Dimyati Achmad
Divisi Bedah Onkologi, Kepala dan Leher, Departemen Ilmu Bedah Fakultas Kedokteran Universitas Padjadjaran Rumah Sakit Dr. Hasan Sadikin Bandung

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Ekspresi Protein B-RAF Mutan pada Karsinoma Tiroid Papilifer yang Bermetastasis ke Kelenjar Getah Bening Regional

Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

AbstrakKarsinoma tiroid papilifer (KTP) dapat tumbuh progresif dan sekitar 33−61% kasus secara klinis telah metastasis ke kelenjar getah bening (KGB) regional pada saat diagnosis ditegakkan. Mutasi gen B-RAF dihubungkan dengan sifat biologis progresivitas KTP. Mutasi gen B-RAF akan mengkode protein B-RAF mutan yang bertindak sebagai regulator sentral pada jalur mytogen activated-pathway kinase (MAPK) dalam proses proliferasi dan dediferensiasi. Mutasi gen B-RAF dapat diidentifikasi pada tingkat deoxyribosenucleic acid (DNA), ribonucleic acid (RNA), dan protein. Masih terdapat kontroversi antara hubungan mutasi B-RAF dan metastasis KGB regional. Tujuan penelitian ini untuk mengetahui hubungan protein B-RAF mutan dengan metastasis ke KGB regional pada KTP. Penelitian ini merupakan penelitian observasional rancangan kuantitatif, studi kasus kontrol berpasangan. Penelitian dilakukan di Subbagian Bedah Onkologi, Kepala dan Leher, Departemen Ilmu Bedah dan Patologi Anatomi Fakultas Kedokteran Universitas Padjadjaran/ Rumah Sakit Dr. Hasan Sadikin Bandung. Sampel penelitian terdiri atas 38 kasus KTP dengan metastasis dan 38 kasus kontrol tanpa metastasis ke KGB regional yang dirawat di Rumah Sakit Dr. Hasan Sadikin Bandung pada periode Januari 2003−Desember 2010 dan dipilih berdasarkan proses matching. Masing-masing kelompok diperiksa B-RAF mutan dengan metode imunohistokimia. Hubungan antara tiap variabel bebas dan variabel tergantung diuji menggunakan analisis bivariat Uji McNemar.Hasil penelitian menunjukkan protein B-RAF mutan memiliki hubungan bermakna (p=0,023) dengan metastasis ke KGB regional pada KTP. Terdapat protein B-RAF mutan pada KTP mempunyai risiko untuk metastasis ke KGB regional sebesar 5,92 kali dibandingkan dengan tanpa mutasi B-RAF. Penelitian ini juga menunjukkan prevalensi B-RAF mutan sebesar 65,8% (32 kelompok kasus dan 18 kelompok kontrol). Simpulan, protein B-RAF mutan memiliki hubungan dengan metastasis ke KGB regional pada KTP. [MKB. 2013;45(4):245–50]Kata kunci: Imunohistokimia, karsinoma tiroid papilifer, metastasis ke KGB regional, mutasi B-RAFMutant B-RAF Protein Expression in Regional Lymph Node Metastasized Papillary Thyroid CarcinomaPapillary thyroid carcinoma (PTC) can become progressive and in about 33−61% of cases it has metastasized to regional lymph nodes at diagnosis. Mutation of B-RAF gene correlated with the biological characteristic of lymph node progressivity. Mutation of B-RAF will encode mutant B-RAF protein which acts as the central regulator on mytogen activated-pathway kinase (MAPK) pathway in terms of proliferation and dedifferentiation processes. B-RAF gene mutation can be identified at deoxyribosenucleic acid (DNA), ribonucleic acid (RNA) and protein levels. There are still controversies in corelation between B-RAF mutation and regional lymph node metastasis. The purpose of this study was to discover the correlation between mutant B-RAF protein and regional lymph node metastasis on PTC. This is a quantitative observational paired case-control study. The study was conducted at the Surgical Oncology, Head and Neck Division Departement of Surgery and Pathology Anatomy Departement, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung in April 2011–January 2012. The sample consisted of 38 PTC cases with metastasis and 38 control cases without regional lymph node metastasis treated in Dr. Hasan Sadikin Hospital between January 2003–December 2010 which have been selected based on the matching process. Each group was examined using the immunohistochemistry method. Correlation between each dependent and non-dependent variables were tested using McNemar bivariate analysis. The results showed that mutant B-RAF protein have a significant correlation (p=0.023) with lymph node metastasis in PTC. The risk of metastasis in B-RAF mutant group was 5.92 times higher than without mutation. This study also showed that from 76 PTC cases studied, the prevalence of mutant B-RAF was about 65.8% (32 in cases and 18 in control group). In conclusion, there is a correlation between mutant B-RAF protein and regional lymph node metastasis in papillary thyroid carcinoma. [MKB. 2013;45(4):245–50]Key words: B-RAF mutation, immunohystochemistry, papillary thyroid carcinoma, regional lymph node metastasis DOI: http://dx.doi.org/10.15395/mkb.v45n4.200

