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"ABSTRAKRuang lingkup dan cara penelitian: Telah dilakukan penelitian induksi kanker hati tikus dengan aflatoksin B1. Penelitian ini ingin melihat apakah asam sialat meningkat lebih dini dari AFP pada induksi kanker hati tersebut. 50 ekor tikus perlakuan diinduksi dengan intubasi lambung 42 x 20 ug aflatoksin B1 Sebagai kontrol, 50 ekor tikus diintubasi dengan sejumlah sama akuades. Pengamatan dilakukan dengan mengambil plasma dan jaringan hati setiap bulan selama 10 bulan pemeliharaan. Pada contoh uji dilakukan pengukuran kadar asam sialat, deteksi AFP plasma dan pengamatan histopatologis jaringan hati. Pengukuran kadar asam sialat dilakukan dengan cara spektrofotometri, sedangkan deteksi AFP dengan cara ELISA. Pengukuran AFP dengan teknik ELISA memerlukan antigen AFP dan antibodi anti AFP tikus, yang ternyata tidak tersedia dipasaran. Antibodi anti AFP dibuat dengan imunisasi kelinci menggunakan protein amnion. Setelah imunisasi ke 3 titer antibodi sebesar 1280, setelah imunisasi ke 5 sebesar 2560. Purifikasi antibodi dilakukan dengan kolom imunoafinitas AminoLink. Purifikasi AFP dari amnion dilakukan dengan kolom afinitas Cibacron Blue. Uji statistik yang dipakai untuk analisis hasil adalah analisis Marian dua arah, dengan batas kemaknaan p<0,05.Hasil dan kesimpulan: Hasil penelitian menunjukkan bahwa kadar asam sialat plasma kelompok tikus perlakuan berbeda bermakna dengan kelompok kontrol sejak bulan pertama (p<0,05). Deteksi AFP menunjukkan peningkatan AFP pada kelompok tikus perlakuan dan tidak pada kelompok tikus kontrol sejak bulan pertama (p<0,05). Pengamatan histopatologis menunjukkan adanya perubahan yang dapat menuju kearah keganasan. Dengan demikian hasil pengamatan petanda tumor pada tikus yang diinduksi kanker hati menunjukkan bahwa baik kadar AFP maupun asam sialat meningkat pada waktu dini, satu bulan setelah induksi dengan aflatoksin B1 .

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ABSTRACT

Determination of The Earliness of Rat Plasma α-Fetoprotein (AFP) and Sialic Acid Levels as Tumor Markers in the Process of Liver Carcinogenesis Induction By Aflatoxin B1 (AFB1) Scope and method of study: An experimental study of aflatoxin B1 induced liver carcinogenesis has been done. The aim oh this study was to prove the increase of plasma sialic acid level is earlier than the AFP level in liver carcinogenesis. Fifty rats that were treated with daily intubations of 20 gg for a period of 42 days. Fifty control rats were intubated with equal volumes of aquadest. Observation of the plasma and liver tissues were done every month, including measurement of plasma AFP, sialic acid level, and histopatology of the liver tissue. Sialic acid level was done by spectrophotometric technique, and ELISA technique was used for the detection of plasma AFP. The ELISA technique for rat AFP needs rat AFP antigen and antibody anti rat AFP which were not available from chemical suppliers. The antibody anti rat AFP was developed by immunization of rabbits with rat amniotic protein. After the 3rd immunization, rabbit antibody anti rat amniotic titter was 1280, and after the 5th immunization 2560. Antibody purification was done by immunoaffinity chromatography column (AminoLink). Purification of the rat AFP from amniotic fluid was done by affinity chromatography column (Cibacron Blue). The result were analyzed by Analysis of varians, with p<0,05.

Results and conclusions: The results showed that the plasma sialic acid level of rats treated with aflatoxin B1 were significantly different from that of the control rats, p<0,05. Besides, plasma AFP was detected in the treated rats, but not in the control rats, from the first month. The histopathologic observation of the treated rat livers showed that there were changes that could lead to neoplastic livers. Both plasma and sialic acid levels were seen early, starting from the first month after induction of carcinogen by aflatoxin B1."

