Irinotecan chemotherapy combined with fluoropyrimidines versus irinotecan alone for overall survival and progression-free survival in patients with advanced and/or metastatic colorectal cancer.

Background: Without early recognition and Kasai procedure, biliary atresia (BA) results in liver cirrhosis and leads to either transplantation or death at a young age. We aimed to characterize the liver histopathological findings for prediction of cirrhosis and survival in BA patients after Kasai surgery. Methods: We retrospectively reviewed all histopathological results for BA patients who underwent liver biopsy during Kasai surgery from August 2012 to December 2018 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Results: Fifty infants with BA were ascertained in our study, of whom 27 were males and 23 were females. The median age of Kasai procedure was 102.5 days (interquartile range (IQR), 75.75-142.25 days). There were 33 (66%) and 17 (34%) BA patients with and without liver cirrhosis, respectively, while the overall survival was 52%. The patients with a severe bile duct proliferation, severe cholestasis, and severe portal inflammation have a higher risk by 27-, 22-, and 19.3-fold, respectively, to develop liver cirrhosis compared with patients with a moderate/mild bile duct proliferation, moderate/mild/without cholestasis, and moderate/mild portal inflammation, respectively (p = 3.6 × 10 − 6 , 5.6 × 10 − 4 , and 1.6 × 10 − 3 , respectively), while the giant cell transformation was not associate with the development of liver cirrhosis (p = 0.77). The bile duct proliferation was strongly correlated with cholestasis and portal inflammation (p = 7.3 × 10 − 5 and 2 × 10 − 4 , respectively), and cholestasis was also significantly correlated with portal inflammation (p = 0.016). Interestingly, the age at Kasai procedure was strongly associated with the development of liver cirrhosis (p = 0.02), but not with the patients' survival (p = 0.33), while the degree of fibrosis and cholestasis were significantly correlated with the patients' survival, with HR of 3.9 (95% CI = 1.7-9.0; p = 0.017) and 3.1 (95% CI = 1.4-7.0; p = 0.016), respectively. Conclusions: Histopathological findings of bile duct proliferation, cholestasis, and portal inflammation can predict the liver cirrhosis development in patients with BA. Furthermore, degree of fibrosis and cholestasis affect the patients' survival following the Kasai operation.

There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016–2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all—186/197 (99.45%)—MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as “Probable Lynch” (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, p = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both “Probable Lynch” and non-LS (sporadic) groups (n = 227) was comparable (p = 0.59), with follow up period of 0–1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (p < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72–11.2; p = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.

Background:The O6-methylguanine-DNA methyltransferase (MGMT) gene prevents mismatch in DNA replication and transcription by repairing mutagenic DNA lesions. MGMT is a predictor biomarker of chemotherapy in high-grade and low-grade gliomas based on high-risk clinical conditions. It also can be used for therapeutic decisions to predict hypermutation in recurrence in newly diagnosed low-grade gliomas. The gold standard examination for the methylation is Polymerase Chain Reaction (PCR). However, this technique is not widely available in Indonesia for daily practice. Thus, an uncomplicated and simpler method such as immunohistochemistry (IHC) is needed as an alternative examination. This study aimed to predict the diagnostic accuracy of immunohistochemistry (IHC) in detecting the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) in glioma. Methods: This research was a cross-sectional study using formalin-fixed paraffin embedded (FFPE) tissue samples of glioma patients, dating between October 2017 until March 2021. Diagnosis of glioma was established based on clinical, radiological, and histopathological findings. MGMT methylation status was investigated using the IHC and PCR techniques. Diagnostic value of IHC was analyzed, with PCR as a gold standard method. Optimum threshold to determine positivity of IHC was determined by the Area Under the Curve (AUC) on Receiver Operating Characteristics (ROC) curve and Youden index. Results: Among 75 samples examined, 29 (38.7%) patients were methylated. IHC detected MGMT methylation with sensitivity of 86.2%, specificity of 63.0%, positive predictive value of 59.5%, negative predictive value of 87.9% and accuracy of 72.0%. The AUC was 0.746, indicating moderate diagnostic value. Optimum positivity threshold of the IHC examination based on Youden Index was 10%. Conclusion: IHC examination can be used to detect MGMT methylation status of glioma patients in limited resources setting, where PCR technique is not available.

