170707469 gist workshop
TRANSCRIPT
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WORKSHOP GIST SEMARANG 14 SEPTEMBER 2013
INTESTINAL GIST
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ANAMNESIS
Laki-laki 44 tahun,
12 bulan perut merasa tidak enak,kadang-kadang mules, pernah berak kehitaman. Hanya diobatkan ke dokter puskesmas
3 bulan teraba benjolan yang makin lama makin membesar, perut terasa sebah dan mules sekali dan berak hitam makin jelas
Nafsu makan kurang dan berat badan menurun
Riwayat family dengan tumor abdomen disangkal
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PEMERIKSAAN FISIK
Laki-laki berat badan: 42 Kg, TB 165 cm, BMI : 15,44
Kurus, nampak pucat Abdomen kembung ringan, terlihat bulging perut
dibagian tengah, gambaran dan gerakan usus tidak terlihat.
Palpasi teraba tumor diameter sekitar 12 cm, bulat dengan permukaan tidak rata, konsistensi keras, nyeri tekan (-), relatif mobile
Auscultasi: Peristaltik normal, tidak terdengar bising diatas tumor
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LABORATORIUM
Hb 7,8 Mg%, Ht 24, Lekosit 6500
Alb 2,8 mg%, Glob 2,3 mg%
Na 134, K 3,2, Cl 98, Ca 2,10
Lain-lain baik.
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DIAGNOSA BANDING
LYMPHOMA MALIGNA
HODGKIN DISEASE
SCWANOMA MALIGNA
LEIOMYOSARCOMA
INSTESTINAL GIST
PERLU KEPASTIAN DIAGNOSIS SEBELUM OPERASI?
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PERSIAPAN PRA-BEDAH
ANEMIA: BLOOD TRANFUSION
SEVERE MALNUTRITION
PRE-OPERATIVE NUTRITIONAL SUPPORT
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LAPARATOMI
TUMOR USUS HALUS PERTENGAHAN (PERBATASAN ILEUM-JEJENUM) SEKITAR 14 CM, KERAS, LN MESENTERIKA (-), PERITONEAL
SEEDING (-), METASTASE HEPAR (-)
TANDA PARTIAL OBSTRUKSI USUS (+)
DILAKUKAN RESEKSI USUS HALUS ISTAL DAN PROKSIMAL TUMOR, ANASTOMOSIS END TO END
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PASCA BEDAH
PASIEN BAIK PULANG TANPA KOMPLIKASI
PA SPINDEL CELL TUMOR CURIGA GIST, BATAS RESEKSI BEBAS TUMOR, MITOSIS(?)
IHC CD 117 (+)
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PEMBAHASAN
Diagnostic procedure?
Grade?
Surgery?
Chemotherapy (preoperative? post-operative?)
Prognosis?
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DIAGNOSTIC PROCEDURE?
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PREOPERATIVE DIAGNOSIS
ENDOSCOPY:
DOUBLE BALLON ENTEROSCOPY?
CAPSULE ENDOSCOPY?
LAPARATOMY/ LAPAROSCOPY BIOPSY?
NO NEED DIRECT LAPARATOMY & RESECTION OR BIOPSY.
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GRADING
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POLSKIE ARCHIWUM MEDYCYNY WEWNTRZNEJ 2008; 118 (4)
HUMAN PATHOLOGY Volume33, No. 5 (May 2002)
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NIH Classification for Risk of Recurrence
Very Low Risk Low Risk Intermediate Risk High Risk
NIH consensus criteria1
Tumor size < 2 cm Mitotic index < 5
Tumor size 2-5 cm Mitotic index < 5
Tumor size 5-10 cm Mitotic index < 5
OR Tumor size < 5 cm Mitotic index 6-10
Tumor size > 5 cm Mitotic index > 5
OR Tumor size > 10 cm Mitotic index, any
OR Tumor size, any Mitotic index > 10
Modified NIH consensus classification2
Any location: Tumor size < 2 cm Mitotic index 5
Any location: Tumor size 2.1-5 cm Mitotic index 5
Any location: Tumor size < 5 cm Mitotic index 6-10 Gastric: Tumor size 2.1-5 cm Mitotic index > 5
OR Tumor size 5.1-10 cm Mitotic index 5
Any location: Tumor rupture
OR Tumor size > 10 cm
OR Mitotic index > 10
OR Tumor size > 5 cm Mitotic index > 5 Nongastric: Tumor size 2.1-5 cm Mitotic index > 5
OR Tumor size 5.1-10 cm Mitotic index 5
Abbreviations: Mitotic index, number of mitoses per 50 high-power fields; NIH, National Institutes of health. 1. Fletcher CD, et al. Hum Pathol. 2002;33(5):459-465; 2. Joensuu H. Hum Pathol. 2008;39(10):1411-1419.
