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Abstrak :
ABSTRAK
Latar belakang : Insiden Adenokarsinoma di RSCM meningkat pada periode 2001-2006 dibanding periode sebelumnya 1995-2000 . Banyak penderita yang resisten terhadap pengobaan hormonal. Resistensi ini diduga akibat sel tumor mengalami transformasi Neuroendokrin. Akan dilakukan penelitian untuk melihat ekspresi Androgen Receptor AR dan Chromogranin A CgA pada adenokarsinoma prostat di RSCM tahun 2011-2015.Tujuan : Membuktikan korelasi ekspresi AR dan CgA dengan derajat keganasan.Metode : Studi potong lintang analitik terhadap 70 kasus adenokarsinoma prostat di departemen PA FKUI/RSCM tahun 2011-2015. Kasus dipulas imunohistokimia AR dan Cg A serta dilakukan interpretasi hasil. AR dinilai prosentase positivitasnya pada inti epitel dan stromal. CgA dinilai prosentase positivitasnya pada sitoplasma. Uji korelasi dilakukan untuk melihat kemaknaan dan kekuatan korelasi antar variabel terikat.Hasil : Karakteristik sampel usia 47,1 >70 tahun; diferensiasi histopatologik/skor gleason 42,9 buruk/>7, grade group 28,6 grade5 dan PSA 64,3 dalam rentang 11-100ng/ml. Ekspresi CgA berkorelasi negatif lemah dengan ekspresi AR epitel r=-0,288;p=0,016 . Ekspresi CgA tidak berkorelasi dengan ekspresi AR stromal p=0,886 . Terdapat hubungan bermakna ekspresi AR epitel dengan grade group p=0,003 . Tidak terdapat hubungan bermakna ekspresi AR epitel dengan usia, diferensiasi histopatologik/skor gleason dan PSA. Ekspresi CgA berhubungan bermakna dengan diferensiasi histopatologik/skor gleason dan grade group p=0,018;p=0,038 . Tidak terdapat hubungan bermakna ekspresi CgA dengan usia dan PSA. Ekspresi AR stromal tidak berhubungan bermakna dengan usia, diferensiasi histopatologik, grade group, skor gleason, maupun PSA.Kesimpulan : Terdapat korelasi yang lemah antara AR dan CgA sehingga pulasan AR dan CgA dapat dipakai untuk pemilihan terapi.

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ABSTRACT
Background Prevalence of prostate adenocarcinoma doubled in 2001 2006 compared to 1995 2000 in RSCM. Many patients resistant to hormonal treatment. This resistance is thought to be due to tumor cells undergoing neuroendocrine transformation. Study will be conducted to analyze the expression of Androgen Receptor AR and Chromogranin A CgA in prostate adenocarcinoma at RSCM in 2011 2015. Objective To prove correlation of expression of AR and CgA with degree of malignancy. Methods A cross sectional study was carried out on 70 cases of prostate adenocarcinoma in department of Anatomic Pathology FKUI RSCM from 2011 2015. AR expressed in stromal and epithelial nuclei, CgA expressed in cytoplasm. Statistical tests used to discover significance and correlation between the dependent variables. Results Most samples are more than 70 years old 47,1 , has poor histologic gleason score 42.9 , are in clinical grade 5 28.6 , and has PSA score range between 11 100 ng ml. CgA expression negatively correlates to epithelial AR expression r 0,288 p 0.016 , while no correlation are found between CgA expression and stromal AR expression p 0.886 . There is significant difference between epithelial AR expression with grade group p 0.003 , but not with age, histopathologic differentiation Gleason score and PSA. There are significant difference between CgA expression and histopathologic differentiation grade group and Gleason score p 0.018 p 0.038 , but not with age and PSA. No significant difference observed between stromal AR expression with age, histopathologic differentiation gleason score, grade group or PSA. Conclusion There rsquo s a weak correlation between AR and CgA so that AR and CgA expression can be used for the selection of therapy.

