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"Latar belakang: Sebagian besar pasien karsinoma sel hati (KSH) tahap lanjut memiliki masalah vaskular seperti trombus tumoral vena porta. Terapi sistemik yang direkomendasikan cenderung mahal dan belum terjangkau oleh banyak pasien. Oleh karena itu, perlu mencari alternatif terapi, seperti transarterial chemoembolization (TACE). Di Indonesia, TACE telah menjadi pilihan terapi untuk pasien dengan trombus tumoral vena porta (TTVP) berdasarkan PNPK, tetapi belum ada penelitian yang mengkaji hubungan antara TTVP parsial pada KSH dan respons terapi sesuai mRECIST setelah TACE.Tujuan: Untuk menganalisa hubungan antara respons terapi secara mRECIST pasca TACE dengan ada tidaknya TTVP parsial pada pasien KSH.Metode: Selama periode Januari 2020 hingga Juli 2023 terdapat 36 pasien KSH diterapi TACE dan memiliki imaging sebelum serta sesudah tindakan. Respons terapi dievaluasi berdasarkan modified Response Evaluation Criteria in Solid Tumors (mRECIST).Hasil: Terdapat 36 pasien yang memenuhi kriteria inklusi dengan 27 pasien KSH tanpa TTVP dan 9 pasien KSH dengan TTVP parsial. Setelah TACE, 22% pasien dengan TTVP parsial masuk dalam kategori responder, sedangkan pada kelompok tanpa TTVP, 41% pasien termasuk dalam kategori responder, dengan nilai p = 0,438.Kesimpulan: Tidak terdapat perbedaan respons tumor yang bermakna antara kelompok subjek KSH dengan TTVP parsial dan kelompok tanpa TTVP. Meskipun proporsi non responder pada kelompok TTVP parsial lebih banyak dibandingkan kelompok tanpa TTVP, namun masih terdapat 22% yang menunjukkan respons subjektif sehingga TACE masih dapat dipertimbangkan sebagai terapi pada pasien KSH dengan TTVP.

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Background: Most advanced-stage hepatocellular carcinoma (HCC) patients face vascular complications such as portal vein tumor thrombus (PVTT). Recommended systemic therapies tend to be costly and often inaccessible to many patients. Therefore, alternative treatments, such as transarterial chemoembolization (TACE), need to be explored. In Indonesia, TACE has become a treatment option for patients with portal vein tumor thrombus (PVTT) based on national guidelines, but no studies have yet examined the relationship between partial PVTT in HCC and treatment response according to mRECIST.

Objective: : To analyze the relationship between post-TACE treatment response according to mRECIST and the presence of partial PVTT in HCC patients. Methods: From January 2020 to July 2023, 36 HCC patients underwent TACE and had pre- and post-procedure imaging. Treatment response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Results: Among the 36 included patients, 27 had HCC without partial PVTT, and 9 had HCC with partial PVTT. After TACE, 22% of patients with partial PVTT were classified as responders, while in the group without partial PVTT, 41% were responders, with a p-value of 0.438.

Conclusion: There was no significant difference in tumor response between the HCC patient groups with partial PVTT and those without. Despite a higher proportion of non-responders in the partial PVTT group, 22% still showed subjective response, suggesting that TACE may still be considered as a treatment option for HCC patients with partial PVTT."

