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"Pendahuluan: World Health Organization (WHO) mendefinisikan Giant Cell-Tumour (GCT) merupakan tumor tulang yang bersifat jinak, mempunyai sifat dan kecenderungan untuk agresif lokal. Tujuan tata laksana GCT adalah menghilangkan jaringan tumor, mempertahankan fungsi tulang yang terkena, serta mencegah rekurensi. Sampai saat ini belum ada konsensus seragam untuk tata laksana GCT primer. Denosumab merupakan antibodi monoklonal yang berikatan dengan RANKL. Dengan adanya ikatan antara denosumab dengan RANKL, ikatan antara RANKL dengan RANK tidak terjadi, sehingga diharapkan tidak terjadi pertumbuhan tumor. Akan tetapi masih ada beberapa masalah yang masih menjadi pertanyaan antara lain: apakah pemakaian denosumab menurunkan angka rekurensi dibandingkan tata laksana konvensional sebelumnya, bagaimana efikasi denosumab pada tata laksana GCT, serta berapa dosis dan lama terapi denosumab diberikan. Dengan belum adanya pedoman baku penggunaan denosumab, dan belum adanya telaah sistematis serta penelitiannya di Indonesia, maka meta-analisis ini dilakukan untuk menjawab pertanyaan-pertanyaan tersebut dalam membantu menyusun pedoman penggunaannya sehingga menghasilkan kebijakan baru dalam tata laksana GCT di Indonesia.Metode: Telah dilakukan pencarian dalam lima database menggunakan kata kunci ("DENOSUMAB" AND ("GIANT CELL TUMOR" OR "GCT") AND "OUTCOME"). Penilaian risiko bias studi dengan desain randomized controlled trial dilakukan dengan Cochrane Collaboration’s tool for assessing risk of bias, sedangkan penilaian risiko bias studi dengan desain nonrandomized controlled trial dan kohort dilakukan dengan Newcastle-Ottawa Quality Assessment Form for cohort study.Hasil Setelah diseleksi, didapatkan 21 studi yang dilakukan penilaian risiko bias. Meta-analisis menemukan bahwa terdapat 85,5% (IK95%: 74,9-96,0%) pasien mendapatkan perbaikan klinis; perbaikan radiologis pada 82.4% (95% IK: 73,3-91,4%) pasien; perubahan histopatologis pada 96,5% (95% IK: 93,6-99,3%) pasien; serta rekurensi sebesar 27,2% (95% IK: 18,7-35,7%) dan rekurensi pada denosumab dibanding kontrol yakni RR: 2,6 (95% CI: 1,66-4,09); total kejadian efek samping berat pada rahang sebesar 2,7% (95% IK: 1,4-4,0%).Kesimpulan: Administrasi Denosumab pada pasien GCT sebagai terapi sistemik memiliki efikasi yang baik dalam perbaikan klinis; perbaikan radiologis; penurunan aktivitas sel GCT; potensi efek samping yang rendah; akan tetapi angka kejadian rekurensi lebih tinggi dibanding kontrol. Meski demikian, studi komparatif eksperimen acak terkontrol dirasa perlu lebih banyak untuk meningkatkan kualitas hasil studi.

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Introduction: The World Health Organization (WHO) defines GCT as a benign bone tumor, with the nature and tendency for local aggressiveness. The goal of GCT management is to remove tumor tissue, maintain the function of the affected bone, and prevent recurrence. To date there has been no uniform consensus for primary GCT management. Denosumab is a monoclonal antibody that binds to RANKL. With the bond between denosumab and RANKL, the bond between RANKL and RANK does not occur, so that no tumor growth is expected. However, there are still a number of questions that remain questionable, among others: whether the use of denosumab reduces recurrence rates compared to previous conventional management, how the efficacy of denosumab in the management of GCT, and how much dose and duration of denosumab therapy is given. With no standard guidelines for using denosumab, and no systematic study and research in Indonesia. This meta-analitic study was conducted to answer these questions in helping to develop guidelines for their use so as to produce new policies in the management of GCT in Indonesia.

Methods: Five databases have been searched using keywords ("DENOSUMAB" AND ("GIANT CELL TUMOR" OR "GCT") AND "OUTCOME"). After being selected, 21 studies were carried out with a bias risk assessment with the Newcastle-Ottawa Quality Assessment Form for cohort studies for studies with cohort designs and nonrandomized controlled trials while for one study a randomized controlled trial was conducted with the Cochrane Collaboration's tool for assessing risk of bias with results 4 poor quality studies.