"Latar Belakang: Meskipun berbagai kemajuan pengobatan dicapai selama lebih dari satu dekade terakhir, secara keseluruhan prognosis karsinoma sel hati tetap buruk. Efek samping terapi serta progresifitas penyakit itu sendiri sangat mempengaruhi kualitas hidup pasien. Selain kesembuhan dan survival rate, kualitas hidup menjadi poin akhir penting dalam pengobatan kanker. Kualitas hidup pada penderita karsinoma sel hati penting untuk diteliti, karena merupakan faktor prognostik penting dari survival time, selain dapat juga mengevaluasi keuntungan dan kerugian dari modalitas terapi yang dipilih. Sampai saat ini belum ada kuesioner yang andal dan sahih untuk menilai kualitas hidup pasien karsinoma sel hati secara akurat di Indonesia. Penelitian ini bertujuan untuk mendapatkan kuesioner European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Hepatocellular Carcinoma-18 (EORTC QLQ-HCC18) yang andal dan sahih untuk digunakan di Indonesia.Metode: Penelitian ini adalah studi potong lintang. Penelitian diawali dengan menerjemahkan EORTC QLQ-HCC18 ke dalam bahasa Indonesia dan kemudian diujicobakan pada 10 responden. Setelah itu, EORTC QLQ-HCC18 hasil terjemahan digunakan pada penelitian utama dengan jumlah sampel yang lebih besar. Keandalan dinilai dengan pendekatan tes ulang dan konsistensi internal. Tes ulang dinilai dengan intraclass correlation coefficient (ICC). Konsistensi internal dinilai dengan Cronbach Alpha. Kesahihan konstruksi dinilai dengan multi-trait scaling analysis. Kesahihan kriteria dinilai dengan melihat korelasi antara domain kuesioner EORTC QLQ-HCC18 dengan Short Form 36 (SF36).Hasil: Pengambilan data dilakukan terhadap 65 pasien karsinoma sel hati yang berobat ke Poli Hepatologi maupun yang sedang dirawat di RSUPN Cipto Mangunkusumo selama Oktober 2015 ? Februari 2016. Nilai ICC (interval 1 jam) pada semua domain EORTC QLQ-HCC18 sangat baik (ICC > 0,8), kecuali domain ikterus yang termasuk dalam kategori baik (ICC 0,61-0,8). Nilai Cronbach Alpha > 0,7 pada separuh jumlah domain EORTC QLQ-HCC18 kecuali domain ikterus (0,137), nyeri (0,474), dan citra tubuh (0,599). Sedangkan nilai Cronbach Alpha yang diperoleh dari penggabungan seluruh domain tetap baik, yaitu 0,897. Multi-trait scaling analysis menunjukkan korelasi cukup tinggi antara skor butir pertanyaan dengan skor domainnya sendiri. Sedangkan hubungan butir pertanyaan dengan domain yang berbeda selalu mempunyai korelasi yang lebih rendah dibandingkan dengan domainnya sendiri. Pada uji kesahihan kriteria, didapatkan 42 korelasi (dari total 64 korelasi) dengan r ≥ 0,3 dan p < 0,05 antara domain EORTC QLQ-HCC18 dengan SF36.Simpulan: Kuesioner EORTC QLQ-HCC18 merupakan alat ukur yang andal dan sahih untuk menilai kualitas hidup pasien karsinoma sel hati di Indonesia.

