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Case presentation
DR. MOHAMMAD
ASHRAFUL AMIN(ASIF)
ID-927
NAME : SHILA RANI
AGE : 27YRS
RELIGION : HINDU
ADRESS : GUMGOAN,FULPUR,MYMENSHING
MARRIAL STATUS : MARRIED
HUSBAND’S NAME : RATAN CHANDRA
DOA : 16/9/14
CASE PROFILE
1) h/o amenorrhoea for 6weeks.
2) H/O vomiting several times for 12days.
3) H/O chest tightness for same duration.
4) H/O fever and weakness also same duration.
PATIENT HISTORY
M.CYCLE >>>>>> 3-4Days
M.Period >>>>>> Regular
LMP>>>>>> 1ST JULY, 2014
MENSTRUATION HISTORY
MARRIED FOR : 12 yrs.
PARA : 2(NVD)- 1(ND) + 1 (Ab)
GRAVITA : 4th
CONTRACEPTIVE HISTROY : nil
AGE OF LAST CHILD : 6yrs
NUMBER OF LIVING CHILD : 1
OBSTRUCTIVE HISTROY
Appearance : ill looking with resp distress
Pulse : 120/min
B/P : 90/60
Temp : 100 degree F
Resp. Rate : 24/min
Anaemia : Mild
Oedema : absent
Dehydration : absent
ON EXAMINATION
P/A/E : SOFT,TENDER,NOT
DISTENDED
P/V/E : NO ACTIVE BLEEDING
ON EXAMINATION
CBEWBC : 13500 /cu mm
N : 85%L :12%
HB : 10.2 gm/dlPlatelets : 210 k/cu mmESR : 58 mm in 1st hrBlood group : B+(ve)
ON INVESTIGATION
Microscopic examination :
E.C : 4-5/HPF
R.B.C : 1-2/HPF
P.C : 2-3/HPF
CAST : NIL
URINE R/M/E
Na+ : 136 mmol/L
K+ : 3.8 mmol/L
Cl- : 105 mmol/L
HCO3 : 20.3 mmol/L
pH : 7.38
SERUM ELETROLYTES
Uterus : is bulky in size and anteverted in position. AP diameter is 49mm.
Myometrium shows uniform echo texture all over. Endometrium is thickened
(16 mm)
Right ovary : normal
Left ovary : a cystic lesion with internal irregular echogenic area measuring
about (35*20) mm is seen in left ovary.
A mixed echogenic area measuring about (7.4*6.6)cm is seen in left adnexal
region.no definite gestational sac could be detected.
Mild pelvic collection is seen.
N.B : pelvi-calyceal systems of left kidney is moderately dilated. left ureter
is dilated.
IMPRESSION : 1) suggestive of ectropic pregnancy (left) with mild pelvic
collection
2) Left ovarian haemorrhagic cyst.
3)Left sided hyroureteronephrosis
USG
B-HCG – 1483100.00 mIU/ml
(Other hospital on 15/9/14)
B-HCG -1805.0 mIU/ml
( JIMCH – ON 17/9/14)
B-HCG
Trachea – normal in position
Diaphragm – both domes of the diaphragm are normal in
position, contour and definition. The costophrenic
angles are clear.
Heart : normal in transverse diameter.
Lungs – multiple variables size rounded opacity notes in
both lugs field.
Bony thorax – reveals no abnormality.
IMPRESSION : suggestive of secondary's
CHEST X-RAY
CHEST X-RAY(19/9/14)
Lungs – multiple variables size
rounded opacity notes in both lugs
field.
IMPRESSION : suggestive of
secondary's
Laparotomy followed by
biopsy taken from ovary ,
pelvic mass. Endometrial
curettage for
histopathology.
NAME OF OPERATION
DATE:17/9/14
there was no pelvic collection. Both tubes
were healthy, ovaries were polycystic.