Results: The meta-analysis found that there were 85.5% (CI 95%: 74.9-96.0%) patients received clinical improvement, there was a reduction in VAS scale pain in 98.9% (CI 95%: 96.5-101.4% ) patient; radiological improvement in 85.5% 82.4% (95% CI: 73.3-91.4%) patients; histopathological changes in 96.5% (95% CI: 93.6-99.3%) patients; and recurrence of 27.2% (95% CI: 18.7-35.7%) and recurrence in denosumab compared to controls namely RR: 2.6 (95% CI: 1.66-4.09); the total incidence of severe side effects on the jaw was 2.7% (95% CI: 1.4-4.0%).

Conclusions: Denosumab administration in GCT patients as a systemic therapy has good efficacy in clinical improvement; radiological repair; decreased GCT cell activity; low potential for side effects; however the recurrence rate is higher than the control. However, comparative studies of randomized controlled trials are deemed necessary to improve the quality of study results."

"[ABSTRAKPendahuluan: GCT tulang merupakan lesi jinak tetapi secara lokal dapat bersifat agresif pada daerah epifisis. Angka rekurensi yang tinggi, dilaporkan mencapai 75%. Tumor dapat bermetastasis ke paru (2-9%) dan tercatat 0-37% angka mortalitas akibat metastasis. Beberapa penelitian menghasilkan variasi berbeda penanganan tumor ini terhadap luaran onkologi dan fungsional serta angka kematian paska pembedahan. Penelitian ini bertujuan melaporkan pengalaman dalam penatalaksanaan pembedahan tumor ini dan untuk melihat adanya hubungan antara tatalaksana pembedahan dengan dampak klinis.Metode: Penelitian ini merupakan kohort retrospektif, sebanyak 99 pasien GCT tulang menjalani tindakan kuretase ataupun wide resection di Rumah Sakit Cipto Mangunkusumo pada 1995 - 2014. Luaran onkologi berdasarkan angka rekurensi lokal, metastasis tumor serta mortalitas dan luaran fungsional berdasarkan sistem penilaian Musculoskeletal Tumor Society (MSTS).Hasil: Lokasi tumor terutama di distal femur (25,2%). Rekurensi lokal terjadi pada 4 pasien, terutama di distal femur (50%). Rekurensi lokal terjadi seimbang pada wide resection dan kuretase dan secara statistik tidak bermakna (p 0.578, uji eksak Fischer). Tidak dijumpai kejadian rekurensi lokal pada seluruh pasien yang mengalami metastasis. Metastasis terjadi pada kelompok wide resection. Kematian terjadi pada 4 pasien yang mengalami metastasis. Sebagian besar pasien (51,1%) menunjukkan luaran fungsional kategori sangat baik (skor MSTS di atas 75%). Analisis kesintasan bebas rekurensi lokal secara statistik tidak bermakna (p 0.564). Analisis multivariat (regresi Cox) hanya faktor metastasis yang berpengaruh pada mortalitas (p. 0.001)Kesimpulan: Terdapat hubungan yang bermakna antara stadium tumor dengan metastasis dan jenis tindakan operasi. Tidak terdapat perbedaan bermakna antara kejadian rekurensi lokal dan metastasis serta luaran fungsional dengan jenis tindakan operasi.