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CA 19-9 merefleksikan derajat keparahan adenokarsinoma kaput pankreas ditunjukkan oleh beberapa studi berhasil menemukan korelasi peningkatan CA 19-9 dengan resektabilitas adenokarsinoma kaput pankreas. Penelitian ini bertujuan melakukan evaluasi hubungan dan nilai diagnostik CA 19-9 dalam memprediksi resektabilitas adenokarsinoma kaput pankreas. Penelitian dilakukan secara potong lintang mengambil data dari rekam medis Rumah Sakit dr. Cipto Mangunkusumo tahun 2016–2019. Pasien terdiagnosis adenokarsinoma kaput pankreas secara histopatologis atau pencitraan abdomen, berusia ≤65 tahun, dan memiliki catatan pemeriksaan kadar CA 19-9 diikutsertakan dalam penelitian ini. Selain kadar CA 19-9, peneliti juga menilai factor terkait operabilitas. Tercatat 54 subjek dengan rerata usia 53,78±11,13 tahun. Ditemukan adanya korelasi positif (0,850) dan signifikan antara tingginya kadar CA 19-9 dengan resektabilitas tumor kaput pankreas. Untuk operabilitas, ditemukan perbedaan bermakna kadar CA 19-9, albumin, dan skor Karnofsky pada kelompok pasien tumor kaput pankreas resectable dan unresectable. Titik potong kadar CA 19-9 tercatat sebesar 140,65 U/mL, dengan sensitivitas sebesar 82,76% (64,23%–94,15%), spesifisitas sebesar 72,00% (50,61%–87,93%), dan AUC sebesar 0,784. CA 19-9 berhubungan secara signifikan dengan resektabilitas tumor kaput pankreas. CA 19-9 memiliki nilai diagnostik yang baik dalam mempredisksi resektabilitas tumor ini. ......CA 19-9 reflects the degree of severity of pancreatic head adenocarcinoma shown by several studies to find a correlation of elevated CA 19-9 with resectability of pancreatic head adenocarcinoma. This study aimed to evaluate the relationship and diagnostic value of CA 19-9 in predicting resectability of pancreatic head adenocarcinoma. The study was conducted in a cross-sectional manner, taking data from the medical records of dr. Cipto Mangunkusumo 2016–2019. Patients diagnosed with adenocarcinoma of the head of the pancreas by histopathologic or abdominal imaging, aged ≤65 years, and who had a record CA level of 19-9 were included in this study. In addition to CA levels of 19-9, the investigators also assessed operability-related factors. There were 54 subjects with a mean age of 53.78 ± 11.13 years. Found a positive correlation (0, 850) and significant between high levels of CA 19-9 with resectability of head tumors of the pancreas. For operability, there were significant differences in CA 19-9 levels, albumin, and Karnofsky scores in the resectable and unresectable group of pancreatic head tumors. The cut-off point for CA 19-9 levels was recorded at 140.65 U / mL, with a sensitivity of 82.76% (64.23% -94.15%), a specificity of 72.00% (50.61% -87.93 %), and AUC of 0.784. CA 19-9 was significantly associated with pancreatic head tumor resectability. CA 19-9 has a good diagnostic value in predicting the resectability of these tumors. The cut-off point for CA 19-9 levels was 140.65 U / mL, with a sensitivity of 82.76% (64.23% -94.15%), a specificity of 72.00% (50.61% -87.93 %), and AUC of 0.784. CA 19-9 was significantly associated with pancreatic head tumor resectability. CA 19-9 has a good diagnostic value in predicting the resectability of these tumors. The cut-off point for CA 19-9 levels was 140.65 U / mL, with a sensitivity of 82.76% (64.23% -94.15%), a specificity of 72.00% (50.61% -87.93 %), and AUC of 0.784. CA 19-9 was significantly associated with pancreatic head tumor resectability. CA 19-9 has a good diagnostic value in predicting the resectability of these tumors

Abstrak :
