Download - Kanker Kuliah s2 Revisi 28 Ag 2010
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KANKER PARUKANKER PARU
Dr Ana Rima SpPDr Ana Rima SpP
Dr dr Eddy Surjanto, SpP(K)Dr dr Eddy Surjanto, SpP(K)
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KANKER PARU KANKER PARU Kanker paru : kanker paru primer, tumor Kanker paru : kanker paru primer, tumor ganas yang berasal dari epitel bronkus ganas yang berasal dari epitel bronkus atau karsinoma bronkus atau karsinoma bronkus
Kanker paru dalam arti luas :Kanker paru dalam arti luas :Semua penyakit keganasan di paru, Semua penyakit keganasan di paru, mencakup keganasan yang berasal dari mencakup keganasan yang berasal dari paru sendiri mapun keganasan dari luar paru sendiri mapun keganasan dari luar paru (metastasis tumor di paru )paru (metastasis tumor di paru )
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Perubahan/mutasi gen hiperekspresi onkogen &/ hilangnya fx gen tumor supresor
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Risk Factors for LUNG CaRisk Factors for LUNG Ca
Smoking (85% of cases)Smoking (85% of cases)
Environmental factorsEnvironmental factors– Second-hand smokeSecond-hand smoke– RadonRadon
Radiation exposureRadiation exposure
Prior lung disease (“scar carcinoma”) Prior lung disease (“scar carcinoma”)
Exposure to other carcinogensExposure to other carcinogens
Genetic factorsGenetic factors
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DIAGNOSIS DIAGNOSIS
Anamnesis : Anamnesis : Sesak napas Sesak napas Sulit / sakit menelan Sulit / sakit menelan Benjolan di pangkal leherBenjolan di pangkal leher Sembab muka dan leher Sembab muka dan leher
Disertai keluhan yang tidak khas :Disertai keluhan yang tidak khas : Berat badan berkurang Berat badan berkurang Nafsu makan hilang Nafsu makan hilang Demam hilang timbul Demam hilang timbul
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PEMERIKSAAN JASMANIPEMERIKSAAN JASMANI PEMERIKSAAN PENUNJANGPEMERIKSAAN PENUNJANG PEMERIKSAAN KHUSUSPEMERIKSAAN KHUSUS
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GAMBARAN RADIOLOGIS GAMBARAN RADIOLOGIS
Foto thoraks lateralFoto thoraks lateral
CT scan thorax dg CT scan thorax dg kontras include upper kontras include upper abdomenabdomen
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Lung Cancer Histology
Non-small cell (NSCLC)– 75-80% of all lung
cancers– Squamous-cell,
adenocarcinoma (including bronchoalveolar), large-cell
Small-cell (SCLC)– 20-25% of all lung cancers
Carcinoid– 2% of all lung tumors– Typically indolent– Good prognosis
Squamous-cell30%
Adenocarcinoma30-40%
Large-cell10-15%
Small-cell20-25%
Bronchoalveolar4%
Carcinoid2%
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PENDERAJATAN (STAGING)PENDERAJATAN (STAGING)KANKER PARU jenis KPKBSK KANKER PARU jenis KPKBSK
T: tumorT: tumor N : Kelenjar getah bening N : Kelenjar getah bening M : Metastasis M : Metastasis
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Stad IA: T1, N0, M0 Stad IB: T2, N0,M0 T1: <3cm, invasi≤ bronkus lobus; T2: >3cm, br utama>2 cm
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IIA: T1N1M0 IIB: T2N1M0 T3N0M0
T3: perluasan langsung dinding dada, diafragma, pleura mediastinum, Brchus utama <2cm,
atelektasis/pneumonitis paru
N1: KGB peribronkialHilus ipsilateral
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T1N2M0 ; T2N2M0 T3N1M0 ; T3N2M0
N2: KGB mediastinum ipsilateral, KGB subkarina
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T4: Sbrng ukuran mengenai mediastinum/jantung, vaskuler besar, trakhea, esofagus, karina, dg efusi pl ganas,satelit nodul ipsilateral lobus sama
N3: hilus/mediastinum kontralateral; skalenus/supraklavikuler
Sembarang T, N3, M0T4, sembarang N, M0
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PENDERAJATAN KANKER PARU
Berdasarkan Proposals for the revision of the TNM stage groups in the forthcoming(seventh) edition of the TNM Classification of malignant tumours.J.Thorac Oncol 2007 penderajatan kanker paru sebagai berikut:
Goldstraw P, Crowley J, Chansky K. Proposals for The revision of the TNM stage group in the forthcoming (seventh) edition of TNM classification of malignant tumours. J .Thorac Oncol 2007; 2 :706.
