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Abstrak :
ABSTRAK
Latar Belakang: Pengaruh metastasis sebagai penyebab peningkatan procalcitonin (PCT) pada pasien tumor padat nonsepsis masih belum jelas. Studi-studi sebelumnya memberikan hasil yang tidak konklusif. Nilai titik potong PCT untuk diagnosis sepsis pada tumor padat metastasis juga belum diketahui. Tujuan: Mengetahui peran PCT dalam diagnosis sepsis pada pasien tumor padat dengan metastasis. Metode: Studi potong lintang terhadap pasien tumor padat yang berobat di RSCM September-Desember 2015. Pada pasien ditentukan ada tidaknya sepsis menggunakan kriteria sepsis ACCP/SCCM 2001, dilakukan pemeriksaan darah perifer, serta PCT. Dilakukan analisis untuk mengetahui perbedaan kadar PCT pasien tumor padat metastasis dan tanpa metastasis yang tidak sepsis. Selain itu, dilakukan pula pencarian nilai titik potong PCT untuk diagnosis sepsis pada pasien tumor padat metastasis dengan menggunakan ROC. Hasil dan Pembahasan: Didapatkan 112 pasien tumor padat, pria sebanyak 51%, dengan rerata usia 47,9 ±12,47 tahun. Sebanyak 71 (63,4%) pasien sudah didapatkan metastasis, 36 (32,1%) diantaranya sepsis, dan 6 (5,3%) mengalami SIRS. Dari 41 (36,6%) pasien tanpa metastasis, 9 (8%) mengalami sepsis, dan 5 (4,4%) SIRS. Terdapat perbedaan bermakna kadar PCT pada pasien tumor padat metastasis dibandingkan tanpa metastasis pada kondisi nonsepsis [0,25 ng/mL (0,07-1,76) vs. 0,09 ng/mL (0,03-0,54); p<0,001]. Pasien tumor padat metastasis yang mengalami sepsis memiliki kadar PCT lebih tinggi dibandingkan nonsepsis [3,5 ng/mL (0,66-189,4) vs. 0,25 ng/mL (0,07-1,76); p<0,001]. Dari kurva ROC kadar PCT pada tumor padat metastasis, didapatkan AUC [0,956, IK 0,916-0,996] untuk mendiagnosis sepsis. Nilai titik potong PCT untuk diagnosis sepsis pada pasien tumor padat metastasis adalah 1,14 ng/mL dengan sensitivitas 86% dan spesifisitas 88%. Kesimpulan: Pada kondisi nonsepsis, kadar PCT pasien tumor padat metastasis lebih tinggi dibandingkan pasien tanpa metastasis. Nilai titik potong PCT untuk diagnosis sepsis pada tumor padat metastasis adalah 1,14 ng/mL. ABSTRACT
Background: The effect of metastasis as a cause of increased procalcitonin (PCT) in patients with solid tumors without sepsis remains unclear. Previous studies did not provide conclusive results. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors is also unknown. Objective: To determine the role of PCT in the diagnosis of sepsis toward metastatic solid tumors patients. Methods: A cross sectional study was conducted in solid tumor patients who were admitted to Cipto Mangunkusumo, Jakarta between September 2015 and December 2015. The ACCP/SCCM 2001 criteria was used to identify sepsis or SIRS in patients. Procalcitonin level, as well as routine blood examination, was performed to determine the differences of PCT level among solid tumor patients with and without metastasis. Cut off point of PCT for diagnosing sepsis in patients with metastatic solid tumors was determined using ROC curve. Results and Discussion: There were 112 patients with solid tumors, 51% male, with mean of age 47,9 ± 12,47 years. A total of 71 (63,4%) patients had metastasis, while 36 (32,1%) of them had sepsis and 6 (5,3%) experienced SIRS. Among 41 (36,6%) patients without metastasis, 9 (8%) had sepsis and 5 (4,4%) had SIRS. In the absence of sepsis, the PCT level was significantly higher in patients with metastatic solid tumors compared those without metastasis [0,25 ng/mL (0,07-1,76) vs. 0,09 ng/mL (0,03-0,54); p<0,001]. Metastatic solid tumor patients with sepsis had PCT levels higher than those without sepsis [3,5 ng / mL (0,66 to 189,4) vs. 0,25 ng / mL (0,07-1,76); p <0,001]. ROC curve showed that level of PCT for sepsis in metastatic solid tumors was AUC [0,956, IK 0,916-0,996]. Cut off point of PCT for sepsis in patients with metastatic solid tumors was 1.14 ng / mL with a sensitivity of 86% and specificity of 88%. Conclusion: In the absence of sepsis, PCT levels of patients with metastatic solid tumors is higher than patients without metastasis. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors was 1,14 ng / mL. ;Background: The effect of metastasis as a cause of increased procalcitonin (PCT) in patients with solid tumors without sepsis remains unclear. Previous studies did not provide conclusive results. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors is also unknown. Objective: To determine the role of PCT in the diagnosis of sepsis toward metastatic solid tumors patients. Methods: A cross sectional study was conducted in solid tumor patients who were admitted to Cipto Mangunkusumo, Jakarta between September 2015 and December 2015. The ACCP/SCCM 2001 criteria was used to identify sepsis or SIRS in patients. Procalcitonin level, as well as routine blood examination, was performed to determine the differences of PCT level among solid tumor patients with and without metastasis. Cut off point of PCT for diagnosing sepsis in patients with metastatic solid tumors was determined using ROC curve. Results and Discussion: There were 112 patients with solid tumors, 51% male, with mean of age 47,9 ± 12,47 years. A total of 71 (63,4%) patients had metastasis, while 36 (32,1%) of them had sepsis and 6 (5,3%) experienced SIRS. Among 41 (36,6%) patients without metastasis, 9 (8%) had sepsis and 5 (4,4%) had SIRS. In the absence of sepsis, the PCT level was significantly higher in patients with metastatic solid tumors compared those without metastasis [0,25 ng/mL (0,07-1,76) vs. 0,09 ng/mL (0,03-0,54); p<0,001]. Metastatic solid tumor patients with sepsis had PCT levels higher than those without sepsis [3,5 ng / mL (0,66 to 189,4) vs. 0,25 ng / mL (0,07-1,76); p <0,001]. ROC curve showed that level of PCT for sepsis in metastatic solid tumors was AUC [0,956, IK 0,916-0,996]. Cut off point of PCT for sepsis in patients with metastatic solid tumors was 1.14 ng / mL with a sensitivity of 86% and specificity of 88%. Conclusion: In the absence of sepsis, PCT levels of patients with metastatic solid tumors is higher than patients without metastasis. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors was 1,14 ng / mL. ;Background: The effect of metastasis as a cause of increased procalcitonin (PCT) in patients with solid tumors without sepsis remains unclear. Previous studies did not provide conclusive results. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors is also unknown. Objective: To determine the role of PCT in the diagnosis of sepsis toward metastatic solid tumors patients. Methods: A cross sectional study was conducted in solid tumor patients who were admitted to Cipto Mangunkusumo, Jakarta between September 2015 and December 2015. The ACCP/SCCM 2001 criteria was used to identify sepsis or SIRS in patients. Procalcitonin level, as well as routine blood examination, was performed to determine the differences of PCT level among solid tumor patients with and without metastasis. Cut off point of PCT for diagnosing sepsis in patients with metastatic solid tumors was determined using ROC curve. Results and Discussion: There were 112 patients with solid tumors, 51% male, with mean of age 47,9 ± 12,47 years. A total of 71 (63,4%) patients had metastasis, while 36 (32,1%) of them had sepsis and 6 (5,3%) experienced SIRS. Among 41 (36,6%) patients without metastasis, 9 (8%) had sepsis and 5 (4,4%) had SIRS. In the absence of sepsis, the PCT level was significantly higher in patients with metastatic solid tumors compared those without metastasis [0,25 ng/mL (0,07-1,76) vs. 0,09 ng/mL (0,03-0,54); p<0,001]. Metastatic solid tumor patients with sepsis had PCT levels higher than those without sepsis [3,5 ng / mL (0,66 to 189,4) vs. 0,25 ng / mL (0,07-1,76); p <0,001]. ROC curve showed that level of PCT for sepsis in metastatic solid tumors was AUC [0,956, IK 0,916-0,996]. Cut off point of PCT for sepsis in patients with metastatic solid tumors was 1.14 ng / mL with a sensitivity of 86% and specificity of 88%. Conclusion: In the absence of sepsis, PCT levels of patients with metastatic solid tumors is higher than patients without metastasis. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors was 1,14 ng / mL. ;Background: The effect of metastasis as a cause of increased procalcitonin (PCT) in patients with solid tumors without sepsis remains unclear. Previous studies did not provide conclusive results. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors is also unknown. Objective: To determine the role of PCT in the diagnosis of sepsis toward metastatic solid tumors patients. Methods: A cross sectional study was conducted in solid tumor patients who were admitted to Cipto Mangunkusumo, Jakarta between September 2015 and December 2015. The ACCP/SCCM 2001 criteria was used to identify sepsis or SIRS in patients. Procalcitonin level, as well as routine blood examination, was performed to determine the differences of PCT level among solid tumor patients with and without metastasis. Cut off point of PCT for diagnosing sepsis in patients with metastatic solid tumors was determined using ROC curve. Results and Discussion: There were 112 patients with solid tumors, 51% male, with mean of age 47,9 ± 12,47 years. A total of 71 (63,4%) patients had metastasis, while 36 (32,1%) of them had sepsis and 6 (5,3%) experienced SIRS. Among 41 (36,6%) patients without metastasis, 9 (8%) had sepsis and 5 (4,4%) had SIRS. In the absence of sepsis, the PCT level was significantly higher in patients with metastatic solid tumors compared those without metastasis [0,25 ng/mL (0,07-1,76) vs. 0,09 ng/mL (0,03-0,54); p<0,001]. Metastatic solid tumor patients with sepsis had PCT levels higher than those without sepsis [3,5 ng / mL (0,66 to 189,4) vs. 0,25 ng / mL (0,07-1,76); p <0,001]. ROC curve showed that level of PCT for sepsis in metastatic solid tumors was AUC [0,956, IK 0,916-0,996]. Cut off point of PCT for sepsis in patients with metastatic solid tumors was 1.14 ng / mL with a sensitivity of 86% and specificity of 88%. Conclusion: In the absence of sepsis, PCT levels of patients with metastatic solid tumors is higher than patients without metastasis. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors was 1,14 ng / mL. ;Background: The effect of metastasis as a cause of increased procalcitonin (PCT) in patients with solid tumors without sepsis remains unclear. Previous studies did not provide conclusive results. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors is also unknown. Objective: To determine the role of PCT in the diagnosis of sepsis toward metastatic solid tumors patients. Methods: A cross sectional study was conducted in solid tumor patients who were admitted to Cipto Mangunkusumo, Jakarta between September 2015 and December 2015. The ACCP/SCCM 2001 criteria was used to identify sepsis or SIRS in patients. Procalcitonin level, as well as routine blood examination, was performed to determine the differences of PCT level among solid tumor patients with and without metastasis. Cut off point of PCT for diagnosing sepsis in patients with metastatic solid tumors was determined using ROC curve. Results and Discussion: There were 112 patients with solid tumors, 51% male, with mean of age 47,9 ± 12,47 years. A total of 71 (63,4%) patients had metastasis, while 36 (32,1%) of them had sepsis and 6 (5,3%) experienced SIRS. Among 41 (36,6%) patients without metastasis, 9 (8%) had sepsis and 5 (4,4%) had SIRS. In the absence of sepsis, the PCT level was significantly higher in patients with metastatic solid tumors compared those without metastasis [0,25 ng/mL (0,07-1,76) vs. 0,09 ng/mL (0,03-0,54); p<0,001]. Metastatic solid tumor patients with sepsis had PCT levels higher than those without sepsis [3,5 ng / mL (0,66 to 189,4) vs. 0,25 ng / mL (0,07-1,76); p <0,001]. ROC curve showed that level of PCT for sepsis in metastatic solid tumors was AUC [0,956, IK 0,916-0,996]. Cut off point of PCT for sepsis in patients with metastatic solid tumors was 1.14 ng / mL with a sensitivity of 86% and specificity of 88%. Conclusion: In the absence of sepsis, PCT levels of patients with metastatic solid tumors is higher than patients without metastasis. Cut off point of PCT for sepsis diagnosis in metastatic solid tumors was 1,14 ng / mL.

