GIST short note by by S.

Wichien (SNG KKU)

GIST -rare tumor of GI (0.1%) -most common mesenchymal tumor of GI -M>F -50-60 years -Interstitial Cell of Cajal (ICC) : pacemaker of GI tract -abnormal KIT receptor 1.mutation of C-Kit protoonco 90% 2.mutation of PDGFR gene 5-10% -wide type GIST : no mutation of C-Kit nor PDGFR : DOG 1 gene KIT mutation -exon9response Glivec -exon11double dose Glivec -wild typenot rxn Glivec Location 1.stomach (fundus) 50-60% 2.jejunum/ileum 25% 3.duodenum 5% 4.colon,rectum,anus 4% 5.esophagus/appendix <1% E-GIST -extra GI GIST -omentum, mesentery, retroperi, abdo wall -often metas from GI GIST Metastasis GIST -liver, peritoneumcommon -lung, boneadvanced disease -LNrare Clinical -70% non specific symptom :GI bleed, abdo mass/pain -20% incidental finding :endoscope/intraop finding DDx -smooth muscle tumor :leiomyoma,leiomyosarcoma -peripheral N sheath tumor :schwannoma -intraabdo fibromatosis Histology 1.spindle cell 70% 2.epitheloid cell 20% 3.mixed/pleomorphic 10% Immunohistochemistry 1.GIST :CD117 90-95% :CD34 60-70% :SMA 20% :S100 5% 2.smooth muscle tumor :SMA/desmin 100% :CD34 10-15% 3.schwannoma :S100 100% Tissue biopsy I/C -planning neoadjuvant Tx -suspicious lymphoma -other primary/metas tumor *EUS biopsy1st choice > percu biopsy *if can curative resectnot Bx :hemorrhage (hypervascular tumor) :tumor dissemination

GIST short note by by S.Wichien (SNG KKU)

Surgical Tx -primary Tx -only chance for cure -all resectable non metas GISTEL -margin 2 cm -dont tear pseudocapsule -if adhere adjacent organ (cant dissect) :En bloc resection -rare LN metasnot LND Gastric GIST -wedge resectionfree margin 2 cm -should preserve EGJ & pylorus (if can do) SMB & LB GIST -segmental resectionmargin 2 cm Rectal GIST -LAR -APR Periampullary GIST -PD Small or microscopic GIST Depend on size 1.<1 cmf/u 2.1-2 cmcontroversy 3.>2cmshould Sx Marginal resectable or locally advance GIST -if sx=significant morbid -EUS/Bxthen Glivec -assess rxnCT scan -max rxn 3-6 mo -if rxnSxthen Glivec if not rxn2nd line drug Advance or unresect or recur or metas GIST -Targeted Tx -3-6 mo -if can resectSxthen Glivec if not rxninc dose/2nd line drug -cytoreductive sxnot good than glivec Role of palliative resection -large mass+significant symptom -c/p = bleeding, abscess, fistula Risk for progressive disease risk Size mitotic Very low <2 <=5 Low 2-5 <=5 Intermediate 2-5 >5 <5 5-10 5-10 <=5 High any any any >10 >10 any >5 >5 2-5 >5 5-10 <=5

primary T any any gastric any gastric rupture any any any non gastric non gastric

Imainib Mesylate (Glivec) -Tyrosine kinase inhibitor -1st line Tx -400 mg/d -800 mg/d (max) 1.progressive despite 400 mg/d 2.exon 9 mutation -give until intolerance or resistance -adjuvnat Tx in hi risk group (despite R0) -advance/unresect/metasglivec (continue) Side effect -edema -n/v, diarrhea -muscle cramp -skin rash, dermatitis -anemia -leucopenia Sunitinib Malate (Sutent) -Tyrosine kinase inhibitor -can inh KIT+PDGFR -50 mg/d * 4wk then stop 2 wk -2nd line drug -inc survival 6 wk to 27 wk Side effect -fatigue -diarrhea -skin reaction -hypothyroidism

GIST short note by by S.Wichien (SNG KKU)

Modified Choi CT criteria Complete rxn -no mass -no new lesion Partial rxn -dec size >=10% -dec tumor density >=15% -no new lesion Progressive disease -inc size >=10% -new lesion -inc density Stable disease -not CR PR PD Follow up very low/low risk -CT q 6 m *5 yr Intermediate/hi risk -CT q 3 m*3 yr -CT q 6 m until 5 yr Survival rate 1.size <5 cm >10 cm 2.mitotic rate <5/50 HF >10/50 HF 3. Resection R0 R1 5yr survival 60% 20% metas 20% 69% 5yr survival 40-55% 5%

Prognosis not good in 1.tumor>10 cm 2.mitotic >10/50 HF 3.SMB & rectum lesion 4.hi risk GIST 5.R1/2 resection 6.rupture tumor