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Tumor primer (T)T1 : Tumor diameter < 3 cm terletak di paru atau
pleura visceral, belum mengenai proksimal bronkus.
T1a : diameter tumor < 2 cm T1b : diameter tumor > 2 cm T2 : Tumor > 3cm tetapi < 7 cm dengan :
Mengenai brokus utama > 2 cm bawah karina. Mengenai pleura visceral Dengan atelektasis obstruktif pneumonia meluas ke hilus tetapi tidak seluruh paru.
Goldstraw P, Crowley J, Chansky K. Proposals for The revision of the TNM stage group in the forthcoming (seventh) edition of TNM classification of malignant tumours. J .Thorac Oncol 2007; 2 :706.
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T2a : tumor < 5 cm
T2b : tumor > 5 cm
T3 : Tumor > 7 cm atau bila didapatkan: invasi tumor ke dinding dada,nervus prenikus diafragma, mediastinum, pleura parietal, pericardium, bronkus utama < 2 cm dari karina (belum mengenai karina).
Atelektasis atau obstruksi pneumonitis seluruh paru.
Nodul tumor terpisah di lobus yang sama.
Goldstraw P, Crowley J, Chansky K. Proposals for The revision of the TNM stage group in the forthcoming (seventh) edition of TNM classification of malignant tumours. J .Thorac Oncol 2007; 2 :706.
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T4 : tumor dengan ukuran sembarang
menginvasi:
mediastinum,jantung,pembuluh
darah besar, trakea, nervus rekuren
laryngeal, nervus esophagus, tulang
belakang, karina atau dengan nodul
tumor di ipsilateral lobus berbeda.
Goldstraw P, Crowley J, Chansky K. Proposals for The revision of the TNM stage group in the forthcoming (seventh) edition of TNM classification of malignant tumours. J .Thorac Oncol 2007; 2 :706.
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Kelenjar limfe regional (N)NO : tidak ada metastase ke kelenjar limfe regional.N1 : metastase ke peribronkial ipsilateral dan atau hilus ipsilateral dan kelenjar intrapulmonal.N2 : metastase ke ipsilateral mediastinum dan atau kelenjar limfe subkarina.N3 : metastase ke mediastinum kontralateral,hilus kontralateral, kontralateral mediastinal, kontralateral hilar, ipsilateral atau kontralateral skapula atau kelenjar limfe supraklavikular
Goldstraw P, Crowley J, Chansky K. Proposals for The revision of the TNM stage group in the forthcoming (seventh) edition of TNM classification of malignant tumours. J .Thorac Oncol 2007; 2 :706.
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Metastase luas (M)
M0 : tidak ada metastase luas.
M1 : Metastase luas
M1a : nodul tumor terpisah di
kontralateral lobus : dengan
nodul pleura atau keganasan
pleura atau efusi pleura.
M1b : metastase luas ke organ lain
Goldstraw P, Crowley J, Chansky K. Proposals for The revision of the TNM stage group in the forthcoming (seventh) edition of TNM classification of malignant tumours. J .Thorac Oncol 2007; 2 :706.
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PenderajatanStadium IA :T1a-T1bNOMO
Stadium IB :T2aNOMO
Stadium IIA:T1a-T2aN1MO
:T2bNoMO
Stadium IIB:T2bN1MO
:T3NOMO
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Penderajatan
Stadium IIIA :T1a-T3N2MO
T3N1MO
T4NO-N1MO
Stadium IIIB :T4N2MO
T1a-T4N3MO
Stadium IV :sembarang T,sembarang N
M1a atau M1b
Goldstraw P, Crowley J, Chansky K. Proposals for The revision of the TNM stage group in the forthcoming (seventh) edition of TNM classification of malignant tumours. J .Thorac Oncol 2007; 2 :706.
