Stomach: GIST

Question 1

What are Gastrointestinal Stromal Tumours (GIST)?

Answer 1

Submucosal soft tissue lesions of mesenchymal origin (sarcoma) that arise throughout the GI tract.

GISTs are the most common mesenchymal tumour of the gastrointestinal tract.

Question 2

What is the incidence of GISTs?

Answer 2

Rare. 15 per million. Represent 0.1-3% of GI tumours and 5% of sarcomas.

GISTs are predominantly found in the gastric region.

Question 3

What is the distribution of GISTs in the GI tract?

Answer 3

• Gastric: 60-70%
• Small Bowel: 20-30%
• Other (oesophagus, mesentery, omentum, colon): 10%

There are no sex differences in incidence.

Question 4

What is the median age for GIST diagnosis?

Answer 4

58 years old (unimodal).

Question 5

From which cells do GISTs originate?

Answer 5

Interstitial cells of Cajal (Pacemaker cells responsible for gastric motility).

Question 6

What is the pathogenesis associated with GISTs?

Answer 6

85% associated with mutations in cKIT or PDGFRA genes.

Common cKIT mutations occur in exons 11 and 9.

Question 7

What is the universal marker expressed in GISTs?

Answer 7

CD117 antigen.

Question 8

What type of GISTs are resistant to tyrosine kinase inhibitors?

Answer 8

GISTs with PDGFRA mutations.

Question 9

What percentage of GISTs are wild type?

Answer 9

15%.

Question 10

What genetic syndrome is associated with GISTs?

Answer 10

Familial GIST syndrome (cKIT mutation).

Other associations include NF1 and Carney syndrome.

Question 11

What are the most common clinical manifestations of GISTs?

Answer 11

• GI bleed (50%)
• Obstruction or change in bowel habit (especially colorectal)
• Abdominal pain or mass

Small GISTs (<2cm) are usually asymptomatic.

Question 12

What imaging method is used to stage GISTs?

Answer 12

CT chest/abdo/pelvis.

Question 13

What are the CT features of GISTs?

Answer 13

• Extraluminal mass with central necrosis
• Smooth walled, homogenous, soft tissue mass
• Enhances brightly with contrast

Large tumours may show mucosal ulceration and central necrosis.

Question 14

What are the criteria for treatment response to imatinib in GISTs?

Answer 14

Choi criteria (10% reduction in size, 15% reduction in density).

Question 15

What is the role of endoscopy and EUS in GIST diagnosis?

Answer 15

Shows smooth submucosal lesion often with punctum and overlying normal mucosa.

Biopsy can often be normal as GISTs are not mucosal.

Question 16

What is the preferred method for tissue diagnosis in suspected GIST cases?

Answer 16

Needle-guided or percutaneous biopsy via EUS – FNA.

Question 17

What is crucial for therapeutic purposes in GISTs?

Answer 17

Testing for cKIT mutations.

Question 18

What is the staging system used for GISTs?

Answer 18

AJCC 8th TNM.

Question 19

What are key prognostic indicators for GISTs?

Answer 19

• Size less than 2cm
• Any N stage or M stage greater than 0 is Stage 4.

Size is a very good prognostic indicator.

Question 20

What factors influence tumour biology and risk of progression in GISTs?

Answer 20

• Location (gastric has better prognosis)
• Size of primary tumour
• Mitotic rate (less than 5 mitosis per 50 HPF).

Question 21

What factors does the management of GISTs take into account?

Answer 21

Confirmation of diagnosis, tumour location and size, clinical presentation, risk of progression/recurrence

These factors help determine the appropriate treatment approach.

Question 22

What is the purpose of preoperative confirmation of diagnosis in GIST management?

Answer 22

To distinguish it from other mesenchymal tumours

This is especially important for locally advanced or initially irresectable disease.

Question 23

What is the indication for neoadjuvant treatment?

Answer 23

Locally advanced or borderline resectable disease

Neoadjuvant treatment helps in better surgical outcomes.

