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"Kanker ovarium memiliki mortalitas mencapai 70%, dan 85% dari pasien yang datang pada kondisi stadium lanjut. Sebanyak > 80% pasien stadium lanjut merespons pada kemoterapi lini pertama yang menggunakan obat berbasis platinum, namun median kesintasan bebas penyakitnya (disease-free survival) hanya mencapai 18 bulan, sebagian besar merupakan pasien kambuh, dan tidak merespons pada kemoterapi lini berikutnya. Pada moda moda kemoresistensi, yang paling dapat diintervensi adalah adanya sel punca kanker (CSC) pada jaringan kanker ovarium pasien. Kemoresistensi pada CSC memiliki beberapa mekanisme berbeda, salah satunya adalah tingginya aktivitas protein ATM dan ATR yang dapat bersifat kompetitif terhadap obat berbasis platinum dalam berikatan dengan DNA. Selama ini, telah banyak penelitian eksperimental yang menarget CSC kanker ovarium, namun penelitian terbaru menggunakan RNA microarray menemukan bahwa gen ADAM19 diekspresikan secara eksklusif pada CSC kanker ovarium sehingga dapat digunakan sebagai marker spesifik. Oleh karena itu, penelitian ini ditujukan untuk mengeksplorasi kemoresistensi pada CSC kanker ovarium dari jaringan segar pasien dan korelasinya dengan ekspresi gen ATM dan ATR, serta mengonfirmasi ekspresi gen ADAM19 sebagai marker spesifik subpopulasi CSC kanker ovarium yang dipilah menggunakan metode MACS dengan penanda CD133. Dari 67 pasien subjek penelitian yang diambil dan dikultur jaringan metastasisnya, dua di antaranya dapat dikultur tanpa batas, menghasilkan kultur dengan dominan sel epitel, dan tidak mengalami senescence. Setelah itu, sel-sel kultur dipilah menggunakan MACS dengan penanda CD133 untuk mendapatkan CSC, kemudian diuji menggunakan metode pembuatan sferoid, RT-qPCR, dan uji kemoresistensi. Dari pembentukan sferoid yang dilakukan pada tiga jenis sel yang digunakan, yakni lini sel SKOV3, serta kultur primer OV1 dan OVM1, ditemukan secara konsisten bahwa jumlah sferoid yang didapatkan pada kultur CSC CD133+ lebih banyak dibandingkan main population (MP) dan CD133-. Dari RT-qPCR juga ditemukan secara konsisten bahwa seluruh ekspresi gen ATM, ATR, NANOG, ADAM19, Ki-67, dan kaspase-3 pada CSC CD133+ lebih tinggi dibandingkan MP dan CD133. Pada uji kemoresistensi terhadap kemoterapi karboplatin, didapatkan bahwa sel CD133+ juga lebih kemoresisten dibandingkan dengan MP dan CD133-. Berdasarkan uji korelasi Spearman Rho, ekspresi gen ATM dan ATR berkorelasi positif sedang menuju sangat kuat dengan sifat kemoresistensi terhadap karboplatin. Pada akhir penelitian, disimpulkan bahwa CSC dengan CD133+ memiliki kemampuan proliferasi yang lebih tinggi dengan ekspresi gen Ki-67 yang meningkat, memiliki stemness yang lebih kuat terlihat pada ekspresi gen Nanog-nya yang lebih tinggi, dan memiliki kemampuan kemoresistensi yang lebih besar ditunjukkan oleh ekspresi gen ATM dan ATR-nya yang tinggi serta berkorelasi positif dengan hasil uji kemoresistensi.

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Ovarian cancer has a mortality rate of up to 70% where 85% of patients present at an advanced stage. More than 80% of advanced stage patients respond to first-line chemotherapy using platinum-based drugs, but the median disease-free survival is only 18 months. Most patients relapse, and do not respond to subsequent lines of chemotherapy. In the chemoresistance modes, the easiest way to intervene is through the presence of cancer stem cells (CSC) in the patient's ovarian cancer tissue. Chemoresistance in CSC has several different mechanisms, one of which is the high activity of ATM and ATR proteins that can be competitive against platinum-based drugs in binding to DNA. So far, there have been many experimental studies targeting ovarian cancer CSCs, but a recent study using RNA microarray found that ADAM19 gene expression is expressed exclusively in ovarian cancer CSCs so that it can be used as a specific marker. Therefore, this study aimed to explore chemoresistance in ovarian cancer CSC from fresh patient’s tissue and its correlation with ATM and ATR gene expression, as well as to confirm ADAM19 gene expression as a specific marker for ovarian cancer CSC subpopulations sorted using the MACS method with the CD133 marker. Out of 67 patients who were the subjects of the study, the samples were taken and cultured for their metastatic tissues, 2 of them could be cultured indefinitely, could produce cultures with a predominance of epithelial cells, and did not experience senescence. After that, the culture cells were sorted using MACS with the CD133 marker to obtain CSC, then tested using the spheroid preparation method, RT-qPCR, and chemoresistance test. From the spheroid culture performed on the 3 types of cells used, namely the SKOV3 cell line, as well as OV1 and OVM1 primary cultures, it was found consistently that the number of spheroids obtained in CD133+ CSC cultures was higher than the main population (MP) and CD133-. From RT-qPCR it was also found consistently that all genes expression ATM, ATR, NANOG, ADAM19, Ki-67, and Caspase-3 in CD133+ CSCs were higher than MP and CD133. In the chemoresistance test to carboplatin chemotherapy, it was found that CD133+ cells were also more chemoresistant than MP and CD133-. Based on the Spearman Rho correlation test, ATM and ATR gene expression had a moderately strong positive correlation with chemoresistance to carboplatin. At the end of the study, it was concluded that CSCs with CD133+ had a higher ability to proliferate with increased expression of the Ki-67 gene, had stronger stemness as seen in the higher expression of the NANOG gene, and had greater chemoresistance ability as indicated by the expression of the ATM gene. and high ATR and positively correlated with chemoresistance test results."

