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Abstrak :
Penelitian ini bertujuan untuk membandingkan ROMA dengan RMI dalam memprediksi keganasan tumor ovarium epitelial di RS dr. Cipto Mangunkusumo (RSUPNCM). Penelitian ini merupakan uji diagnostik dengan desain potong lintang yang dilakukan di Departemen Obstetri dan Ginekologi, RSUPNCM. Pada penelitian ini, dari 213 subjek diperoleh sensitivitas dan spesifisitas RMI 85.3%, dan 66.3%, Nilai Duga Positif dan Negatif RMI 79.7%, dan 74.3%, Rasio Kemungkinan Positif dan Negatif RMI 2.53, dan 0.22; dan sensitivas dan spesifisitas ROMA 95.4%, dan 32.5%, Nilai Duga Positif dan Negatif 68.9%, dan 81.8%, Rasio Kemungkinan Positif dan Negatif 1.41, dan 0.14. AUC ROMA lebih baik daripada RMI, tetapi tidak bermakna secara statistik (seluruh kelompok: AUC 69.56%>67.49%, perbedaan AUC 0.0207, p 0.526; kelompok pascamenopause: AUC 91.47%>88.97%, perbedaan AUC 0.0250, p 0.0571; kelompok premenopause: AUC 86.20%>78.16%, perbedaan AUC 0.0804, p 0.0571). Pada titik potong ideal (RMI 330, ROMA premenopause 30,4; dan pascamenopause 53.1), ROMA mempunyai sensitivitas dan spesifitas yang lebih baik dibandingkan RMI (sensitivitas 82.31% vs 74.62%; spesifisitas 78.31% vs 75.9%). Dapat disimpulkan bahwa tidak terdapat perbedaan antara ROMA dengan RMI, tetapi sensitivitas dan spesifisitas ROMA lebih baik daripada RMI pada titik potong ideal. ......The purpose of this research is to compare ROMA with RMI to predict malignancy of ovarian tumor, epithelial type in Indonesia, especially at the Cipto Mangunkusumo hospital. It was a cross sectional study with a diagnostic design, which was performed in the Oncology Gyneology division. From 213 sampels, the RMI showed a sensitivity of 85.3%, a specificity of 66.3%, a PPV of 79.7%, a NPV of 74.3%, a LR+ of 2.53, LR- 0.22 and an accuracy of 0.77; while ROMA has a sensitivity of 95.4%, a specificity of 32.5%,a PPV 68.9% of, a NPV of 81.8%, a LR+ 1.41, LR- 0.14 and an accuracy of 0.71. Overall AUC ROMA indicated better results compared to those results using the RMI diagnostic method, (all groups: AUC 69.56%>67.49%, p 0.526; as with the postmenopause group: the AUC was 91.47%>88.97%, p 0.0571; and the premenopause group: the AUC 86.20%>78.16%, p 0.0571). At ideal the cut-off point (RMI 330, ROMA premenopause 30,4; and postmenopause 53.1), ROMA has shown better sensitivity and specificity than RMI (sensitivity 82.31% vs 74.62%; specificity 78.31% vs 75.9%). It can be concluded that there is no significantly different between ROMA and RMI, but at ideal cut off, sensitivity and specificity ROMA better than RMI.

