AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs can also originate in the mesentery and omentum. Overall, GISTs are rare and rank a distant third in prevalence behind adenocarcinomas and lymphomas among the histologic types of gastrointestinal tract tumors. Historically, these lesions were classified as leiomyomas or leiomyosarcomas because they possessed smooth muscle features when examined under light microscopy.

Since the term GIST was introduced by Mazur and Clark in 1983, laboratory investigations aimed at the subcellular and molecular levels have demonstrated that GISTs do not possess the ultrastructural and immunohistochemical features characteristic of smooth muscle differentiation, as are seen in leiomyomas and leiomyosarcomas.¹ Therefore, the determination was made that GISTs do not arise from smooth muscle cells, but from another mesenchymal derivative such as the progenitors of spindle and epithelioid cells.

According to the work of Kindblom and associates reported in 1998, the actual cell of origin of GISTs is a pluripotential mesenchymal stem cell programmed to differentiate into the interstitial cell of Cajal.² These are GI pacemaker cells and are largely responsible for initiating and coordinating GI motility. This finding led Kindblom and coworkers to suggest the term GI pacemaker cell tumors.² Perhaps the most critical development that distinguished GISTs as a unique clinical entity was the discovery of c-kit proto-oncogene mutations in these tumors by Hirota and colleagues in 1998.³

These advances have led to the classification of GISTs as an entity separate from smooth muscle tumors, helped elucidate their etiology and pathogenesis at a molecular level, and led to the development of molecular-targeted therapy for this disease.

Pathophysiology

GISTs can occur anywhere in the gastrointestinal tract. They are submucosal lesions, which most frequently grow endophytically in parallel with the lumen of the affected structure. GISTs may also manifest as exophytic extraluminal excrescences. These tumors have been reported ranging in size from smaller than 1 cm to as large as 40 cm in diameter. Approximately 50-70% of GISTs originate in the stomach. The small intestine is the second most common location, with 20-30% of GISTs arising from the jejunoileum. Less frequent sites of occurrence include the colon and rectum (5-15%) and esophagus (<5%). Primary omental or mesenteric GISTs have been reported but are very rare.

Frequency

United States

Approximately 10-20 persons per million population are diagnosed with GISTs each year.

International

The international prevalence of GISTs is comparable to that reported in the United States. Retrospective reviews from Western Europe, Asia, and Africa have produced similar rates of disease.

Mortality/Morbidity

Outcomes in patients with GISTs are highly dependent on the clinical presentation and the histopathological features of the tumor. The overall 5-year survival rate ranges from 28-60%. This can be stratified for patients presenting with localized primary disease and those presenting with metastatic or recurrent disease. The median survival rate in the former group is 5 years, while the median survival rate in the latter group is approximately 10-20 months. Larger GISTs are associated with complications such as GI hemorrhage, GI obstruction, and bowel perforation. This is discussed further in Surgical Care and Complications.

Tumors can be classified into high- and low-risk categories based on size and mitotic activity. The implications of these tumor characteristics are discussed in Prognosis and Histologic Findings.

Race

GISTs have no known racial proclivity.

Sex

Slightly more males are diagnosed with GISTs than females, although many reviews have reported no sex predilection.

Age

GISTs are most commonly diagnosed in the latter half of the sixth and the first half of the seventh decades of life (ie, 55-65 y). On occasion, they are discovered in younger adults. GISTs are extremely uncommon in children.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Up to 75% of GISTs are discovered when they are less than 4 cm in diameter and are either asymptomatic or associated with nonspecific symptoms. They are frequently diagnosed incidentally during endoscopic or surgical procedures or during radiologic studies performed to investigate protean manifestations of gastrointestinal tract disease or to treat an emergent condition such as hemorrhage or obstruction. Lesions greater than 4 cm in diameter are more likely to be symptomatic.
• The most common symptoms associated with GISTs are vague, nonspecific abdominal pain or discomfort.
• • Patients also describe early satiety or a sensation of abdominal fullness. Rarely, an abdominal mass is palpable.
  • GISTs may also produce symptoms secondary to obstruction or hemorrhage. GI bleeding is produced by pressure necrosis and ulceration of the overlying mucosa with resultant hemorrhage from disrupted vessels. Patients who have experienced significant blood loss may report malaise, fatigue, or exertional dyspnea. Obstruction can result from intraluminal growth of an endophytic tumor or from luminal compression from an exophytic lesion. The obstructive symptoms can be site-specific (eg, dysphagia with an esophageal GIST, constipation with a colorectal GIST, obstructive jaundice with a duodenal tumor).
  • In some cases, the GIST is an unexpected finding during emergency surgery for a perforated viscus.

