Lisnawati Rachmadi
Department Of Anatomical Pathology, Faculty Of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital

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Phylogenetic analysis and predicted functional effect of protein mutations of E6 and E7 HPV16 strains isolated in Indonesia Wulandari, Dwi; Rachmadi, Lisnawati; Sudiro, Tjahjani M.
Medical Journal of Indonesia Vol 24, No 4 (2015): December
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (577.88 KB) | DOI: 10.13181/mji.v24i4.1197

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Background: E6 and E7 are oncoproteins of HPV16. Natural amino acid variation in HPV16 E6 can alter its carcinogenic potential. The aim of this study was to analyze phylogenetically E6 and E7 genes and proteins of HPV16 from Indonesia and predict the effects of single amino acid substitution on protein function. This analysis could be used to reduce time, effort, and research cost as initial screening in selection of protein or isolates to be tested in vitro or in vivo.Methods: In this study, E6 and E7 gene sequences were obtained from 12 samples of  Indonesian isolates, which  were compared with HPV16R (prototype) and 6 standard isolates in the category of European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and North American (NA) branch from Genbank. Bioedit v.7.0.0 was used to analyze the composition and substitution of single amino acids. Phylogenetic analysis of E6 and E7 genes and proteins was performed using Clustal X (1.81) and NJPLOT softwares. Effects of single amino acid substitutions on protein function of E6 and E7 were analysed by SNAP.Results: Java variants and isolate ui66* belonged to European branch, while the others belonged to Asian and African branches. Twelve changes of amino acids were found in E6 and one in E7 proteins. SNAP analysis showed two non neutral mutations, i.e. R10I and C63G in E6 proteins. R10I mutations were found in Af-2 genotype (AF472509) and Indonesian isolates (Af2*), while C63G mutation was found only in Af2*.Conclusion: E6 proteins of HPV16 variants were more variable than E7. SNAP analysis showed that only E6 protein of African-2 branch had functional differences compared to HPV16R.
Aspek Klinik dan Karakteristik Tipe Histopatologik Timoma Maria Mayella Vianney; Lisnawati Rachmadi
Majalah Patologi Indonesia Vol 30 No 1 (2021): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Indonesia (IAPI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (725.761 KB) | DOI: 10.55816/mpi.v30i1.455

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BackgroundThymoma is the most common neoplasm found in thymus gland and is classified into 5 main histopathological types, A, AB, B1, B2,and B3. Thymomas are most commonly found in the anterior mediastinum and accompanied with myasthenia gravis. The aim of thisstudy was to find out clinical feature and histopathological characteristics of thymomas in Department of Anatomical Pathology, Facultyof Medicine, University of Indonesia/Dr. Cipto Mangunkusumo Hospital (FKUI/RSCM) in 2014-2018.MethodsThis is a descriptive study, using a cross-sectional design. Clinical and histopathological data obtain from the medical records andarchives of the Department of Anatomical Pathology of FKUI/RSCM. Clinical data consists of age, sex, tumor location, clinicalsymptom, concomitant disease, metastasis, and treatment. Histopathological assessment consists of histopathology type using WorldHealth Organization criteria and staging using Masaoka-Koga staging system.ResultsThere were 31 thymoma cases matched the inclusion criteria. Nineteen (61.3%) of 31 cases were women. The mean age of thesubjects was 46.7 years old. A total of 12 cases (37.5%) had muscle weakness due to myasthenia gravis as chief complaint and 21cases (67.7%) of tumor mass in the anterior mediastinum. There 9 cases of type AB and 2 cases of type B2.ConclusionThymoma is more common in women with an average age of 46.7 years. The most common paraneoplastic syndrome is myastheniagravis and mostly found in the anterior mediastinum. The most common histopathologic type is type AB, while type B2 is the least.
Papiloma Sinonasal dan Keganasan Terkait Papiloma Sinonasal: Studi dari Pusat Rujukan Tersier di Indonesia David Sitinjak; Lisnawati Rachmadi; Yayi Dwina Billianti
Majalah Patologi Indonesia Vol 31 No 2 (2022): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Indonesia (IAPI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (628.983 KB) | DOI: 10.55816/mpi.v31i2.498

