PRETEST 1
LATAR BELAKANG
• Kanker serviks adalah kanker wanita tersering nomor 3 dari segi insiden (527.600 kasus baru) dan mortalitas (265.700 kematian) di seluruh dunia, setelah kanker payudara dan kolorektal.
• Angka kejadian kanker serviks di Indonesia pada tahun 2012 sebesar 20.928 kasus dengan angka kematian sebanyak 9.498. Kebanyakan pasien datang pada stadium lanjut yaitu stadium IIB-IVB, sebanyak 66,4%.
• Human Papilloma Virus (HPV) sangatlah penting pada perkembangan neoplasma serviks dan bisa dideteksi pada 99,7% kasus kanker serviks.
• 2 Tipe histologi dari kanker serviks terbanyak adalah karsinoma sel skuamous (69% dari kanker serviks) dan adenokarsinoma (25%).
DEFINISI
• Kanker serviks adalah keganasan pada serviks yang disebabkan oleh infeksi HPV grup onkogenik risiko tinggi; terutama HPV 16 dan 18 serta filogeniknya.
• Lebih dari 95% kanker serviks adalah tipe epithelial yang terdiri atas jenis karsinoma sel skuamosa dan adenokarsinoma.
ETIOLOGI
Ada 4 langkah utama perkembangan kanker serviks:
• Infeksi HPV onkogenik pada epitel metaplasia dari zona transformasi serviks.
• Infeksi HPV persisten
• Perkembangan klon sel epitel dari infeksi virus persisten menuju pra kanker - Perkembangan menjadi kanker dan invasi melalui membran basalis
Infeksi HPV terdeteksi pada hingga 99% wanita dengan karsinoma serviks skuamosa. HPV adalah agen penyebab, baik pada skuamosa dan adenokarsinoma serviks, tetapi masing-masing tumor mungkin memiliki jalur karsinogenik yang berbeda.
Secara umum, perkembangan displasia menjadi kanker invasif memerlukan beberapa tahun, meskipun waktu dapat sangat bervariasi. Perubahan molekuler yang terlibat dengan karsinogenesis serviks adalah kompleks dan tidak sepenuhnya dipahami. Karsinogenesis saat ini diduga merupakan hasil interaksi antara paparan lingkungan, imunitas, dan variasi genom sel somatik.
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You can simply impress your audience and add a unique zing and appeal to your Presentations. Easy to change colors, photos and Text. Get a modern PowerPoint Presentation that is beautifully designed. You can simply impress your audience and add a unique zing and appeal to your Presentations. Easy to change colors, photos and Text. Get a modern PowerPoint Presentation that is beautifully designed.
Mekanisme HPV mempengaruhi
pertumbuhan dan diferensiasi sel
adalah melalui interaksi protein
virus E6 dan E7 dengan
masing-masing gen penekan tumor p53
dan Rb.
Protein E7 berikatan dengan
protein
penekan
tumor
retinoblastoma (Rb), sedangkan
E6 berikatan dengan protein
penekan tumor p53.
Penghambatan p53 mencegah
penghentian siklus sel dan apoptosis
seluler, yang biasanya terjadi ketika
DNA rusak, sedangkan
penghambatan Rb mengganggu
faktor transkripsi E2F, yang
mengakibatkan proliferasi seluler
yang tidak diregulasi.
Kedua langkah ini berperang penting
dalam transformasi maligna sel epitel
serviks dengan proliferasi sel yang tidak
terkontrol dan kegagalan sel dalam
memicu apoptosis sel.
