricular tachycardia, and weight loss. DIC can develop in long-standing hydatidiform moles , when there is embolization of trophoblastic tissue to the lung, leads to thromboplastic substances which stimulate fibrin,and platelet deposition.
  28. 28. History and examination : From the history of amenorrhea ,passage of vesicles vaginally with bleeding ;the size and consistency of the uterus.
  29. 29. The increasing use ofultrasound in earlypregnancy has probablyled to the earlierdiagnosis of molarpregnancy
  30. 30. By the U/S examination canbe diagnosed from very earlypregnancy ,characterized by“Snow-storm" appearance.
  31. 31. •31
  32. 32. By very high levels of serumhCG than the normal singletonpregnancy ,which is diagnosticand prognostic to the course ofthe disease ,with very shortdappling time.
  33. 33. The risks of hydatidiform mole are: Immediate hemorrhage ,sepsis, or pre- eclampsia; the treatment of these conditions has vastly improved recently. Molar metastases : Of a non proliferative ”benign” type can occur.
  34. 34.  Choriocarcinoma: The most important danger association with the hydatidiform mole is the development of malignant GTD(Invasive mole or choriocarcinoma) in about 10% of cases,
  35. 35. The aim of treatment is to eliminate all trophoblastic tissue from the maternal systems ; If the hydatidiform mole diagnosed ,steps should be taken to evacuate the uterus, and this achieved by:
  36. 36. Suction & curettage(S&C): The method ofchoice even whenevacuation large mole
  37. 37.  Under GA. Cervix dilation till 12mm.and S&C induced to the uterine cavity. I.V oxytocin infusion is started . S&C started by negative pressure of about 60 to 70cmHg. The curette is genteelly rotated to ovoid perforation of the soft uterus, and the majority of the molar tissue is evacuated rapidly ,and the uterine size decreases
  38. 38. Uterine stimulation.
  39. 39. Medical termination of complete molar pregnancies including cervical preparation prior to suction evacuation, should be avoided where possible.
  40. 40.  The contraction of the myometrium may force tissue into the venous spaces at the site of the placental bed. The dissemination of this tissue may lead to the profound deterioration in the woman, with embolic and metastases disease occurring in the lung
  41. 41. Surgical evacuation:
  42. 42.  Surgical evacuation: Hysterectomy has been recommended as a suitable method of treating hydatidiform mole in older women who completed their family ,to reduce the risk of post-molar trophoblastic disease . .The hysterectomy should be carried out with little monopolization to ovoid precipitating mobilization of trophoblastic tissue.
  43. 43.  Inpartial molar pregnancies where the size of the fetal parts deters the use of suction curettage, medical termination can be used.
  44. 44.  After the uterus has been evacuated : About 90% of cases ,the trophoblastic tissue die out completely. About 10% of cases the trophoblastic tissue does not die out completely and may persist or recur as : invasive mole or choriocarcinoma.
  45. 45. So it is important that women who have had a hydatidiform mole: should have close follow-up by serum hCG levels after the evacuation of the uterus,To ensure early recognition of persistent trophoblastic tissue .
  46. 46.  After a molar pregnancy ,the hCG levels will usually have returned to non pregnant levels by 4 to 6 weeks after evacuation. The follow-up is recommended for 2 years in cases of complete moles, and 6 months of cases of partial moles after the evacuation of uterus.
  47. 47.  Serial quantitative measurement of serum hCG level at weekly intervals, after evacuation of moles till 4 to 5 weeks when the hCG become normal. Then every other week .When the titer gets negative the measurements are done every month fore 1 year.
  48. 48.  Indicationof chemotherapy after the evacuation of the hydatidiform mole in:Serum hCG >20000 i.u/L , at any time after evacuation of mole. Raised hCG at 4 to 6 weeks after evacuation of mole.
  49. 49. Evidence of metastases ,hepatic,brain,and pulmonary.Persistent uterine hemorrhage after evacuation of mole with raised hCG levels.
  50. 50.  To achieve effective follow-up ,the pregnancy is better to be avoided ,and also the use of oral contraceptive pills until the hCG levels returns to normal after the evacuation of the mole. Early diagnosis of persistent trophoblastic disease ensures a good prognosis and an effective system of follow-up.
  51. 51. Malignant trophoblastic disease can exist in two forms:Invasive mole = non-metastatic form.Choriocarcinoma = metastatic form .
  52. 52.  Both treated with the chemotherapy and monitored by hCG tumor marker. Choriocarcinoma subdivide into : good-prognosis (Low-risk) ,and poor- prognosis (High-risk).
  53. 53.  The diagnosis of invasive moles or “chorioadenoma destruens” is applied to the moles characterized by : Abnormal peneterativeness and, Extensive local invasion, along with Excessive trophoblastic proliferation , With preserved villous pattern.
  54. 54.  The proliferative villi may invade the myomatrum ,paramatrum or the vaginal wall, although there is rarely evidence of metastasis. The morbidity and mortality of this disease results from the penetration of the tumar through the myomatrum and to the pelvic vessels with the resultant hemorrhage “the morbidity and mortality rate 10 %” .
  55. 55.  Choriocarcinoma subdivide into:good-prognosis (low risk).Poor- Prognosis (High risk).
  56. 56. •56
  57. 57.  The incidence of choriocarcinoma in the West: 1 :10000 and 1:70000 pregnancies; and In Asia between 1:250 and 1:6000 pregnancies..
  58. 58.  The antecedent pregnancy is :Hydatidiform mole in about 57% of cases.Normal pregnancy in about 26% of cases.Abortion and ectopic pregnancy in about 17% of cases.
  59. 59.  The risk of Choriocarcinoma after a hydatidiform mole is about 2-4% which is 1000 times greater than after a normal pregnancy.