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Latar Belakang: Kanker primer tahap lanjut dapat bermetastasis ke sistem saraf pusat (SSP) yaitu otak dan spinal, maupun ke selain SSP. Perbedaan gejala klinis antara metastasis SSP dan tanpa keterlibatan SSP adalah defisit neurologis pada metastasis SSP. Kedua metastasis tersebut dapat berisiko menyebabkan indeks massa otot skeletal yang rendah akibat gejala klinis dan peningkatan metabolisme akibat kanker. Namun, belum diketahui perbedaan di antara keduanya. Tujuan penelitian ini untuk mengetahui perbedaan appendicular skeletal muscle index (ASMI) pada pasien metastasis dengan dan tanpa keterlibatan SSP. Metode: Penelitian ini adalah studi potong lintang pada subjek berusia 18-65 tahun. Karakteristik subjek berupa usia, jenis kelamin, indeks massa tubuh, status gizi berdasarkan ASPEN, lokasi tumor primer, lokasi metastasis, waktu terdiagnosis metastasis, defisit neurologis, asupan energi dan protein, Karnofsky Performance Scale, kemoterapi, terapi glukokortikoid, dan nilai ASMI. Analisis bivariat digunakan untuk menilai perbedaan nilai ASMI antara metastasis SSP dan tanpa keterlibatan SSP. Hasil: Terdapat 59 subjek dengan nilai ASMI rendah. Rerata nilai ASMI pada metastasis SSP lebih rendah (3,81±1,19 kg/m2) dibandingkan dengan metastasis tanpa keterlibatan SSP (3,97±0,93 kg/m2) dengan perbedaan tidak signifikan pada kedua kelompok (p = 0,568). Terdapat perbedaan bermakna antara ASMI rendah dengan jenis kelamin (p=0,000), asupan energi (p=0,012), disfagia (p=0,027), nyeri kepala (p=0,033), dan gangguan kognitif (p=0,032). Kesimpulan: Tidak ditemukan perbedaan bermakna antara subjek yang memiliki ASMI rendah pada metastasis SSP dan tanpa keterlibatan SSP. Perbedaan bermakna ditemukan antara ASMI dengan karakteristik subjek yaitu jenis kelamin, asupan energi, disfagia, nyeri kepala, dan gangguan kognitif. ......Background: Advanced primary cancer can metastasize to the central nervous system (CNS), namely the brain and spinal cord, or to other than the CNS. The difference in clinical symptoms between CNS metastases and those without CNS involvement is the neurological deficit in CNS metastases. Both metastases may be at risk for low skeletal muscle mass index due to clinical symptoms and increased metabolism due to cancer. However, the differences between them are unknown. The aim of this study was to determine the difference of appendicular skeletal muscle index in metastatic patients with and without CNS involvement. Methods: This study was a cross-sectional study on subjects aged 18-65 years. Subject characteristics included age, gender, body mass index, nutritional status based on ASPEN, primary tumor location, metastasis location, time of metastasis diagnosis, neurological deficits, energy and protein intake, Karnofsky Performance Scale, chemotherapy, glucocorticoid therapy, and ASMI value. Bivariate analysis was used to assess the difference in ASMI value between CNS metastasis and without CNS involvement Results: There were 59 subjects with low ASMI values. The mean ASMI value in CNS metastasis was lower (3,81±1,19 kg/m2) compared to metastasis without CNS involvement (3,97±0,93 kg/m2) without significant difference in both groups (p=0,568). There was a significant difference between low ASMI and gender (p=0,000), energy intake (p=0,012), dysphagia (p=0,027), headache (p=0,033), and cognitive impairment (p=0,032). Conclusion: No significant difference was found between subjects who had low ASMI in CNS metastasis and without CNS involvement. Significant differences were found between ASMI and subject characteristics such as gender, energy intake, dysphagia, headache, and cognitive impairment.