Latar Belakang: Adenokarsinoma duktal pankreas dan adenokarsinoma ampula vateri, tanpa melihat gambaran episentrum tumor, sulit dibedakan secara histopatologi. Gejala klinis tidak spesifik sehingga kasus yang ditemukan seringkali tidak memenuhi kriteria resectable. Gambaran radiologi juga tidak spesifik, padahal terapi dan prognosis keduanya berbeda. Adenokarsinoma duktal pankreas memiliki angka kesintasan rendah dibanding adenokarsinoma ampula vateri. Penentuan asal tumor, berasal dari duktal pankreas atau ampula vateri, sangat penting. SMAD4 diduga dapat menjadi salah satu panel diagnostik imunohistokimia. Penelitian ini dilakukan dengan melihat perbandingan ekspresi SMAD4 di adenokarsinoma ampula vateri dan adenokarsinoma duktal pankreas. Tujuan: Mengetahui perbandingan ekspresi SMAD4 pada adenokarsinoma duktal pankreas dan adenokarsinoma ampula vateri. Metode: Penelitian analitik observasional, desain potong lintang pada sediaan reseksi adenokarsinoma duktal pankreas dan adenokarsinoma ampula vateri, periode Januari 2013 hingga September 2021. Pengambilan sampel dilakukan secara total sampling. Adenokasinoma ampula vateri dengan subtipe pankreatobiliar dieksklusi. Pemeriksaan imunohistokimia menggunakan antibodi primer SMAD4. Data imunohistokimia dianalisis untuk melihat adakah perbedaan ekspresi SMAD4 pada adenokarsinoma di ampula vateri dan adenokarsinoma duktal pankreas. Hasil: Loss of SMAD4 didapatkan pada 12 kasus (60 %) adenokarsinoma duktal pankreas dan 8 kasus (44,4 %) adenokarsinoma ampula vateri. Tidak didapatkan hubungan loss of SMAD4 pada adenokarsinoma duktal pankreas dan adenokarsinoma ampula vateri (p=0,338). Kesimpulan: Tidak terdapat hubungan bermakna loss of SMAD4 pada adenokarsinoma duktal pankreas dan adenokarsinoma ampula vateri. Namun terdapat trend loss of SMAD4 lebih tinggi pada adenokarsinoma duktal pankreas dibanding adenokarsinoma ampula vateri subtipe intestinal dan mixed type dominansi intestinal. ......ackground: Differentiating pancreatic ductal adenocarcinoma and ampullary adenocarcinoma without knowing the epicenter of the tumor is difficult. The clinical symptoms are non-specific. The cases found usually do not meet the operable criteria. Radiological examination is also non-specific, although the treatment and prognosis are different. Pancreatic ductal adenocarcinoma has lower survival rate than ampullary adenocarcinoma. It is very important to determine the origin of the tumor from pancreatic ductal or ampulla of Vater. SMAD4 is expected to be one of immunohistochemical diagnostic panel for the pancreatic ductal adenocarcinoma. This study compares the SMAD4 expression in pancreatic ductal adenocarcinoma and ampullary adenocarcinoma. Objective: Knowing the comparison of SMAD4 expression in pancreatic ductal adenocarcinoma and ampullary adenocarcinoma. Methods: Observational analytical study with cross sectional design, total sampling was performed on the resection specimens of pancreatic ductal adenocarcinoma and ampullary adenocarcinoma, period January 2013 to December 2021. Ampullary adenocarcinoma with pancreatobilliary subtype was excluded. Immunohistochemical examination using SMAD4 primary antibody. Immunohistochemical data will be analyzed to see SMAD4 expression difference between pancreatic ductal adenocarcinoma and ampullary adenocarcinoma. Results: Loss of SMAD4 was found in 12 cases (66,7 %) of pancreatic ductal adenocarcinoma and 6 cases (44,4 %) of ampullary adenocarcinoma. There was no significant relationship between loss of SMAD4 in pancreatic ductal adenocarcinoma and ampullary adenocarcinoma (p=0,338). Conclusions: There was no significant relationship between loss of SMAD4 in pancreatic ductal adenocarcinoma and adenocarcinoma of the ampulla of vater. However, there was a trend of higher SMAD4 loss in pancreatic ductal adenocarcinoma than ampullary vater adenocarcinoma of intestinal subtype and mixed type with intestinal dominance.