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ABSTRACTIntroduction: Giant cell tumor of bone is benign lesion with ability to be locally aggressive in epiphysis. Its recurrence rate was reported as high as 75%. Tumor can metastasize to lungs (2-9%) and up to 37% mortality rate due to metastasis. Several studies have reported different rates of local recurrence, lung metastasis, mortality rate, and functional outcome. This study aims to report our experience and analyze the correlation between surgery and clinical findings.Methods: In this retrospective cohort, 99 patients GCT of bone undergone curettage or wide resection in Cipto Mangunkusumo Hospital during 1995-2014. Oncological outcome were analyzed according to local recurrence rate, metastasis, and mortality rate, while functional outcome were measured according to Musculoskeletal Tumor Society Score (MSTS).Results: Tumor location were predominantly in distal femur (25.2%). Local recurrence were observed in 4 patient and mainly in distal femur (50%). Local recurrence were evenly balanced between surgical curettage and wide resection (50% each) and thus not statistically significant (Exact Fischer, p=0.578). Metastasis were observed in patients who undergone wide resection, however, no significant correlation were found between metastasis incidence and types of surgical intervention (Exact Fischer, p=0.318). Four have died related to metastasis. No local recurrence were observed in patients suffering from metastasis. In more than half of patients (51.5%), the functional status were very good (MSTS >75. Recurrence-free survival analysis not significant statistically (p 0.564).Multivariate analysis (Cox regression) showed that only metastasis was found to be significantly correlated to mortality (p. 0.001).Conclusion: Tumor stage was correlated to metastasis, and type of surgical intervention. No significant correlation were found between local recurrence, metastasis, and functional outcome to types of surgical intervention., Introduction: Giant cell tumor of bone is benign lesion with ability to be locally aggressive in epiphysis. Its recurrence rate was reported as high as 75%. Tumor can metastasize to lungs (2-9%) and up to 37% mortality rate due to metastasis. Several studies have reported different rates of local recurrence, lung metastasis, mortality rate, and functional outcome. This study aims to report our experience and analyze the correlation between surgery and clinical findings.Methods: In this retrospective cohort, 99 patients GCT of bone undergone curettage or wide resection in Cipto Mangunkusumo Hospital during 1995-2014. Oncological outcome were analyzed according to local recurrence rate, metastasis, and mortality rate, while functional outcome were measured according to Musculoskeletal Tumor Society Score (MSTS).Results: Tumor location were predominantly in distal femur (25.2%). Local recurrence were observed in 4 patient and mainly in distal femur (50%). Local recurrence were evenly balanced between surgical curettage and wide resection (50% each) and thus not statistically significant (Exact Fischer, p=0.578). Metastasis were observed in patients who undergone wide resection, however, no significant correlation were found between metastasis incidence and types of surgical intervention (Exact Fischer, p=0.318). Four have died related to metastasis. No local recurrence were observed in patients suffering from metastasis. In more than half of patients (51.5%), the functional status were very good (MSTS >75. Recurrence-free survival analysis not significant statistically (p 0.564).Multivariate analysis (Cox regression) showed that only metastasis was found to be significantly correlated to mortality (p. 0.001).Conclusion: Tumor stage was correlated to metastasis, and type of surgical intervention. No significant correlation were found between local recurrence, metastasis, and functional outcome to types of surgical intervention.]"

"ABSTRAKLatar Belakang Giant cell tumor (GCT) merupakan tumor jinak yang bersifat lokal agresif destruksif. Tumor ini memiliki rekurensi yang tinggi sebanyak 25-50% setelah tindakan pembedahan. Berbagai macam pemberian zat kimia lokal sebagai terapi ajuvan, telah digunakan pada tatalaksana pembedahan. Namun perbandingan efektifitas untuk masing-masing zat kimia ini belum diketahui. Studi mengenai sitotoksisitas dan mekanisme kematian sel dengan membandingkan pemberian etanol dan H2O2 pada sel GCT tulang secara in vitro masih sedikit dan belum ada di Indonesia.Metode Penelitian ini merupakan studi in vitro eksperimental dengan mengambil empat sampel jaringan tumor dari pasien yang didiagnosis GCT tulang dan dilakukan isolasi-kultur sel. Cell line yang didapatkan dikarakterisasi melalui analisis morfologi serta pemeriksaan ekspresi penanda gen Nanog dan Oct 4 dengan Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Sel yang telah 80% konfluens dilakukan terapi dengan H2O2 1%, 3%, 5% dan etanol 75%, 85%, 95% selama10 menit serta dosis in vitro H2O2 (0,003%, 0,005%, 0,01%, 0,03%, 0,1%, 0,3%) selama 5 menit serta inkubasi selama 24 jam. Morfologi sel dievaluasi dibawah mikroskop cahaya dengan membandingkan kontrol dan setelah pemberian zat kimia, viabilitas sel dihitung menggunakan automatic cell counter serta toksisitas sel dinilai dengan uji Annexin V dan Propidium Iodida (PI) pada flow cytometry.Hasil Kultur jaringan sel GCT dengan metode eksplan dan kolagenase mempunyai angka keberhasilan yang sama dalam mendapatkan cell line GCT. Namun metode eksplan membutuhkan waktu yang lebih cepat dan memiliki jumlah sel yang lebih banyak. Sel yang tumbuh dari jaringan GCT terkarakterisasi dengan analisis morfologi serta ekspresi gen Oct 4 dan Nanog. Viabilitas sel GCT menurun secara signifikan setelah paparan terhadap dosis klinis H2O2 1% (p = 0,046), H2O2 3% (p = 0,043), dan H2O2 5% (p = 0,043) selama 10 menit dibandingkan dengan kontrol. Tidak ada perbedaan yang bermakna untuk viabilitas sel antara konsentrasi H2O2 1%, 3% dan 5%. Sementara pada konsentrasi in vitro (0,003%, 0,005%, 0,01%, 0,03%, 0,1%, 0,3%), konsentrasi H2O2 0,3% (p < 0,001) selama 5 menit memiliki efektivitas paling baik dalam sterilisasi GCT secara in vitro. Terdapat fenomena fiksasi sel setelah pemberian etanol pada semua konsentrasi. Dari uji RT-PCR didapatkan penurunan ekspresi gen Oct 4 dan Nanog seiring dengan peningkatan konsentrasi H2O2 pada dosis in vitro. Flow cytometry dengan marker Annexin V dan propidium iodide (PI) didominasi oleh marker PI yang menunjukkan kematian sel akibat nekrosis dengan persentase terbesar pada konsentrasi 0,3%.Kesimpulan Eksplan merupakan metode terbaik dalam isolasi dan kultur sel GCT. Semua sel hasil isolasi dan kultur terkarekterisasi sebagai GCT. Pemberian ajuvan kimia lokal dengan dosis klinis H2O2 konsentrasi 1%, 3%, dan 5% selama 10 menit secara in vitro mempunyai efektivitas yang sama dalam membunuh sel GCT. Sedangkan konsentrasi H2O2 0,3% selama 5 menit merupakan terapi optimal dalam sterilisasi GCT secara in vitro dengan mekanisme kematian nekrosis sel.