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Latar Belakang : FGF2 merupakan ligan bagi Fibroblast Growth Factor Receptor2(FGFR2). Interaksi dengan reseptor ini memediasi dimerisasi reseptor, fosforilasi, dan aktivasi jalur pensinyalan, seperti jalur Ras-MAPK dan PI3K. Mutasi yang berlebihan melalui sumbu FGF / FGFR dapat menginduksi proliferasi sel kanker, memicu angiogenesis dan limfogenesis, yang mendorong terjadinya metastasis. Penelitian ini mencoba mengevaluasi peran FGF2 pada metastasis kelenjar getah bening aksila pada pasien kanker payudara stadium dini. Tujuan : Mengetahui hubungan nilai ekspresi FGF 2 pada tumor primer terhadap kejadian metastasis kelenjar getah bening aksila. Metode : Digunakan studi potong lintang dengan mengevaluasi ekspresi FGF2 pada 47 pasien kanker payudara stadium dini yang menjalani mastektomi di Rumah Sakit Umum Pusat Nasional Cipto Mangunkusumo (RSCM) pada periode Januari 2014 sampai Desember 2018. Ekspresi FGF2 diperiksa dengan pemeriksaan imunohistokimia, kemudian dievaluasi dan dihubungkan antara ekspresi FGF2 dengan metastasis kelenjar getah bening aksila. Hasil : Uji Chi Square memperlihatkan nilai p=0.044 (p<0.05) yang menunjukkan bahwa terdapat hubungan yang signifikan antara nilai FGF2 pada tumor payudara dengan kejadian metastasis kelenjar getah bening aksila. Odds ratio 4,22 (CI 95% 0,983-18,1). Kesimpulan : Peran FGF2 dalam metastasis kelenjar getah bening berhubungan dengan interaksi antara berbagai faktor limfangiogenik dalam mempromosikan limfangiogenesis dan metastasis limfatik. Ekspresi FGF2 yang tinggi memiliki korelasi signifikan dengan angka kejadian metastasis kelenjar getah bening aksila. ......Background : FGF2 is a ligand for Fibroblast Growth Factor Receptor 2 (FGFR2). Interaction with this receptor mediate dimerization of receptor, phosphorilation, and activation of signaling pathway, such as Ras-MAPK and PI3K. Overmutation through FGF/FGFR induced proliferation of cancer cells, promoted angiogenesis, lymphogenesis, and metastasis. This study tried to evaluate the role of FGF2 in axillary lymph node metastasis in early-stage breast cancer patients. Aim : To determined the relationship of FGF 2 expression values in primary tumors to the incidence of axillary lymph node metastases. Methods :A cross-sectional study was used by evaluating the expression of FGF2 in 47 early-stage breast cancer patients who underwent a mastectomy at the Cipto Mangunkusumo National Center General Hospital (RSCM) from January 2014 to Desember 2018. FGF2 expression was examined by immunohistochemistry, then evaluated and linked between expression FGF2 with axillary lymph node metastases. Results : The Chi Square test had a value of p=0.044 (p<0.05) that showed there was a significant relationship between FGF2 value in breast tumors with the incidence of axillary lymph node metastasis. Odds ratio 4.22 (95% CI 0.983-18.1). Conclusions The role of FGF2 in lymph node metastasis is related to the interaction between various lymphangiogenic factors in promoting lymphangiogenesis and lymphatic metastasis. High expression of FGF2 has a significant correlation with the incidence of axillary lymph node metastasis.