"Diagnosis kanker ovarium stadium lanjut memberikan kontribusi terbesar terhadap tingginya kasus kematian. Imunoterapi sebagai alternatif pengobatan diharapkan dapat mengobati pasien dengan kanker ovarium secara lebih cepat menggunakan sel imun bawaan yang dapat membunuh sel kanker secara permanen. Studi imunoterapi pada penelitian ini dilakukan dengan memanfaatkan interaksi antara ligan di dalam lingkungan mikro tumor dan reseptor sel NK. Reseptor NKP44 merupakan satu-satunya reseptor dengan dua mekanisme persinyalan berbeda yang secara aktif berperan penting dalam fungsi sel NK teraktivasi. Salah satu ligan potensial yang dapat meningkatkan fungsi pengenalan sel tumor melalui reseptor NKP44 adalah Nidogen-1 (NID1). Penelitian ini bertujuan untuk mengembangkan studi imunoterapi pasien dengan kanker ovarium serta mempelajari pengaruh interaksi ligan NID1 dengan reseptor NKP44 terhadap aktivitas sel NK. Metode penelitian yang dilakukan mencakup analisis ekspresi granul sitotoksik, analisis ekspresi NID1, uji keberhasilan ikatan ligan NID1 dengan sel NK, hingga analisis ekspresi NKP44. Hasil menunjukkan bahwa kelompok sel NK terinduksi memiliki aktivitas sitotoksik yang lebih baik dibandingkan kelompok sel NK tidak terinduksi melalui peningkatan ekspresi granul sitotoksik. Terdapat ekspresi NID1 meskipun dalam jumlah yang sedikit dan terkonfirmasi berhasil berikatan dengan sel NK. Namun, terjadi penurunan ekspresi NKP44 pada kelompok sel NK terinduksi sehingga perlu dilakukan analisis lanjutan penyebab penurunan ekspresi NKP44.

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Diagnosis of advanced ovarian cancer provides the largest contribution to the high number of deaths. Immunotherapy as an alternative treatment is expected to treat patients with ovarian cancer more quickly using innate immune cells that can permanently kill cancer cells. The development of immunotherapy in this study was carried out by utilizing the interaction between ligands in the tumor microenvironment and NK cell receptors. NKP44 is the only receptor with two different signaling mechanisms that actively play the most important role in the function of activated NK cells. One of the potential ligands that can improve tumor cell recognition function through the NKP44 receptor is Nidogen-1 (NID1). This research is aimed to develop immunotherapy studies for patients with ovarian cancer and to study the effect of the interaction of the NID1 ligand with the NKP44 receptor on NK cell activity. The research methods carried out included analysis of cytotoxic granule expression, analysis of NID1 expression, success test of NID1 ligand bonding with NK cells, and NKP44 expression analysis. The results showed that the induced NK cell group had better cytotoxic activity than the uninduced NK cell group through increased cytotoxic granule expression. There is expression of NID1 even in small numbers and it is confirmed that it binds successfully to NK cells. However, there was a decrease in the expression of NKP44 in the induced NK cell group so that further analysis needs to be carried out on the causes of the decrease in NKP44 expression."