Abstrak :
Latar Belakang: Berdasarkan fitur radiologisnya seperti ukuran, lokasi, tepi nodul, serta adanya kavitas dan air bronchogram intratumoral, CT scan dapat membantu membedakan antara adenokarsinoma (AK) dan karsinoma sel skuamosa (KSS). CT scan merupakan modalitas non invasif. Tujuan: Mengetahui gambaran radiologi pada subtipe AK dan KSS paru menggunakan CT toraks sebagai alat bantu dalam mendiagnosis karsinoma paru. Metode: Dilakukan evaluasi CT scan berupa lokasi, kavitas dan airbronchogram intratumoral, tepi tumor dan densitas tumor pada 31 subjek AK dan 16 subjek KSS yang memenuhi kriteria penelitian. Analisis bivariat dilakukan dengan uji Chi Square atau Fisher. Analisis multivariat dilakukan dengan analisis regresi logistik. Hasil: Proporsi tumor AK lebih banyak berlokasi di perifer, sedangkan KSS lebih banyak di sentral. Kavitas intratumoral lebih sering bermanifestasi pada KSS dibandingkan AK. Tepi berspikulasi lebih banyak terlihat pada AK dibandingkan KSS. Air bronchogram dan lesi subsolid lebih sering bermanifestasi pada AK. Kesimpulan: Terdapat perbedaan yang signifikan pada variabel densitas tumor di mana lesi subsolid lebih sering bermanifestasi pada AK dibandingkan KSS. ......Background: Based on its radiological features such as size, location, nodule margins, as well as the presence of intratumoral cavities and air bronchograms, CT scans can aid in distinguishing between adenocarcinoma (AK) and squamous cell carcinoma (KSS). CT scans are a non-invasive modality. Objective: To assess the radiological characteristics of lung cancer subtypes AK and KSS using thoracic CT scans as a diagnostic tool. Methods: CT scans were evaluated for location, intratumoral cavities, air bronchograms, tumor margins, and tumor density in 31 AK subjects and 16 KSS subjects who met the study's criteria. Bivariate analysis was conducted using the Chi-Square or Fisher's test. Multivariate analysis was performed using logistic regression. Results: The proportion of AK tumors is more often located in the periphery, whereas KSS tumors tend to be more central. Intratumoral cavities are more frequent in KSS than AK. Spiculated margins are more common in AK than KSS. Air bronchograms and subsolid lesions are more frequent in AK. Conclusion: There is a significant difference in tumor density, with subsolid lesions being more common in AK than in KSS.

Abstrak :
Latar belakang : Efek potensial EGFR-TKI terhadap fungsi paru belum diinvestigasi secara mendalam. Penelitian ini bertujuan untuk menilai efek pemberian EGFR TKI terhadap fungsi paru terutama nilai DLCO. Metode : Penelitian berlangsung secara prospektif dari September 2018 hingga Juni 2019 di Rumah Sakit Persahabatan Jakarta. Terdapat 20 subjek adenokarsinoma paru dengan mutasi tunggal di exon 19/21 yang dapat menyelesaikan pemeriksaan DLCO baik sebelum mendapat EGFR TKI dan setelah tiga bulan terapi. Hasil : Penelitian ini mendapatkan peningkatan bermakna nilai rerata KVP prediksi dari 60,6% menjadi 68,25% (p=0,03), nilai rerata VEP1 Prediksi dari 59,7% menjadi 67,05% (p=0,036), nilai rerata DLCO dari 11,55 ml/menit/mmHg menjadi 13,72 ml/menit/mmHg (p=0,004) dan DLCO prediksi dari 53,4% menjadi 63,85% (p=0,03). Peningkatan nilai rerata DLCO prediksi paling besar pada kelompok dengan hasil RECIST partial response yaitu sebesar 16,43% (p=0,056). Kesimpulan : Terapi EGFR TKI selama tiga bulan pada subyek adenokarsinoma paru dengan mutasi tunggal exon19/21 dapat meningkatkan fungsi paru secara bermakna baik nilai KVP prediksi, VEP1 prediksi, DLCO, dan DLCO prediksi.

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Background : The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are drugs of choice in non-small cell lung cancer possessing EGFR mutation. Its effect on the lung function is not well understood. This study aims to assess lung function using the lung diffusion capacity (DLCO) test in lung cancer patients treated with EGFR-TKIs. ming Method : This prospective study included lung cancer patients treated with EGFR-TKIs at Persahabatan Hospital Jakarta, Indonesia, between September 2018 andGrowt June 2019. The study recruited 20 lung adenocarcinoma patients presented with a single mutation at exon 19 or 21 as subjects in the process. Their DLCO was examined before and three months after receiving EGFR-TKI. Subjects were grouped according to the Response Evaluation Criteria in Solid Tumors (RECIST) assessment. Results: There was an increase in predicted FVC from 60.60% to 68.25% (p=0.03), predicted FEV1 from 59.7% to 67.05% (p=0.036%), DLCO from 11.5 mL/minute/mmHg to 13.72 mL/minute/mmHg (p=0.004), and predicted DLCO from 53.4% to 63.85% (p=0.03) during the therapy. The largest increase of predicted DLCO was shown in RECIST group of partial response (16.43%, p=0.056) Conclusion: This study found an improvement in lung function (predicted FVC, predicted FEV1, DLCO, and predicted DLCO) among lung adenocarcinoma subjects exhibiting single mutation at exon 19 or 21 after three months of EGFR-TKIs treatment.