"Latar Belakang: Karsinoma sel hati (KSH) adalah lesi neoplastik ganas pada hati tersering. Transformasi keganasan sel hati normal menjadi KSH melibatkan berbagai faktor seperti inflamasi dan perubahan genetik yang menyebabkan KSH menjadi sangat heterogen pada tingkat histologik dan molekular. Perbedaan fenotipe yang dipengaruhi berbagai perubahan molekular menghasilkan berbagai derajat diferensiasi, subtipe histologik dan gambaran klinik yang berbeda dan sebagian berhubungan dengan prognosis pada KSH. Mutasi pada gen TP53 yang berfungsi menontrol proliferasi sel melalui perbaikan DNA, apoptosis, dan penuaan sel terbukti sebagai salah satu perubahan molekular tersering pada KSH dan sering dikaitkan dengan beberapa faktor risiko, derajat diferensiasi, subtipe histologik tertentu dan prognosis. Penelitian ini bertujuan menginvestigasi ekspresi p53 pada derajat diferensiasi, subtipe histologik dan stadium patologi tumor KSH.Bahan dan cara: Penelitian dilakukan di Departemen Patologi Anatomik FKUI/RSCM, Jakarta terhadap 41 kasus KSH yang diperoleh seara reseksi. Sampel kasus diklasifikasikan berdasarkan kelompok derajat diferensiasi (WHO), subtipe histologik dan stadium patologi tumor. Selanjutnya dilakukan pulasan imunohistokimia (IHK) protein 53 (p53) pada seluruh kasus dan dilakukan analisis untuk mengetahui ekspresi p53 pada variabel penelitian.Hasil: Ekspresi p53 ditemukan pada 35 kasus (85%). Berdasarkan derajat diferensiasi, ekspresi p53 ditemukan paling banyak pada derajat diferensiasi sedang dan buruk, yaitu 21 dan 14 kasus (91% dan 93%). Ekspresi p53 berdasarkan stadium patologi tumor ditemukan paling banyak pada pT1b dan pT2, yaitu 8 dan 14 kasus ( 88% dan 93%). Berdasarkan subtipe histologik, seluruh kasus macrotrabecular massive (MTM) menunjukkan ekspresi p53 (4 kasus, 100%), subtipe clear cell (CC) terpulas pada 15 kasus (93%), klasik (CL) ditemukan 16 kasus (88%) dan tidak ditemukan ekspresi p53 pada seluruh kasus steatohepatitic (SH). Terdapat perbedaan rerata bermakna ekspresi p53 pada kelompok baik dan sedang (p=0,011), baik dan buruk (p=0,015) dan tidak terdapat perbedaan rerata bermakna antara kelompok sedang dan buruk (p=0,339). Tidak ditemukan perbedaan rerata bermakna ekspresi p53 pada seluruh kelompok stadium patologi tumor (p=0,948) dan subtipe histologik (p=0,076).Kesimpulan: Terdapat perbedaan bermakna ekspresi p53 pada KSH kelompok diferensiasi baik dan sedang serta baik dan buruk.

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Background: Hepatocellular cell carcinoma (HCC) is the most common malignant neoplastic lesion of the liver. Malignant transformation of hepatocytes involves various factors such as inflammation and genetic causing HCC to be very heterogeneous at the histological and molecular level. Differences in phenotypes affected by various molecular changes produce different differentiation grade, histological subtype, clinical features and prognosis. TP53 as one of the most common molecular changes in HCC play an important role in cycle cell by controlling cell proliferation through DNA repair, apoptosis and cellular senescence, associates with several risk factors such as certain differentiation grade, histologic subtypes, and prognosis. This current study aimed to investigate p53 expression at HCC’s differentiation grade, tumor pathology stage and histologic subtype.

Materials and methods: The study was conducted at the Department of Anatomical Pathology FKUI / RSCM, Jakarta on 41 cases of resected HCC. Case samples are classified based on groups of differentiation grade (WHO), histologic subtypes and tumour pathology stage. Furthermore immunohistochemical (IHC) staining of protein 53 (p53) carry out in all cases and an analysis statistic was performed to evaluated the expression of p53.

Results: p53 expression was found in 35 cases (85%). Based on the differentiation grade, the expression of p53 was found mostly in the moderate and poor differentiation (91%, 21 cases and 93%, 14 cases). Based on tumour pathology stage, p53 expression was found mostly in pT1b and pT2, which were 8 and 14 cases (88% and 93%). Based on histologic subtypes, all macrotrabecullar massive (MTM) cases showed p53 expression (4 cases, 100%), clear cell (CC) subtypes were in 15 cases (93%), classic (CL) 16 cases (88%) and negative expression was found in all cases of steatohepatitic (SH). There were significant differences in mean expression of p53 in the well and moderate groups (p = 0.011), well and poor (p = 0.015) and there were no significant mean differences between the moderate and poor groups (p = 0.339). There were no significant mean differences in p53 expression in all groups of tumour pathology stages (p = 0.948) and histologic subtypes (p = 0.076).

Conclusion: There is significant difference mean of p53 expression in well and moderate as well as well and poor differentiation."