Question 24

What are the goals of neoadjuvant therapy?

Answer 24

• Down staging for potentially irresectable disease
• Facilitate complete surgical resection
• Reduce morbidity
• Allow less invasive approaches
• Avoid multi-visceral resection

Question 25

What are indications for neoadjuvant therapy?

Answer 25

* Unresectable or borderline primary * Local recurrence * Anorectal GIST where sphincter-preserving surgery is possible ## Footnote These indications help to decide when neoadjuvant therapy is appropriate.

Question 26

What is the treatment approach for resectable disease?

Answer 26

Surgery ## Footnote Surgical resection is the primary treatment for resectable GISTs.

Question 27

What is the recommended management for tumours less than 2cm?

Answer 27

Options include surveillance, resection, or endoscopic removal ## Footnote Treatment should be individualized based on risk features.

Question 28

What is the approach for tumours greater than 2cm?

Answer 28

All lesions greater than 2cm should be resected with the goal of macroscopically clear margins ## Footnote Clear resection margins are crucial to reduce disease-specific mortality.

Question 29

What is the disease-specific mortality for GIST based on resection margins?

Answer 29

* 11% if R0 * 75% if R1/R2

Question 30

What surgical techniques may be used for stomach GIST resections?

Answer 30

* Wedge resection * Sleeve resection * Partial gastrectomy * Subtotal gastrectomy * Total gastrectomy ## Footnote Small lesions can be approached laparoscopically.

Question 31

What is the common approach for oesophageal GISTs?

Answer 31

Oesophagectomy is required; FNA is important as leiomyomas can be enucleated ## Footnote Local invasion may necessitate en-bloc resection.

Question 32

What is the role of adjuvant therapy in GISTs?

Answer 32

Imatinib ## Footnote Imatinib is used to reduce the risk of recurrence post-surgery.

Question 33

What factors are considered to estimate the risk of recurrence in GISTs?

Answer 33

* Tumor size * Mitotic rate * Primary tumor site * Presence or absence of tumor rupture * Completeness of resection ## Footnote These factors help in assessing the prognosis and treatment plan.

Question 34

What mutations are assessed for susceptibility to Imatinib?

Answer 34

* KIT mutations * PDGFR mutations ## Footnote 20% of GISTs do not respond to Imatinib due to being KIT or PDGFRA wild type.

Question 35

What is Imatinib also known as?

Answer 35

Gleevec ## Footnote It is a tyrosine kinase inhibitor used in GIST treatment.

Question 36

How does Imatinib work?

Answer 36

* Inhibits constitutively active tyrosine kinases of ABL * Inhibits kinase activity * Arrests proliferation * Causes apoptotic cell death ## Footnote This mechanism is crucial for the treatment of GISTs.

Question 37

What is the common side effect rate for Imatinib?

Answer 37

Serious adverse events in 20%, most commonly tumour haemorrhage

Question 38

What is the initial dosing strategy for Imatinib?

Answer 38

Start with low dose 400mg then increase to 800mg if progression ## Footnote Treatment duration is a minimum of 3 years.

Question 39

What is the prognosis for patients with GISTs when the tumor is >10cm and mitotic count >5/50 HPF?

Answer 39

These are high risk features with high risk of recurrence during long term follow up ## Footnote These characteristics indicate a higher risk of recurrence and poorer outcomes.

Question 40

True or False: Conventional chemotherapy and radiotherapy are effective for metastatic GISTs.

Answer 40

False ## Footnote Imatinib has revolutionized treatment for metastatic GISTs.

Question 41

What percentage of patients survive more than 5 years with Imatinib treatment?

Answer 41

50% ## Footnote This statistic highlights the effectiveness of Imatinib in improving survival rates.

Question 42

What is the role of surgery in metastatic disease?

Answer 42

Limited, possible in patients with low volume liver disease, possibly with neoadjuvant Imatinib to downstage ## Footnote Surgical options are constrained due to the nature of metastatic disease.