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DAFTAR ISI HALAMAN JUDUL ....................................................................................... LEMBAR PENGESAHAN ............................................................................ PERNYATAAN............................................................................................... KATA PENGANTAR..................................................................................... DAFTAR ISI ................................................................................................... DAFTAR TABEL ........................................................................................... DAFTAR GAMBAR......................................................................................... DAFTAR SINGKATAN................................................................................... INTISARI.......................................................................................................... ABSTRACT....................................................................................................... BAB I. PENDAHULUAN .............................................................................. A. Latar Belakang Penelitian .......................................................................... B. Pertanyaan Penelitian ................................................................................. C. Tujuan Penelitian ........................................................................................ D. Manfaat Penelitian ...................................................................................... 1. Pasien ..................................................................................................... 2. Tenaga Kesehatan .................................................................................. 3. Institusi Kesehatan ................................................................................. E. Keaslian Penelitian ..................................................................................... BAB II. TINJAUAN PUSTAKA .................................................................... A. Kanker Kolorektal ...................................................................................... 1. Definisi Kanker Kolorektal .................................................................... 2. Epidemiologi Kanker Kolorektal ........................................................... 3. Gejala Kanker Kolorektal ...................................................................... 4. Faktor Risiko Kanker Kolorektal ........................................................... 5. Deteksi Kanker Kolorektal ..................................................................... 6. Stadium Kanker Kolorektal .................................................................... 7. Derajat diferensiasi tumor....................................................................... 8.Derajat diferensiasi dan kanker kolorektal.............................................. 9.Faktor yang berhubungan dengan derajat diferensiasi tumor.................. B. Sitokin Peradangan dan Keganasan ............................................................ C. Interleukin 6 ............................................................................................... 1. Definisi Interleukin-6 .............................................................................. 2. Fungsi Interleukin-6 ................................................................................ 3. Hubungan Interleukin-6 dan Kanker Kolorektal ..................................... 4.Inteleukin-6 sebagai prognosis kankerkolorektal……………………… 5.Ekspresi IL-6 terhadap derajat diferensiasi karsinoma kolorekal………… 6.Faktor-faktor yang mempengaruhi ekspresi IL-6........................................
i ii iii iv vi viii ix x xi xii 1 1 4 4 4 4 4 5 5 7 7 7 9 10 11 13 17 19 19 20 18 20 22 23 26 30 31 32
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D. Kerangka Teori ............................................................................................ E. Kerangka Konsep ........................................................................................ F. Hipotesis ......................................................................................................
35 36 36
BAB III. METODE DAN CARA PENELITIAN ........................................... A. Rancangan penelitian .................................................................................. B. Tempat dan Waktu Penelitian ..................................................................... C. Subyek Penelitian ........................................................................................ D. Estimasi Besar Sampel ................................................................................ E. Skema Alur Penelitian ................................................................................. F. Cara Penelitian ........................................................................................... G. Identifikasi Variabel .................................................................................... H. Pengukuran .................................................................................................. I. Definisi Operasional .................................................................................... J. Analisis Statistik .......................................................................................... K. Pertimbangan Etika ..................................................................................... BAB IV HASIL DAN PEMBAHASAN ......................................................... BAB V SIMPULAN DAN SARAN................................................................ DAFTAR PUSTAKA........................................................................................ LAMPIRAN......................................................................................................