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Background: Despite various therapeutic progress has been achieved over the past decade, the overall prognosis of hepatocellular carcinoma remains poor. Each therapy undertaken certainly has side effects. Adverse effect of treatment and the progression of the disease itself greatly affect the patient?s quality of life. In addition to recovery and survival rate, quality of life becomes extra important end point in cancer treatment. Quality of life in hepatocellular carcinoma is important to investigate, because quality of life has become an important prognostic factor of survival time, whilst quality of life can also evaluate the cost and benefit of chosen therapeutic modalities. Currently there is no specific questionnaire that can assess the quality of life of hepatocellular carcinoma patients accurately in Indonesia. This study aims to get a reliable and valid EORTC QLQ-HCC18 questionnaire to assess the quality of life of patients with hepatocellular carcinoma in Indonesia.Methods: This is a cross-sectional study. The study began by translating the EORTC QLQ-HCC18 into Indonesian and then tested on 10 respondents. After that, the Indonesian version of EORTC QLQ-HCC18 is used in the main study with a larger sample size. The questionnaire reliability was assessed with test-retest and internal consistency approach. Test-retest was assessed with intraclass correlation coeficient (ICC). Internal consistency was assessed by Cronbach alpha. Construct validity was assessed by multi-trait scaling analysis. The criteria validity assessed by looking at the correlation between domains of EORTC QLQ-HCC18 with Short Form 36 (SF36).Results: Data was collected from 65 hepatocellular carcinoma patients who came to Hepatology Polyclinic or were hospitalized at Cipto Mangunkusumo National General Hospital from October 2015 to February 2016. ICC value (1 hour interval) in all domains of EORTC QLQ-HCC18 is very good (ICC> 0.8), except icterus domain which categorized as good value (ICC 0,61-0,8). Cronbach alpha values > 0.7 obtained in almost half of domains of EORTC QLQ-HCC18, except icterus (0,137), pain (0,474), dan body image domain (0,599). Whereas the Cronbach Alpha obtained from merging the entire domains was still good (0,897). Multi-trait scaling analysis showed a fairly high correlation between the scores of the questions with a score of his own domain. While the relationship of the questions with different domains always have a lower correlation than the domain itself. In criteria validity test, obtained 33 correlations with r ≥ 0,4 and p < 0,05 between domains of EORTC QLQ-HCC18 with SF36.Conclusion: EORTC QLQ-HCC18 is a reliable and valid instrument for assessing quality of life of hepatocellular carcinoma patients in Indonesia.

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"Primary liver cancer : surveillance, diagnosis and treatment focuses on the many therapies rapidly evolving to assist with controlling hepatocellular carcinoma as well as emerging technologies to assist in early diagnosis as well as prevention. All chapters are written by experts in their fields and include the most up to date information for diagnosis, treatment, surveillance, epidemiology, staging, recurrence and prevention. "

"ABSTRACTPurposes This study compared the effectiveness of 1 day vs 3 days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection.MethodWe performed a randomized controlled non inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1 day regimen for antimicrobial prophylaxis, or a 3 day regimen. The primary endpoint was the incidence of SSI.ResultsAmong 480 randomized patients, 232 assigned to the 1 day regimen and 235 to the 3 day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9,5%) in the 1 day group vs 23 patients (9,8%) in the 3 day group (difference, -0,30; 90% CI -4,80 to 4,19% (95% CI -5,66% to 5,05%); one sided P = 0,001 for non inferiority), meeting the non inferiority hypothesis. In both groups, remote site infection (16 (6,9%) vs 22 (9,4%), P 0,001 for non inferiority) and drain-related infection (5 (2,2%) vs 4 (1,7%), P 0.001 for non inferiority) were comparable.ConclusionTo prevent SSI in liver cancer surgery, a 1 day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage."

