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Gastrointestinal Stromal Tumor

GIST

Gastrointestinal stromal tumors originate from interstitial cells of Cajal and correspond to the most common type of mesenchymal neoplasm of the digestive tract. They are most frequently located in stomach or small intestines.

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Presentation

Most patients suffering from GIST are either asymptomatic or report non-specific complaints.

Fatigue
  • GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass[orpha.net]
  • He reported a three-month history of diffuse abdominal pain, fatigue, and blurred vision.[ncbi.nlm.nih.gov]
  • The most common adverse reactions, as noted in previous imatinib studies, were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain.[ncbi.nlm.nih.gov]
  • The most common adverse reactions, as noted in previous imatinib studies, were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Imatinib Gleevec Kit CD117 Gastrointestinal stromal tumors AlphaMed Press[doi.org]
  • GISTs may also produce symptoms secondary to obstruction or hemorrhage (GI bleeding, malaise, fatigue, and dyspnea).[secure.ssa.gov]
Anemia
  • A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia.[ncbi.nlm.nih.gov]
  • The article presents the case of a 44-year-old otherwise healthy man with anemia, who was diagnosed lower gastrointestinal bleeding. An abdominal CT scan revealed a clearly demarcated solid tumor in hypogastric region, measuring 65 x 45 mm.[ncbi.nlm.nih.gov]
  • GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass[orpha.net]
  • Laboratory investigations revealed iron deficiency anemia and conjugated hyperbilirubinemia. Tumor markers were normal.[ncbi.nlm.nih.gov]
  • Fifty-six percent of patients presented with anemia or gastrointestinal bleeding. The tumors were located in the stomach (65%) and in the small bowel (35%). The mean tumor sizes were 4.6 cm (stomach) and 3.7 cm (small bowel).[ncbi.nlm.nih.gov]
Malaise
  • GISTs may also produce symptoms secondary to obstruction or hemorrhage (GI bleeding, malaise, fatigue, and dyspnea).[secure.ssa.gov]
  • Clinical manifestations of GISTs are as follows: Vague, nonspecific abdominal pain or discomfort (most common) Early satiety or a sensation of abdominal fullness Palpable abdominal mass (rare) Malaise, fatigue, or exertional dyspnea with significant blood[emedicine.medscape.com]
Transient Hypothyroidism
  • Mostly, patients suffer transient hypothyroidism rarely presents with overt acute symptoms requiring levothyroxine replacement. Onset is variable in published literature.[ncbi.nlm.nih.gov]
Dyspnea
  • GISTs may also produce symptoms secondary to obstruction or hemorrhage (GI bleeding, malaise, fatigue, and dyspnea).[secure.ssa.gov]
  • Case A 49-year-old man, a former smoker with no relevant family history, presented in 2002 with rapidly progressive dyspnea, chest pain, and superior vena cava syndrome.[em-consulte.com]
  • Clinical manifestations of GISTs are as follows: Vague, nonspecific abdominal pain or discomfort (most common) Early satiety or a sensation of abdominal fullness Palpable abdominal mass (rare) Malaise, fatigue, or exertional dyspnea with significant blood[emedicine.medscape.com]
Exertional Dyspnea
  • Clinical manifestations of GISTs are as follows: Vague, nonspecific abdominal pain or discomfort (most common) Early satiety or a sensation of abdominal fullness Palpable abdominal mass (rare) Malaise, fatigue, or exertional dyspnea with significant blood[emedicine.medscape.com]
Abdominal Pain
  • We report the case of a 70-year-old man who presented with sudden right lower quadrant abdominal pain and was diagnosed with a spontaneously ruptured hepatic metastasis of a malignant gastric GIST.[ncbi.nlm.nih.gov]
  • A 72-year-old woman presented with a 2-mo history of right upper abdominal pain unrelated to diet and indigestion. Fourteen years earlier, she had been diagnosed with NF-1, which manifested as café au lait spots and multiple nodules on the skin.[ncbi.nlm.nih.gov]
  • We present a case of a 59-year-old woman who came with abdominal pain and severe upper gastrointestinal bleeding (hemoglobin 3.5 g dL).[ncbi.nlm.nih.gov]
  • He reported a three-month history of diffuse abdominal pain, fatigue, and blurred vision.[ncbi.nlm.nih.gov]
  • A 64-year-old female presenting with right upper abdominal pain and thirsty for more than 20 days. A diagnosis of a 15   14   7 cm liver mass located in the posterior right lobe of liver and spread to the right adrenal gland was confirmed.[ncbi.nlm.nih.gov]
Vomiting
  • A 95-year-old Japanese woman presented to our hospital with intermittent vomiting and several episodes of melena. Abdominal computed tomography revealed intussusception of the gastric tumor into the duodenum.[ncbi.nlm.nih.gov]
  • GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass[orpha.net]
  • These may include: Abdominal discomfort or pain Vomiting Blood in stools or vomit Fatigue due to anemia (low blood counts) Feeling full after eating only a small amount (early satiety) Loss of appetite These symptoms may be the result of GIST or of other[stanfordhealthcare.org]
  • The most common adverse reactions, as noted in previous imatinib studies, were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain.[ncbi.nlm.nih.gov]