Lymphadenopathy is a non-specific enlargement of lymph nodes which may be caused by infection, cancer, or autoimmune disease. To date, only a few studies reported the diagnostic value of fine-needle aspiration biopsy (FNAB) in lymphadenopathy. This study was performed to evaluate diagnostic reliability of FNAB for benign and malignant lymphadenopathy. This was a retrospective cross-sectional study. The obtained data were statistically analyzed for its sensitivity, specificity, and accuracy. Out of 126 collected FNAB cases with histopathological confirmed results in Dr. Sardjito General Hospital, Yogyakarta, 85 (67.4%) were malignant lymphadenopathy, consisting of 42 metastatic tumor cases, 38 non-Hodgkin lymphoma (NHL) cases, and 4 Hodgkin lymphoma (HL) cases.The overall diagnostic sensitivity, specificity, and accuracy of FNAB in lymphadenopathy was 85.88, 70.73, and 80.95%, respectively. In diagnosing metastatic tumors, FNAB had sensitivity of 83.33%; specificity of 89.28%; and accuracy of 87.3%. The sensitivity, specificity, and accuracy of FNAB in diagnosing NHL was 60.52, 94.31, and 84.12%, respectively. FNAB had a sensitivity of 25%, specificity of 95,90%, and accuracy of 93.65% to diagnose HL. Meanwhile, the accuracy of FNAB in diagnosing malignancies in generalized lymphadenopathy, head-neck lymphadenopathy, and inguinal lymphadenopathy was 90.90; 81.39 and 44.44%, respectively. In conclusion,FNAB has moderate diagnostic value in diagnosing overall malignant lymphadenopathy, including metastatic tumors. FNAB also has some limitations in diagnosing NHL and HL, with sensitivity less than 70% for both diseases. However, it has high accuracy to diagnose generalized lymphadenopathy. ABSTRAKLimfadenopati adalah pembesaran kelenjar getah bening non-spesifik yang mungkin disebabkan oleh infeksi, kanker, atau penyakit autoimun. Sampai saat ini, hanya beberapa penelitian yang melaporkan nilai diagnostik biopsi aspirasi jarum halus/fine-needle aspiration biopsi (FNAB) pada limfadenopati. Penelitian ini dilakukan untuk memberikan diagnostik FNAB yang teruji pada limfadenopati jinak dan ganas. Ini adalah penelitian potong lintang retrospektif. Data yang diperoleh dianalisis secara statistik untuk sensitivitas, spesifisitas, dan akurasinya. Dari 126 kasus FNAB yang dikumpulkan dengan hasil histopatologis dikonfirmasi di Rumah Sakit Umum Pusat Dr. Sardjito Yogyakarta, 85 (67,4%) adalah limfadenopati ganas, yang terdiri dari 42 kasus tumor metastasis, 38 kasus non-Hodgkin lymphoma (NHL), dan 4 kasus Hodgkin lymphoma (HL). Sensitivitas diagnostik keseluruhan, spesifisitas, dan akurasi FNAB dalam limfadenopati berturut-turut adalah 85,88; 70,73 dan 80,95%. Dalam mendiagnosis tumor metastasis, FNAB memiliki sensitivitas 83,33%; spesifisitas 89,28%; dan akurasi 87,3%. Sensitivitas, spesifisitas, dan akurasi FNAB dalam mendiagnosis NHL berturut-turut adalah 60,52; 94,31 dan 84,12%. FNAB memiliki sensitivitas 25%; spesifisitas 95,90%; dan akurasi 93,65% untuk mendiagnosis HL. Sementara itu, akurasi FNAB dalam mendiagnosis kega...