"Sorafenib adalah tata laksana sistemik pertama pada hepatoseluler karisonoma. Resistensi HCC terhadap sorafenib dapat berkembang cepat dan melibatkan disregulasi apoptosis. Apoptosis diregulasi oleh protein anti-apoptosis dan pro-apoptosis seperti Bcl-2 dan Bax serta dimediasi oleh caspase. Alpha-mangostin telah ditemukan menginduksi apoptosis dengan meningkatkan rasio Bax/Bcl-2 serta caspases di sel kanker payudara serta mengembalikan resistensi doksorubisin di HCC. Tujuan dari penelitian ini adalah untuk mempelajari efek alpha-mangostin di sel HepG2 tahan terhadap sorafenib. Lini sel HCC, sel HepG2 dibagi menjadi 6 kelompok;.01% DMSO, alphamangostin 20μM, sorafenib 10μM, sorafenib 10μM + sorafenib 10μM, sorafenib + alpha-mangostin 20μM, and sorafenib 10μM + sorafenib 10μM + alpha-mangostin 20 μM. Sel diambil dan dihitung, serta RNA diisolasi diikuti dengan sintesis cDNA. Ekspresi dari Bcl-2, Bax, caspase-9, dan -3 diukur menggunakan q-RT PCR.Pemberian alfa-mangostin terhadap sel HepG2 tahan sorafenib secara signifikan meningkatkan ekspresi mRNA Bcl-2 dan Bax bersamaan, sedangkan perbedaan rasio Bax/Bcl-2 tidak ditemukan signifikan. Sementara, ekspresi dari mRNA caspase-9 juga tidak menunjukkan perubahan yang signifikan. Namun, ditemukan peningkatan yang signifikan pada ekspresi mRNA caspase-3, tetapi juga menurun signifikan setelah administrasi sorafenib dan alpha-mangostin bersamaan. Kesimpulan: Alfa-mangostin menginduksi apoptosis di sel HepG2 tahan sorafenib ditunjukkan dengan peningkatan caspase-3 pada pemberian. Namun, mekanisme apoptosis dapat tidak melibatkan jalur intrinsik yang diindikasikan oleh perubahan yang tidak signifikan pada rasio Bax/Bcl-2 dan caspase-9......Sorafenib is the first-line systemic treatment in hepatocellular carcinoma. Sorafenib-resistance HCC may develop rapidly, which may involve apoptosis dysregulation. Apoptosis is regulated by anti-apoptotic and pro-apoptotic proteins such as Bcl-2 and Bax and mediated by caspases. Alpha-mangosin has been reported to induce apoptosis by increase Bax/Bcl-2 ratio and caspases in breast cancer cells as well as reverse doxorubicin resistance in HCC. The purpose of this research is to explore alpha-mangostin effect in sorafenib-surviving HepG2 cells. HCC cell line, HepG2 cells were divided into 6 groups; 0.01% DMSO, alphamangostin 20μM, sorafenib 10μM, sorafenib 10μM + sorafenib 10μM, sorafenib + alpha-mangostin 20μM, and sorafenib 10μM + sorafenib 10μM + alpha-mangostin 20 μM. The cells were taken and counted, and RNA was isolated followed with cDNA synthesis. The expression of Bcl-2, Bax, Bax/Bcl-2 ratio caspase-9 and -3 were measured using q-RT-PCR.The treatment of alpha-mangostin to sorafenib-surviving HepG2 cells significantly increase Bcl-2 and Bax mRNA expression concurrently. In the ratio of Bax/Bcl-2 mRNA, the change was not significant. Meanwhile, the expression of caspase-9 mRNA was neither found to significantly change. However, the expression of caspase-3 mRNA was found to be significant, yet significantly lower in the coadministration of sorafenib and alpha-mangostin. Conclusion: Alpha-mangostin induces apoptosis in sorafenib-surviving HepG2 cells due to increase of caspase-3 upon its administration. However, the mechanism may not be through the intrinsic pathway given the insignificant changes in Bax/Bcl-2 ratio and caspase-9 expression."