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ABSTRACTBackground Giant cell tumor (GCT) is a benign, aggressive local tumor with high tendency to recur after surgery. Various chemicals have been used as an adjuvant treatment for GCT. However, the comparative effect of these chemicals remains unclear. To date, there are no studies about the cytotoxicity and mechanism of injury to etanol and H2O2 in GCT in Indonesia especially in vitro experiment. The present study aims to find the best method to isolation and culture of GCT from primary human patients, the optimal treatment of etanol and H2O2 for reducing GCT recurrence.Methods This is an experimental in vitro study that took four tumor tissue samples from patients diagnosed with bone GCT and conducted cell-culture isolation. Cell line characterized by morphology, gene markers Nanog and Oct 4 expression with Polymerase Chain Reaction (RT-PCR) Reverse Transcriptase was obtained. Cells that had 80% confluence were treated with H2O2 1%, 3%, 5% and etanol 75%, 85%, 95% for 10 minutes and in vitro doses of H2O2 (0.003%, 0.005%, 0.01%, 0.03 %, 0.1%, 0.3%) for 5 minutes and were incubated for 24 hours. Cell morphology was evaluated under a light microscope by comparing the morphology of controls and after exposure a chemical agents, cell viability was calculated using automatic cell counter and cell toxicity was assessed by Annexin V and Propidium Iodida (PI) on flow cytometry.Results Collagenase and explant methods had the same success rate in obtaining GCT cell line characterized by morphology, the gene expression Oct 4 and Nanog. But explants need a less time and had more cell than collagenase method. Viability of GCT cells decreased significantly after exposure to the clinical dose of H2O2 1% (p = 0,046), H2O2 3% (p = 0,043), and H2O2 5% (p = 0,043) for 10 minutes compared to controls. There was no significant difference for cell viability between 1%, 3% and 5% H2O2 concentrations. While in in vitro doses (0,003%, 0,005%, 0,01%, 0,03%, 0,1%, 0,3%), 0.3% H2O2 concentration for 5 minutes has the best effectivity in sterilizing GCT in vitro. There was a phenomenon of cell fixation after exposure of GCT cells to etanol in various concentrations, in which all cells die and its viability could not be analyzed. From the RT-PCR test it was found that there was a decrease in the expression of Oct 4 and Nanog genes along with an increase in the concentration of H2O2 in vitro. Flow cytometry using Annexin V in conjunction with propidium iodide (PI) was dominated with PI marker detection which showed cell death due to necrosis, with the highest concentration amounted to 0.3%Conclusion Explant was the best method for isolation and GCT cell culture. All of the cell from isolation and culture result had a characterization of GCT. Giving local a chemical adjuvants with clinical doses of H2O2 concentrations of 1%, 3%, and 5% for 10 minutes in vitro had the same effectiveness in killing GCT cells. While the concentration of 0.3% H2O2 for 5 minutes is the optimal therapy in GCT sterilization in vitro with necrosis cell death mechanism."