Abstrak :
Kanker kolorektal merupakan jenis kanker terbanyak ketiga di Indonesia. Hal ini disebabkan oleh pola hidup yang tidak sehat seperti merokok, pola makan yang mengadopsi makanan cepat saji, kegemukan, dan kurangnya aktivitas fisik. Penatalaksanaan medis utama pada kasus kolorektal yaitu pembedahan dengan cara mereseksi kanker, kemudian membuat stoma, dan penyambungan kembali usus yang disebut anastomosis. Salah satu masalah utama pada pasien postoperasi adalah nyeri akut. Penelitian ini bertujuan untuk menyajikan hasil analisis asuhan keperawatan pada pasien post operasi close colostomy dan dan laparatomi adhesiolisis. Metode yang digunakan adalah studi kasus. Adapun intervensi berbasis bukti yang diterapkan yaitu intervensi manajemen nyeri berupa teknik relaksasi napas dalam guna menurunkan intensitas nyeri pada pasien post operasi close colostomy dan laparatomi adhesiolisis. Penerapan teknik relaksasi napas dalam diharapkan dapat diaplikasikan oleh perawat bedah di ruangan khususnya untuk mengurangi nyeri akut post operasi close colostomy dan laparatomi adhesiolisis. Kata kunci : kanker kolorektal, close colostomy, laparatomi adhesiolisis, nyeri akut, relaksasi napas dalam. ......Colorectal cancer is the third most common type of cancer in Indonesia. This is caused by unhealthy lifestyles such as smoking, eating patterns that adopt fast food, obesity, and lack of physical activity. The main medical management in colorectal cases is surgery by resecting the cancer, then making a stoma, and reconnecting the intestine which is called anastomosis. One of the main problems in postoperative patients is acute pain. This study aims to present the results of the analysis of nursing care in postoperative patients with close colostomy and adhesiolysis and laparotomy. The method used is a case study. The evidence-based intervention applied is pain management intervention in the form of deep breathing relaxation techniques to reduce pain intensity in postoperative close colostomy and adhesionic laparotomy patients. It is hoped that the application of deep breathing relaxation techniques can be applied by surgical nurses in the room especially to reduce acute pain after close colostomy surgery and adhesiolysis laparotomy. Keywords : colorectal cancer, close colostomy, laparotomy adhesiolisis, acute pain, deep breat relaxation.