"Pendahuluan: Hampir 85% kasus karsinoma ovarium terjadi overekspresi endothelin-1 (ET-1) yang memodulasi persinyalan tumorigenesis dan metastasis. Disisi lain, cisplatin sebagai kemoterapi kanker ovarium menimbulkan efek samping dan resistensi terapi. Berbagai penelitian menunjukkan kurkumin berpotensi sebagai antikanker yang meningkatkan efikasi cisplatin dan menekan overekspresi ET-1 pada lini sel nonkanker. Namun, belum banyak penelitian yang mengidentifikasi penekanan ekspresi ET-1 oleh kurkumin dalam regimen terapi bersama cisplatin di kanker ovarium. Oleh karena itu, penelitian ini bertujuan melihat efek ko-kemoterapi kurkumin bersama cisplatin pada kanker ovarium terkait ekspresi relatif mRNA ET-1. Metode: Jaringan ovarium tersimpan dari 24 tikus betina galur Wistar dibagi kedalam 4 kelompok: tikus yang hanya dibedah dan diberi aquadest (sham), tikus yang diimplantasi DMBA tanpa intervensi terapi, tikus yang diimplantasi DMBA dan diberi terapi tunggal cisplatin intraperitoneal 4 mg/kgBB/minggu, tikus yang diimplantasi DMBA dengan diberi terapi cisplatin 4 mg/kgBB/minggu dan kurkumin oral 100 mg/kgBB/hari. Implantasi DMBA dilakukan selama 28 minggu dan intervensi pada hewan coba selama 4 minggu. Setelah itu, jaringan ovarium tersimpan dianalisis ekspresi relatif mRNA ET-1 dengan mesin qRT-PCR menggunakan metode Livak-Schmittgen (2(-Ct)). Hasil: Didapatkan rerata ekspresi relatif mRNA ET-1 [p=0,021] pada kelompok sham (0,349±0,24), kelompok DMBA (3,117±1,532), kelompok DMBA+cisplatin (0,993±0,651), dan kelompok DMBA+kurkumin+cisplatin (0,117±0,081). Ketiga kelompok tidak memiliki perbedaan bermakna dibandingkan sham. Meski demikian, terdapat perbedaan bermakna pada kelompok kombinasi cisplatin serta ko-kemoterapi kurkumin dengan kelompok tanpa intervensi terapi [p=0,019]. Kesimpulan: Terjadi penurunan ekspresi relatif mRNA endothelin-1 di jaringan ovarium model tikus yang diinduksi DMBA setelah pemberian kombinasi cisplatin dan ko-kemoterapi kurkumin.

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Introduction: Endothelin-1 overexpression happens in 85% ovarian carcinoma cases that modulate metastatic and tumorigenesis. Meanwhile, cisplatin as ovarian cancer chemotherapy cause side effects and therapy resistances. Prior studies show potential effect of curcumin as an anticancer could enhance cisplatin efficacy and attenuate ET-1 overexpression in non-cancer cell lines. However, not many studies have identified suppression effect of ET-1 expression by curcumin with cisplatin in ovarian cancer. Therefore, this study is conducted to identify the effect of curcumin with cisplatin in ovarian cancer treatment especially its relation to relative expression of ET-1 mRNA.

Methods: Frozen ovarian tissue samples from 24 female Wistar rats were divided into 4 groups: a group that only operated on and treated with distilled-water (sham), group with DMBA-implantation, group with DMBA-implantation and intraperitoneal cisplatin 4mg/kgBW/week, group with DMBA-implantation and cisplatin with same dose as before plus oral curcumin 100mg/kgBW/day. After 28 weeks of DMBA-implantation and 4 weeks of intervention, frozen ovarian tissue samples were taken to measure its relative expression of ET-1 mRNA level with qRT-PCR machine.

Results: The mean of relative expression of ET-1 mRNA level [p=0,021] in frozen tissue sample of sham group (0,349±0,24), DMBA-implantation group (3,117±1,532), DMBA+cisplatin-treated group (0,993±0,651), and DMBA+curcumin+cisplatin-treated group (0,117±0,081). This study shows those 3 groups did not have significant difference compared with sham. But among group with cisplatin+curcumin-treated compared to DMBA-implantation shows a significant difference (p=0,019).

Conclusion: The relative expression of ET-1 mRNA in ovarian tissue of DMBA-induced rats model decreases after given by a combination of cisplatin+curcumin co-chemotherapy."