"Latar belakang: Giant Cell Tumor of Bone (GCT tulang) adalah tumor tulang primer yang bersifat jinak-agresif dan dapat bermetastasis. Rentang usia pasien GCT tulang adalah antara 13 sampai 69 tahun. Tumor ini sering ditemukan di bagian distal femur, distal radius, dan proximal tibia. Berdasarkan tipe tulang, GCT tulang sering ditemukan pada ujung tulang panjang. Namun, GCT tulang juga dapat ditemukan pada tipe tulang lainya. Pada beberapa keganasan tulang, seperti osteosarcoma, terdapat korelasi antara usia dengan lokasi tumor. Namun, untuk GCT tulang korelasi ini masih belum diketahui. Penelitian ini bertujuan untuk melihat adanya korelasi usia dengan lokasi pada GCT tulangMetode: Peneliti mengambil data rekam medis pasien GCT tulang di RSUPN dr.Cipto Mangunkusumo dari tahun 2016 sampai 2020. Kemudian, data usia dengan lokasi (topografi dan tipe tulang) dianalisis menggunakan tabel baris kolom.Hasil: Pada kelompok usia 10-39 tahun ditemukan 52 kasus pada tulang apendikular dan 1 kasus pada tulang axial. Pada kelompok usia 40-69 tahun ditemukan 29 kasus pada tuang apendikular dan 4 kasus pada tulang axial. Korelasi antara usia dan lokasi topografis tidak bermakna (p>0.05). Pada kelompok usia 10-39 tahun ditemukan 49 kasus pada tipe tulang panjang dan 4 kasus pada tipe tulang lainnya. Pada kelompok usia 40-69 tahun, ditemukan 27 kasus pada tulang panjang dan 6 kasus pada tipe tulang lainnya. Korelasi antara usia dengan lokasi tipe tulang tidak bermakna (p>0.05).Kesimpulan: Tidak ada hubungan bermakna antara usia dengan lokasi tumor (topografi dan tipe tulang) pada kasus GCT tulang

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Introduction: Giant cell tumor of bone (GCTB) is a primary bone tumor with benign- aggressive behavior and capacity to metastasize. The age range for GCTB is 13 to 69 years old. GCTB is commonly in distal femur, distal radius, and proximal tibia. Based on bone type, GCTB is frequently found on meta epiphyseal site of long bone. Although, some GCTB can be found on other bone type such as flat bone, short bone, and irregular bone. In some bone neoplasms, like osteosarcoma, there is a correlation between age and tumor site. Unfortunately for GCTB, this correlation is still unknown. This study aims to determine the correlation between age and tumor site of GCTB

Method: Medical record of patients with the diagnosis of GCTB in RSUPN dr.Cipto Mangukusumo from 2016 to 2020 is included in this study. Age at diagnosis and tumor site (topographically and bone type) of patient are analyzed using cross tabulation. Result: For age group 10-39 years old, there are 52 cases of GCTB in appendicular skeleton and one case in axial skeleton. For age group 40-69 years old there are 29 cases of GCTB in appendicular skeleton and 4 cases in axial skeleton. The correlation between age and tumor topographic site is statistically not significant (p > 0.05). For the bone type, there are 49 cases of GCTB in long bone and 4 cases in other bone type for age group 10- 39 years old. For age group 40-69 years old, there are 27 cases of GCTB in long bone and 6 cases in other bone type. The correlation between age and bone type is statistically not significant (p> 0.05)

Conclusion: There are no significant correlation between age and tumor site (topographically and bone type) in GCTB"

"Latar belakang: Giant cell tumor of bone (GCT tulang) adalah tumor tulang lokal agresif dengan gambaran histopatologik terdiri atas kumpulan sel besar multinuklear dan proliferasi sel mononuklear di stroma. Berdasarkan data Departemen Patologi Anatomik RSUPN Dr. Cipto Mangunkusumo, terdapat 86 kasus GCT tulang pada tahun 2016-2020. Adanya invasi limfovaskular adalah petunjuk prognosis buruk beberapa tumor. Riset ini bertujuan untuk mengetahui hubungan kejadian invasi limfovaskular dengan lokasi tumor, ukuran tumor, dan kejadian rekurensi lokal pada pasien GCT tulang di RSUPN Dr. Cipto Mangunkusumo.Metode: Data dari 86 kasus GCT tulang di RSUPN Dr. Cipto Mangkunkusumo pada tahun 2016-2020 diambil melalui formulir pemeriksaan patologi anatomi. Variabel bebas berupa lokasi tumor, ukuran tumor, dan kejadian rekurensi lokal diuji statistik menggunakan uji kai-kuadrat dengan variabel terikat berupa invasi limfovaskular. Hasil: Invasi limfovaskular ditemukan pada 18 (20,9%) pasien GCT tulang. Uji statistik kai-kuadrat menunjukkan hubungan tidak bermakna lokasi tumor pada ekstremitas atas (p=0,227) dan ekstremitas bawah (p=0,521) dengan invasi limfovaskular. Hubungan ukuran tumor <8 cm dengan invasi limfovaskular ditemukan tidak bermakna (p=0,956). Hubungan kejadian rekurensi lokal dengan invasi limfovaskular juga tidak bermakna (p=0,692 dengan uji Fisher).Kesimpulan: Tidak terdapat hubungan invasi limfovaskular dengan lokasi tumor, ukuran tumor, dan kejadian rekurensi lokal pada pasien GCT tulang di RSUPN Dr. Cipto Mangunkusumo.