"Studi biodistribusi pada hewan uji memainkan peran utama dalam menentukan efektivitas dan keamanan radiofarmaka sebelum uji klinis pada manusia. Namun, sejauh pengetahuan peneliti berdasarkan literatur, belum ada studi biodistribusi lutesium hidroksiapatit (177Lu-HA) yang dilakukan. Oleh karena itu, pada penelitian ini dilakukan studi biodistribusi kemanan 177Lu-HA untuk terapi kanker hati dengan cara menentukan organ at risk (OAR) radiofarmaka tersebut. Data farmakokinetik 177Lu-HA pada tikus Wistar dari organ yang berbeda, seperti hati, ginjal dan limpa, diperoleh dari literatur. Administrasi radiofarmaka dilakukan secara langsung pada intra arteri hati tikus Wistar dengan cara operasi. Secara total, 13 fungsi sum of exponentials (SOE) dan 1 fungsi logistik digunakan untuk fitting data farmakokinetik. Goodness of fit ditentukan berdasarkan visualisasi grafik, Coefficient of Variation (CV <50%) dan elemen-elemen off-diagonal dari Correlation Matrix (-0,8 ≤ CM ≤ 0,8). Fungsi terbaik dipilih berdasarkan Corrected Akaike Information Criterion (AICc) dan digunakan untuk perhitungan Time-Integrated Activity Coefficients (TIACs). TIACs manusia diprediksi dengan mentranslasikan TIACs tikus menggunakan metode time-scalling. Dalam penelitian ini OAR ditentukan dengan metode perbandingan TIACs/massa organ pada seluruh organ. Dengan metode perbandingan TIACs/massa organ ini, nilai terbesar mengindikasikan OAR. Secara umum, fitting data farmakokinetik 177Lu-HA dengan fungsi SOE berhasil dilakukan pada semua organ dengan terpenuhinya kriteria goodness of fit. Prediksi massa TIACs/organ manusia menunjukkan bahwa hati yang merupakan organ target akan menerima dosis internal yang paling tinggi (TIACs/masahati=2,78E+0 jam/gram). Tulang dan limpa akan menerima dosis lebih sedikit daripada hati tetapi relatif lebih tinggi daripada organ lainnya (TIACs/masatulang=7,40E-2 jam/gram, TIACs/massalimpa=5,55E-2 jam/gram). Berdasarkan perhitungan TIACs/massa organ tersebut, dapat disimpulkan bahwa OAR radiofarmaka 177Lu-HA yang diadmisitrasikan langsung ke intra arteri hati tikus Wistar adalah hati, tulang, dan limpa.

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Biodistribution study in animal plays a major role in determining the effectiveness and safety of radiopharmaceutical before clinical test in human. However, to the best of author knowledge, there is no biodistribution study of Lutetium Hydroxyapatite (177Lu-HA) available in the literature. Therefore, this study conducted 177Lu-HA biodistribution study of safety for liver cancer therapy by determining organ at risk (OAR) of the radiopharmaceutical. Pharmacokinetics data of 177Lu-HA in Wistar rats from different organs, such as liver, kidneys, and spleen, was obtained from the literature. Radiopharmaceutical administration was carried out directly on the intra artery of Wistar rat liver by surgery. In total, 13 sum of exponentials (SOE) functions and 1 logistic function were used and were fitted to the pharmacokinetics data. The goodness of the fittings was tested based on the visualization of the fitted graphs, coefficient of variations of the fitted parameters (CV<50%) and the elements of correlation matrix (-0,8 ≤ CM ≤ 0,8). The best function was selected based on the corrected Akaike information criterion (AICc) and was used for the subsequent calculation of time-integrated activity coefficients (TIACs). Human's TIACs was predicted by extrapolating rat's TIACs using time-scalling method. In this study, OAR was determined by comparison method of TIACs/organ mass in all organs. With this comparison method, the biggest value indicates the OAR. In general, the SOE functions were successfully fitted to the pharmacokinetic data of 177Lu-HA in all organs with a good fit based on the goodness of fit criteria. Human's TIACs/organ mass prediction shows that liver as the organ target will receive high internal doses (TIACs/massliver=2,78E+0 hour/gram). Skeleton and spleen will receive less doses then liver but relatively higher than other organs. (TIACs/massskeletpm=7,40E-2 hour/gram, TIACs/massspleen=5,15E-2 hour/gram). Based on that calculation of TIACs/organ mass, it can be concluded that the OAR of 177Lu-HA pharmaceutical that was administrated directly into the intra-arterial liver of the Wistar rat are liver, skeleton, and spleen."