"ABSTRAKNama :Nugraha Utama PelupessyProgram Studi :S3 Ilmu KedokteranJudul :Marker Cancer Stem Cells CD133, CD44, dan ALDH1A1 Sebagai Faktor Prognostik pada Kanker Ovarium Tipe Epitelial Kanker ovarium merupakan penyakit yang bersifat heterogen dan kebanyakan pasien datang dengan stadium lanjut. Kanker ovarium epitelial tipe II mempunyai sifat pertumbuhan tumor yang cepat dan secara genetik labil dibandingkan tipe I. Keberadaan cancer stem cells CSC dianggap sebagai salah satu faktor prognostik terjadinya kemoresisten dan kesintasan hidup yang rendah.Penelitian ini bertujuan untuk membuktikan CSC sebagai faktor prognostik dengan menggunakan marker CD133, CD44, dan ALDH1A1 pada kanker ovarium tipe epitelial.Marker CD133, CD44, dan ALDH1A1 diperiksa dengan imunohistokimia dan flowcytometry. Hasil ekspresi marker CSC pasien kanker ovarium tipe I dan tipe II dimasukkan kedalam suatu tabel yang dihubungkan dengan respons kemoterapi dan kesintasan hidup. Analisis data dilakukan dengan program computer STATA 14. Analisis kesintasan dilakukan dengan analisis Kaplan-Meier dan uji asumsi cox proportional hazard. Analisis multivariat dipakai untuk model prognosis selama 10 bulan. Sistem skoring dibuat dengan menggunakan receiver operating characteristic ROC curve analyses.Data demografi kelompok terbanyak adalah usia ge; 45 tahun; 40 sampel 72,7 , stadium I, 23 sampel 41,8 , diferensiasi buruk 30 sampel 54,5 , dan tipe II 16 sampel 29,1 . Perbedaan yang bermakna antara tipe histopatologi dengan marker CSC hanya terlihat pada marker CD44. Skor Prediksi Kemoresisten SPKr 10 bulan yang dihubungkan dengan 4 variabel yaitu usia ge; 45 tahun, tipe II, stadium III minus;IV, dan CD44 tinggi dengan ROC 72,47 dan probabilitas post test 82,5 . Kurva ROC berdasarkan kombinasi marker CSC dan faktor klinikopatologi yaitu stadium III minus;IV, usia ge; 45 tahun, diferensiasi buruk, tipe II, CD133 negatif, CD44 tinggi, dan ALDH1A1 tinggi adalah 0,841. Skor Prediksi Kematian SPKm 10 bulan yang dihubungkan dengan 3 variabel yaitu stadium III minus;IV, tipe II, dan CD44 tinggi dengan AUC 80,44 dan probabilitas post test 78,7 . Kurva ROC berdasarkan kombinasi marker CSC dan faktor klinikopatologi yaitu stadium III minus;IV, usia ge; 45 tahun, diferensiasi buruk, tipe II, CD133 positif, CD44 tinggi, dan ALDH1A1 tinggi adalah 0,841.Simpulan: Marker CD44 terbukti berperan pada kanker ovarium tipe II. Skor Prediksi Kemoresisten dan Skor Prediksi Kematian dapat ditentukan selain dengan faktor klinikopatologi, juga dengan memakai marker CSC. Kata kunci: ALDH1A1, CD44, CD133, CSC, kanker ovarium epitelial, kesintasan hidup, respons kemoterapi.

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ABSTRACTName : Nugraha Utama PelupessyStudy Program : Doctoral Program Medical SciencesTitle :Cancer Stem Cell CD133, CD44 andALDH1A1 Markers As Prognostic Factors on Epithelial Ovarian Cancer. Ovarian cancer is a heterogeneous disease and most of the patients came with an advanced stage. Epithelial ovarian cancer type II has the characteristic of rapid tumor growth and genetically more labile than that of type I. The presence of cancer stem cells CSC is considered as one of the prognostic factors of low mortality and survival.The aims of this study was to prove CSC as prognostic factors using CD133, CD44, and ALDH1A1 markers on epithelial ovarian cancer.Clinicopathology and demographic data were collected from medical records. CD133, CD44, and ALDH1A1 markers were examined with flowcytometry and immunohistochemistry. CSC marker expression of the patients with ovarian cancer type I and II was connected with chemotherapy and survival response. Data analysis was done by using STATA 14 software. Survival analysis was done by using Kaplan-Meier analysis and Cox proportional hazard test. Multivariate analysis is used for prognosis model for ten months. Receiver Operating Characteristic ROC curve analyses was used as the system scoring. The highest group demographic data were age ge; 45 years; 40 samples 72.7 , stage I, 23 samples 41.8 , poor differentiation 30 samples 54.5 , and type II 16 samples 29.1 . A significant difference between the histopathologic type and the CSC marker was seen only in CD44 marker. Chemoresistance Prediction Score in 10 months was associated with 4 variables ie age ge; 45 years, type II, stage III minus;IV, and CD44 high with ROC 72.47 and posttest probability 82.5 . The highest chemoresitency scoring ROC curve based on the combination of CSC marker and clinicopathology factors; stage III minus;IV, age ge; 45 years, poor differentiation, type II, negative CD133, high CD44, and high ALDH1A1, was 0.841. Mortality Prediction Score in 10 months was associated with 3 variables is stage III minus;IV, type II, and CD44 high with AUC 80.44 and posttest probability 78.7 . The highest mortality scoring ROC curve based on the combination of CSC marker and clinicopathology factors; stage III minus;IV, age ge; 45 years, poor differentiation, type II, positive CD133, high CD44, and high ALDH1A1, was 0.841. Conclusion: The CD44 marker has a role in type II ovarian epithelial cancer. Chemoresistance Prediction Score and Mortality Prediction Score can be determined from clinicopathological factors and using CSC marker. Keywords: ALDH1A1, CD44, CD133, chemotherapy response, CSC, Epithelial Ovarian Cancer, survival"