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Latar Belakang : Sampai saat ini kanker ovarium masih menjadi salah satu kanker dengan angka mortalitas yang tinggi pada wanita dikarenakan tidak dijumpainya gejala yang khas sehingga lebih banyak kasus terdiagnosis pada stadium lanjut. Belum adanya metode skrining menjadikan pentingnya metode diagnostik yang mempunyai sensitivitas dan spesifisitas yang tinggi. Evaluasi biomarker yang baru diperlukan untuk dapat mendeteksi tumor ovarium ganas pada stadium awal. Objektif : Penelitian ini dilakukan untuk menilai ekspresi Immediate Early Response Gene X-1 (IEX-1) saliva sebagai prediktor keganasan pada tumor ovarium epitelial. Metode : Merupakan penelitian uji diagnostik pada pasien tumor ovarium yang direncanakan operasi elektif dengan mengambil 3-5 ml saliva pasien sebelum tindakan operasi. Subjek penelitian yang memenuhi kriteria inklusi dan eksklusi dibagi menjadi dua kelompok berdasarkan hasil histopatologi yaitu tumor ovarium epitelial jinak dan ganas. Dilakukan pemeriksaan ekspresi IEX-1 saliva dengan metode Real Time qPCR. Hasil : Hasil penelitian ini didapat dari 47 subjek, 22 subjek tumor ovarium epitelial ganas dan 25 subjek merupakan tumor ovarium epitelial jinak. Rerata ekspresi IEX-1 saliva lebih tinggi pada tumor ovarium epitelial jinak (1,976) dibandingkan ganas (0,554) (p<0,001). Didapatkan nilai AUC ekspresi IEX-1 0,949 (IK95% 0,894-1,000), nilai cut off point IEX-1 saliva ≥ 0.9115 dengan sensitivitas 84%, spesifisitas 86,4%, nilai duga positif 82,6% dan nilai duga negatif 87,5%. Terdapat hubungan yang signifikan antara ekspresi IEX-1 saliva dengan kejadian tumor ovarium epitelial ganas (OR 5,031, IK95% 2,039-12,41; p<0,001). Kesimpulan : Terdapat hubungan yang bermakna antara penurunan ekspresi IEX-1 saliva dengan kejadian tumor ovarium epitelial ganas dengan sensitivitas dan spesifisitas yang cukup baik. ......Backgound: Ovarian cancer is still one of the cancers with a high mortality rate in women because there are no typical symptoms so that more cases are diagnosed at an advanced stage. The absence of a screening method makes the importance of a diagnostic method that has high sensitivity and specificity. Evaluation of new biomarkers is needed to detect malignant ovarian tumors at an early stage. Objectives: This study was conducted to assess the expression of salivary Immediate Early Response Gene X-1 (IEX-1) as a predictor of malignancy in epithelial ovarian tumors. Methods: This is a diagnostic test study in ovarian tumor patients who are planned for elective surgery by taking 3-5 ml of patient's saliva before surgery. Research subjects who met the inclusion and exclusion criteria were divided into two groups based on the histopathological results, benign and malignant epithelial ovarian tumors. The salivary IEX-1 expression was examined using the Real Time qPCR method. Results: The results of this study were obtained from 47 epithelial ovarian tumors subjects, 22 malignant tumors and 27 benign tumors. The mean salivary IEX-1 expression was higher in benign epithelial ovarian tumors (1.976) than in malignant (0.554) (p<0.001). The AUC expression value of IEX-1 was 0.949 (95% CI 0.894-1,000), salivary IEX-1 cut off point value was 0.9115 with sensitivity 84%, specificity 86.4%, positive predictive value 82.6% and negative predictive value 87, 5%. There was a significant relationship between salivary IEX-1 expression and the event of malignant epithelial ovarian tumors (OR 5.031, 95% CI 2.039-12.41; p<0.001). Conclusions: There is a significant correlation between decreased salivary IEX-1 expression and the event of malignant epithelial ovarian tumors with a good sensitivity and specificity.

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ABSTRAK
Nama :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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ABSTRACT
Name : 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

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Latar Belakang : Kanker ovarium adalah kanker ketiga terbanyak yang ditemukan pada perempuan di Indonesia. Pada saat diagnosis ditegakkan, sebagian besar pasien mencapai stadium III atau IV dengan penyebaran tumor ke rongga peritoneum dan organ-organnya. Perluasan peritoneal karsinomatosis dapat dinilai melalui Peritoneal Carcinomatosis Index (PCI). Perluasan peritoneal karsinomatosis pada lokasi kritikal seperti mesenterium usus halus atau lapisan serosa usus halus dapat menjadi faktor penyebab pasien mendapatkan tatalaksana optimal maupun suboptimal debulking. Sehingga, nilai PCI dapat menjadi salah satu faktor yang memengaruhi resektabilitas tumor. MRI