FAKTOR RESIKO
Hubungan seks dini / berganti – ganti pasangan
Riwayat penyakit menular seksual
kondisi immunosupresi (HIV, penggunaan obat immunosupresi)
Merokok
REKOMENDASI SKRINING SERVIKS (ACOG/
AMERICAN COLLEGE OF OSTETRICIANS AND
GYNECOLOGISTS
)
JENIS PEMERIKSAAN DAN USIA FREKUENSI
Pap smear untuk wanita > 20 Tahun Setiap 1-3 tahun sekali Pemeriksaan HPV DNA untuk wanita > 30
tahun
Setiap 1-3 tahun sekali
Pemeriksaan co testing Pap smear + HPV DNA untuk wanita > 30 tahun
Setiap 1-3 tahun sekali
IVA untuk wanita > 20 tahun Setiap 1-3 tahun sekali
> 65 tahun tidak memerlukan skrining, jika hasil 2 kali pemeriksaan skrining sebelumnya negatif
SKRINING SECARA SITOLOGIK
http://www.ps21.gov.sg/papsmear.jpg
http://www.brooksidepress.org/Pap/c5320x_lg.jpg
Source: EngenderHealth, Wright TC, 1996
Normal servik
Servik dengan IVA +
IVA tes
•
Vaksin dapat diberikan mulai usia 10-55
•
Jadwal pemberian : 0, 1, 6 bulan (Bivalent); 0, 2, 6
bulan (Quadrivalent), pemberian ketiga bisa bulan
6-12. Interval minimum antara dosis pertama dan
kedua adalah 4 minggu, interval minimum antara
dosis kedua dan ketiga adalah 12 minggu.
•
Pada usia 9-13 tahun, kedua vaksin dapat diberikan
pada 0, 6 bulan (2 kali pemberian)
REKOMENDASI VAKSIN HPV (ACOG/
AMERICAN COLLEGE OF
OSTETRICIANS AND GYNECOLOGISTS
)
•
Kontra indikasi: Hamil, Terkena Lesi Pra kanker
atau kanker terkait HPV, Demam tinggi,
Hipersensitivitas thd vaksin
•
Boleh diberikan saat laktasi
•
Penyimpanan Vaksin : pada suhu 2-8°C (tidak boleh
dibekukan)
•
Cara pemberian IM (Deltoid)
•
Vaksin pada pria terbukti menurunkan insiden
kanker terkait HPV (10-26 th)
•
Vaksin pada wanita yang telah terpapar HPV
terbukti menurunkan insiden kanker terkait HPV
•
Bukan untuk terapi lesi pra kanker atau kanker
PERJALANAN KANKER SERVIK
Sel Normal Lesi Pra Kanker Kanker
SERVIKS NORMAL (LEHER RAHIM)
GAMBARAN KLINIS KANKER
SERVIKS
Jika kanker sudah metastasis :
Sulit BAK dan mungkin gagal ginjal.
Nyeri BAK dan kadang2 kencing darah .
Bengkak di kaki
Diarrhea, atau nyeri di daerah anus atau BAB
berdarah
Mual, lemas, BB turun, nafsu makan turun, dan terasa
nyeri.
Konstipasi
Lubang Abnormal di leher rahim (fistula)
pembesaran kelenjar limphe di leher atau ketiak.
Penyebaran lanjut ke tulang, paru, usus atau otak
memberikan tanda – tanda abnormal.
Pengobatan Kanker Serviks
Surgery
Radiation Therapy
External Radiation
Chemotherapy
Paliatif Therapy
TATALAKSANA
Stadium IA1
• Konisasi adalah pilihan terapi utama pada stadium IA1.
• Follow up pasca terapi dengan Pap smear dilakukan setiap 3 bulan
selama 2 tahun,kemudian setiap 6 bulan pada 3 tahun berikutnya.
Stadium IA2
• Terapi yang direkomendasikan adalah histerektomi radikal tipe 2
dengan limfadenektomi kelenjar getah bening pelvis.
• Bila fungsi reproduksi masih diperlukan, pilihan terapi adalah :
• 1. Konisasi serviks dengan limfadenektomi pelvik, atau
• 2. Trakhelektomi radikal (abdominal, vaginal atau laparoskopi) dan
limfadenektomi pelvik.
Stadium IB-IIA
• Terapi pembedahan untuk stadium IB-IIA adalah
modified histerektomi radikal tipe 2 atau
histerektomi radikal tipe 3 (laparotomi atau
laparoskopi) dan limfadektomi pelvis.