Strategi Pemakaian Epoetin Alfa dalam Mempertahankan Kadar Hemoglobin pada Kemoterapi Ajuvan Berbasis Antrasiklin Karsinoma Payudara Operabel

Indonesian Journal of Cancer Vol 7, No 1 (2013): Jan - Mar 2013
Publisher : "Dharmais" Cancer Center Hospital

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Abstract

Pada kanker payudara operabel dengan metastasis regional, pemberian kemoterapi ajuvan berbasis antrasiklin dapat menyebabkan terjadinya anemia ringan sampai berat pada sekitar 4% - 63% kasus. Telah dilakukan berbagai penelitian tentang peran epoetin alfa sebagai alternatif pengganti transfusi, tetapi hasilnya masih belum memuaskan. Dilakukan penelitian uji klinik desain paralel dengan randomisasi blok terhadap 64 sampel penelitian yang dibagi atas 2 kelompok, yaitu kelompok perlakuan yang mendapatkan epoetin alfa dan kelompok kontrol. Kadar Hb pasca-operasi yang termasuk dalam kriteria inklusi adalah > 10 gr/dL - 12 gr/dL. Epoetin alfa diberikan 1 minggu pasca-mastektomi diteruskan sampai 6 kali pemberian dengan dosis 40.000 IU/ minggu dan kadar Hb dinilai mulai dari pemberian kemoterapi siklus pertama sampai 3 minggu setelah kemoterapi siklus keenam. Hasil penelitian menunjukkan pemberian epoetin alfa dengan strategi di atas mampu mempertahankan kadar hemoglobin di atas 10 gr/dL dan tidak dibutuhkan transfusi selama kemoterapi. Sedangkan pada kelompok kontrol membutuhkan transfusi sebanyak 28,1% kasus dan kebutuhan transfusi paling banyak terjadi pada kemoterapi siklus keempat. Kesimpulan: strategi pemakaian epoetin alfa yang dapat dipilih adalah mulai 1 minggu pasca-mastektomi yang diteruskan sampai kemoterapi siklus kedua atau 6 kali pemberian dengan dosis 40.000 IU/minggu dan kadar Hb pasca-mastektomi harus > 10 gr/dL - 12 gr/dL.Kata kunci: kanker payudara, anemia, epoetin alfa.

Faktor yang Berhubungan dengan Terinfiltrasinya Areola dan Papilla pada Karsinoma Payudara Operabel

Indonesian Journal of Cancer Vol 8, No 1 (2014): Jan - Mar 2014
Publisher : "Dharmais" Cancer Center Hospital