"Kanker ovarium merupakan kanker paling mematikan ke-8 pada perempuan di dunia. Pasien kanker ovarium umumnya akan mengalami kemoresistensi, kekambuhan dan prognosis buruk setelah operasi sitoreduktif dan kemoterapi berbasis platinum. Hal tersebut berhubungan dengan peningkatan ekspresi Cancer Stem Cells (CSCs) CD44+/CD24-, RAD6, dan penurunan DDB2. Penelitian ini bertujuan untuk menganalisis hubungan ekspresi CSCs, RAD6 dan DDB2 dengan kemoresistensi kanker ovarium di jaringan kanker ovarium dan sirkulasi darah.Penelitian kohort ambispektif ini dilakukan di RSUP Cipto Mangunkusumo, RSUD Tarakan, RSUP Dharmais, dan RSUP Fatmawati pada Februari 2018–Februari 2022. Subjek adalah 64 orang pasien yang dibagi menjadi dua kelompok. Semua subjek menjalani operasi sitoreduktif dan pemeriksaan histopatologi. Kemoterapi diberikan sebanyak enam seri diikuti enam bulan observasi, kemudian ditentukan respons terapi dengan kriteria Response Criteria in Solid Tumors (RECIST). Uji imunohistokimia dilakukan langsung ke jaringan kanker ovarium (retrospektif) dan uji flowsitometri darah (prospektif) untuk menilai Ekspresi CSCs, RAD6 dan DDB2.Terdapat peningkatan Ekspresi CSCs, RAD6 serta penurunan bermakna ekspresi DDB2 (p < 0,05) di jaringan kanker ovarium kemoresisten, dan peningkatan bermakna Ekspresi CSCs, dan RAD6 yang bermakna (p < 0,05) di sirkulasi darah penderita kanker ovarium. Ekspresi DDB2 di uji imunohistokimia adalah protein dengan nilai AUC terbaik sedangkan di uji flowsitometri, CSCs memiliki nilai AUC terbaik. Disusun skor IHC-UNEDO (imunohistokimia) dan skor FCM- UNEDO (flowsitometri) untuk membantu memprediksi respons terapi.Penelitian ini menunjukkan bahwa terdapat peningkatan Ekspresi CSCs, RAD6 dan penurunan DDB2 di jaringan kanker ovarium, serta peningkatan Ekspresi CSCs di sirkulasi darah penderita kanker ovarium dan protein tersebut merupakan prediktor respons terapi kanker ovarium yang baik."

"ABSTRAKLatar Belakang: Kanker ovarium merupakan salah satu kanker yang menyebabkan kematian paling tinggi pada wanita. Tujuh puluh persen saat didiagnosis ditemukan pada stadium lanjut, dengan angka kesintsan dalam 5 tahun hanya 46 . Modalitas terapi saat ini adalah sitoreduksi dengan kemotterapi adjuvant platinum based sebagai lini pertama. Efektivitas kemoterapi hanya 60 pada stadium lanjut, untuk selanjutnya berkembang menjadi rekuren. Oleh karena itu dibutuhkan jenis terapi tambahan berdasarkan jenis atau agen yang bekerja spesifik di sel kanker dan dapat bersinergi dengan pengobatan standar saat ini. Kurkumin sebagai salah satu agen yang banyak diuji memiliki efek anti-kanker. Kurkumin berpotensi sebagai anti kanker dan bekerja pada semua multistep karsinogenesis. Kurkumin dapat bekerja sebagai antiproliferasi dan meningkatkan apoptosis.Tujuan: untuk mengetahui antiproliferasi ekspresi Ki67 dan apoptosis caspase 3 dan caspase 8 kombinasi cisplatin dengan nanokurkumin pada sel hayati SKOV3.Metode: Penelitian ini dilakukan uji eksperimental in vitro dengan menggunakan sel hayati SKOV3 untuk mengetahui antiproliferasi ekspresi Ki67 dan apoptosis caspase 3 dan caspase 8 kombinasi cisplatin dengan nanokurkumin pada sel tersebut. Uji analisis data dengan T tidak berpasangan bila sebaran normal / uji Mann Whitney bila sebaran tidak normal serta menggunakan Graph Pad Prism.Hasil: Berdasarkan penelitian ini, didapatkan cc50 nanokurkumin 67 m dan cc50 cisplatin 54 m dengan menggunakan metode MTT Assay. Viabilitas sel pada penelitian ini menurun sesuai dengan dose dependent, dimana pada dosis kombinasi nanokurkumin 134 m dengan cisplatin 108 m ditemukan sel hidup yang paling rendah 24.3 p