Stadium IIB
• Kemoradiasi merupakan terapi standar pada stadium
IIB
• Dosis radiasi eksternal yang disarankan adalah 45-50
Gy pada 180-200 cGy per fraksi.
Stadium IIIA – IVA
• Standar terapi adalah radiasi atau kemoradiasi : radiasi
eksternal yang disarankan adalah 45-50 Gy +
brachytherapy 2100 cGy atau modifikasi box system
(bila
brachytherapy
tidak
tersedia)
dengan
radiosensitizer
Stadium IVB
• Terapi Sistemik
• Radiasi paliatif untuk gejala lokal
PROGNOSIS &
FOLLOW UP
•
Dari review sistematik 17 percobaan klinis tentang
follow up pasien pasca terapi kanker serviks
didapatkan waktu median kekambuhan setelah terapi
bervariasi antara 7- 36 bulan setelah terapi primer.
•
Pada Follow Up dilakukan anamnesa tentang keluhan
pasien, pemeriksaan fisik dan ginekologi rutin untuk
mendeteksi adanya kekambuhan, efek samping terapi
dan juga morbiditas psikoseksual yang mungkin
terjadi. Pemeriksaan biopsi jaringan, foto thorax, USG,
CT scan, MRI, PET dapat dilakukan apabila
1. Which human papillomavirus (HPV) subtype is associated with adenocarcinoma of the cervix? most strongly • a. HPV 6 • b. HPV 16 • c. HPV 18 • d. HPV 31
2. Which of the following statements regarding cervical cancer risk factors is FALSE?
• a. Cervical cancer is an acquired immune deficiency syndrome (AIDS)-defining illness.
• b. Transplant recipients have an increased risk of cervical cancer.
• c. In general, women who have an autoimmune disease and take immunosuppressant therapy do not have an increased risk of cervical cancer.
• d. Combination oral contraceptives are associated with an increased risk of cervical cancer due to the higher number of sexual partners in users.
• 3. Which histologic subtype of cervical carcinoma is represented in this micrograph? Arrows point to keratin pearls.
• a. Melanoma
• b. Adenocarcinoma
• c. Squamous cell carcinoma
4. A woman presents for a routine health maintenance visit. The following is visualized during speculum examination. What is the most appropriate next step?
• a. Perform a Pap test
• b. Perform a cervical biopsy
• c. Refer to a gynecologic oncologist
5. What is the most appropriate surgical approach for a woman who has a stage IAI squamous cell carcinoma of the cervix and has completed childbearing?
• a. Cold-knife conization
• b. Extra fascial hysterectomy
• c. Type III radical hysterectomy
6. Both urinary and genital systems develop from which of the following cell types?
• a. Ectoderm
• b. Endoderm
• c. Mesoderm
7.Embryos of male or female gender are indistinguishable from each other until which number of weeks of development? • a. 7 • b. 10 • c. 12 • d. 14
8. During a first-trimester ultrasound or pregnancy dating, you discover that your patient has a subseptate uterus. While counseling her, you explain that this müllerian anomaly developed in utero secondary to failure of the midline uterine septum to reabsorb completely. Normally,
reabsorption of the uterine septum in a fetus should occur by how many weeks of gestation?
• a. 20
• b. 28
• c. 32
9. In the male fetus, dihydrotestosterone (DHT ) is involved in which of the following?
• a. Enlargement of the phallus
• b. Lengthening of the anogenital distance
• c. Fusion of the labioscrotal folds to form the scrotum
10. When aced with ambiguous external genitalia of a newborn at delivery, the obstetrician should do which of the following?
• a. Examine the mother for signs of hyperandrogenism.
• b. Refer to the newborn as “your baby” and not as “it.”
• c. Refrain from gender assignment by explaining that the genitalia are incompletely formed.
11. During menopausal transition, which of the following results from cessation of ovarian steroid
hormone release?