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Latar Belakang: Kanker payudara merupakan jenis kanker yang paling sering terjadi pada wanita di seluruh dunia dan menyumbangkan angka mortalitas yang tinggi akibat risiko metastasis. Metastasis dapat terjadi meskipun pasien telah diterapi secara adekuat. Epitel-mesenchymal transition (EMT) adalah salah satu mekanisme utama terjadinya metastasis. Sel yang mengalami perubahan fenotip menjadi mesenkimal bersifat agresif, motil dan potensial menjadi metastasis. Vimentin merupakan salah satu biomarker spesifik yang muncul ketika sel mengadopsi fenotip mesenkim. Vimentin dapat memprediksi metastasis dan survival pada kanker payudara. Tujuan: Mengetahui hubungan antara ekspresi vimentin terhadap kejadian metastasis dan survival pada pasien kanker payudara. Metode: Desain studi ini adalah kohort retrospektif. Subjek berasal dari pasien kanker payudara di RSUP dr. Ciptomangunkusumo periode 2017–2018. Dilakukan pemeriksaan imunohistokimia untuk mengetahui ekspresi vimentin. Pasien diobservasi selama 4 tahun untuk mengetahui keluaran metastasis dan survival. Hasil: Terdapat 43 subjek, terdiri dari 39 ekspresi vimentin positif (90,7%), 10 subjek metastasis (23,3%), 16 subjek meninggal (37,2%). Pasien dengan ekspresi vimentin positif memiliki risiko 2,99 kali terjadi metastasis. Rerata overall survival (OS) pasien ekspresi vimentin positif lebih rendah dibandingkan negatif (162,0 minggu vs 174,5 minggu). Namun, secara statistik tidak terdapat hubungan bermakna antara vimentin terhadap kejadian metastasis (p=1,000) dan survival (p=0.971). Kesimpulan: Ekspresi vimentin tidak berhubungan dengan kejadian metastasis dan survival. Namun, ekspresi vimentin positif memiliki kecenderungan meningkatkan risiko metastasis dan mortalitas yang lebih cepat pada pasien kanker payudara. ......Background: Breast cancer is the most common of cancer in women around the world and contributes to a high mortality rate because of the risk of metastases. Metastases can still occur even if the patient has been adequately treated. Epithelial-mesenchymal transition (EMT) is one of the main mechanisms of metastasis. Cells that have a phenotypic change to mesenchymal are aggressive, motile, and prone to become metastatic. Vimentin is the specific biomarker that appears when cells have changed to mesenchymal phenotype. Vimentin can predict metastasis and survival in breast cancer. Aim: to find the association between vimentin expression with metastases and survival in breast cancer patients. Methods: This study design is a retrospective cohort. The subjects are breast cancer patients at Dr. Ciptomangunkusumo from 2017 to 2018. Immunohistochemical staining was performed to analyze the expression of vimentin. Patients were followed-up for 4 years to determine metastasis event and survival outcome. Results: There were 43 subjects, consist of 39 positive vimentin expressions (90.7%), 10 metastases (23.3%), and 16 death (37.2%). Patients with positive vimentin expression have 2.99-times the risk of developing metastases. The mean overall survival (OS) of patients with positive was lower than negative vimentin expression (162.0 weeks vs. 174.5 weeks). However, the association between vimentin with metastatic (p=1,000) and survival (p=0.971) outcome was not statistically significant. Conclusion: Vimentin expression is not associated with metastatic events and survival outcome. However, positive vimentin expression tends to increase the risk of metastasis and increase mortality rates in breast cancer patients.

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Latar Belakang/Tujuan. Angka kematian dan kejadian metastasis kanker payudara cukup tinggi. Faktor metabolik termasuk resistensi insulin mempunyai peranan terhadap progresivitas kanker payudara namun terdapat hanya sedikit penelitian yang menilai hubungan resistensi insulin dengan kejadian metastasis kanker payudara. Terdapat hubungan yang erat antara beberapa variabel dalam kelompok pasca-menopause terhadap kejadian metastasis, pemberian terapi hormonal aromatase inhibitor dan kemoterapi terhadap nilai HOMA-IR. Mengetahui hubungan resistensi insulin yang dinilai menggunakan nilai homeostatic model assessment for insulin resistance (HOMA-IR) dengan kejadian metastasis kanker payudara.

