Gastrointestinal Stromal Tumors: Symptoms, Treatment and Prognosis

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Gastrointestinal stromal tumors (GISTs) are the most common (80%) mesenchymal tumors of the gastrointestinal tract, constituting about 5% of all sarcomas

Annual Incidence: The annual incidence is estimated to be approximately 15 cases per million, with a prevalence of 129 cases per million.

Age Predominance: GISTs occur most often in adults over the age of 50 years and are quite rare in children, although they can occur across the entire age spectrum.

Location of GISTs: GISTs can arise anywhere in the gastrointestinal tract, but most commonly involve the stomach (60%), jejunum and ileum (30%), duodenum (4%–5%), and colorectal (< 5%).

Pathophysiology: Originate from stem cells that differentiate towards the interstitial cells of Cajal (ICC). ICC arise from precursor mesenchymal cells that intercalate between nerve fibers and muscle cells in the adult intestine acting as pacemaker cells of the GIT, with regulation of peristalsis. Not all GISTs arise from ICC, as some come from the mesentery or omentum which lack ICCs, suggesting an origin in multipotential mesenchymal stem cells. Approximately 80%–95% of GISTs harbor an activating mutation in the KIT gene, and about 80% of KIT-negative GISTs have an activating mutation in the PDGFRA gene. Oncogenic kinase mutations in the KIT gene result in constitutive receptor activation, uncontrolled proliferation, enhanced survival, reduced adhesion (anoikis), increased invasion, metastasis, and angiogenesis.

GIST Presentatation: Half of the patients with GIST present with metastatic disease, and nearly two-thirds of those patients have liver metastases, but extra-abdominal and lymph node metastases are rare at presentation.

  • Mostly asymptomatic.
  • Tumor induce GI bleed and anemia
  • Other symptoms secondry to mass effects:
  • Abdominal discomfort, early satiety, palpable abdominal mass
  • Bowel obstruction or perforation
  • Dysphagia

Diagnosis: Gold standard test is endoscopy with biopsy, on endoscopy there will be single or multiple polypoidal mass which was farm in consitency, when applying forcep for biopsy

Histopathology: Spindle cell in 70 to 80%, epitheliods cells in 20 to 30 #

Radiology: there is no role of radiology in GISTS, they just help to find out the location of GISTS, sometimes appears as calcifications. CT scans help for location and staging the disease, shows the heterogeneously enhancing tumor with ulceration

Immunohistochemical Stainning: GISTs are characterized most commonly by cell surface expression of the receptor TK protein known as KIT (which is coded as “CD117”), detectable by immunohistochemical staining of pathology or cytology specimens. Up to 95% of GISTs are positive for KIT expression and 60%–70% are positive for CD34 expression.

Treatment:

Goals

  • Multidisciplinary Management Strategies
  • Reducing risks of recurrence
  • Optimizing organ preservation and function
  • Increasing the number of resectable cases through pharmacologic debulking of initially unresectable GIST
  • Possibly enhancing response to imatinib through surgical cytoreduction
  • Prolonging survival

Surgery: Current NCCN guidelines recommend that all GISTs ≥ 2 cm should be resected. Appropriate management of incidentally encountered GISTs < 2 cm remains controversial, and certain situations of watchful waiting and surveillance for such very small GISTs might be reasonable.

Medical Management: Imatinib mesylate is an oral adenosine triphosphate (ATP)–competitive TKI that selectively inhibits the activity of KIT, PDGFRA.  In 2002, the FDA approved imatinib for the treatment of patients with KIT-positive unresectable and/or metastatic GIST on the basis of a phase II study that showed durable clinical benefit and objective tumor responses in most patients with GIST. Dose of imitanib start with 400 mg, imtanib colud then be increased to 800 mg if there is sign of progression

In case of imitanib resistance: patients can be switched directly from low-dose imatinib (400 mg/day) to another TKI, such as the only approved second-line therapy, sunitinib.

Follow-up intervals: In patients who have undergone surgical resection of GISTs, abdominal/pelvic CT should be obtained approximately every 3 to 6 months. For very low risk GISTs, less frequent follow-up may be appropriate. In patients with unresectable, recurrent, or metastatic GIST, response assessment by CT is an excellent imaging modality to monitor disease during the course of treatment and surveillance. CT should be performed within 1–3 months of initiating TKI therapy; imaging before 3 months may be appropriate in some patients based on symptoms or other clinical concerns. FDG-PET can be considered when CT findings are inconclusive. In patient with no finding present on  CT scan may follow up through endoscopy 3-4 month intervals.

Author’s Bio:

  1. Professor Dr. Muhammad Sadik Memon works as a head of department in Gastroenterology Department of Isra University hospital Hyderabad, Pakistan. He can be reached at sadikmemon@gmail.com.
  2. Dr. Madiha Zaki works as a resident in Gastroenterology in Asian Institute of Medical Sciences, Hyderbad, Pakistan. She can be reached at madiha_smart@hotmail.com.