"Latar belakang: Karsinoma sel hati (KSH) merupakan jenis keganasan primer hatitersering dengan gambaran histologik menunjukkan diferensiasi sel hepatoselular. Selaininsiden yang tinggi, beban yang berat dari keganasan ini adalah prognosis yang sangatburuk dengan angka rekurensi yang tinggi. Terdapat banyak faktor resiko secaraklinikopatologik yang telah diketahui mempengaruhi prognosis KSH, seperti kadar alfafetoprotein, derajat diferensiasi, dan invasi mikrovaskular. Secara molekular, mutasi p53dan β-catenin merupakan dua mutasi tersering dalam KSH. β-catenin merupakan proteinmultifungsi yang dikode oleh gen CTNNB1 yang dapat ditemukan pada 3 kompartemensel, yaitu di membran sel, sitoplasma dan inti. Jalur Wnt/β-catenin meregulasi prosesseluler yang terkait inisiasi, pertumbuhan, survival, migrasi, diferensiasi, dan apoptosis.Meski sudah banyak diketahui beberapa jalur patofisiologi molekularhepatokarsinogenesis, hubungan dengan aplikasi klinik membutuhkan pemahaman lebihmengenai hubungan sifat molekuler dan sifat fenotip tumor, terutama dalam penentuanfaktor prognosis dan pengembangan terapi target. Penelitian ini bertujuan untuk menilaiekspresi β-catenin pada KSH dan hubungannya dengan berbagai faktor prognosis yaituAFP, derajat diferensiasi dan invasi mikrovaskular.Bahan dan cara: Penelitian ini menggunakan desain potong lintang. Sampel terdiri atas35 kasus KSH yang sudah ditegakkan diagnosisnya berdasarkan pemeriksaanhistopatologik dan/atau imunohistokimia di RSCM dari Januari 2013 sampai September2019. Dilakukan pulasan β-catenin dan analisis statistik dengan uji komparatif terhadapberbagai karakteristik klinikopatologik dan faktor resiko berupa AFP, derajat diferensiasidan invasi mikrovaskular.Hasil: Terdapat perbedaan bermakna ekspresi β-catenin terhadap AFP (p=0,037) danderajat diferensiasi (p=0,043) pada KSH. Ekspresi β-catenin pada inti dengan/tanpasitoplasma lebih sering ditemukan pada kasus KSH dengan kadar AFP rendah dan derajatdiferensiasi baik-sedang. Tidak ditemukan perbedaan bermakna ekspresi β-cateninterhadap invasi mikrovaskular pada KSH (p=1,000).Kesimpulan: Terdapat perbedaan bermakna ekspresi β-catenin terhadap AFP dan derajatdiferensiasi pada KSH.

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Background: Hepatocellular carcinoma (HCC) is the most common primary livercancer, displaying histologically hepatocellular differentiation. In addition to its highincidence, the disease burden of HCC is due to its poor prognosis with high recurrencerate. Some of the previously known clinicopathologic prognostic factors of HCC includealpha-fetoprotein (AFP) level, tumor grade and microvascular invasion. At molecularlevel, p53 and β-catenin are the two most common driver mutations in HCC that aremutually exclusive. β-catenin is a multifunction protein that is encoded by CTNNB1 gen.It is found in 3 compartments of cells, which are membrane cell, cytoplasm and nucleus.Wnt/ β-catenin pathway regulates cellular process which is related to initiation, growth,survival, migration, differentiation and apoptosis. Although molecular pathogenesispathways of hepatocarcinogenesis are known, clinical application warrants moreunderstanding in terms of molecular characteristic and tumor phenotype, especially indetermining prognosis and target therapy development. This current study aims to analyzethe expression of β-catenin and its association with prognostic factors, such as AFP,tumor grade and microvascular invasion.Material and method: A cross-sectional study was conducted comprising 35 samples ofsurgically resected HCCs between January 2013 to September 2019 in CiptoMangunkusumo General Hospital. The cases were diagnosed based on histopathologicaland immunohistochemical findings and was then performed β-catenin staining. β-cateninexpression was analyzed with statistical tests to determine expression difference betweenAFP level, tumor grade and microvascular invasion.Result: There were statistically significant difference of β-catenin expression in AFPlevel and tumor grade (p=0.037 and 0.043, respectively). Nuclear with/withoutcytoplasmic expression of β-catenin was more frequently found in HCC with low AFPlevel and well-to-moderately differentiated tumors. No significant difference wasobserved in β-catenin expression between HCC with and without microvascular invasion(p=1.000).Conclusion: β-catenin expression was significantly different in AFP level and tumorgrade."