sebagai modalitas non- invasif dapat menjadi alternatif dalam menentukan tatalaksana debulking. Tujuan : meningkatkan peranan MRI dalam menilai perbedaan antara nilai PCI, nilai ADC tumor dan nilai ADC peritoneal karsinomatosis pasien kanker ovarium dengan asites untuk memprediksi tatalaksana optimal maupun suboptimal debulking. Metode : Penelitian dilaksanakan dengan desain penelitian perbandingan potong lintang. Didapatkan 23 sampel MRI abdomen dalam rentang waktu bulan September 2020 hingga Juni 2023. Hasil : Pada uji Mann Whitney didapatkan nilai P 0,688 pada hubungan antara nilai ADC tumor dengan tatalaksana debulking, sementara pada hubungan antara nilai ADC peritoneal karsinomatosis dengan tatalaksana debulking didapatkan nilai P 0,450. Didapatkan nilai P 0,000 pada analisisi hubungan antara nilai PCI dengan tatalaksana debulking, dengan titik potong nilai PCI yang optimal sebesar 9 dengan sensitivitas 100% dan spesifisitas 100% untuk menentukan luaran tatalaksana suboptimal debulking. Kesimpulan : Didapatkan hubungan yang bermakna antara nilai PCI dengan tatalaksana debulking, namun tidak didapatkan hubungan yang bermakna antara nilai ADC tumor dan nilai ADC peritoneal karsinomatosis dengan tatalaksana debulking. ......Background: Ovarian cancer is the third most common cancer found in women in Indonesia. At the time of diagnosis, most patients reach stage III or IV with the spread of tumors to the peritoneal cavity and its organs. The extent of peritoneal carcinomatosis can be assessed using the Peritoneal Carcinomatosis Index (PCI). The expansion of peritoneal carcinomatosis in critical locations such as the mesentery of the small intestine or the serosal layer of the small intestine can be a factor in predicting debulking management. Therefore, PCI value can be one of the factors influencing tumor resectability. MRI, as a non-invasive modality, can be an alternative in determining debulking management. Objective: To enhance the role of MRI in assessing the differences between PCI values, tumor ADC values, and peritoneal carcinomatosis ADC values in ovarian cancer patients with ascites to predict optimal or suboptimal debulking management. Method: The study was conducted using a cross-sectional comparative research design. A total of 23 abdominal MRI samples were obtained between September 2020 and June 2023. Results: The Mann-Whitney test showed a P value of 0.000 was obtained in the analysis of the relationship between the PCI value and debulking management, with an optimal PCI cutoff value of 9, showing 100% sensitivity and 100% specificity in determining the outcome of suboptimal debulking management. Conclusion: There is a significant relationship found between PCI value and debulking management. However, no significant relationship was found between the tumor ADC value and the peritoneal carcinomatosis ADC value with debulking management.

Abstrak :
Kanker ovarium masih menempati urutan kedua terbanyak dalam keganasan ginekologi dan merupakan penyebab utama kematian akibat kanker pada perempuan. Banyak bukti menunjukkan bahwa kanker ovarium umunya dalam pengaruh stress oksidatif. Dalam penelitian ini bertujuan untuk mengetahui aktivitas stress oksidatif melalui pengukuran enzim Superoxide Dismutase (SOD) dan kadar Malondialdehyde (MDA) pada penderita keganasan ovarium dibandingkan dengan penderita tumor jinak ovarium. Penelitian dilakukan dengan uji potong-lintang yang dilaksanalan di Ruang Rawat Kebidanan Ginekologi RSCM Jakarta, RS Persahabatan Jakarta dan RS Fatmawati Jakarta pada Juli hingga Desember 2018. Seluruh penderita keganasan ovarium dan penderita tumor jinak ovarium yang memenuhi kriteria diikutsertakan dalam penelitian ini. Darah penderita tumor ovarium diambil sebelum dilakukan operasi, lalu sampel dilakukan pengukuran kadar SOD dan MDA. Terdapat 35 penderita keganasan ovarium dan 43 penderita tumor jinak ovarium yang diikutsertakan dalam penelitian ini. Rerata atau median kadar SOD dan MDA pada penderita keganasan ovarium adalah 1,23 (0,24-5,709) dan 0,803 ± 0,316 , sementara rerata atau median kadar SOD dan MDA pada penderita tumor jinak ovarium adalah 0,488 (0,101-1,86) dan 0,634 ± 0,266. Terdapat perbedaan kadar SOD dan MDA yang bermakna antara kedua kelompok. Terdapat perbedaan kadar SOD yang bermakna antara penderita keganasan ovarium stadium awal dengan penderita keganasan ovarium stadium lanjut. Sementara pada pemeriksaan MDA tidak terdapat perbedaan bermakna antara penderita stadium awal dengan stadium lanjut. Kesimpullan pada penelitian ini terdapat perbedaan kadar SOD dan MDA yang bermakna antara penderita keganasan ovarium dengan penderita tumor jinak ovarium.