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TAMPILAN TAMPILAN SKALA SKALA
KARNOFSKIKARNOFSKISKALA SKALA
WHOWHOKETERANGANKETERANGAN
90 – 10090 – 100 00 Aktivitas nrmalAktivitas nrmal
70 – 8070 – 80 11 Ada keluhan tetapi masih aktif dan Ada keluhan tetapi masih aktif dan dapat mengurus sendridapat mengurus sendri
50 – 6050 – 60 22 Cukup aktif namun kadang-kadang Cukup aktif namun kadang-kadang memerlukan bantuanmemerlukan bantuan
30 – 4030 – 40 33 Kurang akti perlu perawatanKurang akti perlu perawatan
10 – 2010 – 20 44 Tidak dapat meninggalkan tempat tidur, Tidak dapat meninggalkan tempat tidur, perlu rawat di rumah sakitperlu rawat di rumah sakit
0 – 100 – 10 -- Tidak sadarTidak sadar
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PILIHAN MODALITAS TERAPI
Jenis sel kanker
Stadium
Performance status (tampilan)
Faktor lain
Kewajiban dokter
Memilihkan dan menjelaskan modalitas terbaik bagi px saat itu meski keputusan akhir adalah hak pasien
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Pembedahan: Stad I & II ”curable” Wedge resection, lobectomy, pneumectomy
Wedge resectionWedge resection
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KEMOTERAPI
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Farmakologi sitostatika
Alkylating agent
Antibiotic antineoplastics
Antimetabolites
Antineoplastic that alter hormon balance
Biological response modifiers
Miscellaneous antineoplastics
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Alkylating agent (rest phase)
Alkil klasik:
Nitrogen mustards(Cyclophosphamide, Melphalan, Ifosfamide )
- G1
Alkylating-like / metal salt (cisplatin, carboplatin)
- G1
- berikatan dg adenin, guanin
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Plant Alkaloids
Anti microtubule agent:
- Vinca alkaloids: Vincristine, Vinblastine and Vinorelbine.
- Taxanes ( fase M): Paclitaxel and Docetaxel.
Topoisomerase inhibitors (fase G2):
- Podophyllotoxins: Etoposide and Tenisopide.
- Camptothecan analogs: Irinotecan and Topotecan
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Antitumor Antibiotics ( multiple phases of the cell
cycle ) cell-cycle specific Anthracyclines: Doxorubicin, Chromomycins:
Miscellaneous: Mitomycin and Bleomycin.
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Antimetabolites
Folic acid antagonist: Methotrexate.
Pyrimidine antagonist (fase S): 5-Fluorouracil, Gemcitabine.
Purine antagonist:
Adenosine deaminase inhibitor:
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Indikasi kemoterapi
KPKSK
KPKBSK inoperable. Bisa dikombinasi dg radioterapi
Kemoterapi Adjuvan
Kemoterapi neoadjuvan
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Kemoterapi
Semua staging (termsuk stad I, II yg tidak layak bedah) Syarat 2 terpenuhi
- fx hematopoetik, ginjal & hati - tampilan 2 skala WHO
Tujuan utama tatalaksana KPKBSK advanced adalah: Memperpanjang survivalMeningkatkan kualitas hidup – Mengurangi gejala paliatif – Manajemen efek samping akibat terapi
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Standar rejimen berbasis platinum Kemoterapi minimal 2 siklus, penilaian subjektif dan objektif (foto toraks) untuk menentukan dapat dilanjutkan atau tidak. Penilaian objektif yang lebih baik dilakukan dengan CT-scan toraks setelah 3 siklus. Respons baik (complete, partial /Stable Disease) kemoterapi diteruskan hingga 4 – 6 x. Progresif: harus diganti
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Radioterapi
Dapat pd semua staging Tampilan boleh > 2 Dosis 5.000 – 6.000 cGy pada tumor primer
Kombinasi kemoterapi dan radioterapi memberikan hasil lebih baik ( alternating/ konkuren/ sekuensial )
-Radio ± kemoterapi sbg tx kuratif yg potensial untuk stad I dan II pd kasus yg scr medis tdk dpt dioperasi tp tampilan dan life expectancy memungkinkan-
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Therapeutic Options by StagePotential Options Prognosis*
Stage I • Surgery
• Radiation
• Adjuvant chemotherapy(stage Ib only)
• Generally best prognosis• Surgery may reveal more-
extensive disease than previously suspected
• Radiation is given to medically inoperable patients
• 5-year survival rate of 38%–67%
Stage II
• Surgery
• Radiation
• Adjuvant chemotherapy
• 5-year survival rate of 24%–55%
Stage
IIIA
• Surgery (selected cases)
• Chemotherapy combined with other modalities
• Surgery and radiation (selected cases)
• Radiation
• 5-year survival rate of 13%–23%
13%
10%
22%
Percent atPresentation†
•Based on both clinical and surgical-pathologic staging information.†Based on clinical staging information.