Biopsy from ovary was taken. Pelvic mass
in post.wall of urinary bladder. For this
assoc prof.dr.Rezaul islam took biopsy
from pelvic mass. then diagnostic D&C was
done & endometrial tissue was taken for
histopathology examination
FINDING
then she was sent to HDU on 17/9/14 in due to
respiratory distress and SPO2-50%
After on HDU (ON EXAMINATION) :
B/P : 125/78 mm Hg
Pulse : 84/min
Temp : N
SPO2 : 100% ( through BAIN circuit, 4-5L 02/min)
HDU
1. NPO-Till further order.
2. Bed rest with propped up position
3. 02 inhalation through BAIN circuit (4-6l/min)- cont
4. O-P, E-TT suction- Q1H
5. Chest and limb physiotherapy- Q1H
6. Close the both eyes with chloramphenicol eye drop-Q8H
7. Use oroclean mouth wash –Q8H
8. Inf DNS(1l) + inf DA(1L) +inf hartsol(1L)
I/V a 20drops/min-cont
9. Nebulization with windel plus –Q4H and SOS
10. Inj nutridex (100ml)
I/V over 1H-SOS (if RBS<6mmol/L)
HDU ORDER ON ADMISSION
17/9/14
INJ CEFTRON(1gm) – 1vial I/v –Q 12H
INJ METRYL (100ML) 1 bottle I/V – Q8H
INJ HYPNOFAST 3AMP(9cc) +N/S(36cc)=total 45cc,
I/V by S/P 1ml/H-Cont (stops if the BP falls)
INJ ESONIX(40mg) – 1vial I/V –Q12H
INJ EMISTAT (8mg) 1amp I/V –Q12H
INJ ANADOL (50mg)--½ Amp I/V – Q12H
PRE PAGE TREATMENT
ABG-
REPORT(18/9/14)
SUGGESTIVE : This is a patient of
choriocarcinoma with secondary
metastasis to lung’s and pt’s need
referred to oncologist for further
management.
OPINION ON MEDICINE WARD
DATE: 18/9/14
Pulse : 130/min
B/P : 100/60 mm Hg
R.R : 30/min
Temp : normal
Heart : s1,s2 HS audible
Lungs : VBS with Ronchi
FOLLOW UP
20/9/14
DATE DRUG AMOUNT
17/9/14 (1st dose) MTX 1 VIAL
21/9/14 (2nd dose) MTX 1 VIAL
23/9/14 (3RD dose) MTX 1 VIAL
MTX
LEUCOVORIN CALCIUM
Date Dose Route
22/9/14 1st I.V
(slowly)
24/9/14 2nd …..not yet
Appearance : ill looking with Resp distress
Pulse : 150/min
B/P : 100/60
Temp : 99 degree F
Resp. Rate : 28/min
Heart: s1,s2 audible (very loud)
Lungs: VBS on BL with crebs thoughout lungs.
Anaemia : Mild
Oedema : absent
Dehydration : absent
SPO2 : 66%
urine: high colour urine.
TODAY’S FOLLOW UP (24/09/14)
CHORIOCARCINOMA
DR. MOHAMMAD
ASHRAFUL AMIN(ASIF)
ID-927
SEMINAR ON:
• Gestational Trophoblastic Disease (GTD) is a
spectrum of proliferation abnormalities of
trophoblasts associated with pregnancy .
• GTD includes
- complete & partial H. mole
- invasive mole
- choriocarcinoma
- placental site trophoblastic tumour
Gestational Trophoblastic Disease
PATHOLOGIC CLASSIFICATION
CLINICAL CLASSIFICATION
Hydatidiform mole
*complete
*incomplete
Benign gestational trophoblastic disease
Invasive moleMalignant
trophoblastic diseaseNonmetastatic
Placental site trophoblastic tumor
Metastatic
Choriocarcinoma High risk Low risk
Pathologic and clinical classifications for
gestational trophoblastic disease
• Non metastatic ( confined to uterus)
• Metastatic
LOW RISK
-< 4 months duration
-initial serum HCG levels < 40,000miu/ml
-metastasis limited to lungs and vagina
-no prior chemotherapy
-no preceding term delivery
HIGH RISK
-duration > 4 months
-serum HCG levels > 40, 000
-brain or liver metastasis
-failure of prior chemotherapy
-Following term pregnancy
-WHO score>7
GTN(modified WHO classification
1998)
CHORIOCARCINOMA
DEFINITION
This is extremely malignant form of
trophoblastic tumour may be considered a
carcinoma of chorionic epithelium, although an
its growth and metastasis behave like sarcoma
• Characterized by abnormal trophoblastic
hyperplasia and anaplasia , absence of
chorionic villi
Pathology:
• Incidence: 1: 250-5000 pregnancies in Asia and 1:4000 in the west.
• Origin:
* Choriocarcinoma is a malignant tumour of the trophoblast.
1- About 50% of cases follow molar pregnancy.
2- 25% follow abortion
3- 23% follow normal pregnancy
4- 2% follow ectopic pregnancy.