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Introduction:Giant cell tumor of bone is a local aggressive bone tumor with histopathologic features of multinuclear large cell aggregates and mononuclear cell proliferation in the stroma. According to data from Department of Anatomical Pathology RSUPN Dr. Cipto Mangunkusumo, there are 86 giant cell tumor of bone cases in 2016- 2020. Lymphovascular invasion is believed to have a bad prognostic sign for some tumors. Hence, this research aims to describe the association between tumor location, tumor size, and tumor local recurrence with lymphovascular invasion in giant cell tumor of bone patients at RSUPN Dr. Cipto Mangunkusumo.

Method: 86 giant cell tumor of bone cases at RSUPN Dr. Cipto Mangkunkusumo in 2016-2020 were collected from anatomical pathology examination form. Independent variables being tumor location, tumor size, and tumor local recurrence are statistically tested with the dependent variable, being lymphovascular invasion. A Chi-square test was used to describe the association.

Result: Lymphovascular invasion was found in 18 (20,9%) giant cell tumor of bone patients. Chi-square test showed no association between tumor location at upper extremity (p=0,227) and lower extremity (p=0,521) with lymphovascular invasion. Association of tumor size <8 cm with lymphovascular invasion was also not found (p=0,956). Similarly, association of tumor local recurrence with lymphovascular invasion was not found (p=0,692, using Fisher’s test).

Conclusion: No association was found between tumor location, tumor size, and tumor local recurrence with lymphovascular invasion of giant cell tumor of bone patients at RSUPN Dr. Cipto Mangunkusumo in 2016-2020."

"Latar belakang: Giant cell tumor of bone (GCT tulang) merupakan tumor tulang primer dengan sifat jinak agresif. Dalam perjalanan penyakitnya, GCT tulang dapat disertai dengan aneurysmal bone cyst (ABC) sekunder sehingga menyulitkan dalam mendiagnosis. Penelitian ini dilakukan untuk menilai kejadian ABC sekunder pada pasien GCT tulang di RSUPN Dr. Cipto Mangunkusumo serta mengetahui hubungan antara usia dan lokasi tumor dengan kejadian ABC sekunder.Metode: Sebanyak 86 pasien yang berasal dari RSUPN Dr. Cipto Mangunkusumo terdiagnosis GCT tulang oleh dokter spesialis patologi anatomik dalam periode 2016 sampai 2020. Diagnosis ditegakkan berdasarkan hasil pemeriksaan histopatologik, korelasi klinis, dan gambaran radiologi.Hasil: ABC sekunder ditemukan pada 31 (36%) pasien GCT tulang dengan terbanyak ditemukan pada kelompok usia 20-29 tahun (n=12; 38,7%) dan kelompok usia 30 sampai 39 tahun (n=8; 25,8%). Analisis statistik menunjukkan hasil tidak bermakna antara kedua kelompok usia dengan kejadian ABC sekunder (p=0,463 dan p=0,674). Lokasi GCT tulang di tulang femur distal ditemukan paling banyak memiliki ABC sekunder (n=10; 32,3%). Analisis statistik menunjukkan hasil yang signifikan antara lokasi tulang femur distal dengan kejadian ABC sekunder (p=0,029). Perhitungan odd ratio menunjukkan peluang seseorang dengan GCT tulang yang disertai ABC sekunder ada pada lokasi tulang femur distal adalah 3,265 kali lipat dibandingkan lokasi lainnya (IK 95% 1,094- 9,747).Kesimpulan: Lokasi GCT tulang pada tulang femur distal memiliki hubungan yang bermakna secara statistik dengan kejadian ABC sekunder.