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Abstract

Mastectomy is one of the most frequent surgery performed for operable breast cancer and included resection of the nipple-areola complex (NAC). The risk of local recurrence behind the nipple areolar complex (NAC) is the main limitating of the nipple-sparing mastectomy (NSM) procedure. The aim of this study is to investigate the incidence and to determine associated risk factors with cancer infiltration to nipple-areola complex (NAC) in operable breast cancer patients. This is an observational analytic, cross sectional study using retrospective medical record of patients with mastectomy, at Soedarso Hospital Pontianak from 2006 to 2013. Results: In a period of 7 year, we included 310 patients, the mean age is 47,3 years (24-78 years). The NAC involvements 30,6%. In bivariate analysis showed that age, tumor size, tumor stage, lymh node status, lymvovascular invasion and tumor distance are associated with NAC involvement. In the multivariate analysis showed that only lymh node status (p = 0,001; prevalence odds ratio [POR], 1.52; 95% confidence interval [CI], 1.18?1.95), tumor distance (p<0.001; POR, 0.47; CI, 0.36?0.61) and tumor size (p = 0.012; POR, 2.05; CI, 1.17?3.60) are the only variables that remain significant predictors of NAC involvement. In the logistic regression analysis showed that high risks of NAC involvement are tumor distance >1?2 cm with T2 and lymph node status > 4 or with T3 and lymph node status negative or positive> 1; tumor distance >2?3 cm with T3 and lymph node status > 4. Conclusions: NAC involvement is 30,6%. Predictor factors of NAC involvement are lymh node status, tumor distance and tumor size. High risks of NAC involvement are tumor distance >1?2 cm with T2 and lymph node status > 4 or with T3 and lymph node status negative or positive> 1; tumor distance >2?3 cm with T3 and lymph node status > 4.

Kontroversi Tindakan Bedah Dalam Penatalaksanaan Karsinoma Tiroid Diferensiasi Baik

Indonesian Journal of Cancer Vol 6, No 1 (2012): Jan - Mar 2012
Publisher : "Dharmais" Cancer Center Hospital

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Abstract

Karsinoma tiroid merupakan keganasan sistem endokrin yang paling sering ditemukan dan dalam tiga dekade terakhir insidensinya meningkat tajam. Hampir 90% kasus tergolong kedalam Karsinoma Tiroid diferensiasi baik yang tumbuh lambat dengan prognosis yang baik. Diagnosis ditegakkan berdasarkan pemeriksaan sitologi dari biopsi jarum halus atau melalui pemeriksaan histopatologi dari lobektomi tiroid.Sampai saat ini tindakan bedah dalam penatalaksanaan Karsinoma Tiroid diferensiasi baik masih kontroversial terutama untuk kasus dengan risiko rendah. Satu pihak menganjurkan untuk tiroidektomi total, pihak yang lain cukup lobektomi tiroid saja. Kontroversi juga terjadi dalam hal perlu tidaknya diseksi limfatik level sentral bersama-sama tindakan tiroidektomi total pada KTP.American Thyroid Association merekomendasikan tindakan tiroidektomi total dan diseksi limfatik level sentral untuk Karsinoma Tiroid Papilifer khususnya untuk tumor primer yang invasif dan untuk Karsinoma Tiroid Folikuler cukup tiroidektomi total saja.Kata kunci: Karsinoma Tiroid diferensiasi baik, tindakan bedah.

Strategy for the Use of Erythropoetin Alpha to Maintain Hemoglobin Level in Breast Cancer Patient Treated with Anthracycline-base of Adjuvant Chemotherapy

International Journal of Integrated Health Sciences VOL 1, NO 1, July (2013)
Publisher : International Journal of Integrated Health Sciences

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Abstract

Objective: To evaluate the value of erythropoietin alpha (epoetin) administration, as an alternative treatment of anemia in the operable breast cancer patients.Methods: This is a multicenter phase III randomized clinical trial to evaluate the value of epoetin administration among anemic breast cancer patients who are undergoing anthracyclin-based adjuvant chemotherapy. Sixty four patients were incuded in this trial with initial hemoglobin (Hb) level of 10–12 g/dL. The patients were randomly distributed into two groups: one group received aministration of 40,000 IU epoetin/week for six times a week after operation and the other did not.  In the third week after the operation, both groups were started on a 6 cycles of adjuvant chemotherapy with three weeks intervals. Hb levels were evaluated during every chemotherapy cycle. Results: The Hb levels in the epoetin group were always above 10 g/dL up until the end of the sixth chemotherapy cycle or until the twenty first week post operation without blood transfusion. Conclusions: The administration of epoetin 3 weeks prior and 3 weeks after the first cycles of chemotherapy, maintains a sufficient/normal Hb level in breast cancer patients receiving anthracycline-based chemotherapy.Keywords: Anthracyclin-based chemotherapy, breast cancer, erythropoietin alpha DOI: 10.15850/ijihs.v1n1.102

Faktor yang Berhubungan dengan Terinfiltrasinya Areola dan Papilla pada Karsinoma Payudara Operabel