* In rare cases, the tumour arises as a teratoma in the ovary or testicle.
• Macroscopic appearnce:
The tumor arises in the endometrium as
1. a soft friable dark red hemorrhagic mass projecting into the uterine cavity and may from a polyp.
2. Malignant tissue may be buried within the myometrium , inaccessible to the curette, or hidden in a distant metastasis.
3. However, any of these tumor patterns secretes (hCG) which causes cystic changes of the ovaries in about 30% of cases..
Gross specimen of choriocarcinoma
• Microscopic appearance:
The tumour consists of cyto-and
synecytiotrophoblasts showing malignant
characters, invading the myometrium and blood
vessels. Chorionic villi are absentthis differentiates Choriocarcinoma from invasive
mole.
Microscopic image of choriocarcinoma
absence of chorionic villi
• Mode of spread:
1. direct spread: to the parametrium, tubes and
ovaries.
2. Blood spread: occurs early to distant organs.
The commonest sites are lunges (80%),
vegina (30%), brain (10%) and liver (10%)
Diagnosis:
• A- symptoms:
1- Persistent or irregular vaginal bleeding: it is the commonest symptom occurring after labor, abortion or evacuation of a vesicular mole. Bleeding can occur within days or months but rarely after 2 years.
2- Vaginal discharge: which is blood stained and offensive due to ulceration and infection of the growth .
3- amenorrhea: may be present due to continuous hCG production.
4- Acute abdominal pain: due to intraperitoneal haemorrhage as a result of perforation of the uterus by the growth.
5- Abdominal or vaginal swelling: may develop.
6- Symptoms of metastases: as dysponea, haemoptesis, jaundice and neurological symptoms as headache may be the first manifestation of the tumor.
7- pallor
8- vomiting.
• B- signs:
(1) cachexia and severe anaemia.
(2) fever may be present due to infection and
necrosis
(3) the uterus may be normal size or enlarged and
soft.
(4) the ovaries: may be enlarged and eystic.
(5) metaststic nodules: in the vulva or vagina
PATIENT MAY COMMONLY PRESENT WITH SIGN OF METASTASIS
Pulmonary metastasis
• 80% of patient with metastatic GTT lung involvement patient present with chest pain, cough, hemoptysis, dyspnea.
Principle of pulmonary pattern
• Alveolar or snow strom pattern.
• Discrete rounded densities- cannon ball appearance
• Embolic pattern caused by pulmonary arterial occlusion
Vaginal metastasis
• occur in about 30%
Liver metastasis
• Occur in about 10%
Central Nervous System
• Involve brain in 10% cases
C- investigations:
(1) uterine curettage: should be done in every case
of persistent or irregular uterine bleeding after
labour, abortion or molar pregnancy. However,
intramural tumour cannot be detected by
curettage.
(2) serum β- subunite of hCG: persistent or rising
titres in absence of pregnancy are indicative of
trophoblastic neoplasia.
(3) biopsy: from metastatic valvar or vaginal
lesions.
• (4) imaging:
a- plain X-ray chest: may show secondaries in the form of " cannon balls" or "snowstorm" appearance.
b- ultrasonography: to detect tumour, cystic ovaries and exclude remnants of conception.
c- CT scan: for lungs, liver, brain and bone.
• (5) lumbar puncture: plasma hCG/ CSF hCGratio less than 60 strongly CNS involvement my metastases
• (6) blood studies:
a- complete blood picture including platelet count
b- Renal, liver and thyroid function tests
c- Blood group.
Β-hCG VS hCG-H
Β-hCG
• Produced by
syncytiotrophoblasts
• Present through. out
the normal
pregnancy
•
• in all forms of GTD
• Method of action is endocrine
• Maintains progesterone
production
hCG-H
• Invasive cytotrophoblasts
• Present in implantation
phases of normal
pregnancy
GTN
• Paracrine
• Promotes trophoblastic
growth and invasion
WHO PROGNOSTIC SCORING SYSTEM
Score
Prognostic factor 0 1 2 4
Age(years) ≤39 >39 — —
Pregnancy historyHydatidiform mole
Abortion,
ectopic
Term pregnancy
—
Interval (months) of treatment
<4 4-6 7-12 >12
Initial hCG(mIU/ml) <103 103-104 104-105 >105
ABO Group O-A B-AB
Largest tumor(cm) <3 3-5 >5 —
Sites of metastasis Lung Spleen,
kidneyGI tract, liver Brain
No. of metastasis — 1-4 4-8 8
Previous (treatment) — — Single drug 2 or more
0-4 low risk, 5-7 intermediate risk, >8 high risk for death
Stage I confined to uterine corpus.