"Latar belakang dan tujuan: Karsinoma sel hati merupakan keganasan primer hati yang paling sering dan menempati urutan kelima sebagai kanker tersering di seluruh dunia. Meskipun faktor risiko karsinoma sel hati sudah diketahui, namun insidensnya tetap tinggi dengan angka kesintasan yang tetap rendah. Bedah merupakan terapi definitif untuk pasien karsinoma sel hati. Penelitian ini bertujuan untuk mengetahui angka kesintasan pascareseksi dan faktor-faktor yang memengaruhi.Metodologi: Penelitian ini merupakan suatu penelitian kohort dengan analisis kesintasan di Departemen Klinik Ilmu Bedah Fakultas Kedokteran Universitas Indonesia RSCM. Data diperoleh dari rekam medis pasien karsinoma sel hati di RSCM selama periode Januari 2010 hingga Desember 2020. Variabel bebas yang diteliti adalah jenis kelamin, jumlah lesi, ukuran tumor, invasi vaskular, kadar AFP, sirosis hati, skor Child-Pugh, derajat histopatologi. Uji chi-square dilakukan untuk mengetahui hubungan antara variabel bebas dan terikat.Analisis multivariat dilakukan dengan Cox Proportional Hazard Regeresion test. Metode Kaplan Meier digunakan untuk menentukan tingkat kesintasan.Hasil: Sebanyak 86 subjek dikumpulkan pada penelitian ini. Terdapat 17 subjek dieksklusi karena data penelitian yang tidak lengkap. Median usia keseluruhan subjek adalah 54 tahun (33-76). Tingkat kematian subjek secara keseluruhan adalah 62,3%. Kesintasan subjek 6 bulan, 1 tahun, dan 3 tahun masing-masing adalah 66,6%; 56,5%; dan 37,6%. Pada penelitian ini tidak didapatkan satupun faktor risiko yang berhubungan dengan kesintasan.Kesimpulan: Dari hasil penelitian ini belum didapatkan faktor-faktor risiko yang signifikan memengaruhi kesintasan pasien karsinoma sel hati pascareseksi,.Perlu dilakukan penelitian dengan jumlah subjek lebih besar agar dapat diketahui faktor-faktor apa saja yang memengaruhi kesintasan pada pasien karsinoma sel hati pascareseksi.

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carcinoma is the most common primary liver cancer and the fifth most common cancer in the world. Despite the risk factors of hepatocellular carcinoma have been identified, its incidence is still high and survival rate is still low. Surgery is thought to be a definitive treatment for hepatocellular carcinoma patients. This research focuses on postresection survival rate and its associated factors.

Method: This cohort retrospective data study was conducted at DR Cipto Mangunkusumo National General Hospital between January 2010 and December 2020. Information about sex, number of tumor, tumor size, vascular invasion, Alpha fetoprotein level, hepatic cirrhosis, Child-Pugh Score, and histopathologic stage were collected from medical record. Chi square analysis was done to investigate relationship between independent variables and dependent variable. Multivariate analysis was performed by using Cox Proportional Hazard Regression test. Kaplan Meier method was used to calculate survival rate.

Result: A total of 86 subjects were recruited in this study, 17 subjects were excluded due to incomplete medical record. The median age of subjects in this study was 54 years old (33-76). The overall mortality in this study was 62.3%. Six months, 1 year, and 3 years survival rate were 66.6%; 56;5%; and 37.6% respectively. Our study showed that none of the factors analyzed associated with survival rate.

Conclusion: We had not found any risk factors which associated with survival of patients with hepatocellular carcinoma. We suggest future research with larger number of subjects to identify any factors associated with survival of hepatocellular carcinoma subjects following resection."

"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."

"Pendahuluan: Efikasi neoadjuvan kemoembolisasi transarterial (N-TACE) pada karsinoma hepatoseluler (KSH) yang dapat direseksi masih diperdebatkan. Meskipun N-TACE dapat mengurangi ukuran tumor, dampaknya terhadap luaran jangka panjang masih belum dapat disimpulkan.Metode: Meta-analisis ini meninjau studi terkait N-TACE vs. Reseksi Hati (RH) pada karsinoma sel hati soliter besar (KSHSB) hingga Maret 2023 dari empat database online.Hasil: 5 penelitian dengan total sampel 1556 pasien (N-TACE = 474; LR = 1082) dilakukan analisis. Dari hasil analisis, tidak ada perbedaan signifikan antara kelompok N-TACE dan RH yang diamati pada KS dan KBT 1, 3, atau 5 tahun. Odds Ratio yang didapatkan adalah 0,91 (95% CI 0,54 – 1,54), 0,80 (95% CI 0,56 – 1,15), dan 0,88 (95%CI 0,47 – 1,65) untuk KS 1, 3, dan 5 tahun dan 0,66 ( 95% CI 0,32 – 1,34), 0,70 (95% CI 0,37 – 1,33), dan 0,75 (95% CI 0,28 – 1,98) masing- masing untuk KBT 1, 3, dan 5 tahun. Tidak ada perbedaan signifikan yang diamati pada kehilangan darah intraoperatif antar kelompok. Analisis subgroup menunjukkan KS 1, 3, dan 5 tahun yang mengarah ke N-TACE pada kombinasi kemoterapi dan KS 1 tahun yang lebih baik pada kelompok RH di kemoterapi agen tunggal. Selain itu, KBT 5 tahun lebih mengarah pada RH di kelompok agen kemoterapi tunggal (OR 2,82 95% CI 1,18 – 6,72) dan N-TACE pada kelompok kombinasi (OR 0,75 95%CI 0,28 – 1,98).Kesimpulan: Pengelolaan KSHSB memerlukan pertimbangan yang rumit dan diperlukan peningkatan strategi pengobatan untuk subkelompok HCC yang ini. Pengaruh N-TACE terhadap kelangsungan hidup jangka panjang dan kehilangan darah intraoperatif pada KSHSB memiliki hasil tidak signifikan. Namun, kombinasi kemoterapi pada N-TACE memberikan hasil yang lebih baik terhadap kesintasan pasien KSHSB.