Abstrak :
Keganasan pankreas merupakan keganasan dengan angka kematian yang tinggi, dengan Adenokarsinoma Duktal Pankreas/Pancreatic Ductal Adenocarcinoma (PDAC) mencakup 85-90% kasus. PDAC memiliki perjalanan penyakit yang sangat agresif, dan seringkali baru terdiagnosis pada stadium lanjut. Penegakan diagnosis pasti PDAC seringkali hanya dapat dilakukan melalui sediaan terbatas baik berupa biopsi maupun endoscopic ultrasound-guided fine-needle aspiration/EUS-FNA. Salah satu tantangannya adalah membedakan PDAC dari jaringan pankreas non-neoplastik/reaktif. Penelitian ini akan membahas mengenai peran von Hippel-Lindau gene product/pVHL dalam membedakan PDAC dengan jaringan pankreas non-neoplastik, serta hubungannya dengan profil klinikopatologiradira PDAC. Penelitian ini merupakan penelitian observasional analitik dengan desain cross-sectional pada kasus PDAC dan jaringan pankreas non-neoplastik yang dilakukan di RSCM pada sampel yang diperoleh pada bulan Januari 2012 hingga September 2023. Sampel penelitian dibagi menjadi 2 kelompok besar, yaitu kelompok PDAC dan pankreas non-neoplastik. Pemilihan sampel dilakukan dengan menggunakan simple random sampling dari kasus-kasus yang memenuhi kriteria inklusi dan tidak termasuk dalam kriteria eksklusi. Dilakukan pulasan imunohistokimia pVHL dan perhitungan Histoscore/H-score serta penentuan cut-offnya untuk membagi ekspresi pVHL menjadi tinggi dan rendah dan hubungannya dengan PDAC dan non-neoplastik, serta profil klinikopatologi pada kelompok PDAC. Penelitian ini menunjukkan tidak terdapat perbedaan ekspresi pVHL pada kelompok PDAC dan non-neoplastik, dan staging pN memiliki hubungan bermakna dengan ekspresi pVHL pada PDAC. Ekspresi pVHL yang rendah lebih banyak ditemukan pada PDAC berdiferensiasi sedang, tidak ditemukan invasi limfovaskular maupun invasi perineural, memiliki batas sayatan yang tidak bebas, memiliki staging pT2, pN0, M0, dan kesintasan > 7 bulan. Sebaliknya, ekspresi pVHL yang tinggi juga lebih banyak ditemukan pada PDAC berdiferensiasi sedang, ditemukan invasi limfovaskular, tidak ditemukan invasi perineural, status batas sayatan yang bebas, staging pT2 dan pT3, pN1 dan pN2, M0, dengan kesintasan ≤ 7 bulan. Temuan ini berbeda dengan penelitian sebelumnya yang mendapati hilangnya ekspresi pVHL pada tumor PDAC, dan sebaliknya pada duktus pankreas non-neoplastik. Hal ini kemungkinan disebabkan oleh perbedaan klon antibodi yang digunakan pada penelitian ini dibandingkan dengan penelitian sebelumnya. Klon antibodi yang digunakan adalah VHL40, sedangkan penelitian-penelitian sebelumnya menggunakan klon FL-181 yang berikatan dengan asam amino yang berbeda dan memiliki klonalitas yang berbeda pula. Selain itu, pada PDAC dapat terjadi mutasi pada gen VHL yang menghasilkan protein VHL yang non-fungsional yang kemungkinan masih dapat terdeteksi dengan ikatan antigen-antibodi pada penelitian ini.  ......Pancreatic malignancy is a malignancy with a high mortality rate, with Pancreatic Ductal Adenocarcinoma (PDAC) accounting for 85-90% of cases. PDAC has a very aggressive disease course, and is often only diagnosed at an advanced stage. Establishing a definite diagnosis of PDAC can often only be done through limited sample from biopsy or endoscopic ultrasound-guided fine-needle aspiration/EUS-FNA. In such limited sample, differentiating PDAC from non-neoplastic/reactive pancreatic tissue can be challenging. This research will discuss the role of von Hippel-Lindau gene product/pVHL in PDAC and non-neoplastic pancreatic tissue, as well as their relationship with PDAC pathological factors. This research is an analytical observational study with a cross-sectional design on cases of PDAC and non-neoplastic pancreatic tissue conducted at RSCM on samples obtained from January 2012 to September 2023. The research samples were divided into 2 large groups, namely the PDAC and non-neoplastic pancreatic groups. Sample selection was carried out using simple random sampling from cases that met the inclusion criteria and were not included in the exclusion criteria. Immunohistochemistry of pVHL was performed along with calculation of Histoscore/H-score and determination of cut-offs to divide pVHL expression into high and low and its relationship with PDAC and non-neoplastic, as well as pathological factors in the PDAC group. This study shows that there is no difference in pVHL expression in the PDAC and non-neoplastic groups, and pN staging has a significant relationship with pVHL expression in PDAC. Low pVHL expression is more often found in moderately differentiated PDAC, no lymphovascular invasion or perineural invasion, non-free incision margins, staging pT2, pN0, M0, and survival > 7 months. In contrast, high pVHL expression was also found more frequently in moderately differentiated PDAC, lymphovascular invasion was found, no perineural invasion was found, free incision margin status, pT2 and pT3 staging, pN1 and pN2, M0, with survival ≤ 7 months. This finding is different from previous studies which found loss of pVHL expression in PDAC tumors, and vice versa. This difference in results is likely due to differences in the antibody clones used in this study compared to previous studies. The antibody clone used was VHL40, whereas previous studies used the FL-181 clone which binds to different amino acids and has different clonality. In addition, in PDAC there is a mutation in the VHL gene which may produce a non-functional VHL protein that still be detectable by antigen-antibody binding in this study.