Physical

• No physical findings specifically suggest the presence of a GIST. Some patients present with a palpable abdominal mass. Others may present with nonspecific physical findings associated with GI blood loss, bowel obstruction, or bowel perforation and abscess formation.
• • Patients presenting with significant GI bleeding can manifest vital sign abnormalities or overt shock. In others, fecal occult blood testing may be positive.
  • Physical findings associated with bowel obstruction can include a distended, tender abdomen. Duodenal obstruction involving the ampulla may be associated with jaundice and, rarely, even a distended palpable gallbladder.
  • If perforation has occurred, focal or widespread signs of peritonitis are present.

Causes

• Gain-of-function mutations in exon 11 of the c-kit proto-oncogene are associated with most GISTs. These mutations lead to constitutive overexpression and autophosphorylation of c-Kit, provoking a cascade of intracellular signaling that propels cells toward proliferation or away from apoptotic pathways.
• • This discovery by Hirota and colleagues in 1998 was a landmark elucidation of the etiology of a disease on a molecular level.³ Most of these mutations are of the in-frame type, which allows preservation of c-kit expression and activation. The c-kit proto-oncogene is located on chromosome arm 4q11-12. It encodes KIT, which is a transmembrane tyrosine kinase. Stem cell factor, also called Steel factor or mast cell growth factor, is the ligand for KIT and exists primarily in dimeric form.
  • Under normal circumstances, KIT activation is initiated when stem cell factor binds to the extracellular domain of c-Kit. The result is homodimerization of the normally inactive c-Kit monomers. Autophosphorylation of intracellular tyrosine residues then transpires. This exposes binding sites for intracellular signal transduction molecules. What follows is activation of a signaling cascade that involves phosphorylation of several downstream target proteins, including MAP kinase, RAS, and others. Ultimately, the signal is transduced into the nucleus, resulting in mitogenic activity and protein transcription.
  • KIT is constitutively phosphorylated in the majority of GISTs. In these instances, stem cell factor is not required to initiate the sequence of c-Kit homodimerization and autophosphorylation. This is termed ligand-independent activation. The increased transduction of proliferative signals to the nucleus favors cell survival and replication over dormancy and apoptosis, leading to tumorigenesis.
  • Studies have reported a small subset of KIT-negative GISTs in which mutations of platelet-derived growth factor receptor-alpha (PDGFA), protein kinase C, and FLJ10261 were detected. These mutations and c-kit mutations appear to be mutually exclusive according to the 2003 work of Heinrich and associates. These investigators discovered PDGFA mutations in 14 of 14 subjects with GISTs who lacked c-kit mutations.
• A small minority of GISTs are associated with hereditary syndromes.
• • One is characterized by multiple GISTs with or without the presence of dermal and mucous membrane hyperpigmentation, numerous nevi, and urticaria pigmentosa. Mast cell dysfunction and diffuse hyperplasia of GI spindle cells are other features of this syndrome.
  • GISTs occur with a higher than expected frequency in patients with type 1 neurofibromatosis.
  • GISTs are also a feature of the rare Carney triad, which is observed predominantly in young women. This triad consists of epithelioid gastric stromal tumors, pulmonary chondromas, and extra-adrenal paragangliomas.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Lymphoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No laboratory test can specifically confirm or rule out the presence of a GIST. These tests are generally ordered in the workup of the patient who presents with nonspecific abdominal symptomatology; abdominal pain; or complications of a GIST-like hemorrhage, obstruction, or perforation.
• • Complete blood cell count
  • Coagulation profile
  • Serum chemistry studies
  • BUN and creatinine
  • Liver function tests and amylase and lipase values
  • Type and screen, type and crossmatch
  • Serum albumin