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Introduction: The efficacy of neoadjuvant transarterial chemoembolization (N- TACE) in resectable hepatocellular carcinoma (HCC) remains debated. While N- TACE may reduce tumor size, its impact on long-term outcomes is inconclusive. Methods: This meta-analysis reviewed studies on N-TACE before surgical resection vs. LR SLHCC up to March 2023 from four online databases.

Results: 5 studies with 1556 patients (N-TACE = 474; LR = 1082) were analyzed. No significant differences between N-TACE and LR groups were observed in 1-, 3-, or 5-year OS and DFS. The pooled HRs were 0.91 (95% CI 0.54 – 1.54), 0.80 (95% CI 0.56 – 1.15), and 0.88 (95%CI 0.47 – 1.65) for the 1-, 3-, and 5-year OS and 0.66 (95% CI 0.32 – 1.34), 0.70 (95% CI 0.37 – 1.33), and 0.75 (95% CI 0.28 – 1.98) for 1-, 3-, and 5-year DFS respectively. No significant differences were observed in intraoperative blood loss between groups as well. Subgroup analysis showed favorable 1-, 3-, and 5-year OS with combination chemotherapy N-TACE (combination group) and better 1-year OS in the LR group with single-agent chemotherapy N-TACE (single-agent group). In addition, 5-year DFS favored LR in the single-agent group (OR 2.82 95% CI 1.18 – 6.72) and N-TACE in the combination group (OR 0.75 95%CI 0.28 – 1.98).

Conclusion: Managing SLHCC requires intricate considerations and enhancement of treatment strategies for this challenging subgroup of HCC is needed. The influence of N-TACE on long-term survival and intraoperative blood loss in SLHCC appears limited. However, combination chemotherapy in N-TACE results in better outcomes."

"Cranical metastasic from hepatocellular carcinoma (HCC) prior to diagnosis of the primary tumor without liver dysfunction is a very rare event. Cranial metastatic may be the sole initial presentation of HCC. Early diagnosis is essential in order to treat the primary disease. Cranial metastasis from HCC should be considered in the differential diagnosis in patients with subcutaneous scalp mass and osteolytic defects on X-Ray. A 55 year old female patient without known liver disease, presented with a palpable right occipital scalp mass. On head computed tomography (CT) scan, a tumor on right orbita wall, osteolytic skull and invasion to the right frontal lobe was observed. The histological diagnosis obtained from the biopsy was a poorly differentiated cranial metastasis adenocarcinoma that was difficult to determine the origin. On positron emission tomography (PET) scan, there was a hypermetabolic mass around intra hepatal bile duct which suspicious primary cancer. The histological diagnosis obtained from the liver biopsy was appropriate with HCC grade II. The metastatic tumor was removed via occipital craniectomy. She received a palliative course of external beam radiation therapy to he right orbit. Them, she received symptomatic treatment and herbal medicine with cassava leaves for the last three months. Evaluation of bone survey shows lytic lesion at calvaria and compression fracture at vertebrae thoracal 11-12 appropriate with metastasis process. According to Barcelona clinic liver cancer (BCLC) criteria she suffered from HCC terminal stage D with average survival of about 4 months. "