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Therapeutic Options by StagePotential Options Prognosis*
Stage IIIB
• Radiation
• Chemotherapy with radiation
• Chemotherapy
• Chemotherapy and concurrent radiotherapy followed by resection
• 5-year survival rate of 5%
Stage IV • Chemotherapy
• Radiation for palliative relief of local tumor symptoms
• Best supportive care
• Poor prognosis with all treatments
• 5-year survival rate of 1%
Percent atPresentation
†
22%
32%
*Only clinical staging information available for stages IIIb and IV.
†Based on clinical staging information.
(cont)
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0 2 4 6 8 10 12 14
1970s
1980s
1990s
2000s
BSC:2–5 months
Single-agent platinum:6–8 months
Platinum-based doublets:8–10 months
Median survival (months)
Chemotherapy combinations have
failed to substantially
improve median overall survival
(OS) beyond 8–10 months
Should We Try with More Innovative Approach ?
Therapeutic plateau has been reached; new chemotherapy combinations unlikely to further improve survival
BSC = best supportive careSchiller, et al. NEJM 2002Sandler, et al. NEJM 2006
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BSC:2–5 months
Single-agent platinum:6–8 months
Platinum-based doublets:8–10 months
Median survival (months)
Schiller, et al. NEJM 2002Sandler, et al. NEJM 2006
0 2 4 6 8 10 12 14
2000s
1990s
1980s
1970s
Platinum-based doublet + Avastin12.3 months
Bevacizumab-based therapy is the first treatment to increase OS in non-squamous NSCLC
beyond 1 year
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VEGF and EGFR representrational targets for anticancer therapy
Potential Targets in NSCLC
VEGF is the key mediator of tumour angiogenesisand is essential for tumour growth and metastasis
EGFR plays a vital role in the growthand progression of malignant tumours
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Kemo terapi konvensionalTarget: Pembelahan sel → sel kanker maupun sel sehatRespons rate: Semua kasus 20 -30 %Siklus: max: 6 siklus. (4 siklus / stabil + 2)CYTOTOXIC
TERAPI TARGETTERAPI TARGET
Target: Sinyal transduction Sinyal transduction pathway dari proses karsinogenesis/pathway dari proses karsinogenesis/ pertumbuhan tumorpertumbuhan tumorRespons rate:semua kasus : 9-19%, plus 30% stable diseaseFaktor prediksi positif/ mutasi EGFR: >70%Jumlah siklus: penyakit kronikCYTOSTATIC
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Monoclonal antibody trhdp VEGF
VEGF adalah regulator angiogenesis yg utama baik pd sel normal maupun sel ganas Multiplikasi sel ganas harus ditunjang nutrisi yg cukup → angiogenesis Bevacizumab (Avastin) Mencegah VEGF berikatan dg receptor
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Kanker paru Karsinoma Sel Kecil
Limited
Extensive
Mudah metastasis
Kemoradioterapi
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MANAJEMEN ENDOBRONKHIAL PADA KPBSK
Berbagai modalitas untuk keganasan rongga toraks terutama kanker paru dalam keadaan khusus dapat dilakukan dengan prosedur bronkoskopi terutama untuk mengatasi pendarahan dan obstruksi saluran napas
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Stenting
Tx paliatif invasif minimal bg px dng obstruksi sal napas sentral pd Ca yg unresectable
Dpt dilakukan bersama pemberian laser
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brachiterapy
meradiasi tumor intrabronkus
paliatif untuk menghilangkan simptom (perdarahan , obstruksi)
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cryotherapy
teknik pembekuan untuk menghancurkan
jaringan yang tidak diinginkan
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Photodynamic Therapy
Menyuntikkan photosensitizing agent IVZat diabsorbsi sel Ca. Jaringan Ca tsb diberi sinar khusus(red light) yg akan menghancurkan kanker.