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Introduction: Giant cell tumor (GCT) of bone is a benign aggressive primary bone tumor. GCT of bone may be followed with secondary aneurysmal bone cyst (ABC) which makes it harder to diagnose. This study showed the event of secondary ABC in GCT of bone patients in Cipto Mangunkusumo Hospital and the association between secondary ABC and the age and predilection site of the GCT of bone patients.

Method: 86 patients from Cipto Mangunkusumo Hospital were diagnosed GCT of bone by pathologists in 2016 until 2020. The diagnosis was made from histopathological examination, combined with clinical correlation and radiological imaging.

Result: Secondary ABC were found in 31 (36%) patients with GCT of bone. Age group of 20-29 years old (n=12; 38,7%) and 30-39 years old (n=8; 25,8%) have the most patients. Statistical analysis discovered that there is statistically insignificance between the two age groups and the event of secondary ABC (p=0,463 and p=0,674). GCT of bone with secondary ABC is mainly found at distal femur (n=10; 32,3%). The association between distal femur bone site and the event of secondary ABC was statistically significant (p=0,029). Odd ratio measurement showed the chance of patient who has GCT of bone with secondary ABC located at distal femur is increased 3,265 times compared to other different predilection site.

Conclusion: Femur distal bone predilection site of GCT of bone was statistically associated with the event of secondary ABC."

"Latar Belakang: Glioma merupakan tumor otak primer yang sering ditemukan di Indonesia. Sampai saat ini, terapi glioma belum memuaskan karena sering timbul resistens] dan rekurensi sehingga diperlukan terapi tambahan misalnya terapi gen. MnSOD diduga berperan sebagai supresor tumor, namun peran tersebut masih kontroversial. Tumor padat termasuk glioma mempunyai status oksigen yang kurang baik dibandingkan dengan jaringan normal. MnSOD sebagai antioksidan dapat mempengaruhi kadar ROS (Reactive Oxygen Species) yang meningkat pada kondisi hipoksia. Oleh karena itu perlu dianalisis bagaimana ekspresi gen MnSOD pada sel glioma manusia yang hipoksia. Hipoksia pada sel glioma diduga mempengaruhi respon sel tumor terhadap terapi radiasi. Hipoksia tersebut dapat dideteksi dengan suatu petanda Jaringan hipoksia yaitu HIF-1α. Tujuan: Untuk menganalisis ekspresi gen MnSOD, kondisi hipoksia pada sel glioma melalui analisis ekspresi gen HIF-1a serta menganalisis ekspresi gen MnSOD pada sel glioma yang hipoksia. Desain: Cross Sectional Metode: Ekspresi gen MnSOD dianalisis dengan membandingkan leve] mRNA dan aktivitas spesifik enzim MnSOD pada sel glioma dengan sel lekosit (kontrol). Ekspresi gen HIF-1a@ dianalisis dengan mebandingkan level MRNA HIF-1la pada sel glioma dengan sel jekosit. Ekspresi MnSOD dan HIF-1α dideteksi pada 20 pasien glioma menggunakan quantitative Real Time RT-PCR untuk kadar relatif mRNA MnSOD dan HIF-1α, serta pemeriksaan biokimia untuk mengukur aktivitas enzim MnSOD. Analisis statistik dengan menggunakan SPSS 16.0. Hasil: Ekspresi gen MnSOD baik mRNA maupun aktivitas spesifik enzim MnSOD pada sebagian besar sampel sel glioma manusia ditemukan lebih rendah secara signifikan (p< 0.01) dibandingkan dengan sel lekosit. Sedangkan mRNA HIF-la pada sebagian besar sel glioma manusia ditemukan lebih tinggi secara signifikan (p< 0.05) dibandingkan dengan sel lekosit. Sebanyak 80 % (16 sampel) menunjukkan mRNA HIF-1α yang tinggi, yang berarti terdapat hipoksia pada sel glioma. Dari 16 sampel tersebut, 11 sampel menunjukkan ekspresi mRNA MnSOD yang rendah dan 4 sampel menunjukkan ekspresi mRNA MnSOD yang tinggi. Kesimpulan: Ekspresi gen MnSOD pada sebagian besar sampel ditemukan rendah. Ekspresi HIF-1a@ yang tinggi menunjukkan terdapat hipoksia pada sebagian besar sampel scl glioma. Terdapat perbedaan ekspresi MnSOD pada kondisi hipoksia sel glioma.

