DEPARTEMEN ILMU BEDAH SARAF FAKULTAS KEDOKTERAN UNIVERSITAS SUMATERA UTARA MEDAN 2013

Tesis Program Pendidikan Magister Bedah Departemen Ilmu Bedah Saraf Fakultas Kedokteran Universitas Sumatera Utara

HUBUNGAN KADAR VASCULAR ENDOTHELIAL GROWTH FACTOR(VEGF) SERUM DENGAN PERITUMORAL EDEMA INDEX (PTEI) PADA PENDERITA MENINGIOMA INTRAKRANIAL DI RSUP. H. ADAM MALIK MEDAN OLEH : THOMAS TOMMY NO. CHS :FL 2172 / 2009 NIM : 097116005

DEPARTEMEN ILMU BEDAH SARAF FAKULTAS KEDOKTERAN UNIVERSITAS SUMATERA UTARA MEDAN – 2013

Universitas Sumatera Utara

LEMBAR PENGESAHAN

Judul Tesis

: HUBUNGAN GROWTH

KADAR

FACTOR

PERITUMORAL

VASCULAR (VEGF)

EDEMA

ENDOTHELIAL

SERUM

INDEX

DENGAN

(PTEI)

PADA

PENDERITA MENINGIOMA INTRAKRANIAL DI RSUP H. ADAM MALIK MEDAN.

Nama PPDS

: Thomas Tommy

Nomor CHS

: FL 2172 / 2009

NIM

: 097116005

Bidang Ilmu

: Kedokteran / Ilmu Bedah Saraf

Kategori

: Bedah Saraf

Menyetujui, PembimbingI :

Pembimbing II :

(Prof. dr. Adril A. Hakim, SpS, SpBS(K))

(Prof. dr. Abdul Gofar S., SpBS(K))

NIP : 19460718 197703 1 000

NIP : 19440507 197703 1 001

Ketua Departemen

Ketua Program Studi

llmu Bedah Saraf,

Ilmu Bedah Saraf,

(Prof. Dr. dr. Iskandar Japardi, SpBS(K))

(Prof. dr. Abdul Gofar S., SpBS(K))

NIP : 19490331 197711 1 001

NIP : 19440507 197703 1 001

Tanggal Disahkan :

Universitas Sumatera Utara

Sudah diperiksa penelitian :

JUDUL

: HUBUNGAN GROWTH

KADAR FACTOR

PERITUMORAL

VASCULAR (VEGF)

EDEMA

ENDOTHELIAL

SERUM

INDEX

(PTEI)

DENGAN PADA

PENDERITA MENINGIOMA INTRAKRANIAL DI RSUP. H. ADAM MALIK MEDAN.

PENELITI

: dr. THOMAS TOMMY

DEPARTEMEN : ILMU BEDAH SARAF INSTITUSI

: FAKULTAS KEDOKTERAN UNIVERSITAS SUMATERA UTARA

MEDAN, 5 JUNI 2013 KONSULTAN METODOLOGI PENELITIAN FAKULTAS KEDOKTERAN USU

( Dr. dr. Arlinda Sari Wahyuni, MKes. ) NIP :19690609 199903 2 001

Universitas Sumatera Utara

DAFTAR ISI LEMBAR PENGESAHAN ........................................................................................................................ i DAFTAR ISI .......................................................................................................................................... iii DAFTAR LAMPIRAN ............................................................................................................................ v DAFTAR TABEL, GAMBAR DAN KURVA ....................................................................................... vi DAFTAR SINGKATAN ....................................................................................................................... vii BAB 1 PENDAHULUAN

1.1. 1.2. 1.3. 1.4.

LATAR BELAKANG.................................................................................................. 1 RUMUSAN MASALAH ............................................................................................3 TUJUAN PENELITIAN..............................................................................................3 MANFAAT PENELITIAN ..........................................................................................3

BAB 2 TINJAUAN PUSTAKA

2.1. MENINGIOMA ....................................................................................................... 4 2.1.1. Sejarah dan Definisi Meningioma........................................................................ 4 2.1.2. Epidemiologi Meningioma ..................................................................................4 2.1.3. Patologi ..............................................................................................................4 2.1.4. Klasifikasi Meningioma .......................................................................................5 2.1.5. Karakteristik dan Diagnostik Meningioma ...........................................................6 2.1.6. Prognosis ............................................................................................................7 2.2. EDEMA OTAK ........................................................................................................ 7 2.2.1. Edema Vasogenik................................................................................................8 2.2.2. Edema Sitotoksik ................................................................................................9 2.3. EDEMA PERITUMORAL DAN MENINGIOMA ......................................................... 10 2.3.1. Mengukur Peritumoral Edema .......................................................................... 11 2.4. VASCULAR ENDOTHELIAL GROWTH FACTOR(VEGF) ............................................. 12 2.5. RESEPTOR VEGF .................................................................................................. 19 2.6. PERAN VEGF DAN TERAPI ANTI ANGIOGENIK....................................................... 21 BAB 3 KERANGKA KONSEP DAN DEFINISI OPERASIONAL

3.1. 3.2. 3.3.

KERANGKA KONSEP PENELITIAN.......................................................................... 22 VARIABEL DAN DEFINISI OPERASIONAL ............................................................... 22 HIPOTESIS ........................................................................................................... 30

BAB 4 METODE PENELITIAN

4.1. 4.2. 4.3.