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Background Sinonasal papilloma is a benign tumor arising from Schneiderian epithelia in sinonasal mucosa. It has the propensity towards malignant transformation. This preliminary study aims to report clinicopathological aspects of sinonasal papilloma and its malignant transformation rate. Methods A descriptive, cross-sectional study was conducted in Anatomical Pathology Department, FKUI/RSCM over a period of 2014-2019) A total of 127 histologic specimens with diagnosis of sinonasal papilloma obtained from 80 cases. Results The prevalence of sinonasal papilloma among all sinonasal neoplasms is 17.6%. Inverted papilloma was the most common histologic type 91.3%, exophytic papilloma 6.3% and oncocytic papilloma 2.5%, among male (70%), age rate 50 years old. Malignant transformation of squamous cell carcinoma 12.5%, and recurrence 21.3%, nasal congestion was the most complaint 50%. Cases were usually in T3 of Krouse stage 37.5% and managed with functional sinus endoscopic surgery 51.3%. Histological parameters were grade II 54.4%, surface keratinization 17.5%, bony trabeculae 41.3%, nasal polyps 20% and dense lymphocytic infiltrates 53.8%, foam cell infiltrates 2.5%. Mild to moderate dysplasia 8.8% and severe dysplasia 18.8%. Conclusion Sinonasal papilloma was rare sinonasal benign tumor. Inverted papilloma type was local aggressive, recurrence, dysplastic and malignant transformation, among male, age 50 years old, main complaint of nasal congestion, in Krouse stage T3, and managed by Functional Sinus Endoscopy Surgery (FSES
Epstein-Barr DNA in advanced pediatric nasopharyngeal cancer Marlinda Adham; Namira Kesuma Jelita; Djajadiman Gatot; Soehartati Argadikoesoema Gondhowiardjo; Lisnawati Rachmadi; Astrid E Greijer; I Bing Tan; Jaap M Middeldorp
Paediatrica Indonesiana Vol 61 No 5 (2021): September 2021
Publisher : Indonesian Pediatric Society

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14238/pi61.5.2021.261-70

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Background Studies suggest that the most common type of nasopharyngeal carcinoma (NPC) is WHO-3, which is strongly associated with Epstein-Barr virus (EBV). Objective To assess NPC patient characteristics in a national general referral hospital in Indonesia, with regards to EBV DNA load and treatment response. Methods Twenty-three pediatric patients diagnosed with NPC were included in the study. Data collected were history, physical examination, tissue biopsy, CT scan, staging and EBV DNA load from nasopharyngeal (NP) brushing as well as blood specimens. The NP brushing, blood specimens and CT scan evaluations were done two months post-treatment. Results Pediatric patients with symptoms such as blood tinged secretion, lymph node enlargement, and nasal congestion were more likely to have higher EBV DNA loads in their NP brushings (P<0.05) (including T3 and higher). Despite significant reduction of EBV DNA load in NP brushing post-treatment, it was not associated with treatment response, as evaluated by CT scan. Conclusion Higher DNA load from NP brushings is associated with a higher tumor stage. Larger sample size and follow-up data are needed to assess the usefulness of EBV DNA load assessment in pediatric patients.
Infections of Chlamydia trachomatis and Mycoplasma hominis as Risk Factors for Abnormal Cervical Cells Mardhia, Mardhia; Effiana, Effiana; Irsan, Abror; Natalia, Diana; Rahmayanti, Sari; Indarti, Junita; Rachmadi, Lisnawati; Yasmon, Andi
Makara Journal of Health Research Vol. 22, No. 1
Publisher : UI Scholars Hub