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ABSTRACTBackground Ovarian cancer is one of the most leading cancers in women. Seventy percent at the time of diagnosis are found at an advanced stage, with a 5 year survival rate of only 46 . The current treatment modality is cytoreduction with platinum based adjuvant chemotherapy as first line. The effectiveness of chemotherapy is only 60 at an advanced stage, to further develop into recurrent. Therefore, additional types of therapy are required based on types or agents that work specifically in cancer cells and can synergize with current standard treatments. Curcumin as one of the many tested agents has anti cancer effects. Curcumin has the potential effect as an anti cancer and works on all multisteps of carcinogenesis. Curcumin can work as an antiproliferation and increase apoptosis.Objective to know antiproliferation effect expression Ki67 and apoptosis effect caspase 3 and caspase 8 of combination cisplatin with nanokurkumin on cell SKOV3.Methods This experimental study was conducted in vitro by using biological cell line SKOV3 to know antiproliferation effect expression Ki67 and apoptosis effect caspase 3 and caspase 8 of combination cisplatin with nanokurkumin on the cell. The data was analysed with unpaired T when normal distribution Mann Whitney test when distribution is not normal and also using Graph Pad Prism.Result Based on this result, cc50 of nanokurkumin is 67 m and cc50 of cisplatin is 54 m by using MTT Assay method. The viability of the cells in this study decreased according to the dose dependent, whereas in the combined dose of 134 m nanocurcumin with 108 m cisplatin found the lowest life cell 24.3 p "

"Latar Belakang: Kanker ovarium merupakan kanker kedelapan tersering, terhitung hampir 4% dari semua kanker pada perempuan di dunia. Kanker ovarium memiliki prognosis yang buruk dan angka kematian tertinggi. Setiap tahunnya terdapat 225.000 perempuan yang terdiagnosis kanker ovarium dan 140.000 perempuan meninggal disebabkan oleh penyakit ini. Berdasarkan jumlah tersebut, 90% kasus merupakan kanker ovarium epitelial. Bila berdasarkan stadium, lebih banyak pasien datang terdiagnosis dengan kanker ovarium stadium lanjut dibandingkan dengan stadium dini. Hal ini dikarenakan kanker ovarium bersifat asimtomatik, onset gejala yang terlambat dan belum adanya skrining yang terbukti efektif untuk kanker ovarium. Tujuan utama pengobatan kanker stadium lanjut adalah memperpanjang waktu untuk bertahan hidup dengan kualitas hidup yang baik dan tata laksana standarnya adalah operasi sitoreduksi. Di RSCM, evaluasi kesintasan dari pasien kanker ovarium epitelial stadium lanjut yang menjalani operasi sitoreduksi belum dianalisis.Tujuan: Mengetahui kesintasan pasien kanker ovarium stadium lanjut yang menjalani operasi sitoreduksi di RSCM dan juga mengetahui kesintasannya berdasarkan hasil histopatologi dan pemberian kemoterapi ajuvan.Metode: Penelitian ini merupakan penelitian kohort retrospektif dengan menggunakan data dari rekam medis. Pengambilan sampel dilakukan dengan cara consecutive sampling. Subjek penelitian adalah semua pasien kanker ovarium epitelial stadium lanjut yang menjalani operasi sitoreduksi pada bulan Januari 2013-Januari 2015 di RSCM.Hasil: Dari 48 subjek yang diteliti, didapatkan sebanyak 23 (48%) subjek menjalani operasi sitoreduksi optimal dan 25 (52%) subjek menjalani operasi sitoreduksi suboptimal. Didapatkan kesintasan 5 tahun pada pasien yang menjalani operasi sitoreduksi optimal sebesar 43,5%, sedangkan untuk sitoreduksi suboptimal sebesar 32%. Pada pasien yang menjalani operasi sitoreduksi optimal, yang diberikan kemoterapi ajuvan didapatkan kesintasan 5 tahun sebesar 40%, sedangkan pada pasien yang tidak diberikan sebesar 46,2%. Pada pasien yang menjalani operasi sitoreduksi suboptimal, yang diberikan kemoterapi ajuvan didapatkan kesintasan 5 tahun sebesar 40%, sedangkan pada pasien yang tidak diberikan sebesar 20%. Pada pasien dengan hasil histopatologi seromusinosum didapatkan kesintasan 5 tahun sebesar 100%, sedangkan untuk serosa, musinosa, endometrioid dan sel jernih berturut-turut sebesar 50%, 33,3%, 25%, dan 21,4%.Kesimpulan: Operasi sitoreduksi optimal memiliki kesintasan 5 tahun yang lebih baik dibandingkan dengan operasi sitoreduksi suboptimal. Operasi sitoreduksi suboptimal dan tidak dilanjutkan dengan pemberian kemoterapi ajuvan memiliki kesintasan yang buruk. Jenis histopatologi seromusinosum memiliki kesintasan yang lebih baik dibandingkan dengan jenis serosum, musinosum, endometrioid dan sel jernih.