Indonesian Journal of Cancer Vol 8, No 1 (2014): Jan - Mar 2014
Publisher : Indonesian Journal of Cancer

Show Abstract | Original Source | Check in Google Scholar | Full PDF (610.582 KB)

Abstract

Mastectomy is one of the most frequent surgery performed for operable breast cancer and included resection of the nipple-areola complex (NAC). The risk of local recurrence behind the nipple areolar complex (NAC) is the main limitating of the nipple-sparing mastectomy (NSM) procedure. The aim of this study is to investigate the incidence and to determine associated risk factors with cancer infiltration to nipple-areola complex (NAC) in operable breast cancer patients. This is an observational analytic, cross sectional study using retrospective medical record of patients with mastectomy, at Soedarso Hospital Pontianak from 2006 to 2013. Results: In a period of 7 year, we included 310 patients, the mean age is 47,3 years (24-78 years). The NAC involvements 30,6%. In bivariate analysis showed that age, tumor size, tumor stage, lymh node status, lymvovascular invasion and tumor distance are associated with NAC involvement. In the multivariate analysis showed that only lymh node status (p = 0,001; prevalence odds ratio [POR], 1.52; 95% confidence interval [CI], 1.18?1.95), tumor distance (p<0.001; POR, 0.47; CI, 0.36?0.61) and tumor size (p = 0.012; POR, 2.05; CI, 1.17?3.60) are the only variables that remain significant predictors of NAC involvement. In the logistic regression analysis showed that high risks of NAC involvement are tumor distance >1?2 cm with T2 and lymph node status > 4 or with T3 and lymph node status negative or positive> 1; tumor distance >2?3 cm with T3 and lymph node status > 4. Conclusions: NAC involvement is 30,6%. Predictor factors of NAC involvement are lymh node status, tumor distance and tumor size. High risks of NAC involvement are tumor distance >1?2 cm with T2 and lymph node status > 4 or with T3 and lymph node status negative or positive> 1; tumor distance >2?3 cm with T3 and lymph node status > 4.

Ekspresi Protein B-RAF Mutan pada Karsinoma Tiroid Papilifer yang Bermetastasis ke Kelenjar Getah Bening Regional

Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

Show Abstract | Original Source | Check in Google Scholar

Abstract

AbstrakKarsinoma tiroid papilifer (KTP) dapat tumbuh progresif dan sekitar 33−61% kasus secara klinis telah metastasis ke kelenjar getah bening (KGB) regional pada saat diagnosis ditegakkan. Mutasi gen B-RAF dihubungkan dengan sifat biologis progresivitas KTP. Mutasi gen B-RAF akan mengkode protein B-RAF mutan yang bertindak sebagai regulator sentral pada jalur mytogen activated-pathway kinase (MAPK) dalam proses proliferasi dan dediferensiasi. Mutasi gen B-RAF dapat diidentifikasi pada tingkat deoxyribosenucleic acid (DNA), ribonucleic acid (RNA), dan protein. Masih terdapat kontroversi antara hubungan mutasi B-RAF dan metastasis KGB regional. Tujuan penelitian ini untuk mengetahui hubungan protein B-RAF mutan dengan metastasis ke KGB regional pada KTP. Penelitian ini merupakan penelitian observasional rancangan kuantitatif, studi kasus kontrol berpasangan. Penelitian dilakukan di Subbagian Bedah Onkologi, Kepala dan Leher, Departemen Ilmu Bedah dan Patologi Anatomi Fakultas Kedokteran Universitas Padjadjaran/ Rumah Sakit Dr. Hasan Sadikin Bandung. Sampel penelitian terdiri atas 38 kasus KTP dengan metastasis dan 38 kasus kontrol tanpa metastasis ke KGB regional yang dirawat di Rumah Sakit Dr. Hasan Sadikin Bandung pada periode Januari 2003−Desember 2010 dan dipilih berdasarkan proses matching. Masing-masing kelompok diperiksa B-RAF mutan dengan metode imunohistokimia. Hubungan antara tiap variabel bebas dan variabel tergantung diuji menggunakan analisis bivariat Uji McNemar.Hasil penelitian menunjukkan protein B-RAF mutan memiliki hubungan bermakna (p=0,023) dengan metastasis ke KGB regional pada KTP. Terdapat protein B-RAF mutan pada KTP mempunyai risiko untuk metastasis ke KGB regional sebesar 5,92 kali dibandingkan dengan tanpa mutasi B-RAF. Penelitian ini juga menunjukkan prevalensi B-RAF mutan sebesar 65,8% (32 kelompok kasus dan 18 kelompok kontrol). Simpulan, protein B-RAF mutan memiliki hubungan dengan metastasis ke KGB regional pada KTP. [MKB. 2013;45(4):245–50]Kata kunci: Imunohistokimia, karsinoma tiroid papilifer, metastasis ke KGB regional, mutasi B-RAFMutant B-RAF Protein Expression in Regional Lymph Node Metastasized Papillary Thyroid CarcinomaPapillary thyroid carcinoma (PTC) can become progressive and in about 33−61% of cases it has metastasized to regional lymph nodes at diagnosis. Mutation of B-RAF gene correlated with the biological characteristic of lymph node progressivity. Mutation of B-RAF will encode mutant B-RAF protein which acts as the central regulator on mytogen activated-pathway kinase (MAPK) pathway in terms of proliferation and dedifferentiation processes. B-RAF gene mutation can be identified at deoxyribosenucleic acid (DNA), ribonucleic acid (RNA) and protein levels. There are still controversies in corelation between B-RAF mutation and regional lymph node metastasis. The purpose of this study was to discover the correlation between mutant B-RAF protein and regional lymph node metastasis on PTC. This is a quantitative observational paired case-control study. The study was conducted at the Surgical Oncology, Head and Neck Division Departement of Surgery and Pathology Anatomy Departement, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung in April 2011–January 2012. The sample consisted of 38 PTC cases with metastasis and 38 control cases without regional lymph node metastasis treated in Dr. Hasan Sadikin Hospital between January 2003–December 2010 which have been selected based on the matching process. Each group was examined using the immunohistochemistry method. Correlation between each dependent and non-dependent variables were tested using McNemar bivariate analysis. The results showed that mutant B-RAF protein have a significant correlation (p=0.023) with lymph node metastasis in PTC. The risk of metastasis in B-RAF mutant group was 5.92 times higher than without mutation. This study also showed that from 76 PTC cases studied, the prevalence of mutant B-RAF was about 65.8% (32 in cases and 18 in control group). In conclusion, there is a correlation between mutant B-RAF protein and regional lymph node metastasis in papillary thyroid carcinoma. [MKB. 2013;45(4):245–50]Key words: B-RAF mutation, immunohystochemistry, papillary thyroid carcinoma, regional lymph node metastasis DOI: http://dx.doi.org/10.15395/mkb.v45n4.200

Strategy for the Use of Erythropoetin Alpha to Maintain Hemoglobin Level in Breast Cancer Patient Treated with Anthracycline-base of Adjuvant Chemotherapy

International Journal of Integrated Health Sciences Vol 1, No 1 (2013)
Publisher : International Journal of Integrated Health Sciences

Show Abstract | Original Source | Check in Google Scholar

Abstract

Objective: To evaluate the value of erythropoietin alpha (epoetin) administration, as an alternative treatment of anemia in the operable breast cancer patients.Methods: This is a multicenter phase III randomized clinical trial to evaluate the value of epoetin administration among anemic breast cancer patients who are undergoing anthracyclin-based adjuvant chemotherapy. Sixty four patients were incuded in this trial with initial hemoglobin (Hb) level of 10–12 g/dL. The patients were randomly distributed into two groups: one group received aministration of 40,000 IU epoetin/week for six times a week after operation and the other did not.  In the third week after the operation, both groups were started on a 6 cycles of adjuvant chemotherapy with three weeks intervals. Hb levels were evaluated during every chemotherapy cycle. Results: The Hb levels in the epoetin group were always above 10 g/dL up until the end of the sixth chemotherapy cycle or until the twenty first week post operation without blood transfusion. Conclusions: The administration of epoetin 3 weeks prior and 3 weeks after the first cycles of chemotherapy, maintains a sufficient/normal Hb level in breast cancer patients receiving anthracycline-based chemotherapy.Keywords: Anthracyclin-based chemotherapy, breast cancer, erythropoietin alpha DOI: 10.15850/ijihs.v1n1.102