"Latar belakang: Karsinoma sel hati (KSH) merupakan salah satu kanker dan penyebab kematian akibat kanker tersering. Magnetic resonance imaging (MRI) abdomen multifase adalah modalitas pilihan untuk diagnosis KSH, karena dapat menggambarkan perubahan patofisiologi selama hepatokarsinogenesis melalui sekuens dynamic contrast enhanced (DCE), T1-weighted imaging (T1WI) dengan chemical shift imaging, T2- weighted imaging (T2WI), diffusion-weighted imaging (DWI), peta apparent diffusion coefficient (ADC), serta fase hepatobilier. Alpha fetoprotein (AFP) sebagai penanda serologis KSH terkait surveilans, diagnostik, dan prognostik, juga berperan dalam hepatokarsinogenesis dengan menunjukkan perbedaan agresivitas tumor. Penelitian ini bertujuan menganalisis hubungan antara temuan morfologi dan karakteristik KSH pada MRI dengan kadar serum AFP.Metode: Studi retrospektif ini dilakukan pada pasien KSH yang menjalani MRI abdomen multifase kontras spesifik hepatobilier dan kadar serum AFP di RSUPN dr. Cipto Mangunkusumo, serta belum menjalani prosedur pengobatan apapun. Dilakukan analisis menggunakan uji Chi Square atau uji Mutlak Fisher antara temuan morfologis dan karakteristik KSH pada MRI, serta menggunakan uji Mann-Whitney antara nilai rerata apparent diffusion coefficient (ADC) dengan kadar serum AFP.Hasil: Diperoleh 82 subyek dengan usia rerata subyek 58 tahun, diameter tumor >5cm (58,5%) dan tumor multipel (59,8%) paling banyak ditemukan, serta memiliki perbedaan proporsi yang bermakna dengan kadar serum AFP (nilai p = 0,030 dan p = 0,000). Vaskularisasi tumor, kapsul tumor, lemak intratumoral, tumor hiperintens T2, restriksi difusi, dan tumor hipointens fase hepatobilier lebih banyak ditemukan pada kadar serum AFP ≥ 100ng/mL, namun tidak ditemukan perbedaan proporsi bermakna. Terdapat perbedaan bermakna nilai rerata ADC antara 39 subyek dengan kadar serum AFP < 100ng/mL dan 43 subyek dengan AFP ³ 100ng/mL. Median nilai rerata ADC 1,19 (0,71 – 2,20) pada subyek dengan kadar serum AFP < 100ng/mL, median 0,97 (0,72 – 1,77) pada subyek dengan AFP ≥ 100ng/mL, dan nilai p = 0,003.Simpulan: Proporsi tumor berdiameter > 5cm dan tumor multipel pada subyek dengan AFP ≥ 100ng/mL secara bermakna lebih tinggi dibandingkan pada subyek dengan AFP < 100ng/mL. Nilai rerata ADC pada subyek dengan AFP ≥ 100ng/mL secara bermakna lebih rendah dibandingkan AFP < 100ng/mL. Sehingga nilai rerata ADC dapat membantu memprediksi kadar serum AFP pada pasien KSH.

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Background: Hepatocellular carcinoma (HCC) is one of the most common cancers and cancer-related death. Multiphase contrast-enhanced abdominal magnetic resonance imaging (MRI) is the modality of choice for the diagnosis of KSH, as it can depict pathophysiologic changes during hepatocarcinogenesis through sequences: dynamic contrast enhanced (DCE), T1-weighted imaging (T1WI) with chemical shift imaging, T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and hepatobiliary phase. Alpha fetoprotein (AFP) as a serological marker of HCC related to surveillance, diagnostics, and prognostics, also plays a role in hepatocarcinogenesis by showing differences in tumor aggressiveness. This study aims to analyze the relationship between morphological findings and characteristics of HCC on MRI with serum AFP levels.