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Background: Cervical cancer is the fourth most common cancer among women across the world. Recent studies have shown that cervical cancer is not only caused by persistent infection of human papillomavirus (HPV), but sexually transmitted infections (STIs) also play a role in the pathogenesis of abnormal cervical cells. STIs frequently occur with no specific symptoms, such as the infections caused by Chlamydia trachomatis and Mycoplasma hominis. Asymptomatic STIs could lead to persistent infection. Persistent infections caused by STIs have been hypothesised to increase the access of HPV into the deeper cervical tissue and cause cervical cell abnormalities. Therefore, we conducted this study to assess the association between C. trachomatis and M. hominis infections and abnormal cervical cells. Methods: A cross-sectional study was performed on 58 outpatients at the Department of Obstetrics and Gynecology, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Abnormal cervical cells were detected by a liquid-based cytology Pap smear, and bacterial identification was done by conducting conventional duplex polymerase chain reaction (PCR). Results: 58 patients, 14 (24.1%) showed abnormal cervical cells, whereas 44 (75.9%) patients showed normal cervical cells. The conventional duplex PCR demonstrated a positive result for C. trachomatis and M. hominis bacterial infections in only 1 (7.1%) and 2 (14.3%) patients with abnormal cervical cells, respectively. The statistical analysis revealed no significant association between the bacterial infections and the abnormal cervical cytology in the patients (p > 0.05). Conclusions: Infections caused by C. trachomatis and/or M. hominis were not associated with abnormal cervical cells.
Beyond COVID-19 Paradigm: Devastating Rare Fungal Ocular Complication Edwar, Lukman; Kusumowidagdo, Gladys; Djatikusumo, Ari; Yudantha, Anggun R.; Mardianto, Umar; Rozaliyani, Anna; Rinaldi, Ikhwan; Rachmadi, Lisnawati
eJournal Kedokteran Indonesia Vol. 12 No. 3 (2024): Vol. 12 No. 3 - Desember 2024
Publisher : Faculty of Medicine Universitas Indonesia

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Ocular involvement in COVID-19 is rare and often mild. We report a case of severe bilateral ocular candidiasis post-COVID-19 infection. A male, 48 years old, suffered from sudden blurry vision in the right eye (RE). The patient had a history of COVID-19, ICU stay, ventilator use, and a hypercoagulable state. The patient had a history of tocilizumab and steroid use. The initial best corrected visual acuity (BCVA) was 6/30 (RE), with progressive worsening of light perception and 6/6 on the left eye (LE) to 3/60. Examination revealed string-of-pearls and snowball on vitreous, fibrovascular tissue with exudates and subretinal fluid on the macula. Tractional retinal detachment was found in both eyes, and these findings were consistent with fungal endophthalmitis. Culture was taken from a chest lump and it was positive for Candida albicans. The patient was diagnosed with bilateral ocular candidiasis and treated with a 14-day course of intravenous voriconazole and vitrectomy. The final BCVA was hand movement (RE) and 6/45 (LE).
Comprehensive Histopathological Properties of Dartos Tissue Associated with Hypospadias Severity and Chordee: A Prospective Study Raharja, Putu Angga Risky; Birowo, Ponco; Rachmadi, Lisnawati; Wibowo, Heri; Kekalih, Aria; Duarsa, Gede Wirya Kusuma; Wahyudi, Irfan
Proceedings Book of International Conference and Exhibition on The Indonesian Medical Education Research Institute Vol. 8 No. - (2024): Proceedings Book of International Conference and Exhibition on The Indonesian M
Publisher : Writing Center IMERI FMUI

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.69951/proceedingsbookoficeonimeri.v8i-.243