  • Tell your healthcare provider if you have any signs of bleeding while taking STIVARGA, including: vomiting blood or if your vomit looks like coffee grounds, pink or brown urine, red or black (looks like tar) stools, coughing up blood or blood clots, menstrual[stivarga-us.com]
Nausea
  • A 42-year-old hypothyroid shepherd presented with a progressive abdominal lump accompanied by nausea and abdominal fullness. In addition, he had worsening hypothyroidism, despite supranormal doses of thyroxine.[ncbi.nlm.nih.gov]
  • GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass[orpha.net]
  • The most common adverse reactions, as noted in previous imatinib studies, were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain.[ncbi.nlm.nih.gov]
  • Treatments: Current and Future Perspectives Managing the Side Effects of Immunotherapy Understanding the Role of Immunotherapy in Treating Cancer Taking Your Pills on Schedule: Why It Is So Important in Managing Cancer Preventing Chemotherapy Induced Nausea[cancercare.org]
  • The most common adverse reactions, as noted in previous imatinib studies, were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Imatinib Gleevec Kit CD117 Gastrointestinal stromal tumors AlphaMed Press[doi.org]
Abdominal Mass
  • Computed tomography (CT) scan of the chest and abdomen showed an abdominal mass that involved the small bowel, mesentery, and omentum, with lesions in the right lung and the left rib.[ncbi.nlm.nih.gov]
  • KEYWORDS: Abdominal mass; CD117; Gastrointestinal stromal tumor; Greater omentum[ncbi.nlm.nih.gov]
  • Computed tomography of the abdomen showed a huge heterogeneous mass consisting of cystic and solid components in the left upper abdomen. (18)F-Fluorodeoxyglucose positron-emission tomography revealed high tracer uptake in the abdominal mass.[ncbi.nlm.nih.gov]
  • GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass[orpha.net]
  • A 49-year-old Japanese woman was referred to our hospital with symptoms of anorexia, abdominal discomfort, and a palpable abdominal mass.[ncbi.nlm.nih.gov]
Dysphagia
  • The obstructive symptoms can be site-specific (e.g., dysphagia with an esophageal GIST, constipation with a colorectal GIST, obstructive jaundice with a duodenal tumor, etc.)[secure.ssa.gov]
  • All but one patient presented with dysphagia. The average duration of the dysphagia was 6.7 months, but five patients had dysphagia for 3 or fewer months. Frontal chest radiographs revealed a mediastinal mass in five patients.[doi.org]
  • . • Symptoms are site specific and include: dysphagia for tumors of the esophagus, nausea and vomiting caused by gastric outlet obstruction for gastric tumors, obstructive jaundice for periampullary tumors, and bowel obstruction usually caused by intussusceptions[sages.org]
  • […] variable and reflects the variability of appearance, location, and biological behavior. small tumors are more likely to be asymptomatic, regardless of location tend to grow intramural, bulging intraluminal or extramural if large enough uncommon to cause dysphagia[radiopaedia.org]
Jaundice
  • CASE PRESENTATION: A 66-year-old lady with neurofibromatosis type 1 presented with painless progressive jaundice for six months. Laboratory investigations revealed iron deficiency anemia and conjugated hyperbilirubinemia. Tumor markers were normal.[ncbi.nlm.nih.gov]
  • ., dysphagia with an esophageal GIST, constipation with a colorectal GIST, obstructive jaundice with a duodenal tumor, etc.)[secure.ssa.gov]
  • . • Symptoms are site specific and include: dysphagia for tumors of the esophagus, nausea and vomiting caused by gastric outlet obstruction for gastric tumors, obstructive jaundice for periampullary tumors, and bowel obstruction usually caused by intussusceptions[sages.org]
  • If the common bile duct is compressed, jaundice may manifest. Acute onset of severe abdominal pain, fever, shock and cardiovascular failure may indicate gastrointestinal perforation or tumor torsion and peritonitis.[symptoma.com]
  • Tell your doctor if you have a history of heart disease or risk factors for heart disease or if you experience side effects, including fever, shortness of breath, blood in your stools, jaundice (yellowing of the skin and/or eyes), sudden weight gain,[gleevec.com]
Heart Failure
  • Patients with heart disease or risk factors for heart failure should also be monitored carefully. GLEEVEC is sometimes associated with stomach or intestinal irritation.[gleevec.com]
  • failure, cerebrovascular accident including transient ischemic attack or pulmonary embolism. 6.[clinicaltrialsregister.eu]
  • Imatinib is a rare of cardiotoxicity such as congestive heart failure, arrhythmias or acute coronary syndromes, occurring in less than 1% of treated patients.[bccancer.bc.ca]
Tachycardia
  • Sometimes anemia may cause the patient’s heart to race (tachycardia). The patient may notice weight loss. Very rarely a GIST may rupture, making its presence known with a medical emergency.[gistsupport.org]
Palpitations
  • Case presentation A 47 year old African American male presented to the emergency department with intermittent, severe chest pain associated with palpitations and one episode of vomiting..[bmcresnotes.biomedcentral.com]
Skin Lesion
  • The skin lesions were distributed over his face, trunk and limbs, which improved only after discontinuation of imatinib therapy. To the best of our knowledge, this is the first report of imatinib-induced LDE in the Chinese population.[ncbi.nlm.nih.gov]

