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GIST -Current Trends

Prof SM Chandramohan Professor and HOD Department of Surgical Gastroenterology Center of Excellence for Upper GI Surgery Rajiv Gandhi Government General Hospital Madras Medical College Chennai. GIST -Current Trends. smchandra@yahoo.com. Epidemiology.

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GIST -Current Trends

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  1. Prof SM Chandramohan Professor and HOD Department of Surgical Gastroenterology Center of Excellence for Upper GI Surgery Rajiv Gandhi Government General Hospital Madras Medical College Chennai GIST -Current Trends

  2. smchandra@yahoo.com

  3. Epidemiology • Most common mesenchymal neoplasm of the GI tract. • 0.1%-3% of all GI malignant tumors • Median age of 60 years (40-80) • No predilection for either gender (Miettinen M,Eur J Cancer 2002, Rossi CR,Int J Cancer 2003; )

  4. Clinical Spectrum

  5. History

  6. Location <

  7. Multicentric GISTs - <5% • “Extra” GISTs Sites Other than GIT, - genitourinary,portal vein, pancreas • “Micro” GISTs - Size <2 cm • “Giant” GISTs - ? 5 cm ? 10 cm

  8. CELL OF ORIGIN Interstitial” cells of CAJAL Santiago ramon y cajal -1893 Interposed between smooth muscle and nerve endings. Pacemaker—propagates intrinsic peristalsis

  9. CELL OF ORIGIN –Nobel laureate

  10. Biomarkers in GIST C KIT

  11. KIT is a 145-kDa glycoprotein • CD117 -epitope on the extra-cellular domain of the KIT receptor. • Steel factor (SLF) stem-cell factor ligand for KIT. • Binding of SLF to KIT -activation of KIT tyrosine kinase activity -downstream signaling pathways -uncontrolled cell proliferation

  12. KIT Mutations • 20 mutations • Exon 11 Most common Better response to imatinib • Exon 9 Common in small bowel Poor response to imatinib.

  13. Wild-type GIST (WT-GIST) • GISTs that have no detectable KIT or PDGFRA mutations- (10%-15%) • DOG gene Discovered On GIST-1 gene in CH 11q13 • DOG1 is a calcium dependent, receptor activated chloride channel protein expressed in GIST-independent of mutation type

  14. Immunohistochemistry

  15. GIST CD 117 - >95% CD 34 – 60-70% Vimentin Actin - 15-30% • Lymphoma B-cell- CD 20,CD 79 T-Cell- CD 3,CD 5

  16. D/D

  17. Pathology • Few millimeters to more than 30 cm, (median size -5 and 8 cm.) • Muscularispropria layer of GI wall • Exophytic growth. • Mucosal ulceration-50% cases. • Mass attached to the stomach, projecting into the abdominal cavity and displacing other organs.

  18. Pathological types • Exophytic • Endophytic • Combined

  19. Smooth • Gray and white tumors • Well circumscribed • Pseudocapsule • Small areas of hemorrhage • Cystic degeneration • Necrosis

  20. HistoPathology

  21. Histology Spindle pattern Epitheliod pattern

  22. CLINICAL PRESENTATION… • Asymptomatic, • Especially early in tumor development, • Discovered incidentally by CT or endoscopy

  23. Symptomatic GISTs • Vague abdominal discomfort (60%-70%). • Bleeding (30%-40%). • Perforation (20%) • Anorexia, weight loss, nausea, anemia, and additional GI complaints

  24. Site specfic symptoms • Esophageal GISTs -dysphagia, • Gastric and small intestinal GISTs - Bleeding &Intestinal obstruction. • Duodenal GISTs - Biliary Obstruction • Colorectal GISTs – -pain and GI obstruction, and lower intestinal bleeding.