Methods: This retrospective study was conducted on HCC patients who underwent hepatobiliary-specific contrast-enhanced multiphase abdominal MRI and serum AFP levels at Dr. Cipto Mangunkusumo Hospital, had not undergone any treatment procedures. Chi Square or Fisher's exact test between morphological findings and characteristics of HCC on MRI, and Mann-Whitney test between mean apparent diffusion coefficient (ADC) values and serum AFP levels were analyzed.

Results: There were 82 subjects with a mean age of 58 years, tumor size >5cm (58.5%) and multiple tumors (59.8%) were more common, had a significant difference in proportion with AFP serum levels (p value = 0.030 and p = 0.000). Tumor vascularization, tumor capsule, intratumoral fat, T2 hyperintense tumor, diffusion restriction, and hepatobiliary phase hypointense tumor were more common in serum AFP level ≥ 100ng/mL, but there was no significant difference in proportion. There was a significant difference in mean ADC between 39 subjects with serum AFP level < 100ng/mL and 43 subjects with AFP 100ng/mL. The median ADC score was 1.19 (0.71 – 2.20) in subjects with serum AFP level < 100ng/mL, median 0.97 (0.72 – 1.77) in subjects with AFP ≥ 100ng/mL, and p value is 0.003.

Conclusion: The proportion of tumors > 5cm in diameter and multiple tumors in subjects with AFP ≥ 100ng/mL was significantly higher than that in subjects with AFP < 100ng/mL. The mean value of ADC in subjects with AFP ≥ 100ng/mL was significantly lower than AFP < 100ng/mL. So that the mean value of ADC can help predict serum AFP levels in patients with HCC."

"Kanker hati adalah kondisi ketika sel-sel dalam hati tumbuh di luar kendali. Pada tahun 2020, kanker hati menempati urutan keempat kanker dengan jumlah kasus baru dan kematian tertinggi di Indonesia. Faktor risiko utama kanker hati adalah penyakit hati kronis. Tujuan penelitian ini adalah mengetahui risiko penyakit hati berkembang menjadi kanker hati pada peserta dengan dan tanpa penyakit hati di Indonesia tahun 2019-2021. Penelitian ini menggunakan Data Sampel BPJS Kesehatan tahun 2019-2021 dengan desain kohort retrospektif dan didapatkan jumlah sampel 824.592 terbobot. Analisis menggunakan uji Cox Proportional Hazard. Hasil penelitian menunjukan bahwa peserta dengan penyakit hati memiliki probabilitas dan risiko kanker hati yang lebih tinggi dibandingkan peserta yang tidak memiliki penyakit hati (CEP 1,61%; 95% CI 0,08% – 3,14%; AHR 98,5; 95% CI 40,6 – 239,4). Berdasarkan jenis dan jumlah penyakit hatinya, peserta dengan hepatitis kronis (AHR 153,9; 95% CI 32,3 – 690,7) dan menderita lebih dari 2 jenis penyakit hati (AHR 140,1; 95% CI 18,5 – 1061,7) memiliki risiko kanker hati paling tinggi dibandingkan kategori lainnya. Hasil studi menyimpulkan bahwa penderita penyakit hati, terutama hepatitis kronis, memiliki risiko sangat tinggi mengalami kanker hati. Untuk itu, perlu surveilans kanker hati secara nasional pada kelompok penduduk tersebut guna mencegah penyakit hati berkembang menjadi kanker hati.