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GRADE
TUMOR > 10 CM
MITOTIC INDEX: NOT REPORTED
NEGATIVE MARGIN
LOCATION: NON GASTRIC
HIGH RISK GROUP FOR RECCURRENCE
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SURGERY
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Surgical treatment of gist
The radical surgical treatment is the most effective treatment
The 5-year survival rate after surgery amounts to 2865% It is not necessary to resect the regional lymph nodes
because GIST do not metastasize to the regional lymphatic system
2040% of the surgery patients have intra-abdominal dissemination or liver metastasis paliatif surgery (sympotomatic treatment)
endoscopic dissection (submucosal-mucosal resection) allows a radical therapy of small tumors without malignancy features and limited to the submucosal layer.
POLSKIE ARCHIWUM MEDYCYNY WEWNTRZNEJ 2008; 118 (4)
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CHEMOTHERAPY Preoperative : need histological diagnosis
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PROGNOSIS
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The 5-year survival rate after surgery of GIST amounts to 2865%
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778 patients 18 y Localized and
primary GIST KIT-positive
tumors 3 cm Complete surgical
resection Placebo for 1 y
Imatinib 400 mg/d for 1 y
Imatinib 400/800 mg/d
713 patients randomized
Imatinib 400 mg/d
DeMatteo RP, et al. Lancet. 2009;37(9669)3:1097-1104.
Phase 3 ACOSOG Z9001: Trial Schema
Endpoints:
Primary: Recurrence-free survival Secondary: Overall survival, safety
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At time of recurrence
At time of recurrence
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Abbreviations: CI, confidence interval; HR, hazard ratio. a All randomized patients were included in the analysis; recurrence-free survival was defined as the time from patient registration to the development of tumor recurrence or death from any cause. Intention-to-treat analyses were done for recurrence-free survival (ie, analyzed patients by randomized group). Adapted from DeMatteo RP, et al. Lancet. 2009;373(9669):1097-1104.
Recurrence-Free Survivala
HR = 0.35 (95% CI = 0.22, 0.53); P < .0001 100
90
80
70
60
50
40
30
20
10
0
Re
curr
en
ce-F
ree
and
Aliv
e, %
0 6 12 18 24 30
Time, mo
36 42 48
Imatinib Placebo
359 354
30 70
Total Events
Median follow-up: 19.7 mo
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Size 10 cm
Size 3 and < 6 cm Size 6 and < 10 cm
Recurrence-Free Survival (Tumor Size)
Imatinib adjuvant therapy results in significantly longer RFS in each of the tumor size categories compared with placebo
100 90 80 70 60
50 40 30 20 10
0 Rec
urr
ence
-Fre
e an
d A
live
, %
0 6 12 18 24 30 36 42 48
100 90 80 70 60 50 40
30 20 10
0 Rec
urr
ence
-Fre
e an
d A
live,
%
0 6 12 18 24 30 36 42 48
Imatinib, n = 143 Placebo, n = 149
HR = 0.23 (95% CI = 0.07, 0.79); P = .011
Imatinib, n = 93 Placebo, n = 86
HR = 0.29 (95% CI = 0.16, 0.55); P < .001
Time, mo
Time, mo
100 90 80 70 60 50 40 30 20 10
0 Rec
urr
ence
-Fre
e an
d A
live,
%
0 6 12 18 24 30 36 42 48 Time, mo
Imatinib, n = 123 Placebo, n = 119
HR = 0.50 (95% CI = 0.25, 0.98); P = .041
Abbreviations: CI, confidence interval; HR, hazard ratio; RFS, recurrence-free survival. Adapted from DeMatteo RP, et al. Lancet. 2009;373(9669):1097-1104.
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Follow-up
Follow-up
Phase 3 SSGXVIII: Study Design
Randomized 1:1
Imatinib 12 mo
400 patients
KIT-positive histologically confirmed GIST
High recurrence risk according to modified NIH consensus criteria
Endpoints:
Primary: Recurrence-free survival Secondary: Overall survival, safety
Imatinib 36 mo
Abbreviation: NIH, National Institutes of Health. Data from Joensuu H, et al. JAMA. 2012;307(12):1265-1272.
Key Elements:
Patient stratification: R0 resection, no tumor rupture R1 resection OR tumor rupture
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HR = 0.46 (95% CI = 0.32, 0.65); P < .0001
SSGXVIII: Recurrence-Free Survival (ITT)
Abbreviations: CI, confidence interval; HR, hazard ratio; ITT, intent to treat. Adapted from Joensuu H, et al. JAMA. 2012;307(12):1265-1272.
60.1%
47.9%
86.6%
65.6%
36 mo, n = 198
12 mo, n = 199
0 1 2 3 4 5 6 0
20
40
60
80
100
Median follow-up, 54 mo
Time, y
Re
curr
en
ce-F
ree
an
d A
live
, %
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