Abstrak :
Latar Belakang: Beberapa bukti menunjukkan bahwa quiescent cancer stem cell (CSC) terlibat dalam resistans terhadap gefitinib pada adenokarsinoma paru sebagai mekanisme nonmutasi. Kami sebelumnya telah mempublikasikan bahwa gefitinib- resistant persister (GRP) mengekspresikan stemness factor dengan level yang tinggi dan memiliki ciri khas fenotip CSC. Studi terbaru menunjukkan bahwa FBXW7, merupakan jenis protein F-box, memainkan peran penting dalam pemeliharaan quiescent CSC dengan memediasi degradasi protein c-MYC melalui proses ubiquination. Tujuan dari penelitian ini adalah untuk mengetahui peran FBXW7 dalam resistans terhadap gefitinib pada adenokarsinoma paru dengan mutasi EGFR. Metode: Cell line dari sel adenokarsinoma paru, PC9, yang mengandung mutasi sensitif EGFR dipajankan pada gefitinib dengan konsentrasi tinggi untuk mengembangkan GRP. Kami mencoba melakukan abrogasi ekspresi gen FBXW7, dan mengevaluasi sensitivitasnya terhadap gefitinib dan populasi CD133-positive stem cell di GRP. Kami juga memasukkan plasmid FUCCI melalui proses infeksi lentiviral ke dalam sel dan kemudian menyelidiki siklus sel dan sel pada fase G0 dalam GRP. Selanjutnya, kami telah mengembangkan model gefitinib-resistant tumor (GRT) dengan menyuntikkan sel PC9 ke dalam mencit NOG diikuti dengan pemberian gefitinib setelah pertumbuhan tumor, dan mengevaluasi ekspresi mRNA dan ekspresi protein dari penanda terkait quiescence, FBXW7 in vivo. Hasil: GRP menunjukkan ekspresi yang tinggi dari penanda cancer stem cell, CD133 dan penanda terkait quiescence, FBXW7 dan ekspresi c-MYC yang rendah pada tingkat protein secara in vitro. Analisis siklus sel menunjukkan bahwa mayoritas GRP berada pada fase G0/G1. TIndakan abrogasi gen FBXW7 menurunkan populasi sel CD133-positive di GRPs. Abrogasi FBXW7 juga meningkatkan kerentanan sel terhadap gefitinib, membalikkan populasi sel fase G0/G1 menjadi sel S/G2/M, dan menurunkan jumlah sel GRP. Secara in vivo, pada GRT setelah pengobatan gefitinib menunjukkan ekspresi FBXW7 yang tinggi dan ekspresi c-MYC yang rendah. Kami juga menemukan bahwa ekspresi FBXW7 dalam sel CD133-positive meningkat dan ekspresi c-MYC menurun pada mencit dan pada 9 dari 14 spesimen tumor dari pasien adenokarsinoma paru dengan mutasi EGFR resistan terhadap gefitinib. Kesimpulan: Temuan ini menunjukkan bahwa FBXW7 dapat memainkan peran penting dalam pemeliharaan quiescence pada gefitinib-resistant lung CSC pada adenokarsinoma paru dengan mutasi positif EGFR ......Background: Accumulating evidence indicates that quiescent cancer stem cells (CSCs) are involved in the resistance to gefitinib in non-small cell lung cancer (NSCLC) as non-mutational mechanism. We have previously reported that gefitinib-resistant persisters (GRPs) highly expressed stemness factors and had characteristic features of the CSCs phenotype. Recent studies demonstrate that FBXW7, a type of F-box protein, plays an important role in the maintenance of quiescent CSC by mediating the degradation of c-MYC protein by ubiquination. The aim of this study is to figure out the role of FBXW7 in the resistance to gefitinib in lung adenocarcinoma with EGFR mutation. Methods: lung adenocarcnoma cell lines, PC9, harboring sensitive-EGFR mutation were exposed to high concentration of gefitinib in order to develop GRPs. We tried to knockdown FBXW7 gene expression, and evaluated their sensitivity to gefitinib and CD133-positive stem cell population in GRPs. We also introduced FUCCI plasmid via lentiviral infection in the cells and then investigated the cell cycle and G0-phase cells in GRPs. Furthermore, we established gefitinib-resistant tumor (GRT) model by injecting PC9 cells into NOG-mice followed by gefitinib administration after tumor growth, and evaluated mRNA and protein expression of quiescence-related markers including FBXW7 in vivo. Results: In vitro, GRPs showed high expression of stem cell marker CD133 and quiescence-related markers including FBXW7 and low expression of c-MYC at protein level. Cell cycle analysis revealed that majority of GRPs existed in G0/G1 phase. Silencing of FBXW7 gene reduced CD133-positive cell population in GRPs. Knockdown of FBXW7 also increased susceptibility of cells to gefitinib, reversed population of G0/G1 cells to G2/S/M cells, and decreased cell number of GRPs. In vivo, GRTs after gefitinib treatment revealed high expression of FBXW7 and low expression of c-MYC. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in mice and in 9 out of 14 tumor specimens from EGFR-mutant lung adenocarcinoma patients with acquired resistance to gefitinib. Conclusion: These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in EGFR mutation- positive lung adenocarcinoma.