Workup

Diagnosis of gastrointestinal tumors is initially based on imaging, while the confirmation of GIST requires further analysis of tissue samples.

Gastrointestinal symptoms as described above may prompt endoscopic examinations, and fine-needle aspirations or biopsies should be carried out if submucosal masses are detected. Sonographic guidance is highly recommended to this end. Pathognomonic findings are not to be expected before histopathological analyses are realized. In general, the most striking finding to this end is a strong positivity for c-Kit upon immunohistochemical staining.

In order to ascertain the extension of the tumor, further imaging is necessary - and depending on the clinical presentation, those techniques described hereinafter may even precede endoscopy. In case of large tumors, plain radiography may be a sufficiently sensitive approach to support the tentative diagnosis of an abdominal mass. However, considerable shares of GIST measure very few centimeters in diameter at the time of symptom onset and here, contrast-enhanced computed tomography is better suited for diagnosis [10]. Additionally, the latter technique allows for a precise assessment of mesenterial or omentum infiltration. Magnetic resonance imaging has been recommended to diagnose rectal GIST; positron-emission tomography has proven valuable to detect metastases and to evaluate the patient's response to therapy.

Of note, most GIST are solitary neoplasms, but multiple tumors have also been described [11]. The latter are often associated with familial GIST that manifest in childhood. Sporadic GIST most frequently affect the stomach, but patients suffering from neurofibromatosis type 1 are more prone to develop small intestinal tumors.