• a. A rise in luteinizing hormone (LH) levels
• b. A rise in follicle-stimulating hormone (FSH) levels
• c. A maximal increase in the frequency and amplitude of gonadotropin-releasing hormone secretion
12. Anovulation is the most common cause of erratic bleeding during menopausal transition. However, as shown in this sonogram, endometrial cancer is suspected during this transition in those with abnormal uterine bleeding (AUB). Here, the thickened heterogeneous endometrium measures 26 mm. The overall risk for endometrial cancer increases to what percentage in women with AUB during menopausal transition?
• a. 0.1 percent
• b. 1 percent
• c. 10 percent
13. A 55-year-old postmenopausal, thin, patient who smokes asks for counseling regarding
osteoporosis due to her concern for future bone fracture risk. In addition to the vertebrae and femoral neck, which of the following is most commonly fractured?
• a. Rib
• b. Wrist
• c. Fibula
14. The North American Menopause Society term genitourinary syndrome of menopause(GSM) encompasses which of the following signs and symptoms?
• a. Dyspareunia
• b. Vulvar dryness
• c. Urinary urgency and dysuria
15. In postmenopausal women, unopposed estrogen may be derived from which of the following sources?
• a. Exogenous estrogen
• b. Extragonadal endogenous estrogen production
• c. Decreased sex hormone-binding globulin levels
16. Which of the following regarding thyroid function is true during normal pregnancy?
• A. Foetal thyroid function is largely dependent upon the function of the maternal thyroid
• B. Plasma thyroid-binding globulin concentration increases
• C. Plasma total thyroxine concentration falls
• D. Plasma TSH concentration increases
17. Which of the following is correct regarding the diffusion of gases through the placental membrane?
a. 〖CO〗_2crosses the placenta from foetus to mother because of a high concentration gradient
b. 〖CO〗_2 diffuses through the placental membrane 5 times more quickly than O_2
c. The mean 〖PO〗_2 in the foetus is 50 mmHg
d. The mean 〖PO〗_2in the mother’s blood is approximately 30 mmHg e. The only way the foetus can excrete 〖CO〗_2 is through the placenta
18. Which of the following is not a normal finding in a healthy pregnant patient?
• A. A fourth heart sound
• B. A raised alkaline phosphatase
• C. Tall, peaked T waves in lead III
• D. Left axis deviation on the electrocardiograph (ECG)
19. In a normal pregnancy, which of the following is true regarding uterine blood flow?
• A. Is about 50 mL/minute at term
• B. Is increased during uterine contractions
• C. Is reduced by prostacyclin
• D. Represents about 10% of the cardiac output by the end of the first trimester
• E. Within the choriodecidual space is maintained throughout the cardiac cycle
20. Which of the following is true regarding aortocaval compression in a pregnant woman?
• A. A reduction in cardiac output may be due to compression of the superior vena cava
• B. A wedge should be placed under the left side
• C. Compression of the aorta may cause uterine hypoperfusion
• D. Is greater when lying on the right side
21. Regarding the human placenta, which of the following is true?
• A. Cytotrophoblast is in direct contact with maternal blood
• B. Decidual cells are derived from myometrial stromal cells
• C. Each cotyledon represents a primary stem villi
• D. The anchoring villi are attached to the myometrium
• E. The intervillous space communicates directly with branches of the uterine arteries
22. Which of the following is true regarding human chorionic gonadotropin?
• A. Binds to luteinising hormone (LH) receptors
• B. Has intrinsic anti-thyroid activity
• C. Is a protein molecule
• D. Is synthesised by the corpus luteum of pregnancy
23. The concentrations of which of the following increase during pregnancy?
• A. Albumin
• B. Sodium
• C. Fibrinogen
• D. All of the above
24. Which of the following is not true regarding trophoblast?
• A. Develops from the blastocyst
• B. Enters the maternal circulation during normal pregnancy
• C. Gives rise to the foetal blood vessels in the placenta
• D. Is genetically identical to decidua
25. Which of the following normally decreases during pregnancy?
• A. Heart rate
• B. Stroke volume
• C. Systemic vascular resistance
• D. All of the above