Metode. Studi potong lintang yang meneliti 150 pasien kanker payudara di Rumah Sakit Cipto Mangunkusumo (RSCM) dan Rumah Sakit Siloam Mochtar Riady Comprehensive Cancer Centre (MRCCC) Jakarta dalam rentang waktu agustus 2019-april 2020. Terdapat 150 subjek penelitian, nilai titik potong HOMA-IR ditentukan dengan kurva receiver operating curve (ROC). Dilakukan analisis subgrup kelompok pasca menopause terhadap metastasis, terapi hormonal dan kemoterapi terhadap HOMA-IR.

Hasil. Tidak didapatkan nilai titik potong optimal HOMA-IR terhadap kejadian metastasis (Area under curve (AUC) 0,50, P : >0,05, interval kepercayaan (IK) 95% : 0,406-0,593). Tidak terdapat hubungan bermakna variabel pasca-menopause dengan kejadian metastasis dan kemoterapi terhadap nilai HOMA-IR. Terdapat hubungan bermakna pemberian terapi hormonal aromatase inhibitor terhadap peningkatan nilai HOMA-IR, P : <0,01

Simpulan. Tidak terdapat hubungan yang bermakna antara resistensi insulin dengan kejadian metastasis pada pasien kanker payudara. ......Background/Purpose. Mortality and incidence rate of metastatic breast cancer is quite high. Metabolic factors including insulin resistance have a role in the progression of breast cancer, but there are only a few studies that assess the relationship of insulin resistance with the incidence of breast cancer metastases. There is a close relationship between variables in the postmenopausal group for the occurrence of metastases, administration of hormonal aromatase inhibitors and chemotherapy to the value of HOMA-IR. Knowing the relationship of insulin resistance which was assessed using the value of the homeostatic model assessment for insulin resistance (HOMA-IR) with the incidence of metastatic breast cancer.

Method. A cross-sectional study examining 150 breast cancer patients at Cipto Mangunkusumo General Hospital and Siloam Hospital Mochtar Riady Comprehensive Cancer Center Jakarta in August 2019-April 2020. There are 150 subjects research, the HOMA-IR cutoff value is determined by the receiver operating curve (ROC) curve. Postmenopausal subgroups were analyzed for metastases, hormonal therapy and chemotherapy for HOMA-IR.

Results. There was no optimal HOMA-IR cut off value for metastatic events (Area under curve (AUC) 0.50, P:> 0.05, 95% confidence interval (IK): 0.406-0.593). There was no significant relationship between postmenopausal variables with the incidence of metastasis and chemotherapy on the value of HOMA-IR. There was a significant relationship between the administration of hormonal aromatase inhibitor therapy to the increase of HOMA-IR value, P: <0.01

Abstrak :
ABSTRAK
TUJUAN : Mengetahui insiden metastasis kanker ovarium epitelial yang dilakukan pembedahan primer pada kelenjar getah bening pelvik, paraaorta dan pelvik/paraaorta di RSCM periode Januari 2009 Desember 2015. LATAR BELAKANG : Tatalaksana mengenai limfedenektomi pada kanker ovarium masih merupakan kontroversi. Adanya kekurangan data penelitian prosfektif ataupun RCT tentang patologi antomi merupakan penyebab kontroversi tatalaksana limfedentomi. Namun sampai saat ini sejak 1998 FIGO mengatakan bahwa limfedenektomi pelvik dan paraaorta merupakaan bagian terintegrasi yang tidak dapat dipisahkan pada surgical staging kanker ovarium. Namun penelitian mengenai limfedenektomi masih terbatas, sampai saat belum menemukan adanya publikasi penelitian insiden metastasis kanker ovarium epitelial pada kelenjar getah bening di RSCM. METODE Penelitian ini menggunakan desain penelitian potong lintang, data diambil dari rekam medis, dari data kanker register didapatkan 1584 daftar rekam medik, namun didapatkan 401 pasien kanker ovarium, dan 306 yang ekslusi, didapatkan 55 data yang masuk kriteria inklusi. HASIL Dari 55 sampel yang dilakukan pembedahan primer pada kanker ovarium tipe epitel. Penyebaran kelenjar getah bening pada kanker epitel ovarium yang dilakukan pembedahan primer pada KGB paraaorta adalah 20 , pelvik 9.1 dan pelvik/paraaorta 23,6 . KESIMPULAN : 1. Insiden metastasis KGB kanker epitel ovarium pada paraaorta sebanyak 20 , pelvik 9,1 dan pada pelvik/paraaorta 23,6 di RSCM dari tahun 2009-2015.. 2. Semakin tinggi stadium, maka semakin tinggi keterlibatan KGB pelvik dan paraaorta . 3. Pada subtipe serosum lebih banyak menyebabkan keterlibatan pada KGB pelvik dan paraaorta . 4. Semakin buruk derajat differensiasinya, maka semakin tinggi keterlibatan pada KGB paraaorta . 5. Pada stadium I subtipe musinosum derajat difensiasi baik dengan keterlibatan pada KGB yang minimal sehingga dapat lebih selektif dalam mempertimbangkan risk dan benefit dari limfedenektomi