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Background: Ovarian cancer is the eighth most common cancer, almost 4% of all cancers in women in the world. Ovarian cancer has a poor prognosis and the highest mortality rate. Every year 225,000 women are diagnosed with ovarian cancer and 140,000 women die from this disease. Based on this number, 90% of cases are epithelial ovarian cancer. Based on stadium, more patients diagnosed with advanced-stage ovarian cancer compared with early stage, because ovarian cancer is asymptomatic, delayed onset and there is no screening that has proven effective for ovarian cancer. The standard management for advanced stage ovarian cancer is debulking surgery. At RSCM, evaluation of survival of advanced stage epithelial ovarian cancer patients who were performed debulking surgery has not been analyzed.

Objective: Knowing the survival of patients with advanced-stage ovarian cancer who underwent debulking surgery at RSCM and also knowing their survival based on histopathological results and adjuvant chemotherapy.

Methods: This was a retrospective cohort study using data from medical records. Sampling was done by consecutive sampling. The subjects of this study were all patients with advanced-stage epithelial ovarian cancer patients who were performed debulking surgery in January 2013-January 2015 at RSCM.

Results: From the 48 subjects, 23 (48%) subjects were performed optimal debulking surgery and 25 (52%) subjects were performed suboptimal debulking surgery. Overall survival in patients undergoing optimal debulking surgery is 43.5% with a median survival rate of 39 months, while for suboptimal debulking surgery is 32% with a median survival rate of 29 months. In patients who underwent optimal cytoreduction surgery, those given adjuvant chemotherapy obtained a overall survival is 40%, whereas in patients who were not given is 46.2%. In patients who underwent suboptimal cytoreduction surgery, those who were given adjuvant chemotherapy found a overall survival rate of 40%, whereas in patients who were not given is 20%. In patients with histopathological results seromucinous obtained 5-year survival by 100%, while for serous, mucous, endometrioid and clear cells simultaneously were 50%, 33.3%, 25%, and 21.4%.

Conclusion: Optimal debulking surgery has a better 5-year survival compared to suboptimal debulking surgery. Suboptimal cytoreduction surgery and not followed by adjuvant chemotherapy has poor survival. The histopathological type of seromucinous has better survival compared with the types of serous, mucinous, endometrioid and clear cells."

"Latar belakang: Kanker ovarium khususnya jenis epitelial merupakan salah satu kanker tersering yang diderita oleh perempuan dengan angka mortalitas dan morbiditas yang tinggi. Hingga saat ini, beberapa penelitian telah meneliti berbagai faktor prognostik pada kanker ovarium, khususnya trombosit yang secara patofisiologi memiliki hubungan dengan berbagai marker inflamasi pada kanker. Tujuan: (1) Membuktikan bahwa trombositosis sebagai faktor prognosis pada pasien kanker ovarium jenis epitelial (2) Membuktikan angka OS selama 3 tahun pada pasien kanker ovarium jenis epitelial dengan trombositosis lebih buruk dibandingkan tanpa trombositosis. Metode: Penelitian ini menggunakan studi kohort retrospektif menggunakan data rekam medis pasien kanker ovarium epitelial yang terdaftar pada cancer registry Departemen Obstetri dan Ginekologi Divisi Onkologi Rumah Sakit Cipto Mangunkusumo pada tahun Januari 2014- Juli 2016. Pengamatan dilakukan saat subjek pertama kali didiagnosis kanker ovarium hingga terjadi peristiwa hidup, meninggal, atau hilang dari pengamatan dalam waktu 3 tahun. Hasil: Didapatkan 220 subjek penelitian yang merupakan populasi terjangkau dan memenuhi kriteria inklusi dan eksklusi. Dari 220 subjek penelitian, 132 (60%) dari 220 subjek penelitian merupakan pasien dengan kanker ovarium stadium lanjut (Stadium II/III/IV). Trombositosis didapatkan pada 94 orang subjek penelitian (42,7%). Pasien dengan kanker stadium lanjut memiliki risiko trombositosis yang lebih tinggi dibandingkan subjek pada stadium awal (p=0,005;OR=2,329). Meski begitu, ada atau tidaknya trombositosis secara statistik tidak bermakna pada OS selama 3 tahun (p=0,555). Terdapat mean time survival yang lebih rendah pada pasien dengan trombositosis tetapi tidak ada perbedaan hazard ratio yang bermakna antara subjek dengan atau tanpa trombositosis (p=0,399). Pada penelitian ini, didapatkan faktor prognostik yang bermakna pada OS selama 3 tahun antara lain adalah ada tidaknya asites (HR=3,425; p=0,025), stadium (HR=9,523; p=0,029) dan residu tumor ≥ 1 cm (HR=4,137; p=0,015) dengan stadium kanker ovarium merupakan faktor independen (HR=9,162; p=0,033). Sensitivitas dan spesifisitas trombositosis terhadap kanker ovarium stadium lanjut didapatkan sebesar 50,75% dan 69,32%. Kesimpulan: Trombositosis sebagai faktor prognostik pada pasien kanker ovarium jenis epitelial tidak dapat dibuktikan dan angka OS selama 3 tahun pada pasien dengan trombositosis dibandingkan dengan pasien tanpa trombositosis tidak bermakna secara statistik.