  60. 60.  Choriocarcinoma is more likely to occur after complete mole . The incidence is in excess in maternal blood group A, and deficit in group O.
  61. 61.  Site: In the uterus 90% of cases; 10 % of cases in the ovaries ,vagina, vulva, lung, liver, and brain.
  62. 62.  Macroscopically: Uterus: It may be localized in the form of hemorrhagic polyp or multiple hemorrhagic ,necrotic masses in the cavity. Some times it is present in the uterine wall (intramural) and the cavity is empty.
  63. 63. Ovaries : May show stormal lutein hyperplasia, and theca-lutein cysts. And may be site of secondaries.
  64. 64.  Microscopically: Malignant hyperplasia of both cytotrophoblasts,and syncytiotrophoblasts. Extensive hemorrhage. Absence of villi. Destruction of the surrounding myomatrum.
  65. 65.  Direct : Through the myomatrum and may end in uterine perforation ,internal hemorrhage, and peritonitis .Through the fallopian tubes to the ovaries.
  66. 66. •66
  67. 67.  Blood : The main method of spread ,and occurs to; Genital : Vagina, vulva, and ovary. Extra genital : Lung, liver, brain, and bones especially skull and spine. The lung is the commonest site for secondaries and haemoptysis may be the presenting symptom.
  68. 68.  Lung Vagina Brain Liver •68
  69. 69.  Vaginal bleeding. Haemoptysis. Intraperitoneal hemorrhage. Peritonitis. Metastasis to the vital organs e.g,brain. Pulmonary complications.
  70. 70.  Symptoms : Recent history of expulsion of vesicular mole ,or abortion, or full term pregnancy. Persistent vaginal bleeding is the commonest presentation. Haemoptysis. Abdominal swelling (uterus or ovaries).
  71. 71.  PersistentGTD should be considered in any woman developing: acute respiratory or neurological symptoms after any pregnancy.
  72. 72.  Signs: Marked deterioration of the general condition. An abdominal swelling may be felt.
  73. 73.  Vaginally :The uterus symmetrically enlarged (less than 12 weeks).The ovaries may be enlarged.Hemorrhagic secondaries may be seen in the vagina or vulva
  74. 74.  Investigation: Serum hCG. Chest X-ray for pulmonary metastasis. L.F.T . Liver scan. CAT scan for the secondaries. EEG . U/S for abdomen and pelvis. Diagnostic D&C.
  75. 75. The clinical classification of gestational trophoblastic disease:I. Non-metastatic.II. Metastatic:A. Low risk: All patient of documented metastatic disease who do not have “high- risk factors”.
  76. 76. B. High risk:1. B-hCG level higher than 100.000miu/ml.2. Associated pregnancy episode more than 4 months before the diagnosis.
  77. 77. 3. Following full-term pregnancy.4. Liver or brain metastasis.5. Failure of previous chemotherapy.6. Symptoms of malignancy more than 4 months
  78. 78.  Prophylaxis: After care of vesicular mole; D&C after one week of the evacuation. Monitored for the signs and symptoms of trophoblastic neoplassmic by:.I. serial hCG.
  79. 79. II. Diagnostic D&C is done if : The hCG levels remains high. The hCG levels rises after gets negative. Uterine sub involution. Persistence of theca lutein cysts in the ovaries. Every case of secondary postpartum haemorrhage. Every case of post abortive bleeding.
  80. 80. I. Non metastatic GTD:o Methotrexate (antimetabolite) +folinic acid.o The cytotoxic therapy is controlled by doing CBC,platelet count and LFT.o After the the hCG level gets normal ;stop the therapy and follow-up by weekly estimation of hCG levels.
  81. 81.  Women scoring: Non metastatic GTD,and(low risk) GTD receive intramuscular methotrexate on alternate days, followed by six rest days, with each course consisting of four injections
  82. 82. o Physical examination, chest x- ray, and LFT.o Total abdominal hysterectomy ,if the patient does not desire to maintain child-bearing, in the middle of the first treatment course .
  83. 83. II. Low metastatic GTD:o Methotraxate , or Actinomycin D ,if there is resistance ,change to triple chemotherapy.
  84. 84. o The criteria for initiation, and continuation of each methotraxate treatment ; Platelet count more than 100.000. WBC more than 3000. Absolute neutrophil count between 1000- 1500. Normal LFT, renal function.
  85. 85. III. High risk metastatic GTD :o Triple chemotherapy : Methotraxate, Actinomycin D, and Cytoxan.
  86. 86. o Surgery: TAH may be done in patients not desirous of further reproduction. Surgical extirpation of isolated metastasis e.g. pulmonary if resistant to chemotherapy.
  87. 87. o Irradiation: Whole brain irradiation for cerebral metastases , The whole organ irradiation for hepatic metastases
  88. 88.  After successful therapy ,the hCG levels are obtained : every 2weeks for 3 months, every month for 3months, every 2months for 6 months then every sixes months indefinitely.
  89. 89.  If at any time hCG levels rises, repeat the evaluation , staging ,and chemotherapy. Physical examination, and chest x-ray follow-up at 6 weeks, then every 3months for one year, then every 6 months for one year.
  90. 90.  Pregnancy is not allowed except after one year of negative follow up but with danger of : Molar pregnancy (4-5 times greater risk). Spontaneous abortion. Premature delivery.
  91. 91. If a further molar pregnancy does occur, in 68–80% of cases it will be of the same histological type
  92. 92.  Women who undergochemotherapy are advisednot to concieve for one yearafter completion oftreatment
  93. 93. THIS IS THE END OF THE LECTURE . HOPE YOU ENJOYED IT ! THANK YOU ! ! !

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