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ABSTRACT
AIM To evaluate the incidence of pelvic and paraaortic lymph node metastasis of epithelial ovarian cancer underwent primary surgery in Cipto Mangunkusumo Hospital from Januari 2009 to December 2015. BACKGROUND The definitive objective of lymphadenectomy in ovarian cancer is still controversial due to the lack of prospective research or randomized controlled trial. Since 1998, FIGO has stated that pelvic and paraaorta lymphadenectomy are part of ovarian cancer surgical staging. But, there is still limited research and still not published the incidence of pelvic and paraaortic lymph node metastasis of epithelial ovarian cancer underwent primary surgery in Cipto Mangunkusumo Hospital. METHODS This research is cross sectional from medical records, the INASGO cancer registry. A hundred fifty four medical records were included but we found only 401 ovarian cancer, 306 data were excluded and 55 data were included. RESULTS From 55 epithelial ovarian cancer patients underwent the primary surgery, there are 20 metastasis to paraortic lymph node, 9,1 metastasis to pelvic lymph node, and 23,6 metastasis to both. CONCLUSION 1. Lymph node metastases incident of ovarian epithelial cancer in paraorta amounts 20 , pelvic 9.1 and pelvic or paraortic 23.6 2. Higher the stadium, the lymph node involvements will be higher as well pelvic and paraortic 3. In serous subtype, there is more incidents of lymph node involvements pelvic and paraaortic 4. If the differentiation type is worse, there will be higher rate of pelvic and paraaortic lymph node involvement. 5. In stadium 1 of mucinous subtype with well differentation has minimal lymph node involvement so we can be more selective in considering the risk and benefit of lymphadenectomy. The suggestion is the advanced research needs to be done prospectively by increase the number of samples for finding the metastatic factors to lymph node more accurately.

Abstrak :
ABSTRAK
Latar Belakang: Kanker payudara sampai saat ini memiliki insiden dan prevalensi yangtertinggi dalam diantara penyakit kanker pada perempuan. Lokasi tersering metastasis kanker payudara adalah tulang dimana memiliki overall survival yang baik yang berakibat padapengeluaran biaya yang tinggi dibandingkan dengan metastasis organ viseral. CXCR4 dan RANK diketahui memiliki peran dalam homing sel kanker ke tulang.Dibandingkan dengan biomarker-biomarker yang lain, CXCR4 dan RANK berada padakaskade paling awal dari proses metastasis tulang. Aksis CXCR4 dengan SDF-1 sebagailigannya merupakan pengaturan utama dalam trafficking sel pada beberapa sel punca tubuhmanusia. Aksis RANK/RANKL/OPG mengontrol proses osteoklastogenesis dan resorpsitulang. Dari berbagai studi didapatkan CXCR4 dan RANK diekspresikan tinggi pada kankerpayudara dan berkaitan dengan metastasis tulang. Tujuan Penelitian: Mengetahui hubungan kombinasi ekspresi protein CXCR4 danRANK sebagai faktor prediktor metastasis tulang pada kanker payudara. Metode Penelitian: Jenis penelitian ini adalah case control, analitik, dengan observasional,untuk diagnostik dan prognostik. Penelitian ini dilakukan pada penderita kanker payudarastadium I-IV dengan jumlah sampel 58 pasien. Hasil Penelitian: Faktor Klinikopatologi stadium tumor, mempunyai hubungan yang signifikan terhadap ekspresi kombinasi CXCR4 dan RANK pada metastasis tulang padakasus kanker payudara. Pada penderita kanker payudara terdapat hubunngan yang signifikanantara nilai kombinasi ekspresi CXCR4 dan RANK tinggi dengan kejadian metastasis tulang. Kesimpulan: Faktor Klinikopatologi stadium tumor mempunyai hubungan yang signifikanterhadap ekspresi kombinasi CXCR4 dan RANK pada metastasis tulang pada kasus kankerpayudara. Kombinasi CXCR4 dan RANK dapat digunakan sebagai alat prediktor diagnostikuntuk mengetahui status metastasis tulang kanker payudara, sehingga dapat diberikan terapiawal yang dapat meningkatkan kualitas hidup dan menekan biaya kesehatan di kemudianhari.

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ABSTRACT<>br> Background Until recently, breast cancer has the highest prevalence and incidence offemale cancer. Breast cancer often metastasised to bone, which have better overall survival but consume more health cost than visceral metastasis. CXCR4 and RANK have been known for it's role in cancer cell homing to bone. Instead ofother biomarkers of bone metastasis, CXCR4 and RANK act in the early cascade of bonemetastasis process. CXCR4 SDF 1 axis plays a great role in cell trafficking of many types ofhuman stem cell. RANK RANKL OPG axis mediates osteoclastogenesis and boneresorption. In several studies, CXCR4 and RANK are highly expressed in breast cancer andcorrelate with bone metastasisAim To establish the combination, CXCR4 and RANK are highly expressed in breast cancer and correlate with bone metastasisMethods Case Control study, analytical, observational for prognostic and diagnostic byinvolving 58 patiens with stadium I,II,II,IV at breast cancer Result Clinic pathalogical factor, stadium had significant correlation with combination CXCR4 and RANK expression in breast cancer patients. The High combination CXCR4 and RANK expression in breast cancer patients had significant correlation with bone metastasis. Conclusion: Clinic pathalogical factor stadium tumor had significant correlation with combination CXCR4 and RANK expression in breast cancer patients. The high Combination of CXCR4 and RANK expression can act as a predictor for bone metastasis inbreast cancer, so the patient can start early therapy which increase the quality of life andreduce treatment cost.

