Gastrointestinal Stromal Tumor (GIST)

Complications of gastrointestinal stromal tumors (GISTs) can be preoperative or postoperative.

Preoperative Complications

Preoperative acute complications of GIST typically occur when tumors are larger than 4 cm. They include hemorrhage, bowel obstruction, intussusception, volvulus, and bowel perforation with peritonitis.^1,2

GISTs may be a potentially fatal source of gastrointestinal bleeding.³ Common presentations of gastrointestinal bleeding include hematemesis, hematochezia, melena, dizziness, fatigue, syncopal episodes, and unexplained anemia.³ These are typically the initial symptoms prompting patients to seek medical care. Depending on the severity of the bleeding, transfusions may be necessary. 

Intussusception typically occurs in childhood and causes only 1% of all cases of bowel obstruction in adults. Approximately 70% to 90% of adult cases of intussusception are secondary to underlying diseases, 65% of which are benign or malignant neoplasms, including GISTs.⁴ 

Common presentations of patients with bowel obstruction, intussusception, or volvulus include cramping abdominal pain that waxes and wanes, loss of appetite, vomiting, nausea, constipation, inability to have bowel movements, dyspepsia, abdominal bloating, difficulty passing gas, and hematochezia or melena.^4,5 Prompt medical attention is necessary because necrosis of the obstructed bowel segment may develop as a consequence of reduced blood flow, leading to serious complications.^5,6 

In a literature review conducted in 2014, GIST perforation was rare, typically occurring in individuals more than 50 years old. The presentation in all these cases was abdominal pain on examination. Tumor size was variable, ranging from 1.5 to 14 cm. In most cases of GIST perforation, the potential for malignancy is significant. For an optimal outcome, the management of GIST perforation requires immediate small-bowel resection with primary anastomosis.⁷ 

Postoperative Complications

Postoperative complications after GIST resection are similar to those that generally accompany major abdominal and gastrointestinal surgeries. These include but are not limited to the following¹:

• Incisional infection
• Wound dehiscence with or without evisceration
• Urinary tract infection
• Atelectasis
• Pneumonia
• Marginal ulceration
• Anastomotic stricture
• Anastomotic ulceration
• Abscess formation within the abdominal cavity
• Small-bowel obstruction
• Cardiac arrhythmias
• Pulmonary embolism
• Deep vein thrombosis
• Myocardial infarction
• Alkaline reflux gastritis
• Dumping syndrome
• Cholangitis
• Delayed gastric emptying or gastroparesis
• Internal or enterocutaneous fistula
• Peritoneal seeding due to a large active perforation

Prevention of Surgical Complications

About 60% of GISTs occur in the stomach.⁸ Endoscopic gastric GIST resection is controversial because of the potential for complications such as perforation, which may be related to the tumor growth pattern. The likelihood of perforation following endoscopic resection depends on 2 factors: GIST type and location.⁹ 

GIST tumors are divided into 4 types¹⁰:

• Type I GIST has a very narrow connection to the proper muscle layer (PM) and protrudes into the gastric lumen, like a polyp.
• Type II GIST has a wider connection to the PM and protrudes into the lumen at an obtuse angle.
• Type III GIST is located in the middle of the gastric wall.
• Type IV GIST protrudes mainly into the serosal side of the gastric wall

The rates of gastric wall defects, or perforations, following endoscopic resection are significantly higher for types III and IV GISTs (94.7%) than for types I and II GISTs (15.3%).⁹

The risk for perforation also depends on GIST location; the likelihood of perforation is higher for tumors in the gastric fundus than for tumors in any other location. To reduce the likelihood of serious complications like perforation, a thorough preoperative evaluation of a patient with a GIST with endoscopic ultrasonography (EUS) and computed tomography (CT) is required to select appropriate candidates for endoscopic resection.⁹ 

A retrospective study performed in 2019 compared the safety and outcomes of endoscopic (N=268) vs surgical (N=141) resections of small (<5 cm) primary gastric GISTs. The GISTs removed endoscopically were significantly smaller than those removed surgically. Postoperative hospital stays were shorter and associated costs lower following endoscopic resection, and the incidence of operative and postoperative complications was also significantly lower. Operative and postoperative complications included acute or delayed major hemorrhage (defined as a loss of >200 mL of fresh blood), peritonitis, abdominal abscess, acute postoperative infection, perforation, and pneumoperitoneum. In this study, intraoperative bleeding occurred in 5.7% of the patients undergoing surgical resection and in none of those undergoing endoscopic resection. In the literature, the rates of intraoperative hemorrhage during endoscopic GIST resection range from 0% to 38.7%. Acute infection occurred in 5% of the surgical cases vs 0.7% of the endoscopic cases. However, postoperative hemorrhage (1.1%), perforation (0.4%), and pneumoperitoneum (1.1%) occurred only in the endoscopy group.⁹