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Background: The cause of chordee in hypospadias is not fully understood. Dartos fascia resection has been shown to correct penile curvature, suggesting its potential involvement. This study aimed to evaluate the histopathological properties of dartos tissue and their association with hypospadias severity and chordee.Methods and Materials: Dartos tissue samples were collected from 37 children with hypospadias and ten controls undergoing circumcision between March and October 2024. Histopathological analysis using hematoxylin-eosin and Masson’s trichrome staining assessed for collagen, smooth muscle, and vascular density. Assessment and quantification of all histopathological components were blinded. Results: The hypospadias group showed lower collagen density (60.85±6.75% vs. 67.31±4.61%; p=0.003) and higher smooth muscle density (7.34±4.92% vs. 2.51±2.24%; p<0.001) compared to controls, with no significant difference in vessel density. Sub-analysis showed severe chordee was linked to lower collagen density compared to mild (Mean Difference [MD] -6.24±2.41%; p=0.014) and moderate chordee (MD -5.73±2.54%; p=0.031). Conclusions: The dartos tissue in hypospadias patients exhibited lower collagen density and higher smooth muscle density, with chordee severity specifically linked to decreased collagen density.
Effect of the modified Atkins diet on NLRP3, caspase-1, IL-1β, and IL-10 in patients with tetralogy of Fallot undergoing open-heart surgery: A randomized controlled trial Yanuarso, Piprim B.; Djer, Mulyadi M.; Hendarto, Aryono; Pudjiadi, Antonius H.; Rachmadi, Lisnawati; Wibowo, Heri; Advani, Najib; Murni, Indah K.; Kekalih, Aria; Sukardi, Rubiana; Dilawar, Ismail; Susanti, Dhama S.; Supriatna, Novianti
Narra J Vol. 5 No. 1 (2025): April 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i1.2138

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Cardiopulmonary bypass in tetralogy of Fallot (TOF) corrective surgery induces hyperinflammation by activating NLRP3, caspase-1, and interleukin-1β (IL-1β), subsequently triggering an interleukin-10 (IL-10) response. Despite its known metabolic and anti-inflammatory effects, the impact of the modified Atkins diet (MAD) in pediatric cardiac surgery remains unexplored, with no studies on its use in TOF patients undergoing open-heart surgery. The aim of this study was to assess the effect of MAD on the expression of NLRP3, caspase-1, IL-1β, and IL-10, in TOF patients undergoing open-heart surgery. A double-arm, randomized-controlled trial was conducted with 44 TOF patients. The treatment group (n=22) received the MAD, a low-carbohydrate, high-fat regimen with unrestricted fat and protein intake for at least 14 days preoperatively, while the control group (n=22) followed a standard diet without carbohydrate restriction. Blood plasma and infundibulum heart tissues were collected for analysis. Whole blood samples were collected using a winged infusion needle before the intervention, an Abbocath infusion needle after 14 days of intervention, and a syringe without a needle connected to an arterial line in patients undergoing open-heart surgery at 6, 24, and 48 hours post-surgical correction. Infundibulum heart tissues were collected during the open-heart surgery. This study demonstrated significant differences in NLRP3 protein expression (p=0.015), caspase-1 protein expression (p=0.001), and IL-10 levels between before intervention and 6-, 24-, and 48-hours post-surgery in the MAD group compared to the control group. In contrast, no significant differences in IL-10 levels were observed in the control group between before intervention and 48 hours post-surgery (p=0.654). In conclusion, MAD may modulate perioperative inflammation in TOF patients undergoing open-heart surgery by downregulating NLRP3 and caspase-1 expression while sustaining IL-10 levels. Despite reduced NLRP3 and caspase-1 expression, unchanged IL-1β levels indicate alternative regulatory mechanisms.
Spectrum of rare EGFR mutations in Indonesian lung adenocarcinoma: Findings from an 8-year analysis of 4,778 cases highlighting the need for advanced targeted therapies Heriyanto, Didik S.; Trisnawati, Ika; Rachmadi, Lisnawati; Tenggara, Jeffry B.; Lau, Vincent; Gunawan, Andrew N.; Halim, Brigitta N.; Yuliani, Fara S.; Laiman, Vincent; Gondhowiardjo, Soehartati; Chuang, Hsiao-Chi
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.1721