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Background: Glioma is one of the most frequently found primary brains tumors in Indonesia. Until now, treatment of the glioma is far from succesfull due to resistancy and recurrance. Therefore, additional therapy is required, such as gene therapy. MnSOD is antioxidant enzymes which is suggested as tumor suppressor, despite its controversies. Solid tumor such as glioma have low oxygen level in the tissue compare to normal tissues. MnSOD as antioxidant enzyme have potential effects on increased ROS (reactive oxygen species) concentration in hypoxia condition. Therefore, further analysis is needed to explain MnSOD gene expression in hypoxic human gliomal cells. Hypoxia in gliomal cells are suggested to influence tumor cells responses toward radiotherapy. Hypoxia state can be detected using tissues hypoxic marker, hypoxia inducible factor-la (HIF1α).

Desaign: Cross sectional

Aim: To analyzed MnSOD gene expression, hypoxia condition in human glioma cells by analyzing the gene expression of HIF-αa and to analyzed MnSOD gene expression in hypoxic human gliomal cells.

Methode: MnSOD gene expression was analyzed by comparing MnSOD mRNA level and enzyme specific activity in glioma cells with leucocytes (control). HIF-1α gene expression was analyzed by comparing HIF-la mRNA level in glioma cells with leucocytes. Twenty glioma patients were included in this study. Quantitative Real Time RT-PCR was used to analyzed MnSOD and HIF-1α mRNA level. Biochemistry test was used to analyzed MnSOD enzyme spesific activity. Statistical analysis was performed using SPSS 16.0.

Results: MnSOD gene expression at mRNA level and enzyme spesific activty in most human glioma samples were significantly lower (p< .01) than leucocytes. While HIF-lao mRNA level in most human glioma samples were significantly higher (p< .05) than leucocytes, Eighty percents (16) of the samples showed high HIF-1α mRNA level, this mean that glioma samples were in hypoxic state. Among the 16 samples, 11 samples showed low MnSOD mRNA level and 4 samples showed high mRNA MnSOD level. This mean that there were differences in MnSOD gene expression in hypoxic human glioma cells.

Conclusion: MnSOD gene expression in most human glioma samples were low. High HIF-1α mRNA level were found in mosi of plioma samples, meaning that glioma sample were in hypoxic state. There were differences in MnSOD expression in hypoxic human glioma cells. "

"ABSTRAKThesis ini menyajikan hasil penelitian eksperimen tentang struktur, besaran magnet, specific heat dan giant magnetoresistance dari sampel polikristal manganat tanah jarang seri LaI-XCaxMni-yCuyO3 dengan x = 0,1 ; 0,47 dan 0,73 dan 0 < y < 0,l9. Sampel disiapkan dengan metode reaksi zat padat. Analisis struktur menggunakan difraksi sinar-x dan high resolution powder diffraction (HRPD) dengan program fullprof. Semua sampel mempunyai struktur orthorhombic dengan space group Pnma. Pada suhu kamar semua sampel bersifat paramagnetik dan berubah campuran antara antiferromagnetik (AFM) dengan ferromagnetik (FM) pada suhu rendah dan juga akibat adanya medan magnet luar. Pendopingan Cu pada posisi Mn mengakibatkan menurunnya momen magnet pg. Besaran specific heat pada suhu rendah didominasi oleh faktor charge carriers (70, sedangkan faktor kisi B kcnstan, sementara faktor spin wave-nya diabaikan. Sifat giant magnetoresistance (GMR) pads suhu ruang menunjukkan bahwa pendopingan Cu pada Mn mengakibatkan menurunnya nilai magnetoresistansinya. Semakin tinggi nilai medan magnet luar, maka nilai magnetoresistensinya juga semakin naik.

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ABSTRACTThis thesis presents result of an experimental study on structure, magnetic properties, specific heat and giant magnetoresistance of polychrystal samples manganese rare-earth series LaI-XCaxMni-yCuyO3 with x = 0.1; 0.5, and 0.9 and y = 0; 0.05; 0.l0; 0.15, and 0.20. All samples by solid state reaction. The structure analysis use x-ray diffraction and high resolution powder diffraction with fullprof program. The structure of all samples are orthorhombic with space group Pnma. At room temperature all samples are paramagnetic and change became ferromagnetic at low temperature and consecuence external magnetic field too. The doping Cu at Mn site makes decrease the moment magnetic. The specific heat at low temperature, upon increasing the Cu dopant, the y and therefore the charge carriers increase. The specific heat for all samples are insensitive to the external magnetic field up to 9 T. The presence of external magnetic field has no influence on the p value for samples with and without Cu dopant. At room temperature, the doping of Cu at Mn makes decrease the magnetoresistance. The increasing external magnetic field, the magnetoresistance are increasing to."