Several factors affect the likelihood of hemorrhage during or following endoscopic resection. These include potential coagulopathy, which must be identified during the preoperative evaluation, and the surgeon’s level of skill in endoscopic technique.⁹  

Advanced GIST Complications

Advanced GIST complications include large tumor size and inaccessible tumor location, both of which may render the tumor unresectable. Another complication of advanced GIST is the regional or metastatic spread of malignant cells via lymph or blood to various locations outside the primary tumor. Patients with unresectable or metastatic GIST typically receive first-line treatment with imatinib. This tyrosine kinase inhibitor significantly improves outcomes, resulting in either a partial response or stable disease (lack of GIST progression) within the first 6 months of treatment. A significant complication in cases of advanced GIST treated with imatinib is secondary resistance, which developis in approximately half of patients within 2 years. Patients with multifocal GIST progression who undergo surgical treatment typically have poor outcomes, but cytoreduction surgery may be considered between 6 months and 2 years in cases of metastatic GIST when the patient responds to imatinib treatment. Surgery in patients with metastatic GIST receiving second-line treatment with the tyrosine kinase inhibitor sunitinib is associated with high complication rates, incomplete resections, and lack of a clear survival benefit.¹¹  

Resistance to imatinib in patients with GIST is due to the appearance of subclones with secondary KIT gene mutations. Primary mutations usually occur in exon 11, whereas secondary KIT mutations usually occur in exon 13, 14, 17, or 18. Secondary mutations cause GIST resistance to the effects of imatinib, and the use of second- and third-line therapies such as sunitinib and regorafenib is required to target the secondary mutations specifically. Tyrosine kinase inhibitor resistance continues as advanced GIST progresses, so that fourth-line therapies such as avapritinib may be required in the most advanced cases.¹² 

Another complication of advanced GIST is patient mortality. The 5-year GIST-specific mortality rates are 34% in patients with regionally advanced GIST, 34.3% in patients with metastatic GIST, and 5.6% in individuals with localized GIST. In patients with GIST and no additional cancers, the 5-year GIST-specific mortality rate is 12.9%.¹³   

References

1. Choti MA. Gastrointestinal stromal tumors (GISTs) treatment and management: complications. Medscape. Updated March 17, 2021. Accessed June 28, 2021.
2. Bogomolov NI, Goncharov AG. Acute complications of gastrointestinal stromal tumors. Khirurgiia (Mosk). 2020;(3):67-73. doi:10.17116/hirurgia202003167
3. Zamulko OY, Zamulko AO, Dawson MJ. Introducing GIST and Dieulafoy – think of them in GI bleeding and anemia. S D Med. 2019; 72(11):528-530.
4. Ssentongo P, Egan M, Arkorful TE, et al. Adult intussusception due to gastrointestinal stromal tumor: a rare case report, comprehensive literature review, and diagnostic challenges in low-resource countries. Case Rep Surg. 2018;2018:1395230. doi:10.1155/2018/1395230
5. Intestinal obstruction: symptoms and causes. Mayo Clinic. Accessed June 28, 2021. 
6. Campbell EA, Silberman M. Bowel necrosis. StatPearls. Updated January 17, 2021. Accessed June 28, 2021.
7. Skipworth J, Fanshawe A, West M, Al-Bahrani A. Perforation as a rare presentation of gastric gastrointestinal stromal tumours: a case report and review of the literature. Ann R Coll Surg Engl. 2014;96(1):1-5. doi:10.1308/003588414X13824511650010
8. Gastrointestinal stromal tumor (GIST): statistics. Cancer.Net. Approved January 2021. Accessed June 28, 2021.
9. Pang T, Zhao Y, Fan T, et al. Comparison of safety and outcomes between endoscopic and surgical resections of small (≤ 5 cm) primary gastric gastrointestinal stromal tumors. J Cancer. 2019;10(17):4132-4141. doi:10.7150/jca.29443
10. Kim HH. Endoscopic treatment for gastrointestinal stromal tumor: advantages and hurdles.  World J Gastrointest Endosc. 2015;7(3):192-205. doi:10.4253/wjge.v7.i3.192
11. Keung EZ, Fairweather M, Raut CP. The role of surgery in metastatic gastrointestinal stromal tumors. Curr Treat Options Oncol. 2016;17(2):8. doi:10.1007/s11864-015-0384-y
12. Napolitano A, Vincenzi B. Secondary KIT mutations: the GIST of drug resistance and sensitivity. Br J Cancer. 2019;120(6):577-578. doi:10.1038/s41416-019-0388-7
13. Coe TM, Fero KE, Fanta PT, et al. Population-based epidemiology and mortality of small malignant gastrointestinal stromal tumors in the USA.  J Gastrointest Surg. 2016;20(6):1132-1140. doi:10.1007/s11605-016-3134-y

Article reviewed by Harshi Dhingra, MD, on July 1, 2021.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.