Hemoglobin Decreased
  • Some common side effects that you may experience include: Fluid retention (holding water) Muscle cramps, pain, or bone pain Abdominal pain Anorexia (loss of appetite) Vomiting Diarrhea Decreased hemoglobin (decrease in blood cells which carry oxygen)[gleevec.com]
Gastric Lesion
  • The patient subsequently experienced rapid growth of the gastric lesion without mediastinal or axilla recurrence, which required palliative surgery.[ncbi.nlm.nih.gov]
  • Three months later, CT showed dramatic regression of the gastric lesion ( Figure 1 ), but progression of the lung tumor ( Figure 1 ).[em-consulte.com]
  • After 10 months of treatment a new CT scan showed the most relevant liver lesion with a size of 8.5 x 5 cm, and the gastric lesion with a size of 4 x 3.5 cm ( Fig. 2 ).[scielo.isciii.es]

Treatment

Surgical resection and chemotherapeutic treatment are the mainstays of GIST therapy, but they may be applied differently depending on the results of tumor staging, possible infiltration of adjacent tissues by the primary tumor or its metastases, and the overall condition of the patient.

Ideally, complete surgical resection of a primary tumor that didn't metastasize is carried out. If this is feasible, patients should subsequently be prescribed imatinib, a tyrosine kinase inhibitor that is effective irrespective of whether KIT or PDGFRA mutations gave rise to the neoplasm. In general, drug treatment shows very good results. However, determined mutations may render the tumor little susceptible to the compound and thereby cause relapses.

Complete remission is not to be expected if the tumor cannot be removed surgically. If the respective intervention cannot be carried out, patients may benefit from partial removal of the primary tumor or its metastases. Imatinib should be prescribed, and in some cases, patients with previously unresectable neoplasms may turn into candidates for surgery after neoadjuvant use of imatinib. This drug should not be withdrawn before surgery can be conducted or before the tumor turns resistant to increased doses of the compound, i.e., administration of imatinib may be required for several years. It is given per os.

In case of resistance to imatinib and tumor progression, sunitinib - another tyrosine kinase inhibitor - may be applicated. Sunitinib seems to be particularly effective in patients whose tumors neither present KIT nor PDGFRA mutations. Eventually, use of regorafenib constitutes another treatment option. This compound has been shown to inhibit a variety of kinases, among them KIT and PDGFRA. Due to rather high risks of adverse events, regorafenib should be reserved as a third-line treatment [12].

Of note, radiation therapy has not been proven effective to treat GIST patients.

Prognosis

About two-thirds of GIST are benign, whereas the remaining part is classified as malignant. GIST may metastasize and interestingly, such behavior seems to be more common in non-gastric tumors [8]. While the precise mutation triggering degeneration does not seem to affect the outcome, secondary gene defects do. In fact, those mutations occurring during later stages of the disease may render the tumor resistant to drug therapy. The patient's prognosis further depends on tumor size upon diagnosis, infiltration of adjacent tissues and mitotic index. In sum, GIST usually respond well to treatment and 5-year survival rates of about 75% have been reported after correction of data for mortality not related to the gastrointestinal neoplasm [7].

Etiology

Degeneration of interstitial cells of Cajal accounts for the development of GIST, but a precise trigger for such events has not yet been identified. Patients predisposed for tumor development due to systemic disorders like neurofibromatosis type 1 are diagnosed with GIST more often than the general population.

The majority of GIST patients presents mutations of the KIT gene, an oncogene encoding for a receptor tyrosine kinase. Its gene product is often referred to as c-Kit. Because c-Kit plays an important role in cell growth, division and differentiation, gain-of-function mutations that lead to constitutive activity of the enzyme may result in cancer. In fact, KIT mutations have been reported for a variety of neoplasms, especially for hematopoietic malignancies [2]. Distinct types of cancer as well as different mutations of the same gene render the tumor more or less resistant to tyrosine kinase inhibitors. Fortunately, GIST pertain to the rather susceptible group of such tumors.

Another gene frequently associated with GIST is the PDGFRA gene [1], similarly classified as an oncogene. PDGFRA encodes for platelet-derived growth factor receptor α, which is likewise a receptor tyrosine kinase. Distinct mutations have been described, and they are likely to activate downstream signaling cascades that favor cell growth and division over apoptosis [3].