Imaging Studies

• Acute abdominal series (plain abdominal radiography)
• • Plain abdominal radiography is nonspecific but may be ordered as part of the workup of a patient presenting emergently with a possible bowel obstruction or perforation.
  • Abnormal gas patterns, including dilated loops of bowel or free extraluminal air, are examples of findings that may be detected in these clinical situations.
• Barium and air (double-contrast) series
• • Double-contrast radiographic series can usually detect GISTs that have grown to a size sufficient to produce symptoms.
  • The choice of performing a barium swallow, barium enema, or both depends on the patient's clinical presentation. For example, patients whose primary symptomatology includes dysphagia should have a barium swallow. Those presenting with constipation, decreased stool caliber, or other signs and symptoms referable to the colon should have a barium enema.
  • In these contrast studies, GISTs appear as a filling defect that is sharply demarcated and is elevated compared with the surrounding mucosa, as described by Yamashita and colleagues in 2001.⁴ Typically, the contour of the overlying mucosa is smooth unless ulceration has developed because of growth of the underlying tumor.
  • While these studies can produce striking images, frequently the information they provide is limited. Other modalities listed below have equal or greater sensitivity and can provide more information about the status of surrounding structures.
• Enteroclysis
• • As is frequently the case with other small bowel lesions, GISTs in the small intestine can be difficult to diagnose and localize.
  • Enteroclysis allows delivery of contrast in proximity to the small bowel so it does not become too diluted by the time it reaches the area in question. This may help to better define small intestinal GISTs.
• Abdominal ultrasonography
• • The ultrasonographic appearance of GISTs varies depending on the size of the lesion and the presence or absence of necrosis within the mass. In addition, ulceration or necrosis of the overlying mucosa can change the ultrasonographic characteristics of the tumor.
  • Transcutaneous ultrasonography is probably not the optimum choice for imaging these lesions unless the mass has reached quite a large size. Because GISTs are associated with air-filled viscera, image quality is often degraded by intervening bowel gas.
  • The best ultrasonographic images of these lesions are acquired during endoscopic ultrasonography. This is discussed in Procedures.
• CT scanning of the abdomen and pelvis
• • CT scanning is an important radiographic modality in the diagnosis and staging of GISTs. It provides comprehensive information regarding the size and location of the tumor and its relationship to adjacent structures. CT scanning can also be used to detect the presence of multiple tumors and can provide evidence of metastatic spread.
  • Ghanem and colleagues, as reported in 2003, performed CT scanning on patients with histologically confirmed primary (n = 20) or recurrent (n = 16) GISTs.⁵ These investigators described the CT characteristics of GISTs, dividing them into small (<5 cm), intermediate (5-10 cm), and large (>10 cm) tumors. Small GISTs were sharply demarcated, homogeneous masses, mainly exhibiting intraluminal growth patterns. Intermediate GISTs were characterized by irregular shape, heterogeneous density, an intraluminal and extraluminal growth pattern, and signs of biological aggression, including adjacent organ infiltration in 9 primary and 2 recurrent lesions. Large GISTs featured irregular margins, heterogeneous densities, locally aggressive behavior, and distant and peritoneal metastases.
  • Also in 2003, Tateishi and coworkers correlated CT findings with histologic tumor grade and mortality rates.⁶ Patients with low-grade (n = 44) and high-grade (n = 25) GISTs underwent dual-phase CT scanning. The investigators found that CT criteria associated with high-grade histology and increased mortality included a tumor larger than 11.1 cm with irregular surface contours, indistinct margins, adjacent organ invasion, heterogeneous enhancement, and hepatic or peritoneal metastasis.
• MRI
• • Similar to CT scanning, MRI can depict the tumor or tumors and yield information about surrounding structures. It can also be used to detect the presence of multiple tumors and metastases.
  • MRI has not been studied as intensively as CT scanning in the application of diagnosing GISTs. It appears to be just as sensitive as CT scanning.
  • In 1997, Shojaku and colleagues described a GIST as appearing hypointense on T2-weighted images.⁷
• Positron emission tomography scanning with 2-[F-18]-fluoro-2-deoxy-D-glucose
• • Positron emission tomography scanning has recently been touted as an excellent study for detecting metastatic disease. It has also been used to monitor responses to adjuvant therapies such as imatinib mesylate.
  • In 2003, Stroobants and colleagues reported on positron emission tomography scanning on 21 patients with soft tissue sarcomas (17 with GISTs) prior to beginning therapy with imatinib mesylate and then 8 days after commencing therapy.⁸ Responses were seen on the images in 13 patients with GISTs after 8 days of therapy. The patients underwent CT scanning after a median follow-up of 8 weeks, and CT evidence of responses was seen in 10 of 13 patients. The patients who demonstrated no response on the 8-day positron emission tomography scan image had evidence of stable disease or disease progression. The authors concluded that positron emission tomography scanning was a sensitive modality for detecting early clinical response to therapy with imatinib mesylate.