Stage II metastases to pelvis and
vagina
Stage III metastases to lung
Stage IV metastases to other organs.
FIGO CLASSIFICATION:
FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOUR
Stage I : Disease confined to uterus
Ia : Confined to uterus with no risk factor
Ib : Confined to uterus with 1 risk factor
Ic : confined to uterus with 2 risk factor
Stage II : GTT extending outside uterus but
limited to genital str. (adenexa vagina broad
ligaments)
IIa : GTT involving genital tract with out risk
factor
Iib : GTT involving genital tract with 1 risk factor
IIC : GTT involving genital tract with 2 risk factor
FIGO STAGING SYSTEM FOR GESTATIONAL TROPHOBLASTIC TUMOUR
Stage III : GTT extending of lung with or without
Known genital tract involvement
IIIa : GTT extending to lung with no risk factor
IIIb : GTT extending to lung with 1 risk factor
IIIc : GTT extending to lung with 2 risk factor
Stage IV: All other metastatic sites
IVa : All metastatic sites other site with out risk
factor
IVb : All metastatic sites other site with out 1 risk
factor
IVc: All other metastatic sites site with out 2 risk
factor
Risk Factor ; HCG > 100;000mIU/ml
Diagnostic Evaluation All Patients with persistent GTT should undergo
careful pretreatment evaluation including the
following –
•Complete history and physical examination .
•Measurement of serum HCG value.
•. Hepatic, thyroid and renal function test.
•Determination of baseline peripheral WBC and
platelet count.
•Once the diagnosis established the further
examination should be done to determine the extent
of disease (Chest X- ray, CT scan of abdomen, pelvis
and Head, MRI, USG)
Management
1. Preventive and Curative
a. Preventive – Prophylactic CT in at risk women
following evacuation of molar pregnancy.
Risk Women –
• Age of patient >35 years.
• Level of HCG > 100,000 IU/ 24 Hours.
• Histological diagnosed infiltrative mole.
• Previous history of molor pregnancy.
- Meticulous follow up following evacuation of H. mole of
at least one years to detect early evidence of
trophoblastic reactivation.
Single agent chemotherapy is highly effective in case of
persistent trophoblastic disease.
- Selective hysterectomy in H. mole in patients of
age>35years.
Treatment:
The treatment of choice
chemotheraphy
Chemotherapy:
(I) low- risk group score ≤ 4:
Single cytotoxic drug either methotrexate or
actinomycin D
(II) High-risk group score >8 :
Multiple cytotoxic drugs
Hysterectomy may be indicated in the following
conditions:
• severe uterine bleeding
• perforation of the uterus with intraperitoneal
haemorrhage.
• Massive haemorrhage from the bowel
• Torsion of a theca lutein cyst.
• Durg resistance or toxicity.
• Persistant localised metastases in the vagina,
lung or brain after chemotherapy
Those who want to retain fertility
1. Single agent CT is preferred treatment in patients
with stage I disease who want to retain fertility.
• When patients are resistant to single agent
chemotherapy and desire to retain fertility
combination chemotherapy should be
administered.
• Stage II & III – Vaginal and pelvic metastatics.
Vaginal – In low risk cases.
Single agent chemotherapy have 80% rate of
remission.
High risk patients managed with primary intensive
combination chemotherapy.
Curative Management -
• Chemotherapy.
• Surgery.
• Radiation.
Management of various stages-
Stage I:
Initial – single agent chemotherapy or hysterectomy
with adjunctive chemotherapy .
Resistant – Combination chemotherapy
Hysterectomy with adjunctive chemotherapy.
Local resection, pelvic infusion.
Stage II & III-
Low risk –
Initial - Single agent chemotherapy.
Resistant – Combination chemotherapy.
High Risk –
Initial – Combination chemotherapy.
Resistant – second line combination chemotherapy
Stage IV-
Initial - Combination Chemotherapy.
Brain – Whole heat irradiation (3000 CGY)
craniotomy to manage complications.
Liver – Resection to manage complications.
Resistant – second line combination chemotherapy
hepatic arterial infusion.
Adjuvant chemotherapy is administered for
three reasons
1. To reduce the likelihood of disseminating
viable tumour cell at surgery.
