Small Bowel GIST - a case discussion & literature review

1. Tumor and GI
bleeding : A Case
Review
Rajaie Kamarudin P59895 PPUKM

2. History
❖ Madam WT
❖ 63 Chinese Lady
❖ K/C: COAD (Smoker), under IPR follow up
❖ Complaint of blackish stool for 1 day,
❖ associated with central abdominal discomfort
❖ 26/11/2014

3. History
❖ history of gastritis > 20 years
❖ + giddines
❖ no history of NSAIDS ingestion
❖ no constituinal symptoms
❖ no family history of cancer

4. History
❖ Not Working
❖ living with friend
❖ non alcoholic
Social History

5. Physical examination
❖ Alert conscious
❖ Pale
❖ hydration fair
❖ Spo2 99% (room air)
❖ moderate pulse volume

6. Physical examination
❖ no palpable cervical, supraclavicular nodes
❖ abdomen soft : there is a vague mass at the left iliac
fossa
❖ Per rectal : fresh maelena
❖ bp : 98/54 106/68 ( after saline bolus)
❖ pulse : 133 108

7. Biochemical Ix
❖ Hb 7.9
❖ Wcc 8.6
❖ Plt 273
❖ INR 1.02
❖ Urea 6.4 Creatinine 53
❖ Potassium 3.4/Sodium 140

8. Management
❖ Working Diagnosis & Differential diagnosis?
❖ What to do next?

9. Management
❖ Hourly Vitals and urine, monitoring
❖ To transfuse 2 pint of pack cell
❖ monitor in acute bay
❖ Nil By Mouth
❖ OGDS

10. Management
❖ OGDS : normal
❖ Colonoscopy : normal up till caecum, altered blood
throughout the colon but no stigmata of recent bleed

11. Management
❖ Patient had mild sob
❖ hb 7.9 6.9 10.6
❖ Bp systolic 100-140 & PR : 110-114 overnight
❖ PR : fresh maelena
Day 2 of admission

12. Management
❖ Imp : Bleeding Tumor
❖ For Exploratory laparatomy & proceed

13. Intra operative

14. Intraoperative
❖ Large exophytic tumor arising from the small bowel , 100
cm from DJ junction, 25x25 cm
❖ some part of the tumor was adhered to the posterior
pelvic wall but no involvement of the uterus or adnexa
❖ small bowel resection and primary anastomosis was
done

15. Management
❖ Post operative patient was nursed in icu, for 1 day
❖ post op was uneventful and patient was discharge at day
5
❖ To See in clinic with HPE review

16. Management
❖ Differential diagnosis ?

17. Lorem Ipsum Dolor
Macroscopic : irregular nodular exophytic mass 15x15x8, firm with margin 11 cm . Section
shows haemorraghic and necrotic areas .
Microscopic: malignant spindle cells in storiform pattern with dense cellularity.Malignant
cell display pleomorphic enlarged spindle to oval-shape vesicular with permanent nuclei.
CD117, Vimentin, CD34, DOG -1 are positive, and -ve for SMA, Desmin and s100
Mitotic count 7/50 hpf

18. Management
❖ Diagnosis : Malignant Gist Tumor
❖ Plan
❖ CT Staging
❖ Refer Oncology for Adjuvant Therapy

19. Introduction
❖ Its described in the early literature consisted of a heterogenous group
of mesenchymal tumours , involving the GI wall
❖ Hirota S, Isozaki K, Moriyama y et all, gain of function of mutation of
c-kit in human GIST
❖ C-Kit(CD117) is a type III receptor thyrosine kinase that involved in
the development and maintaince of RBC, mast cell, Melanocytes,
germ cells and intertisial cells of Cajal
❖ GIST share morphologic features and express (Oncogenic mutation)
KIT (80-85%) or Platelet Derived Growth Factor PDGFRA 5-7%
GIST (Gastrointestinal Stromal Tumor)

20. Introduction
❖ its relatively rare neoplasm but most common among
sarcoma of the GI tract.
❖ its account for 5 % of all sarcoma
❖ Can rise in any portion of the GI tract but most common
from the Stomach 60% or the Small bowel 20% and
oesophagus 5%.