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Lung cancer patients in Indonesia exhibit a high prevalence of epidermal growth factor receptor (EGFR) mutations, with a substantial proportion attributed to rare or uncommon variants. The clinical significance of rare EGFR mutations lies in their differential sensitivity to tyrosine kinase inhibitors (TKIs). While they are frequently resistant to first- and second- generation TKIs, they often respond to third-generation TKIs, necessitating tailored treatment options. The need for improving access to advanced targeted therapies in Indonesia also highlights the importance of conducting research on rare EGFR mutations. The aim of this study was to identify the spectrum and frequency of EGFR mutations in patients with lung adenocarcinoma in Indonesia. A cross-sectional observational study with total sampling was conducted from January 2016 to April 2024 to investigate EGFR mutation profiles in lung adenocarcinoma patients. Samples were acquired from patients with a confirmed anatomical pathology diagnosis from various healthcare centers across Indonesia. A total of 4,778 samples were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) on various specimen types to determine EGFR mutation prevalence and patterns. Associations between demographic data and EGFR mutation status were assessed. EGFR mutations were detected in 54.6% of samples, with common mutations (exon 19 deletions/insertions and point mutation L858R) comprising 76.2% of positive cases and rare mutations (exon 20 insertions, point mutation G719X, S768I, T790M, and L861Q) accounted for 20.3%. Significant associations were found between geographic origin, age, and sex with EGFR mutation status. This study confirms substantial genetic variability and geographical differences in EGFR mutations among Indonesian lung adenocarcinoma patients, emphasizing the urgent need for further research to prompt enhanced molecular diagnostics and targeted therapies in the region.
Subcategorization of the AUS/FLUS Thyroid Nodule Based on the 2017 Bethesda System at Dr. Cipto Mangunkusumo Hospital from 2018-2021 Linggodigdo, Michelle; Rachmadi, Lisnawati
Majalah Patologi Indonesia Vol. 34 No. 3 (2025): MPI
Publisher : Perhimpunan Dokter Spesialis Patologi Anatomik Indonesia (PDSPA)

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Objective: The AUS/FLUS (Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance) category is one of the most challenging diagnoses in thyroid fine-needle aspiration biopsy (FNAB) for pathologists. This is due to the heterogeneous cytomorphological features with low Risk of Malignancy (ROM) accuracy, which is crucial to determine further management. The 2017 Bethesda System introduced subcategorization of AUS/FLUS to improve ROM accuracy. However, the widespread adoption of this subcategorization remains limited. Methods: A retrospective analytical cross-sectional study was carried out using secondary data of thyroid FNAB cases diagnosed with AUS/FLUS followed by surgical procedures at the Department of Anatomical Pathology, Faculty of Medicine, University Indonesia/Dr. Cipto Mangunkusumo Hospital from 2018 to 2021. Furthermore, a review and subcategorization into AUS-C1 (focal nuclear atypia), AUS-C2 (mild nuclear atypia), AUS-A (architectural atypia), AUS-C&A (nuclear and architectural atypia), AUS-H (Hűrthle cell aspiration), AUS-NOS (atypia not otherwise specified), and AUS-L (lymphoid cell atypia other than lymphoma) was performed. Result: Among a total of 2,082 patients, 599 (28.7%) were diagnosed as AUS/FLUS. There were 75 patients with AUS/FLUS who proceeded with surgery, while 64 (85.3%) showed malignancy. The most common subcategory was AUS-C1 (60%), followed by AUS-NOS (21.3%), AUS-C&A (9.3%), AUS-C2 (8%), and AUS-H (1.4%). ROM subcategory AUS-C1 was significantly higher compared to AUS-C2 (p=0.009) and AUS-NOS (p=0.011). Conclusion: The percentage of AUS/FLUS diagnoses at Dr. Cipto Mangunkusumo Hospital from 2018 to 2021 was 28.7% with ROM ranging from 10.6% to 85.3%. There was a significant difference in ROM between AUS-C1 and AUS-C2, as well as AUS-C1 and AUS-NOS. Therefore, it was concluded that AUS-C1 thyroid nodules with or without architectural atypia require more aggressive management compared to those with AUS-C2 and AUS-NOS features. Keywords: AUS/FLUS, thyroid FNAB, thyroid nodules, ROM, 2017 Bethesda System