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Tujuan: Penelitian ini membandingkan efikasi dan keamanan radioterapi tubuh stereotaktik (SBRT) dengan atau tanpa kemoembolisasi transarterial (TACE) untuk pasien dengan karsinoma hepatoselular (KHS) stadium BCLC B dan C yang tidak memenuhi syarat untuk reseksi atau ablasi. Metode: Dari Januari 2016 hingga Maret 2019, sebanyak 33 pasien KHS dengan stadium BCLC B dan C, menjalani SBRT+TACE (n = 22) atau SBRT saja (n=11) di RSUPN Dr.Cipto Mangunkusumo. Kesintasan hidup keseluruhan (OS), kesintasan hidup bebas progresifitas (PFS), kontrol lokal (LC), dan toksisitas, dianalisis secara retrospektif. Hasil: Usia rerata adalah 56,5 tahun, dengan mayoritas pasien datang dengan CTP A (81,8%), BCLC stadium B (60,6%). Sebagian besar pasien memiliki tumor dengan PVT (75,8%), ukuran tumor >10 cm (66,7%), dengan rerata diameter terbesar 12,3 cm. Dosis radiasi bervariasi antara 27,5-50 Gy dalam 4-10 fraksi, dengan median EQD2 48 (35-, 5-72) Gy dan median BED10 57,6 Gy (42,6-86,4) Gy. Waktu follow-up rerata adalah 41 minggu untuk semua pasien. Pasien yang diterapi dengan SBRT+TACE menunjukkan peningkatan OS yang signifikan (46 bulan vs 23 bulan, p=0,008). Tingkat OS 1, 2, dan 3 tahun adalah 51%, 37%, dan 27% untuk kelompok SBRT+TACE; dan 18%, 9%, dan 0% untuk kelompok SBRT, masing-masing (p=0,008). Tingkat PFS 1, 2, dan 3 tahun adalah 31%, 19%, dan 13% untuk kelompok SBRT+TACE; dan 10%, 10%, dan 0% untuk kelompok SBRT, masing-masing (p=0,114). Tingkat LC 3, 6, dan 12 bulan adalah 88,9%, 92,9%, dan 75%. Tidak ada perbedaan toksisitas akut dan lanjut antara dua kelompok. Kesimpulan: Kombinasi SBRT+TACE menunjukkan tingkat OS yang lebih baik daripada SBRT saja pada pasien dengan KHS BCLC Stadium B dan C.

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Purpose: This study compared the efficacy and safety of stereotactic body radiation therapy (SBRT) with or without transcatheter arterial chemoembolization (TACE) for patients with BCLC stage B and C hepatocellular carcinoma (HCC) who were ineligible for resection or ablation therapies. Methods and materials: From January 2016 to March 2019, 33 patients with BCLC stage B and C HCC, underwent either SBRT+TACE (n = 22) or SBRT only (n =11) in RSUPN Dr.Cipto Mangunkusumo. The overall survival (OS), progression free survival (PFS), local control (LC), and toxicities were analyzed retrospectively. Results: The mean age was 56.5 years, with the majority of patients presenting with CTP A (81.8%), BCLC stage B (60.6%). Most patients had tumor with PVT (75.8%), tumor size >10 cm (66.7%), with the mean of largest diameter of tumor was 12.3 cm. The radiation dose varies between 27.5-50 Gy in 4-10 fractions, with a median of EQD2 is 48 (35-, 5-72) Gy and a median of BED10 is 57.6 Gy (42.6-86.4) Gy. The median follow-up time was 41 weeks for all patients. Patients treated with SBRT+TACE showed significantly improved OS (46.0 months vs. 23 months, p = 0.008).  The 1-, 2-, and 3-year OS was 51%, 37%, and 27% for the SBRT+TACE group; and 18%, 9%, and  0% for the SBRT group, respectively (p=0,008). The 1-, 2-, and 3-year PFS was 31%, 19%, and 13% for the SBRT+TACE group; and 10%, 10%, and  0% for the SBRT group, respectively (p=0,114). The 3, 6, and 12 month LC was 88,9%, 92,9%, dan 75%. However, there was no difference in acute and late toxicities between two groups. Conclusions: SBRT+TACE had better OS rates than SBRT only in patients with BCLC stage B and C HCC.

 