Abstrak :
Karsinoma nasofaring (KNF) merupakan penyakit endemis di Indonesia dengan tingkat mortalitas yang tinggi. Salah satu penyebab mortalitas adalah metastasis jauh. VEGF-A terbukti berperan pada kejadian metastasis jauh KNF, namun penelitian yang membahas hubungan langsung keduanya masih terbatas. Selain VEGF, terdapat jalur pensinyalan lain terkait VEGF yang mungkin berperan dalam kejadian metastasis jauh, yaitu jalur pensinyalan Hippo. Protein Yes-Associated Protein (YAP) adalah downstream efektor utama dari jalur pensinyalan ini. Dengan dilakukan pulasan YAP serta dievaluasi hubungan antara YAP dengan VEGF-A diharapkan hasilnya dapat memberikan informasi mengenai potensi biomarker sebagai indikator prognostik kejadian metastasis jauh KNF. Penelitian menggunakan metode analitik observasional dengan uji Chi-square dan korelasi koefisien kontingensi. Terdapat perbedaan ekspresi YAP yang bermakna pada kelompok KNF dengan dan tanpa metastasis jauh (p<0,001). Terdapat perbedaan bermakna ekspresi VEGF-A pada kelompok KNF dengan dan tanpa metastasis jauh (p<0,001). Ekspresi YAP yang tinggi berhubungan dengan peningkatan ekspresi VEGF-A (p=0,001). Terdapat korelasi signifikan antara peningkatan ekspresi YAP dan peningkatan ekspresi VEGF-A dengan kekuatan lemah (C=0,397, p=0,01). Terdapat perbedaan bermakna koekspresi YAP tinggi dan VEGF-A tinggi (double co-high-expression) antara kelompok KNF dengan dan tanpa metastasis jauh (p<0,001). Penelitian ini mendukung sifat onkogenik YAP. YAP dan VEGF-A dapat menjadi biomarker potensial untuk memprediksi kejadian metastasis jauh KNF. ......Nasopharyngeal carcinoma (NPC) is an endemic disease in Indonesia with a high mortality rate. Distant metastasis is one of the leading causes of death. Although VEGF-A has been found to play a role in distant NPC metastasis, research on the relationship between the two is still limited. Another VEGF-related pathway, the Hippo pathway, may be involved in distant metastasis. Yes-Associated Protein (YAP) is the main downstream effector of this signaling pathway. It is expected that performing YAP marker and studying the relationship between YAP and VEGF-A, would provide data on the possibility of biomarkers that may be used as a prognostic predictor of the occurrence of distant metastasis in NPC. An observational analytic study was conducted—statistical analysis using SPSS 25.0 with Chi-square and contingency coefficients test. There was a significant difference in YAP expression between NPC with and without distant metastasis (p<0.001). The expression of VEGF-A differed significantly between NPC with and without distant metastasis (p<0.001). There was a significant relationship between YAP and VEGF-A (p=0.001) and a weak correlation (C 0.397, p=0.01). There was a significant difference in the double co-high-expression group between the KNF with and without distant metastasis (p<0.001). This study highlights YAP's oncogenic role in NPC, suggesting that YAP and VEGF-A might be potential biomarkers to predict distant metastasis in NPC.

Abstrak :

Karsinoma payudara (KPD) merupakan kanker terbanyak pada perempuan dan lebih dari 90%
kematian akibat kanker diebabkan oleh adanya metastasis. Diperlukan terapi yang tidak hanya
fokus pada proliferasi, tetapi juga fokus pada proses metastasis. Jalur Rho/ROCK diketahui
memengaruhi invasi dan metastasis. Studi terbaru menunjukkan bahwa jalur Rho/ROCK
berperan penting pada regulasi migrasi dan proliferasi sel, sehingga dapat dijadikan target
terapi. Selain mereduksi biosintesis kolesterol melalui inhibisi 3-hydroxy-3-methylglutaryl
coenzyme A reductase, statin juga mengurangi formasi isoprenoid intermediates yang
diperlukan untuk mediasi pensinyalan melalui jalur Rho/ROCK. Statin diduga dapat
menghambat jalur Rho/ROCK dan aman digunakan dalam jangka panjang. Penelitian ini
bertujuan untuk mengetahui efek antimetastasis (migrasi dan proliferasi) simvastatin terhadap
KPD melalui jalur Rho/ROCK.
Penelitian ini merupakan uji intervensi perioperative “window”, parallel unmatching,
randomized, double-blinded, dan placebo-controlled yang berlangsung sejak November 2014
hingga Juli 2015. Sebanyak 30 pasien KPD diberikan terapi simvastatin 40 mg/hari dan plasebo
selama 4-6 minggu lalu dilakukan mastektomi di RSCM, RSPAD Gatot Subroto, RS
Persahabatan, dan RSUD Koja. Perubahan migrasi (indeks migrasi, aktivitas ROCK dan kadar
mRNA RhoC, CXCR4, dan CD44) dan reduksi proliferasi (ekspresi Ki67) yang didapat dari
jaringan biopsi dan mastektomi dievaluasi sebelum dan sesudah terapi. Kemudian karakteristik
yang berbeda bermakna dianalisis juga hubungannya dengan kadar kolesterol darah, grade,
status ER/PR, dan status HER-2.
Simvastatin 40 mg/harimenurunkan indeks migrasi (p=0,006), aktivitas ROCK (p=0,002), kadar
mRNA CXCR4 (p=0,045) dan ekspresi Ki67 (p<0,001) secara bermakna. Terdapat tren
penurunan kadar mRNA RhoC (p=0,163) dan CD44 (p=0,094). Penurunan aktivitas ROCK
berhubungan dengan kolesterol tinggi (p=0,008), grade rendah (p=0,019) dan amplifikasi HER-
2 (p=0,009). Penurunan kadar mRNA CXCR4 berhubungan dengan kolesterol tinggi (p=0,024),
ER/PR positif (p=0,013), dan amplifikasi HER-2 (p=0,018). Penurunan ekspresi Ki67
berhubungan dengan kolesterol tinggi (p=0,001), grade rendah (p=0,017) dan tinggi (p=0,018),
HER-2 (p=0,002) dan negatif (p=0,034), serta ER/PR positif (p=0,007) dan negatif (p=0,042).
Simvastatin dapat menginhibisi migrasi dan menyupresi proliferasi pada KPD melalui jalur
Rho/ROCK, sehingga dapat digunakan sebagai terapi pencegahan metastasis kanker payudara.