RANCANGAN PENELITIAN .................................................................................... 31 LOKASI DAN WAKTU PENELITIAN......................................................................... 31 POPULASI DAN SAMPEL PENELITIAN ................................................................... 31

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4.3.1. Populasi Penelitian ........................................................................................... 31 4.3.2. Sampel Penelitian ............................................................................................. 31 4.3.2.1 Kriteria Inklusi................................................................................................... 31 4.3.2.2 Kriteria Eksklusi................................................................................................. 32 4.3.3 Estimasi Besar Sampel ...................................................................................... 32 4.4. METODE PENGUMPULAN DATA .......................................................................... 33 4.4.1 Persetujuan Setelah Penjelasan ........................................................................ 33 4.4.2 Etika Penelitian ................................................................................................. 33 4.4.3 Pengumpulan Data ........................................................................................... 33 4.4.4 Pengumpulan dan Penyimpanan Sampel Darah ............................................... 33 4.4.5 Pengolahan Sampel Darah ................................................................................ 34 4.5. METODE ANALISIS DATA ..................................................................................... 34 BAB 5 HASIL PENELITIAN

5.1. KARAKTERISTIK SAMPEL ...................................................................................... 36 5.1.1 Jenis Kelamin .................................................................................................... 36 5.1.2. Umur ................................................................................................................ 36 5.1.3. Frekuensi Lokasi Tumor .................................................................................... 37 5.1.4. Suku ................................................................................................................. 38 5.1.5. Distribusi Berdasarkan Histopatologi ................................................................ 39 5.1.6. Distribusi Peritumoral Edema Index (PTEI) dan Vascular Endothelial Growth Factor (VEGF)........ 39 5.2. PTEI DAN VEGF DIBEDAKAN BERDASARKAN JENIS KELAMIN ............................... 42 5.3. HUBUNGAN ANTARA PTEI DAN VEGF .................................................................. 43 BAB 6 PEMBAHASAN, SIMPULAN DAN SARAN

6.1. 6.2. 6.3.

PEMBAHASAN ..................................................................................................... 45 SIMPULAN........................................................................................................... 51 SARAN................................................................................................................. 51

DAFTAR PUSTAKA ............................................................................................................................ 53 LAMPIRAN .......................................................................................................................................... 58

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DAFTAR LAMPIRAN

Lampiran 1.

: Data Penelitian

Lampiran 2.

: Susunan Peneliti

Lampiran 3.

: Naskah Penjelasan kepada Orang Tua / Kerabat Pasien

Lampiran 4.

: Persetujuan Setelah Penjelasan

Lampiran 5.

: Persetujuan Komite Medik Tentang Pelaksanaan Penelitian Bidang Kesehatan

Lampiran 6.

: Analisis Statistik

Lampiran 7.

: Dokumentasi Penelitian

Lampiran 8.

: Spesifikasi ELISA analyzer yang digunakan

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DAFTAR TABEL, GAMBAR DAN KURVA

Tabel 5.1.

: Jenis kelamin.

Tabel 5.2.

: Analisis deskriptif (Umur).

Tabel 5.3.

: Klasifikasi berdasarkan lokasi tumor.

Tabel 5. 4

: Distribusi berdasarkan suku.

Tabel 5.5.

: Frekuensi berdasarkan histopatologi.

Tabel 5.6.

: Analisis deskriptif PTEI dan VEGF.

Tabel 5.7.

: PTEI dan VEGF berdasarkan jenis kelamin.

Gambar 5.1. : Tampilan micro-wells sebelum pengukuran dengan ELISA analyser. Gambar 5.2. :Box Plot distribusi PTEI dan VEGF.

Kurva 5.1.

: Kurva standar untuk menentukan konsentrasi VEGF.

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DAFTAR SINGKATAN

VEGF

: Vascular Endothelial Growth Factor

VEGFR

: Vascular Endothelial Growth Factor Receptor

PTEI

: Peritumoral Edema Index

MMP

: Matrix Metalloproteinase

HIF1α

: Heat Induced Factor 1α

IL

: Interleukin

bFGF

: Fibroblast Growth Factor

TGFα

:Transforming Growth Factor α

TGF β

: Transforming Growth Factor β

PDGF

: Platelet Derived Growth Factor

Ang

: Angiopoietin

Tie

: Receptor Tirosin Kinase

EMA

: Epithelial Membrane Antigen

CPA

: Cerebellopontine Angle

MIB-1

: Suatu penamaan suatu teknik untuk menentukan index protein Ki67.

LCS

: Liquor cerebrospinal

ATP

: Adenosine Triphosphate

BBB

: Blood brain barrier / Sawar darah otak

OeI / EI

: Edema Index

VPF

: Vascular Permeability Factor

PIGF

: Placental Growth Factor

cDNA

: Complement Deoxyribose Nucleic Acid

Flt-1

: Fms like tyrosine kinase. Disebut juga VEGFR-1

Flk

: Fetal liver kinase. Disebut juga VEGFR-2

Fms

: Macrophage Stimulating Factor

KDR

: Disebut juga VEGFR-2

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HuR

: Human antigen R (HuR), juga dikenal sebagai ELAVL1 sebuah RNA binding protein

mRNA

: Messenger Ribose Nucleic Acid

KDR

: Kinase Insert Domain Receptor

EGF

: Epidermal Growth Factor

RTK

: Receptor of Tyrosine Kinase

CA4P

: Combrestatin A4 3-O-Phosphate

VDA

: Vascular Destoyer Tubulin Binding Agent

ELISA

: Enzyme-Linked Immunosorbent Assay

HRP

: Horse Radish Protein

SNP

: Single Nucleotide Polimorphism

Universitas Sumatera Utara