37 37 37 39 40 41 42 43 44 44 45 46 47 66 67 71
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DAFTAR TABEL
Tabel 1. Daftar penelitian yang serupa dengan penelitian ini ......................... 5 Tabel 2. Stadium Kanker Kolorektal ............................................................... 18 Tabel 3.Makna klinis IL-6 .............................................................................. . 26 Tabel 4.Nilai Kappa Inter-observer Antara Dua Pengamat Pada Penilaian Ekspresi IL-6 .........................................................................................................47 Tabel 5.KarakteristikDasarSubyekPenelitian................................................... 49 Tabel6.AnalisisKruska Wallis dan Mann Whitney perbedaan inteleukin-6 berdasarkan derajat diferensiasi adenokarsinoma kolorektal..........................51 Tabel7. Perbedaan Karakteristik Klinis berdasarkan Derajat Diferensiasi Tumor.....................................................................................................................54 Tabel8. Perbedaan Karakteristik Klinis berdasarkan Ekspresi IL-6 Jaringan Positif dan Negatif..................... .......................................................................................55 Tabel9. Hubungan antara variable ekspresi IL-6 jaringan berdasarkan nilai median denganderajat diferensiasi kolon dan rektum (Uji Chi Square)............................56 Tabel 10. Nilai ratio prevalence dan confidence interval............................57
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DAFTAR GAMBAR
Gambar 1. Anatomi dari sistem pencernaan.............................................................................................7 Gambar 2. Penampang jaringan usus normal .................................................. .......8 Gambar 3. Klasifikasi TNM kanker kolorektal............................................... ... .18 Gambar 4. Peran faktor transkipsi peradangan pada perkembangan tumor .... .....20 Gambar 5. Aktifitas biologis dari IL-6............................................................ .....23 Gambar 6. Signaling IL-6 pada kanker kolorektal .......................................... .....26 Gambar 7. Perbedaan ekspresi mRNA IL-6 pada jaringan kolorektal normal, adenoma, kanker kolorektal .......................................................... .....28 Gambar 8. Skema rancangan penelitian.......................................................35 Gambar9.Alur penelitian mengenai perbedaan ekspresi IL-6 pada jaringansel kanker berdasarkan derajat diferensiasi pada pasien kanker kolorektal..................................................................................... 38 Gambar10.Sebaran ekspresi IL-6 pada jaringan kanker kolorektal subyek penelitian......................................................................................47 Gambar11. Sebaran ekspresi IL-6 pada jaringan kanker kolorektal subyek penelitian...............................................................................................................49 Gambar12.Sebaran derajat diferensiasi sel kanker pada subyek penelitian...............................................................................................................49 Gambar 13.Ekspresi IL-6 pada sel kanker berdasarkan derajat diferensiasi 2 kelompok...............................................................................................................50 Gambar 14.Ekspresi IL-6 pada sel kanker berdasarkan derajat diferensiasi 3 kelompok...............................................................................................................51 Gambar 15. Kurva perpotongan sensitivitas dan spesifisitas batas cut 0ff interleukin-6............................................................................................... Gambar16.Pewarnaanimmunohistokimia IL-6 padajaringankankerkolorektal pembesaran 100x............................................................................................................ 54 Gambar 17. Ekpresi IL-6 jaringan adenokarsinoma kolorektal pembesaran 400x............................................................................................................54
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DAFTAR SINGKATAN APC : antigen presenting cell CEA : carcinoma embryonic antigen CRP : C-reactive protein CT Scan:Computed Tomography scan COX-2 :cyclo oxygenase-2. DNA : deoxy ribonucleic acid FDA : Food and drug administration FOBT : fecal occult blood test GP 130 :glikoprotein 130 HLA :Human Leucocyte Syndrome ICD : International Classification of Disease. IL-6 : interleukin-6. JAK STAT :Janus family tyrosine kinase–signal transducer and activator of transcription K-ras : Kirsten rat sarcoma viral LimfositTC :limfosit T cell cytotoxic NK cell :natural killer cell NSAID :non steroid anti inflammatory drug NF-κB : nuclear factor kappa-light-chain-enchancer of activated B cells P13-K/AKT :phosphoinositide-3-kinase and activating receptor tyrosine kinase P53 :Protein 53 RAS Mapk :mitogen-activated protein kinase RNA : ribonucleic acid STAT-3 :signal transducer and activator of transcription-3 sIL-6R : soluble interleukin-6 receptor Th-17 : T helper-17 TLR : Toll –like Receptor TNF alfa: tumor necrosis factor VEGF :vascular endothelial growth factor WHO :world health organization 1.
