What are the characteristics of Gastrointestinal Stromal Tumors (GISTs) and what conditions cause a rightward shift of the oxyhemoglobin dissociation curve?

Characteristics of Gastrointestinal Stromal Tumors (GISTs) and Rightward Shift of Oxyhemoglobin Dissociation Curve

Gastrointestinal stromal tumors (GISTs) are radioresistant mesenchymal tumors that occur most commonly in the stomach, not the duodenum, and require complete surgical resection rather than enucleation, with lymphatic spread being rare. 1

Characteristics of GISTs

Epidemiology and Location

• GISTs are the most common mesenchymal tumors of the GI tract with an incidence of 10-20 per million 1, 2
• Distribution by location:
  • Stomach: 60-70% (most common site)
  • Small intestine: 20-30%
  • Colorectal: 5%
  • Esophagus: <5%
  • Rarely in extragastrointestinal locations 3, 4

Diagnosis

• Diagnosis relies on morphological assessment and immunohistochemistry 1
• Key diagnostic markers:
  • CD117 (KIT) positive in 95% of cases
  • DOG1 positive in 95% of cases
  • CD34 positive in approximately 70% of cases 1
• About 1% of GISTs are negative for both CD117 and DOG1 1
• Molecular analysis for KIT or PDGFRA mutations is essential for diagnosis confirmation and treatment planning 1, 2

Malignant Potential

• GISTs represent a spectrum from indolent tumors to aggressive sarcomas 4
• Not all GISTs are malignant - benign tumors outnumber malignant ones 3
• Risk stratification depends on:
  • Tumor size
  • Mitotic count
  • Primary tumor location 1, 4
• Gastric GISTs generally have better prognosis than intestinal GISTs with similar parameters 4

Molecular Characteristics

• Approximately 85-90% contain oncogenic KIT or PDGFRA mutations 1, 2
• KIT mutations (80% of GISTs):
  • Exon 11 mutations: 65-70% (highest sensitivity to imatinib)
  • Exon 9 mutations: 8-13% (intermediate sensitivity)
  • Exons 13 and 17 mutations: rare 1, 2
• PDGFRA mutations (10% of GISTs):
  • More common in gastric GISTs
  • D842V mutation in exon 18 is resistant to imatinib 1, 2

Spread Pattern

• GISTs primarily spread hematogenously to the liver and peritoneal cavity 1
• Lymphatic spread is rare (<10%), making lymph node dissection generally unnecessary 1, 5

Treatment

• Complete surgical resection (R0) without rupturing the pseudo-capsule is the primary treatment 1
• Enucleation is not adequate treatment as it risks incomplete removal and tumor rupture 1
• Tyrosine kinase inhibitors (imatinib, sunitinib, regorafenib) are effective for unresectable or metastatic disease 1, 6
• GISTs are generally radioresistant, making radiation therapy not a standard treatment option 5
• However, in select cases, radiotherapy may offer local control in an adjuvant or palliative setting 5

Rightward Shift of Oxyhemoglobin Dissociation Curve

The rightward shift of the oxyhemoglobin dissociation curve occurs with:

Acidosis causes a rightward shift of the oxyhemoglobin dissociation curve, facilitating oxygen release to tissues.

Factors causing rightward shift (increased oxygen release to tissues):

• Acidosis (decreased pH)
• Hyperthermia (increased temperature)
• Increased 2,3-diphosphoglycerate (2,3-DPG)
• Hypercapnia (increased CO2)

Factors causing leftward shift (decreased oxygen release to tissues):

• Alkalosis
• Hypothermia
• Decreased 2,3-DPG
• Hypocapnia
• Methemoglobinemia