2. To maintain cytotoxic level of chemotherapy
in the blood stream and tissue in case viable
tumour cells are disseminated at surgery .
3. To treat any occult metastasis that may
already present at the time of surgery.
Chemotherapy
Single agent chemotherapy with either actinomycin D
or methotrexate has achieved comparable and excellent
remission rates in both non metastatic and low risk
metastatic GTN.
single drug regimen in low rate case –
Drug Dosage Route Days
Methotrexate 1-15 mg/kg IM/IV 1,3,5,7.
Folonic acid 1-015 mg/kg IM 2,4,6,8.
Actinomycin D 12 mg/kg IV 1-5
Cyclophosphamide 3mg/kg IV 1-5
EMA- CO protocol in poor prognosis
metastatic disease
The course will restart after 7-14 days. If possible, Generally 2
additional courses are given after the hCG levels become normal.
Days Drug Dose
Day-1 Etoposide 100mg /m2in 200 ml saline infused over 30 minutes.
Actinomycin D 0.5 mg IV bolus
Methotrexate 100mg /m2 bolus folllowed by 200mg /m2 IV infusion over 12 hours.
Day -2 Etoposide 100mg /m2in 200 ml saline infused over 30 minutes.
Actinomycin D 0.5 mg IV bolus
Folinic acid 15mg IM every 12 hrs for 4 doses begnning 24 hours after starting methotrexate.
Day-8 Cycolphosphamide 600mg/m2 IV in saline over 30 min.
Vincristine (oncovin) 1mg/m2 bolus
• Myelosuppression
• Nausea,vomiting
• Mucositis
• Alopecia
• Neuropathy
• Second malignancy AML, breast and colon
cancer.
SIDE EFFECTS
Leucovorin is used to prevent harmful effects of
methotrexate. when methotrexate is used to treat
certain types of cancer. Leucovorin is also used to
treat people who have accidentally received an
overdose of methotrexate or similar medications.
Leucovorin is in a class of medications called folic
acid analogs. It works by protecting healthy cells
from the effects of methotrexate or similar
medications while allowing methotrexate to enter
and kill cancer cells.
Leucovorin
(Folinic acid )
• Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
1. diarrhoea
2. rash
3. Hives (Urticaria, also known as hives, is an outbreak of swollen, pale red bumps or plaques)
4. itching
5. difficulty breathing or swallowing
side effects can this
medication cause
• Patients with brain metastasis require whole
brain radiation therapy(3000cGY ocer 10 days)
• In liver metastasis hepatic artery ligation or
embolisation or whole liver radiation (2000 c GY
over 10 days)along with chemotherapy may be
effective.
RADIATION
Follow up-
All patients with stage I through stage III disease
should receive follow up with-
1. Weekly measurement of HCG level until they
are normal for 3 consecutive weeks.
2. Monthly measurement of HCG value until level
are normal for 12 consecutive months.
3. Effective contraception during the entire
interval of hormonal follow up.
PROGNOSIS
• Cure rates should approach 100% in
nonmetastatic and low-risk metastatic GTD
• Intensive multimodality therapy has resulted in
cure rates of 80-90% in patients with high-risk
metastatic GTD
FOLLOW-UP AFTER SUCCESSFUL
TREATMENT
• Quantitative serum hCG levels should be
obtained monthly for 6 months, every two
months for remainder of the first year, every 3
months during the second year
• Contraception should be maintained for at
least 1 year after the completion of
chemotherapy. Condom is the choice.
SUMMARY OF PATIENT
FIGO classification:
Stage III metastases to lung.
According WHO Prognostic Scoring System to
this patient
Score
Prognostic factor 0 1 2 4
Age(years) ≤39
Pregnancy historyAbortion,
ectopic—
Interval (months) of treatment
<4
Initial hCG(mIU/ml) >105
ABO Group B
Largest tumor(cm)
Sites of metastasis Lung
No. of metastasis 1-4
Previous (treatment) — —
0-4 low risk, 5-7 intermediate risk, >8 high risk for death
TOTAL SCORE : 8 ( or 5)
Prognostic factorScore
Age(years) 0
Pregnancy history 1
Interval (months) of treatment 0
Initial hCG(mIU/ml) 4 ( if 1st HCG is count, if not then score:1)
ABO Group 2
Largest tumor(cm) ?
Sites of metastasis 0
No. of metastasis 1
Previous (treatment) 0
THANK
YOU