Procedures

• Endoscopy
• • As a result of GI bleeding, abdominal pain, or GI obstructive symptoms, endoscopy is frequently performed early in the workup of patients with GISTs.
  • Endoscopic features of GISTs include the suggestion of a smooth submucosal mass displacing the overlying mucosa.
  • Some may be associated with ulceration or bleeding of the overlying mucosa from pressure necrosis, as described by Pidhorecky and coworkers in 2000.⁹
  • Obtaining reliable biopsy specimens by traditional endoscopic means is fraught with difficulty because of the submucosal location of these tumors. This is a major reason why endoscopic biopsy results yield a diagnosis less than 50% of the time. Obtaining a repeat biopsy in the same site as a prior biopsy may increase the diagnostic yield.
• Endoscopic ultrasonography
• • Endoscopic ultrasonography is a modality that allows localization of lesions and their characterization by ultrasonography. Fine-needle aspiration biopsy specimens also may be obtained via the endoscope under sonographic guidance.
  • The typical endoscopic ultrasonographic appearance of a GIST is a hypoechoic mass situated in the layer corresponding to the muscularis propria.
  • In 1997, Chak and coinvestigators described endoscopic ultrasonographic characteristics of malignant GISTs to include size larger than 4 cm, heterogeneous echogenicity, internal cystic areas, and irregular borders on the extraluminal surfaces.¹⁰
  • In 2002, Belloni and colleagues compared CT scanning and endoscopic ultrasonography in the diagnosis of GIST and in their ability to discriminate benign from malignant disease.¹¹ They found that endoscopic ultrasonography is more accurate in differentiating benign from malignant lesions but that CT scanning allows a more comprehensive evaluation of the mass and the surrounding structures. The authors concluded that the techniques are complementary and helpful in planning operative therapy.
• Angiography
• • Angiography is rarely used in the diagnosis or management of GISTs. It may be used during diagnostic dilemmas or for urgent treatment of complications such as GI hemorrhage. Therefore, much of the literature on GISTs and angiography is limited to case reports.
  • In 1996, Gordon and coworkers reported on the use of angiography to help localize a GIST in the right lower abdominal quadrant.¹²
  • Also in 1996, Au and Peh reported on a patient with melena and anemia in whom angiography delineated an ileal GIST.¹³
  • In 2003, Nakagawa and coinvestigators and Suzuki and colleagues used angiography to localize extragastric GISTs in the greater omentum.^{14, 15}

Histologic Findings

GISTs manifest a wide variety of clinical behavior, from slow-growing indolent tumors to aggressive malignant cancers with the propensity to invade adjacent organs, metastasize to the liver, and recur locally within the abdomen. Clinical presentation provides the most overt evidence for distinguishing benign from malignant behavior. Histologic analysis of biopsy or operative specimens provides objective measures for diagnosis and helps predict clinical behavior.

The morphologic features that appear to be most predictive of outcome and biological behavior are tumor size and the mitotic rate. Unfortunately, no absolute determinations can be made because even small lesions with low mitotic rates can metastasize or behave in a locally aggressive fashion. In 2002, Fletcher and colleagues proposed a classification system to define relative risk for malignant behavior in GISTs.¹⁶ See the Fletcher et al stratification of risk in Prognosis.

GISTs typically stain intensely for the CD117 molecule, which is an epitope of KIT. In contrast, desmoids, schwannomas (S-100–positive, KIT-negative), leiomyomas, and leiomyosarcomas (desmin-positive, KIT-negative) do not. In GISTS, according to Fletcher et al, CD117 appears diffusely in the cytoplasm in a punctate or Golgilike pattern.¹⁶ CD34 staining results are also positive in approximately 60% of GISTs.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The only effective, specific, nonsurgical therapy for GISTs is imatinib mesylate. The optimal dose for imatinib mesylate in the adjuvant or neoadjuvant setting remains to be defined. This drug is discussed in detail in Medication. Discussed below are the roles of systemic and intraperitoneal chemotherapy and the role of radiation therapy. Other, supportive medical care focuses on preparing patients to undergo anticipated extensive operations for GISTs or on the resuscitation and stabilization of those who have experienced GIST-related complications.