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Liver cancer is condition characterized by uncontrolled growth of liver cells. In 2020, Liver cancer ranked fourth among new cancer cases and had highest mortality rate among cancers in Indonesia. The main risk factor for liver cancer is chronic liver disease. This study aimed to determine risk of liver disease progressing to liver cancer in participants with and without liver disease in Indonesia from 2019-2021. Retrospective cohort study was conducted using BPJS Kesehatan Sample Data from 2019-2021, with weighted sample size of 824,592. Cox Proportional Hazard analysis was performed. The results showed that participants with liver disease had higher probability and risk of liver cancer compared to those without liver disease (CEP 1.61%; 95% CI 0.08%–3.14%; AHR 98.5; 95% CI 40.6–239.4). Among different types and numbers of liver diseases, participants with chronic hepatitis (AHR 153.9; 95% CI 32.3–690.7) and those with more than two types of liver diseases (AHR 140.1; 95% CI 18.5–1061.7) had highest risk of liver cancer compared to others. The study concluded that patients with liver disease, particularly chronic hepatitis, have elevated risk of developing liver cancer. Therefore, national surveillance for liver cancer in this group is crucial to prevent progression of liver disease to liver cancer."

"Karsinoma hepatoselular memiliki prognosis yang buruk akibat keterbatasan terapi seperti terlambat diagnosis, kurangnya biomarker spesifik, dan ketidakpekaan terhadap agen tumor ini. Imunoterapi berbasis sel NK autologus dengan stimulasi eksosom menjadi modalitas pengembangan imunoterapi berbasis sel NK untuk pasien karsinoma hepatoseluler. Sel NK pasien karsinoma hepatoseluler diisolasi dari darah vena perifer dan eksosom diisolasi dari serum darah donor sehat. Karakterisasi eksosom dengan particle size analyzer dan flow cytometry. Stimulasi eksosom ke sel NK selama 24 jam kemudian evaluasi ekspresi reseptor NKp44, NKp46, NKp30, NKG2D, KIR2D, dan NKG2A serta ekspresi perforin dan granzyme B. Visualisasi interaksi sel NK dengan fraksi sel mononuklear lainnya (CD4, CD8, CD11c, dan CD19) dengan imunofluorens. Ukuran partikel < 100 nm, muatan listrik negatif dan CD63+CD81+ (positif ganda) hasil isolasi eksosom. Terjadi peningkatan ekspresi reseptor NKp44, NKp46, NKp30, NKG2D, penurunan ekspresi NKG2A, serta peningkatan ekspresi perforin dan granzyme B pada sel NK terinduksi eksosom. Tidak ada interaksi sel berupa sinapsis imun antara sel NK terstimulasi eksosom dengan fraksi sel mononuklear lain pasien karsinoma hepatoseluler. Stimulasi eksosom ke sel NK pasien karsinoma hepatoseluler memulihkan kemampuan sitotoksik sel NK.

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Hepatocellular carcinoma has a poor prognosis due to limitations of therapy such as late diagnosis, lack of specific biomarkers, and insensitivity to this tumor agent. Autologous NK cell-based immunotherapy with exosome stimulation is a modality for developing NK cell-based immunotherapy for hepatocellular carcinoma patients. NK cells from hepatocellular carcinoma patients were isolated from peripheral venous blood, and exosomes were isolated from the blood serum of healthy donors. Exosome characterization with a particle size analyzer and flow cytometry. Stimulation of exosomes on NK cells for 24 hours, then evaluation of expression of NKp44, NKp46, NKp30, NKG2D, KIR2D, and NKG2A receptors, as well as perforin and granzyme B expression. Visualization of interactions of NK cells with other mononuclear cell fractions (CD4, CD8, CD11c, and CD19) by immunofluorescence. Particle size < 100 nm, negative electric charge, and CD63+CD81+ (double positive) exosome isolated results. There was increased expression of receptors NKp44, NKp46, NKp30, NKG2D, decreased expression of NKG2A, and increased expression of perforin and granzyme B in exosome-induced NK cells. There was no cell interaction in the form of immune synapses between exosome-stimulated NK cells and other mononuclear cell fractions in hepatocellular carcinoma patients. Stimulation of exosomes into NK cells of hepatocellular carcinoma patients restores the cytotoxic ability of NK cells."