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"Latar belakang: kanker nasofaring (KNF) adalah keganasan yang umum dijumpai pada nasofaring. Cukup banyak bukti menunjukkan adanya keterkaitan KNF dengan sistem kekebalan tubuh. Tidak semua subset sel T merupakan sel T efektor. Sel T regulator (TReg) yang merupakan salah satu subset dari sel T, memiliki peran penting dalam mengatur imunitas anti tumor. Sampai saat ini belum dapat disimpulkan bahwa keberadaan sel TReg pada lokasi tumor pasti akan memicu pertumbuhan tumor. Akan tetapi, adanya sel T CD4+ dan CD8+ tentunya berpengaruh terhadap kontrol perkembangan tumor. Studi ini bertujuan untuk menilai karakterisitik CD4, CD8 dan FOXP3 pada pasien KNF dan hubungannya terhadap agresivitas tumor.Metode: penelitian ini merupakan studi kohort prospektif. Sel TReg dinilai menggunakan marker FOXP3. Jumlah protein CD4, CD8 dan FOXP3 pada jaringan biopsi tumor dideteksi dan diukur dengan ELISA. Volume tumor primer dan volume total metastasis kelenjar getah bening regional didapatkan dari proses delineasi dengan pencitraan 3D. Spearmen-rho test digunakan untuk menilai korelasi antara CD4, CD8 dan FOXP3 dengan volume tumor primer dan volume total metastasis kelenjar getah bening regional.Hasil: Sebanyak 23 subjek penelitian (14 pria dan 9 wanita) terkumpul berdasarkan kriteria inklusi dan eksklusi. Stadium KNF terbanyak pada studi ini adalah stadium IV (AJCC edisi ke-8). Analisis dengan uji Spearman menunjukkan korelasi kuat antara konsentrasi protein FOXP3 dan volume tumor primer (p=0.02, r=0.60), dan juga antara konsentrasi protein CD8 dan volume tumor primer (p=0.00, r=0.81). Menariknya, juga ditemukan korelasi antara konsentrasi CD8 dan FOXP3 (p=0.00, r=0.85). Tidak ditemukan korelasi antara konsentrasi protein CD4, CD8 dan FOXP3 dengan volume total metastasis kelenjar getah bening regional. Tidak ditemukan juga korelasi antara konsentrasi FOXP3 dan stadium KNF. Sayangnya, belum dapat disimpulkan hubungan antara konsentrasi FOXP3 dan respons terapi pada penelitian ini.Kesimpulan: Keberadaan sel TReg berpengaruh terhadap agresivitias lokal tumor yang ditandai dengan peningkatan volume massa tumor primer. Korelasi antar konsentrasi CD4, CD8 dan FOXP3 memberikan gambaran interaksi dan mekanisme respons imunitas tubuh dalam menjaga keseimbangan antara sel T efektor dan sel T regulator.

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Background: nasopharyngeal cancer (NPC) is a common malignancy found in the nasopharynx area. There is quite a lot of evidence showing a link between NPC and the immune system. Regulatory T cells (TReg), a subset of T cells, have an essential role in regulating anti-tumor immunity. It has not been confirmed that TReg cells at the tumor site will trigger tumor growth. However, the presence of CD4+ and CD8+ T cells certainly affects the control of tumor growth. This study aims to assess the characteristics of CD4, CD8, and FOXP3 in NPC patients and their relationship with tumor aggressiveness.

Methods: a prospective cohort study was conducted on 23 subjects (14 men and 9 women) based on the inclusion and exclusion criteria. TReg cells were assessed using the FOXP3 marker. The number of CD4, CD8, and FOXP3 proteins in tumor biopsy tissue was detected and measured by ELISA kit (MBS2702975, MBS165145, MBS162054). The volume of the primary tumor and the total volume of regional lymph node metastases were obtained from the delineation process based on 3D imaging. Spearmen-rho test was used to assess the correlation of CD4, CD8, and FOXP3 with primary tumor volume and total volume of regional lymph node metastases.

Results: A total of 23 study subjects (14 men and 9 women) were collected based on the inclusion and exclusion criteria. The most common NPC stage in this study was stage IV (AJCC 8th edition). Analysis by the Spearman-rho test showed a strong correlation between; concentration of FOXP3 protein and primary tumor volume (p=0.02, r=0.60) and the concentration of CD8 protein and primary tumor volume (p=0.00, r=0.81). Interestingly, a correlation was also found between the concentration of CD8 protein and FOXP3 (p=0.00, r=0.85). There was no correlation between CD4, CD8, and FOXP3 proteins and the total volume of regional lymph node metastases. There was also no correlation between FOXP3 concentration and NPC stage. Unfortunately, it is impossible to conclude the relationship between FOXP3 concentration and treatment response in this study.

Conclusions: the presence of TReg cells affects the local aggressiveness of the tumor, which is characterized by an increase in the volume of the primary tumor. The correlation between CD4, CD8, and FOXP3 concentrations provides an overview of the interactions and mechanisms of the body's immune response to maintain a balance between effector T cells and regulatory T cells."

