GASTRO INTESTINAL STROMAL TUMOR (GIST) SURGERY

Presentation made by general surgery resident Dr. Manab Tiwari
Gastrointestinal stromal Tumor
Imcludes genetics, IHC, classification diagnosis and treatment modalities. Very useful for all MCH and md residents. Please do comment and give reviews. I will be uploading more useful material like this one.

1. GIST Moderator: Dr. Nabin Pokhrel Dr . Manab Tiwari 2081/02/07

2. Introduction Gastrointestinal stromal tumors (GISTs) are rare, comprising 0.1% to 3% of all gastrointestinal malignancies, yet they constitute 80% of gastrointestinal mesenchymal neoplasms Gastrointestinal stromal tumors (GIST) typically present in adults around 60 years old, with a slight male bias, and are uncommon in children (1.4%-2.6% of cases), often associated with familial syndromes or Carney's triad

3. The term stromal is a historical mistake, as GIST is now recognized to arise from the interstitial cells of Cajal , the pacemaker cells of the gastrointestinal muscularis propria

4. Pathogenesis KIT and PDGFRA are the drivers of the disease. KIT and PDGFRA reside on chromosome 4q12 with both genes encoding homologous transmembrane glycoproteins Gain-of-function mutations of these oncogenes can be found in approximately 80% of GISTs.

5. KIT plays a critical role in the development and maintenance of components of hematopoiesis, gametogenesis, and intestinal pacemaker cells Mutated KIT remains constitutively active even in the absence of ligand binding and results in both unregulated cell growth and malignant transformation KIT and PDGFRA mutations in GIST are mutually exclusive and lead to similar downstream oncogenic signaling pathways .

6. GIST histology

7. GIST Locations

8. Primary GIST Locations Stomach: 50% to 70% Small Intestine: 25% to 35% Colon and Rectum: 5% to 10% Mesentery or Omentum : 7% Esophagus: <5% Occasionally in: Duodenal Ampulla, Appendix, Gallbladder, Urinary Bladder

9. Clinical Feature GISTs are often asymptomatic and found incidentally on imaging or endoscopy. Early symptoms are nonspecific like mild pain, bloating, or dyspepsia. Larger tumors can cause palpable masses, pressure, pain, or other noticeable symptoms. Symptoms typically appear later in the disease due to the tumor's submucosal location and tendency to displace rather than invade adjacent organs

10. GISTs are often highly vascular, soft, and friable, leading to common complaints of bleeding , can cause hemorrhage by eroding into the gastric or bowel lumen. Tumor rupture may result in catastrophic intraperitoneal bleeding and/or dissemination via peritoneal seeding.

11. Radiographic features Specific appearances will vary according to location and size tumours appear as rounded soft tissue masses, arising from the wall of a hollow viscus with an endoluminal or exophytic growth. Small GISTS tend be round while larger GISTs tend to be lobulated

12. Endoscopy

13. Diagnosis

14. Therapy for primary disease Active Surveillance Management of gastric GISTs less than 2 cm is still a debate due to uncertain natural history Studies indicate that sub-centimeter gastric GISTs are relatively common, found in 22.5% of autopsies in older adults and 35% of gastrectomy patients. Despite their frequency, few micro GISTs progress to clinically significant disease.

15. National Comphrehensive Cancer Network (NCCN) guidelines suggest E ndoscopy with EGD +/- EUS every 6 to 12 months for active surveillance. Lesional >2 cm, irregular extraluminal borders, ulceration, heterogeneous echogenic foci, cystic spaces, and/or symptomatic should prompt reconsideration of the management strategy. European Society for Medical Oncology (ESMO) recommends annual surveillance with EUS for presumed <2 cm GISTs, with the option of EUS-FNA. If a GIST diagnosis is confirmed, surgery should be offered. If the patient declines surgery, observation should continue, although an optimal surveillance policy is not well established

16. Management Surgical therapy Standard of care and only curative option for primary, resectable localized GIST Care must be taken not to V iolate tumor pseudocapsule Rupture the tumor Lymphadenectomy not indicated

17. Indications for Surgery Gastric GIST Tumors 2 cm or > Non gastric GIST Regardless of tumor size or morphology Signs of malignancy Irregular margin Ulceration Bleeding Cystic changes Necrosis

18. Goal of surgery: Complete resection with R0 –R1 gross margin Gastric tumor Require partial gastrectomy or wedge resection Small bowel GIST Treated by segmental resection Rectal GIST Treatment based on tumor location & size treated by LAR or APR

19. High risk features • Irregular margin • Ulceration • Bleeding • Cystic change • Necrosis • Heterogeneous echogenicity • Symptomatic • Increase size on survillance Non-gastric gist irrespective of size status needs resection

20. Outcomes Despite complete resection, up to 50% of individuals may experience recurrent disease within approximately 24 months. R0 or R1 resections are linked with 5-year overall survival rates ranging from 34% to 63%, while R2 resections have notably lower rates, as low as 8%. These survival rates may be underestimations due to advancements in adjuvant medical therapy not accounted for in older series

21. What after Surgery??

22. Prognostic Factor And Risk Stratification

23. Modified NIH Criteria

24. Follow-up And Recurrence After Surgical Resection for low risk History and physical exam every 3 to 6 months for 5 years and annually thereafter Serial CT scans every 3 to 6 months for 3 to 5 years and annually thereafter

25. Adjuvant Therapy For Primary Disease

26. N eoadjuvant Trail For Primary Disease

27. Therapy for advanced disease Recurrent GISTs often involve liver metastases (up to two-thirds of cases) and peritoneal disease (about half of cases). Historically, recurrent and metastatic GISTs were managed with surgery, chemotherapy, and radiotherapy, but these methods had limited efficacy. Surgery can be effective for resectable disease, but recurrence rates remain high (up to 50% at a median of 24 months). Traditional intravenous chemotherapy and radiotherapy have shown poor effectiveness

28. Cytoreductive Surgery Cytoreductive surgery is standard for disseminated solid tumors from the colon, appendix, ovary, and testicle. Aggressive cytoreductive surgery benefits some advanced GIST patients due to: Durable periods of partial response (PR) or stable disease (SD) on imatinib . Rare complete responses (<5% of patients). Development of secondary resistance to imatinib after 18 to 24 months, leading to limited or generalized disease progression

29. Cytoreductive surgery for advanced GISTs may: Reduce clonal variability and prevent drug-resistant clones. Make remaining tumors responsive to therapies. Alleviate symptoms and complications like perforation and bleeding. Challenges include timing and extent of surgery for meaningful outcomes. The goal is complete resection, but few patients are surgical candidates. No completed randomized trials compare TKI therapy and surgery with medical therapy alone in advanced GISTs.

30. Imatinib Therapy for Recurrent and Metastatic Disease Three TKIs approved for metastatic GIST are imatinib mesylate , sunitinib malate, and regorafenib , with imatinib as first-line therapy based on extensive trial data. The current standard treatment for advanced GIST is imatinib starting at 400 mg/day. For advanced GIST with a confirmed KIT exon 9 mutation, starting with imatinib at 800 mg/day (400 mg twice daily) is recommended based on trial data showing improved outcomes Imatinib therapy for advanced GIST should be maintained indefinitely unless disease progression or intolerable treatment-related side effects occur

31. Thank You