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Breast cancer is the most common cancer among women and more than 90% of cancer
deaths are caused by metastasis. There is an urgent need for the development of therapeutic
intervention specifically targeted to the metastatic process. The Rho/ROCK pathway is
found to be involved in invasion and metastasis. Recent studies have revealed that the
Rho/ROCK pathway plays a critical role in regulation of cancer cell migration and
proliferation, making it a potential therapy target. Besides reducing cholesterol biosynthesis
by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase, statins also decrease the
formation of isoprenoids intermediates essential for mediating the Rho/ROCK signalling.
Statin is thought to inhibit the Rho/ROCK pathway and is safe for long-term use. This study
aimed to determine the antimetastasis (migration and proliferation) effect of simvastatin on
breast cancer through the Rho/ROCK pathway.
In a parallel unmatching, randomized, double-blinded, placebo-controlled, perioperative
“window” interventional trial conducted from November 2014 until July 2015, 30 breast
cancer subjects were treated with simvastatin 40 mg/day or placebo for 4–6 weeks
followed by mastectomy (n=15 in each arm) at Cipto Mangunkusumo Hospital, Gatot
Subroto Army Hospital, Persahabatan Hospital and Koja Hospital. Changes in
migration (migration index, ROCK activity, mRNA RhoC, CXCR4 and CD44 level)
and proliferation (Ki67 expression) from biopsy and final surgical specimen were
obtained before and after intervention. The relationships of significant factors with
blood cholesterol level, grade, ER/PR and HER-2 status were analyzed.
Simvastatin 40 mg/d significantly reduced migration index (p = 0.006), ROCK activity
(p = 0.002), mRNA CXCR4 level (p = 0.045) and reduced Ki67 expression (p < 0.001).
Decreased was also observed for mRNA RhoC (p = 0.163) and CD44 level (p = 0.094).
Reduced ROCK activity was related to high cholesterol level (p = 0.008), low grade (p
= 0.019) and HER-2 amplification (p = 0.009). Reduced CXCR4 transcription was
related to high cholesterol level (p = 0.024), positive ER/PR (p = 0.013) and HER-2
amplification (p = 0.018). Ki67 expression was related to high cholesterol level (p =
0.001), low (p = 0.017) and high grade (p= 0.018), with (p = 0.002) and without HER-2
amplification (p = 0.034), and positive (p = 0.007) and negative (p = 0.042) ER/PR
status.
Simvastatin inhibits the migration and proliferation in breast cancer through Rho/ROCK
pathway, hence holds a promising potential as prophylaxis for breast cancer metastasis

Abstrak :
Latar Belakang: Kanker payudara merupakan kanker dengan insidensi tertinggi kedua di dunia pada tahun 2018. Setiap 100.000 wanita di Indonesia, 40 mengidap kanker payudara. Mortalitas pada kanker payudara paling banyak disebabkan oleh kejadian metastasis organ viseral yang dilaporkan memiliki prognosis lebih buruk dibandingkan metastasis non viseral. Ekspresi reseptor hormonal (HR) dan protein HER2 atau subtipe intrinsik molekular diindikasikan dapat memprediksi jenis atau lokasi metastasis kanker payudara. Karena itu, perlu ada penelitian tentang hubungan HR dan HER2 terhadap jenis metastasis kanker payudara, terutama pada populasi di Indonesia untuk memperkirakan perjalanan penyakit. Tujuan: Mengetahui hubungan antara reseptor hormonal dan HER2 terhadap jenis metastasis kanker payudara, viseral maupun non viseral. Metode: Penelitian dengan desain cross sectional ini menggunakan data dari sembilan puluh satu pasien kanker payudara dengan metastasis yang dipilih dengan cara consecutive sampling dari RSCM dan RS MRCCC Siloam. Status HR dan HER2 diambil dari pemeriksaan imunohistokimia, sedangkan jenis metastasis diambil dari hasil pemeriksaan radiologi atau patologi anatomi. Data diolah dengan uji chi square dan disajikan dalam bentuk tabel. Hasil: Analisis bivariat antara HR dengan metastasis viseral menghasilkan nilai OR 0,549 (95% CI 0,165-1,829), dengan metastasis non viseral OR 1,533 (95% CI 0,565-4,157), dan dengan kedua metastasis viseral dan non viseral OR 0,960 (95% CI 0,351-2,624). Untuk analisis antara protein HER2 dengan metastasis viseral menghasilkan OR 2,333 (95% CI 0,825-6,599), dengan metastasis non viseral OR 0,538 (95% CI 0,223-1,302), dan dengan kedua metastasis viseral dan non viseral OR 1,061 (95% CI 0,442-2,549). Semua analisis menghasilkan p>0,05. Kesimpulan: Tidak ditemukan adanya hubungan yang bermakna antara HR maupun HER2 terhadap jenis metastasis kanker payudara
Background: Breast cancer is a cancer with the second highest incidence in the world in 2018. For every 100,000 women in Indonesia, 40 suffer from breast cancer. Mortality in breast cancer is mostly caused by the incidence of visceral organ metastases which are reported to have a worse prognosis than non-visceral metastases. Hormonal receptor (HR) and protein expression HER2 or molecular intrinsic subtypes are indicated to predict the type or location of breast cancer metastases. Therefore, there needs to be research on the relationship between HR and HER2 to the type of breast cancer metastases, especially in the population in Indonesia to estimate the course of the disease. Objective: To determine the relationship between hormonal receptors and HER2 on the type of breast cancer metastasis, visceral and non-visceral. Methods: This cross-sectional design study used data from ninety-one breast cancer patients with metastases selected by consecutive sampling from RSCM and MRCCC Siloam Hospital. HR and HER2 status were taken from immunohistochemical examination, while the type of metastasis was taken from the results of radiological examination or anatomical pathology. Data processed with chi square test and presented in tabular form. Results: Bivariate analysis of HR with visceral metastases resulted in OR 0.549 (95% CI 0.165-1.829), with non-visceral metastases OR 1.533 (95% CI 0.565-4.157), and with both visceral and non-visceral metastases OR 0.960 (95% CI 0.351-2.624). For analysis between HER2 protein and visceral metastases resulted in an OR of 2.333 (95% CI 0.825-6.599), with non-visceral metastases OR 0.538 (95% CI 0.223-1.302), and with both visceral and non-visceral metastases OR 1.061 (95% CI 0.442-2.549). All analyzes yielded p>0.05. Conclusion: There was no significant relationship between HR and HER2 on the type of breast cancer metastases