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Peran Th17 dalam keganasan, khususnya karsinoma sel hati, masih menjadi perdebatan. Sel Th17, sel penghasil IL-17, dilaporkan berhubungan dengan efek protumor dan antitumor sekaligus. Di lain sisi, sel Th1 yang menyekresikan IFN-γ memiliki sifat antitumor. Kemoembolisasi transarterial / transarterial chemo-embolization (TACE) diketahui dapat menyebabkan nekrosis tumor, namun peran TACE dalam memengaruhi sel Th17, Th1, IL-17, IFN-γ, dan rasio neutrofil limfosit (RNL) masih belum diketahui. Penelitian ini bertujuan untuk menentukan perubahan Th17, Th1, IL-17, IFN-γ, dan nilai RNL pada pasien KSH yang menjalani TACE.

Penelitian ini dilakukan sepanjang Juni 2015–Januari 2019 di RSCM dan beberapa rumah sakit jejaring di Jakarta. Desain potong lintang digunakan untuk membandingkan respons imun pasien KSH dengan sirosis hati. Desain kohort prospektif diterapkan untuk menilai hubungan respons imun dengan keberhasilan TACE. Pengambilan darah dilakukan sebelum dan 30 hari setelah tindakan TACE pada pasien KSH dan satu kali pada pasien sirosis. Nilai Th17 dan Th1 dianalisis menggunakan teknik flowcytometry, sedangkan nilai IL-17 dan IFN-γ diukur dengan teknik enzyme-linked immunosorbent assay (ELISA). Nilai RNL dihitung dari pembagian kadar neutrofil dengan limfosit yang diperoleh dari pemeriksaan hitung jenis. Respons terhadap TACE dievaluasi berdasarkan kriteria mRECIST.

Sebanyak 40 pasien sirosis dan 41 pasien KSH berpartisipasi dalam penelitian ini. Sebanyak 12 pasien dan 29 pasien termasuk ke dalam kelompok respons dan nonrespons, secara berurutan. Penurunan kadar AFP dan ukuran tumor secara bermakna ditemukan pada kelompok respons. Pada kelompok ini, juga ditemukan peningkatan bermakna kadar Th1, Th17, dan sel T CD4+/IFN-γ+/IL-17+ setelah TACE. Nilai IL-17, IFN-γ, dan RNL tidak berhubungan dengan respons TACE. Di samping itu, didapatkan peningkatan bermakna kadar CD4+/IFN-γ+/IL-17- pada kelompok nonrespons.

Simpulan: Peningkatan kadar Th1 dan Th17 dalam darah perifer yang diiringi dengan peningkatan sel T CD4+/IFN-γ+/IL-17+ didapatkan pada pasien KSH yang berespons baik terhadap TACE.

 

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The role of Th17 cells in malignancy, especially hepatocellular carcinoma, remains controversial. Th17 cells, IL-17 producing cells, were reported to be associated with both protumor and antitumor effects. On the other hand, Th1 cells, IFN-γ producing cells, had antitumor properties. Transarterial chemoembolization (TACE) is known for its potency to cause tumor necrosis, but its impact on Th17, Th1, IL-17, IFN-γ, and neutrophil-to-lymphocyte ratio (NLR) is still unclear. This study aims to determine the changes in Th17, Th1, IL-17, IFN-γ, and NLR levels in HCC patients treated with TACE.

This study was conducted from June 2015 to January 2019 at Cipto Mangunkusumo National General Hospital dan several affiliated hospitals in Jakarta. A cross-sectional study design was used to compare the immune response between HCC and liver cirrhotic patients. A prospective cohort study design was applied to assess the relationship between immune response and tumor response to TACE. Plasma sampling was obtained from HCC and cirrhotic patients that fulfilled the inclusion and exclusion criteria. Blood samples were collected immediately before and 30 days after TACE. Th17 and Th1 levels were measured using flowcytometry technique, while IL-17 and IFN-γ levels were quantified by using enzyme-linked immunosorbent assay (ELISA). The value of NLR was calculated by dividing the neutrophil count by the lymphocyte count. Responses to TACE were evaluated based on mRECIST.

A total of 40 cirrhotic and 41 HCC patients participated in this study. As many as 12 and 29 patients were included in the response and nonresponse group, respectively. In the response group, there were significant reduction of AFP levels and tumor size, as well as significant increase of Th1, Th17 and CD4+/IFN-γ+/IL-17+ T cells levels after TACE. Furthermore, there was an increase of CD4+/IFN-γ+/IL-17- levels in the non-response group. The values of IL-17, IFN-γ, and NLR were not related to TACE response.

Conclusion: Patients with good response to TACE had increased levels of circulating Th1, Th17, and CD4+/IFN-γ+/IL-17+ T cells.

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