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TUMOR MEDIASTINUMTUMOR MEDIASTINUM
Dr Ana Rima SpPDr Ana Rima SpP
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INSIDENSIINSIDENSI
Dapat terjadi pada siapa saja Dapat terjadi pada siapa saja (anak sampai dewasa)(anak sampai dewasa)
Dewasa : Dewasa : ± 75 % jinak± 75 % jinak
Anak-anak : Anak-anak : ± 40-50% ganas± 40-50% ganas
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Secara garis besar mediastinum dibagi atas 4 bagian penting :
Mediastinum superior, mulai pintu atas rongga dada sampai ke vetebra torakal ke-5 dan bagian bawah sternumMediastinum anterior, dari garis batas mediastinum superior ke diafragma di depan jantungMediastinum posterior, dari garis batas mediastinum superior ke diafragma di belakang jantungMediastinum medial (tengah), dari garis batas mediastinum superior ke diafragma di antara mediastinum anterior dan posterior
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GEJALA DAN TANDA-TANDA GEJALA DAN TANDA-TANDA KLINISKLINIS
Lesi jinak Lesi jinak asimtomatis. asimtomatis.
Sebagian besar tumor Sebagian besar tumor mediastinum ditemukan saat foto mediastinum ditemukan saat foto toraks rutin (check up)toraks rutin (check up)
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GEJALA-GEJALA TUMOR MEDIASTINUMGEJALA-GEJALA TUMOR MEDIASTINUMJINAK DAN GANAS (N= 101)JINAK DAN GANAS (N= 101)
JinakJinak GanasGanas
1.1. Sakit dadaSakit dada 3434 5858
2.2. BatukBatuk 2828 5050
3.3. Sesak nafasSesak nafas 2222 3030
4.4. Batuk darahBatuk darah 1212 1010
5.5. Gangguan menelanGangguan menelan 7 7 1515
6.6. Berat badan turunBerat badan turun 5 5 3737
7.7. Suara serakSuara serak 2 2 1212
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FREKUENSI JENIS-JENIS FREKUENSI JENIS-JENIS HISTOPATOLOGI TUMOR MEDIASTINUMHISTOPATOLOGI TUMOR MEDIASTINUM
1.1. Tumor neurogenikTumor neurogenik 21%21%2.2. TimomaTimoma 19%19%3.3. LimfomaLimfoma 12%12%4.4. Germ cell tumorGerm cell tumor 10%10%5.5. Kanker primerKanker primer 4% 4%6.6. Tumor mesenkimalTumor mesenkimal 6% 6%7.7. Tumor endokrinTumor endokrin 7% 7%8.8. Lain-lainLain-lain 3% 3%9.9. KistaKista 18%18%
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DATA RS PERSAHABATANDATA RS PERSAHABATANTAHUN 1970-1990TAHUN 1970-1990
(n=137)(n=137)
Teratoma Teratoma = 44 (32%)= 44 (32%)
TimomaTimoma = 33 ( 24%)= 33 ( 24%)
Tumor neurogenikTumor neurogenik = 11 (8%)= 11 (8%)
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DIAGNOSISDIAGNOSIS
Foto toraks PA dan lateralFoto toraks PA dan lateral
CT- scan /MRICT- scan /MRI
Bronkoskopi, mediastinokopi, esofagoskopi, Bronkoskopi, mediastinokopi, esofagoskopi, torakoskopi diagnostiktorakoskopi diagnostik
TTNA/FNABTTNA/FNAB
EkokardiagrafiEkokardiagrafi
Angiografi (untuk deteksi aneurisma)Angiografi (untuk deteksi aneurisma)
EsofagografiEsofagografi
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Tumor MediastinumTumor Mediastinum
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TUMOR PARU
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TUMOR MEDIASTINUM
TUMOR PARU
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Tumor MediastinumTumor MediastinumGanasGanas
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Tumor MediastinumTumor Mediastinum
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KOMPLIKASI TTB/FNAB PADA TUMOR MEDIASTINUM
Komplikasi
Batuk darah 2 (2,3 %)
Pneumotoraks13 (15,4 %)
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TERAPI
TIROID + PARATIROID
KANKER PRIMER
KISTA
TUMOR NEUROGENIK
TUMOR P.DARAH/ LIMFE
OPERASI
OPERASI
OPERASI
OPERASI
OPERASI
Ajuvan Radioterapi+ Kemoterapi
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TERAPI
TIMOMA
LIMFOMA
TERATOMA
SEMINOMA
KARSINOID
OPERASI
KEMOTERAPI
OPERASI
KEMOTERAPI
OPERASIAjuvan radioterapi
+ Kemoterapi
Neoajuvan kemoterapi
RADIOTERAPI
RADIOTERAPI
Kemo+radio tx
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