21. Epidemiology
❖ Median age is 60 years old
❖ Most GIST arise sporadically
❖ Hereditary is rare such as Neurofibromatosis type 1, Part
of Carney Triad and Carney -Stratakis Dyad
❖ about 70-80% are Benign and 20-30% are malignant

22. Incidence
❖ GIST has been reported to 5000-6000 new cases per
year (15-20 per million)
❖ European 11-15 cases per million

23. Clinical Presentation
❖ GIST commonly arise in the stomach 50-70%, small bowel
25-35%, colon and rectum (5-10%)
❖ Symptomatic 69% Incidental findings during endoscopy or
laparatomy 21 %
❖ bleeding
❖ obstruction, perforation, intussuception
❖ vague abdominal pain
❖ fever

24. Diagnosis
❖ If suspected or confirmed GIST
is Contrasted enhanced CT
Abdomen and pelvis
❖ MRI may help characterise in
rectal Disease
❖ PET Scan- monitor respons to
therapy but not specific for gist.
Radiographic Study

25. Diagnosis
❖Endoscopic
❖EUS FNA
❖Biopsy

26. Usually Fleshy Solid with
haemorrhage or cystic
degeneration

27. Histopathology
❖ Divided in 2 types
❖ Spindle Cell 70%
❖ Epithelial 20% and Mixed 10%
❖ Immunohistochemical staining CD117, CD 34 and DOG-
1

28. ❖ Divided in 2 types
❖ Spindle Cell 70%
❖ Epithelial 20% and Mixed
10%
Microscopic

29. Agorithm to diagnose gastrointestinal Stromal tumors
based on immunohistochemistry

30. Prognostic factor
❖ Tumor size
❖ Mitotic index
❖ Tumos site of origin

31. Nomogram to predict the probabilities of 2-year and 5-year recurrence-free
survival (RFS). Points are assigned for size, mitotic index, and site of origin by
drawing a line upward from the corresponding values to the Points line. The
sum of these three points, plotted on the Total points line, corresponds to
predictions of 2-year and 5-year RFS. HPF, High-power field.

32. Risk aggressive behaviour in
gist
Fletcher CD, Berman JJ, Corless C, et al: Diagnosis of gastrointestinal stromal tum

33. Treatment
❖ Primary (Surgery if 2cm or more)
❖ To achieve R0 resection.
❖ Preoperative treatment neoadjuvant?
❖ Adjuvant Therapy ?
RTOG S0132 multicenter using Imatinib as neoadjuvant. 600 mg
per day for 8-12 weeks, 2 years Reccurent free Survival is 83%

34. Trial Design Dose Eligibility Primary endpoint
ACOSOG
9001
Phase iii
400mg OD for
12 m
Tumor >3 Complete resection
Imatinib 97% vs
Placebo 83% RFS in 1
year
SSGXVIII Phase iii
400 mg od for
12/36 month
Tumor 10 cm, Tumor rupture,
, Mitotic count >10, t: >5 m >
5 hpf
36 m 66 % vs 48 % (p<0.01)
5y RFS
OS (92%vs 82%) p=0.02 in
5 year
Trials in Adjuvant Therapy For GIST

35. Targeted Therapy
❖ Before the advance of TKI Median survival after
recurrence is 18 month
❖ Imatinib commercially as Gleevec or Glivec and Sumatinib
is the choice of treatment
❖ KIT contain 21 types of exon
❖ GIST Pathogenesis loss either Chromosomes 9,11, 13
and 17 exon
❖ best Respon rate is the Exon 11 mutation 72% , exon 9
32%

36. Side effect
❖ edema
❖ nausea
❖ muscle cramps
❖ diarrhea
❖ headache
❖ dermatitis
❖ anemia
❖ nausea

37. Advanced Disease
❖ Cryoreductive surgery
❖ Cytoreductive surgery is good in patient with ongoing
response to imatinib but there is no evidence to compare
between surgery vs TKI alone.
❖ There is a progression of drug resistance to Imatinib

38. Surveillance
❖ Clinic visit with physical assessment
❖ CT scan every 3-6 month first 3-5 years then annually

39. Conclusion
❖ Principal and only potential curative treatment is Surgery
❖ TKI adjuvant therapy has improve in RFS in 5 years
❖ Imatinib is safely used as a neoadjuvant agents
❖ Need more studies regarding Neoadjuvant and adjuvant
imatinib therapy regarding optimal length and dose of
imatinib.
❖ Cytoreductive Studies me be considered in advanced
disease.

40. ❖Thank You