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Background: Ovarian cancer, especially, epithelial ovarian cancer is one of the most common cancer in women with high rate of mortality and morbidity. Some studies have found that some biological factors that can be used as a prognostic factor for epithelial ovarian cancer, particularly, thrombocytes which pathophysiologically correlates with inflammation markers in cancer. Aim: (1) To determine thrombocytosis as a prognostic factor for epithelial ovarian cancer. (2) To determine that 3-year overall survival in epithelial ovarian cancer with thrombocytosis is significantly shorter than patients without thrombocytosis. Method: This study is a retrospective cohort study using medical record of patients with epithelial ovarian cancer which are registed in the cancer registry of Oncology Division in Obstetric and Gynecology Department, Cipto Mangunkusumo Hospital from January 2014 until July 2016. Datas were collected when subjects were first diagnosed with epithelial ovarian cancer until diseases outcomes (survive, death, or loss to follow up) were identified in 3 years. Result: Out of 220 subjects, 132 (60%) were patients with advanced stage epithelial ovarian cancer (stage II/III/IV). 94 (42,7%) subjects had thrombocytosis. Patients with advanced stage of disease had higher risk of having thrombocytosis than the ones with earlier stage (p=0,005;OR=2,329). Correlation between thrombocytosis and 3-year overall survival was known to be insignificant (p=0,555). There was shorter mean time survival between patients with thrombocytosis and the ones without but the there was no significant difference in hazard ratio between the two groups. In this study, several prognostic factors of epithelial ovarian cancer were identifed such as ascites (HR=3,425; p=0,025), stage of disease (HR=9,523; p=0,029), and post-operative residual tumor ≥ 1 cm (HR=4,137; p=0,015) with stage of disease being the independent prognostic factor (HR=9,162; p=0,033). Sensitivity and specificity of thrombocytosis to advance stage of epithelial ovarian cancer were found to be 50,75% and 69,32%, respectively. Conclusion: Thrombocytosis as a prognostic factor in patients with epithelial ovarian cancer cannot be proven statistically. There is also no significant difference of 3-year overall survival between patients with or without thrombocytosis."

"[ABSTRAKPenelitian ini bertujuan untuk mengetahui gambaran umum kanker ovarium di Rumah Sakit Ciptomangunkusumo (RSCM) 5 tahun terakhir beserta faktor-faktor yang berhubungan dengan kanker ovarium. Penelitan ini mengambil data pasien kanker ovarium selain tipe borderline yang terdapat di Cancer Registry divisi Ginekologi Onkologi dan masih memiliki rekam medis di RSCM pada periode Januari 2010 – Desember 2014, dilakukan follow up untuk mengetahui kesintasan hidup selama 4 tahun. Kami mendapatkan 98 subyek penelitian. Pada penelitian ini didapatkan insidensi kanker ovarium terbanyak pada usia 45-54 tahun (33,6%), insidensi kanker ovarium menurun dengan bertambahnya jumlah anak, sebagian besar kanker ovarium merupakan tipe epitelial (76,5%) dan sebagian besar pasien didiagnosa pada stadium lanjut (55.1%). Kesintasan hidup 4 pasien kanker ovarium tipe epitelial 77%; tipe germinal 83.3%; tipe stroma 100%. Kesintasan hidup 4 tahun dengan terapi pembedahan 84.1%; pembedahan disertai kemoterapi adjuvan 83.3%; kemoterapi neoadjuvan sebelum pembedahan 68.4%. Terdapat 63% respon komplit pada kelompok kemoterapi adjuvan; dan 41.2% pada kelompok kemoterapi neoadjuvan.

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ABSTRACTThe aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.;The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.;The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy., The aim of this research is to describe the incidence of ovarian cancer and its characteristic in Ciptomangunkusumo Hospital in the last 5 year. The data was collected from Gynecology Oncology Division’s Cancer Registry and RSCM’s medical record from Januari 2010 – December 2014, follow up was performed to know the survival. There was 98 subject in this research. The result was : majority incidence of ovarian cancer was in the age 45-54 years old (33,6%); ovarian cancer incidence decrease in parity’s group; the majority histotype was epithelial (76.5%); and most of them were diagnosed on advanced stage (55.1%). The 4 year survival rate for epithelial was 77%; germinal was 83,3%; and stromal was 100%. Based on therapy the 4 year survival rate was 84.1%; 83.3% in adjuvant chemotherapy group; and 68.4% in neoadjuvan chemotherapy. In the group of adjuvant chemotherapy there was 63% complete respon and 41.2% in neoadjuvan chemotherapy.]"