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Ovarian cancer is the leading cause of death due to gynecological malignancies among women. A lot of evidence shows that ovarian cancer is generally influenced by oxidative stress. In this study aims to determine the activity of SOD enzymes and MDA levels in patients with ovarian malignancies and patients with benign ovarian tumors. The study was conducted by cross-sectional tests carried out in the RSCM Jakarta Gynecology Obstetric Room and Persahabatan Hospital Jakarta and Fatmawati Hospital Jakarta in July to December 2018. All patients with ovarian malignancies and patients with benign ovarian tumors who met the criteria were included in this study. Blood from ovarian tumor patients taken before surgery, then the samples were measured for SOD and MDA levels. There were 35 ovarian malignancies and 43 patients with benign ovarian tumors included in the study. The mean or median level of SOD and MDA in patients with ovarian malignancy is 1.23 (0.24 - 5.709) and 0.803 ± 0.316, while the mean or median level of SOD and MDA in patients with benign ovarian tumors is 0.488 (0.101-1.86) and 0.634 ± 0.266. There were significant differences in SOD and MDA levels between the two groups. There were significant differences in SOD levels between patients with early-stage ovarian malignancies and those with advanced ovarian malignancies. While on MDA examination there were no significant differences between patients with early stages with advanced stages. Conclusion in this study were significant differences in SOD and MDA levels between ovarian malignancies and patients with benign ovarian tumors

Abstrak :
Kanker ovarium adalah salah satu kanker ginekologi yang paling umum terjadi dan menempat urutan ketiga setelah kanker serviks dan kanker uterus. Sebagian besar kasus kanker ovarium (60%) ditemukan pada stadium lanjut sehingga hasil pengobatan tidak seperti yang diharapkan. Penelitian ini bertujuan untuk mengetahui ketahanan hidup pasien kanker ovarium berdasarkan stadium di Rumah Sakit Umum Pusat Dr. Wahidin Sudirohusodo Makassar Tahun 2014-2018. Desain Penelitian ini menggunakan kohort retrospektif. Pasien yang merupakan kasus baru dan mendapatkan perawatan hanya di rumah sakit masuk ke dalam penelitian. Sampel terdiri dari 295 pasien, 142 pasien dengan stadium awal dan 153 pasien dengan stadium akhir yang didapatkan dari sistem informasi rumah sakit pada periode Januari 2014 – Desember 2018. Pasien diamati dari waktu diagnosis hingga event (meninggal) dalam kurun waktu 57 bulan. Hasil analisis Kaplan Meier menunjukkan probabilitas ketahanan hidup pasien kanker ovarium stadium awal (84%) lebih tinggi dibandingkan pasien kanker ovarium stadium akhir (81%). Rata-rata ketahanan hidup pasien kanker ovarium stadium awal selama 15 bulan sedangkan pasien kanker ovarium stadium akhir selama 9 bulan. Hasil analisis cox regression didapatkan bahwa risiko kematian pasien kanker ovarium stadium akhir 1,4 kali lebih tinggi dibandingkan dengan pasien kanker ovarium stadium awal setelah dikontrol dengan umur, derajat diferensial sel, dan keadaan umum. ......Ovarian cancer is one of the most common gynecological cancers and ranks third after cervical cancer and uterine cancer. Most cases of ovarian cancer (60%) are found at an advanced stage so the treatment results are not as expected. This study aims to determine the survival of ovarian cancer patients based on the stadium at Rumah Sakit Umum Pusat Dr. Wahidin Sudirohusodo Makassar in 2014-2018. Design This study uses a retrospective cohort. Patients who are new cases and get treatment only at the hospital were included in the study. The sample consisted of 295 patients, 142 patients with early stage and 153 patients with final stage obtained from the hospital information system in the period January 2014 - December 2018. Patients were observed from the time of diagnosis to event (death) in a period of 57 months. Kaplan Meier's analysis showed that the probability of survival of patients with early-stage ovarian cancer (84%) was higher than that of end-stage ovarian cancer patients (81%). The average survival of patients with early stage ovarian cancer for 15 months while patients with late stage ovarian cancer for 9 months. The results of cox regression analysis found that the risk of death of end-stage ovarian cancer patients was 1.4 times higher compared to patients with early-stage ovarian cancer after being controlled with age, grade, and performance status.