  25. Acute Presentation • Bleeding peritoneal cavity- Ruptured Gist GI tract lumen- hematemesis, melena or anemia • Obstruction Over growth Intussusception Volvulus

  26. Syndromes linked to GISTs (i) Carney triad Gastric GISTs, Paraganglioma, Pulmonary chondromas. (ii) Type-1 neurofibromatosis Generally wild-type Predominantly located at the small bowel Possibly multicentric . (iii) Carney-Stratakis syndrome Germ-line mutations of succinatedehydrogenase Dyad of GIST and paraganglioma

  27. UGI Scopy

  28. EUS- Management process

  29. Contrast enhanced computed tomography (CECT) • Modality of choice. • To characterize the lesion&evaluateits extent. • To assess the presence or absence of metastasis at the initial staging workup. • Monitoring response to therapy • Performing follow-up surveillance of recurrence

  30. Magnetic Resonance Imaging • Provides better soft-tissue contrast resolution and direct multiplanar imaging • Helps to localise the tumour • Delineate the relationships of the tumour and adjacent organs. • Particularly of benefit in anorectal disease.

  31. MRI • Axial T2-weighted MR image • Extraluminal mass arising from the greater curvature of the stomach. • The mass shows high signal intensity

  32. Benign gastric fundal GIST- MRI Axial T1-weighted Axial T2-weighted Axial enhanced T1-weighted Homogeneous iso-intensity Homogeneous medium lintensity Homogeneous moderate enhancement

  33. CT or MRI • large exophytic tumor with heterogeneous contrast enhancement, arising from the stomach or small bowel. • Metastases, if present, are usually to the liver or peritoneum. • Lymph node enlargement is uncommon.

  34. CT&MRI-D/D • Lymphomas Circumferential with homogeneous enhancement Lymph node enlargement. • Carcinoid tumors Found in the distal ileum,or root of the mesentery, Desmoplastic reaction with calcifications. • Large carcinomas More likely to cause visceral obstruction.

  35. FDG-PET • Reveals small metastases • Establish baseline metabolic activity • Assess therapy response • Helps to clarify ambiguous findings seen on CT or MRI • To assess complex metastatic disease in patients who are being considered for surgery

  36. Changes in the metabolic activity of tumors precede anatomic changes on CECT. • used to assess the response to Imatinib therapy. • Routine use of PET for surveillance after resection is not yet recommended

  37. FNAC/BIOPSY • FNA- controversial -risk of rupture and dissemination • Resectable lesion in the absence of metastatic disease “Preoperative diagnosis may be unnecessary”

  38. Biopsy-Indications • If diagnosis would impact the extent of resection • Prior to Neoadjuant therapy • Unresectable GISTs • Metastatic GISTs

  39. Fletcher 2002

  40. UICC 2010 TNM 7th Edition

  41. Management Guidelines ESOINDIA GUIDELINES International Conference and Workshop, Jan 2014,Chennai.

  42. Management strategies • Surgery • Surgery + adjuvant Imatinib • NeoadjuvantImatinib + surgery

  43. Site specific surgery • Esophagus: Esophagectomy Esophageal sparing wide local excision • Stomach Small-wedge resection Large-subtotal/total gastrectomy (BlumMG et al,AnnThoracSurg2007; WinfieldRDetal.AmSurg2006; WayneJD et al SurgClinNorthAm2005).

  44. Duodenum: Partial duodenal resection Whipple’s Procedure • Small Intestine: Segmental resection • Colon: Colectomy • Rectum: Anterior resection/ Abdominoperineal resection (Blay JY et ai.Ann Oncology 2005;16:566-57 )

  45. Principles of surgery • AIM: To obtain complete resection with maximal organ preservation with macroscopic negative margin. • Great care should be taken to avoid rupture of pseudocapsule • Re resection is generally not indicated for microscopically positive margins on final pathology • Lymphadenectomy is not required

  46. Irregular border Cystic spaces Ulceration Echogenic foci Heterogeneity

  47. Resection margin • 1-2 cm margin is necessary for an adequate resection • Tumor size • Main determining factor for survival • Complete resection with gross negative margin is acceptable. De Matteo et al,Ann Surg 2000

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