Usually, gene defects leading to GIST are acquired, somatic mutations. Familial GIST are very rare [4].

Of note, a minor share of patients does present neither of the aforementioned mutations. Presumably, as of yet poorly described gene defects account for uncontrolled cell division in these cases.

Epidemiology

Although GIST are the most common mesenchymal neoplasms of the gastrointestinal tract, they are still considered rare tumors: Annual incidence rates of less than 5 per 1,000,000 inhabitants have been reported in distinct countries [5] [6], but somewhat higher values can also be found in the literature [7]. They have been estimated to account for less than 3% of malignant tumors of the digestive system [8].

People of all races and both genders may develop GIST, and predilections found in some studies have been refuted by others. However, there is a consensus regarding an age peak among the elderly. In the aforecited studies, for instance, highest incidence rates were calculated for patients aged older than 50 and 70 years, respectively. This is in agreement with a mean age upon diagnosis of 66 years. GIST have rarely been described in pediatric patients [1].

Sex distribution
Age distribution

Pathophysiology

As has been indicated above, GIST originate from the so-called interstitial cells of Cajal. These cells function as pacemakers, trigger smooth muscle contractions and thus contribute to peristalsis. Accordingly, they can be encountered along large parts of the gastrointestinal tract, starting from the esophagus, to stomach, small and large intestines and finally the rectum. And in fact, GIST have been encountered in all these organs, but they show a clear preference for stomach and small intestines: About half of all GIST affect the stomach, one-fourth is detected in jejunum or ileum.

Interstitial cells of Cajal are located in the muscular layer of the intestinal wall. Any tumor arising from these cells may thus grow towards the lumen of the respective hollow organ, or in the opposite direction. Exophytic growth has been reported to be more common in GIST. According to the fact that stomach and small intestines are most frequently affected, many GIST grow in the abdominal cavity. Contrary to endophytically growing tumors that interfere with the gastrointestinal passage during early stages of the disease, exophytic neoplasms may not provoke any symptoms until reaching a considerable size [8]. Upon torsion of pedunculated GIST, however, acute symptom onset may be observed independent of the size of the tumor [9].

Prevention

No specific measures can be recommended to prevent GIST.

Summary

A gastrointestinal stromal tumor (GIST) is a rare type of tumor, yet it is the most common form of mesenchymal gastrointestinal neoplasm. GIST originate from interstitial cells of Cajal, which act as pacemakers and coordinate peristaltic motions along large parts of the digestive system.

In general, GIST are diagnosed in patients aged 50 years and older. However, children have been reported to suffer from GIST as well, and such findings may result from a general disposition for tumor growth, as seen, for instance, in neurofibromatosis patients. Non-specific gastrointestinal symptoms like bloating, early satiety, hemorrhages and obstruction may prompt patients to seek medical attention; in other cases, GIST are incidental findings.

GIST may obstruct the lumen of the affected hollow viscera, but they more commonly invade neighboring tissues like mediastinum, mesenterium and omentum. This fact explains why GIST are often diagnosed only after the tumor has reached a considerable size - case reports of neoplasms measuring more than 30 centimeters in diameter and weighing several kilogram have been published [1].

Workup aims at tumor staging, i.e., assessment of the neoplasm's extension and possible metastazation, and tumor grading. GIST may show features of benign or malignant neoplasms, but histopathological findings don't necessarily correlate with the likelihood of recurrence and formation of metastases. Complete surgical resection and adjuvant administration of tyrosine kinase inhibitors is the therapeutic approach of choice.

Patient Information

In general, intestinal walls consist of an inner mucosal layer, smooth muscle whose contraction permits peristaltic movements, and an outer layer called adventitia. However, there's a wide variety of specific cell types distributed throughout these layers, each of which fulfills important functions. Some are termed interstitial cells of Cajal - these cells function as pacemakers and thus contribute to regular peristaltic motions. If interstitial cells of Cajal grow and divide in an uncontrolled manner, tumors may develop. The affected patient is diagnosed with a gastrointestinal stromal tumor (GIST).