Abstrak :
CA 19-9 merefleksikan derajat keparahan adenokarsinoma kaput pankreas ditunjukkan oleh beberapa studi berhasil menemukan korelasi peningkatan CA 19-9 dengan resektabilitas adenokarsinoma kaput pankreas. Penelitian ini bertujuan melakukan evaluasi hubungan dan nilai diagnostik CA 19-9 dalam memprediksi resektabilitas adenokarsinoma kaput pankreas. Penelitian dilakukan secara potong lintang mengambil data dari rekam medis Rumah Sakit dr. Cipto Mangunkusumo tahun 2016–2019. Pasien terdiagnosis adenokarsinoma kaput pankreas secara histopatologis atau pencitraan abdomen, berusia ≤65 tahun, dan memiliki catatan pemeriksaan kadar CA 19-9 diikutsertakan dalam penelitian ini. Selain kadar CA 19-9, peneliti juga menilai factor terkait operabilitas. Tercatat 54 subjek dengan rerata usia 53,78±11,13 tahun. Ditemukan adanya korelasi positif (0,850) dan signifikan antara tingginya kadar CA 19-9 dengan resektabilitas tumor kaput pankreas. Untuk operabilitas, ditemukan perbedaan bermakna kadar CA 19-9, albumin, dan skor Karnofsky pada kelompok pasien tumor kaput pankreas resectable dan unresectable. Titik potong kadar CA 19-9 tercatat sebesar 140,65 U/mL, dengan sensitivitas sebesar 82,76% (64,23%–94,15%), spesifisitas sebesar 72,00% (50,61%–87,93%), dan AUC sebesar 0,784. CA 19-9 berhubungan secara signifikan dengan resektabilitas tumor kaput pankreas. CA 19-9 memiliki nilai diagnostik yang baik dalam mempredisksi resektabilitas tumor ini. ......This study would like to evaluate the relationship and diagnostic value of CA 19-9 in predicting the resectability of pancreatic head carcinoma. The cross-sectional study took data from the medical records at dr Cipto Mangunkusumo Hospital in 2015–2019. Patients diagnosed with pancreatic head carcinoma based on histopathologic or abdominal imaging, aged ≤75 years, and who had a recorded CA level of 19-9 were enrolled in the study. The investigators also assessed parameters of operability. Of 54 patients with similar characteristics were enrolled, with a mean age of 53.78 ± 11.13 years. It was found that there was a positive (0.850) and significant correlation between high levels of CA 19-9 and unresectable pancreatic head carcinoma. We found significant differences in levels of CA 19-9, albumin, and Karnofsky score in the resectable and unresectable groups of pancreatic head carcinoma. The cut-off point for CA 19-9 levels was 140.65 U / mL, with a sensitivity of 82.76% (64.23%-94.15%), specificity of 72.00% (50.61%-87.93 %), and AUC of 0.784. CA 19-9 was significantly associated with the pancreatic head carcinoma resectability. CA 19-9 has a good diagnostic value in predicting the resectability of these tumors.