GIST may occur along large parts of the digestive system, starting from the esophagus, to stomach, small and large intestines and finally the rectum. Most commonly, stomach and small bowels are affected. Although they may grow towards the lumen of the respective hollow viscera, they tend to expand within the abdominal cavity. Thus, they may reach a considerable size before being detected. In fact, some GIST are incidental findings encountered while realizing endoscopy or radiography for other reasons.

If GIST patients become symptomatic, they may vomit blood or detect blood in their stools. Non-specific gastrointestinal complaints like difficulties when swallowing, bloating, early satiety and constipation. Such symptoms prompt diagnostic imaging; physicians may also need to obtain a tissue sample, either by fine-needle aspiration or by biopsy. Endoscopy, sonography and computed tomography are most frequently applied to this end. The latter also allows for an evaluation of possible infiltration of adjacent tissues.

In general, complete surgical resection is recommended to treat GIST patients. Adjuvant chemotherapy is often required, particularly in case of metastatic cancer. It significantly reduces the probability of recurrence and renewed metastatic spread. In sum, GIST usually respond well to treatment and 5-year survival rates of about 75% have been reported.

References

Article

  1. Kuroiwa M, Hiwatari M, Hirato J, et al. Advanced-stage gastrointestinal stromal tumor treated with imatinib in a 12-year-old girl with a unique mutation of PDGFRA. J Pediatr Surg. 2005; 40(11):1798-1801.
  2. Ashman LK, Griffith R. Therapeutic targeting of c-KIT in cancer. Expert Opin Investig Drugs. 2013; 22(1):103-115.
  3. Velghe AI, Van Cauwenberghe S, Polyansky AA, et al. PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations. Oncogene. 2014; 33(20):2568-2576.
  4. Jones DH, Caracciolo JT, Hodul PJ, Strosberg JR, Coppola D, Bui MM. Familial gastrointestinal stromal tumor syndrome: report of 2 cases with KIT exon 11 mutation. Cancer Control. 2015; 22(1):102-108.
  5. Wang ZH, Liang XB, Wang Y, Ma GL, Qu YQ, Tian XW. [Epidemiology survey of gastrointestinal stromal tumor in Shanxi Province in 2011]. Zhonghua Yi Xue Za Zhi. 2013; 93(32):2541-2544.
  6. Ma GL, Murphy JD, Martinez ME, Sicklick JK. Epidemiology of gastrointestinal stromal tumors in the era of histology codes: results of a population-based study. Cancer Epidemiol Biomarkers Prev. 2015; 24(1):298-302.
  7. Tryggvason G, Gislason HG, Magnusson MK, Jonasson JG. Gastrointestinal stromal tumors in Iceland, 1990-2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer. 2005; 117(2):289-293.
  8. Navarrete A, Momblan D, Almenara R, Lacy A. Giant Gastric Gastrointestinal Stromal Tumor (GIST). J Gastrointest Surg. 2016.
  9. Kittmer TC, Shawyer AC, Zequeira JJ, Bailey KA. GIST with a twist: An extra-luminal pedunculated gastric GIST presenting with tumor torsion and hemoperitoneum. J Pediatr Surg Case Rep. 2013; 1(9):270.
  10. Vernuccio F, Taibbi A, Picone D, et al. Imaging of Gastrointestinal Stromal Tumors: From Diagnosis to Evaluation of Therapeutic Response. Anticancer Res. 2016; 36(6):2639-2648.
  11. O'Sullivan MJ, McCabe A, Gillett P, Penman ID, MacKinlay GA, Pritchard J. Multiple gastric stromal tumors in a child without syndromic association lacks common KIT or PDGFRalpha mutations. Pediatr Dev Pathol. 2005; 8(6):685-689.
  12. Lyseng-Williamson KA. Regorafenib: a guide to its use in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib and sunitinib. BioDrugs. 2013; 27(5):525-531.

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Last updated: 2019-07-11 20:13