• Systemic chemotherapy
• • Systemic chemotherapy trials (ie, before the introduction of imatinib mesylate) for the treatment of GISTs have almost exclusively been associated with poor results. Overall partial response rates were approximately 10% or less.
  • The best results have been achieved using doxorubicin-based regimens, plus dacarbazine, with or without the addition of ifosfamide. Response rates greater than 10% with these regimens were reported by Antman et al in 1993 (n = 60, response = 15%) and Elias et al in 1989 (n = 11, response = 27%).^{17, 18}
  • In the future, the role of systemic chemotherapy will largely be limited to treatment of patients in whom imatinib mesylate fails or in whom imatinib mesylate responses diminish.
• Intraperitoneal chemotherapy
• • Intraperitoneal chemotherapy has been developed because of the disappointing results with systemic chemotherapy.
  • Agents that have been tried include cisplatin and doxorubicin, by Berthet and colleagues in 1999, and mitoxantrone, by Eilber and coworkers in 1999 and 2000.^{19, 20} Some encouraging results have been achieved in patients with disease limited to the peritoneum.
  • With the introduction of imatinib mesylate, intraperitoneal chemotherapy is unlikely to become first-line adjuvant therapy. The role of intraperitoneal chemotherapy as salvage therapy in patients in whom imatinib mesylate fails is being investigated.
• Radiation therapy
• • Radiation therapy is not part of widely accepted adjuvant therapy protocols for GISTs.
  • Case reports describe radiation treatment of lesions fixed to the abdominal wall or adjacent organs.
  • Factors mitigating against successful radiation therapy include bowel motility and intra-abdominal organ sensitivity to large radiation doses.
  • Efficacy in treated patients has been questioned by Crosby et al in 2001, who described GIST recurrences within and external to the treated fields.²¹

Surgical Care

Surgery is the definitive therapy for patients with GISTs. Radical and complete surgical extirpation offers the only chance for cure. Surgery is also indicated in symptomatic patients with locally advanced or metastatic disease. Debulking large lesions is helpful when adjuvant therapy with imatinib mesylate is contemplated.

• In 2003, Wu et al published their experience with 57 patients who underwent surgical treatment of GISTs from 1995-2002.²²
• • Twenty-eight patients (49%) underwent surgery with curative intent. The remainder were referred to the authors with metastatic disease after undergoing operative treatment at other institutions. In the curative-intent group, resections with completely negative margins were accomplished in 22 patients (79%). In 3 of the patients with complete resections, metastatic disease was totally resected along with the primary tumor. An additional 2 patients had subsequent complete resection after favorable clinical responses to imatinib mesylate therapy. CD117 staining was positive in 96% of the resected specimens.
  • In total, 34 patients were diagnosed with metastatic disease during the initial evaluation and treatment or at some point during follow-up. The most common sites of metastatic disease were the liver (71%) and peritoneum (53%).
  • The authors monitored the entire cohort for a median duration of 18 months. Twenty-three patients (40%) remained alive and free of disease. An additional 22 patients (39%) are alive with disease. Of the remainder, 7 are known to have died and 5 have been lost to follow-up. Treatment with imatinib effected disease stabilization or regression in 22 (85%) of the 26 treated, with a median duration of response of 19 months.
  • The authors concluded that complete resection with negative margins is still the only potentially curative treatment for GISTs. Furthermore, imatinib therapy for metastatic disease is associated with good clinical response rates, but the true therapeutic efficacy of this drug will not be known until prospective trials are completed.
• In 2003, Besana-Ciani et al reported on 19 patients with GISTs who underwent surgical resection.²³
• • They were able to achieve complete resection in 78.9% of patients in this series. The mean tumor size was 8.4 cm. These patients received long-term follow-up.
  • Using the Fletcher et al histologic classification, tumors were divided into 2 groups.¹⁶ Tumors classified as very low, low, and intermediate risk comprised one group. The second consisted of tumors classified as high risk. The 5-year survival rates were 63% in the former group and 34% in the latter group.
  • As might be expected, complete resection was also a significant predictor of superior survival compared with incomplete resection.
  • These authors also concluded that radical complete resection offers the only chance for long-term survival in patients with GISTs.

Consultations

The management of GISTs requires the participation of a multidisciplinary team. The team should include a surgeon, gastroenterologist, and medical oncologist.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Imatinib mesylate is the only available drug that has made a significant impact in the treatment of GISTs.

Drug Category: Selective tyrosine kinase inhibitors

Imatinib mesylate (STI 571) is a selective tyrosine kinase inhibitor with action against mutant c-Kit as occurs in association with GISTs. It represents a breakthrough in antineoplastic drug therapy because it is targeted against a specific molecular derangement.

Drug Category: Multikinase inhibitors

Elicit actions via multiple tyrosine kinase inhibitors implicated in tumor growth, pathologic angiogenesis, and metastatic progression.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Preoperative care focuses on managing the acute complications of GISTs (ie, hemorrhage, bowel obstruction, perforation) or on preparing the patient for surgery. Proper postoperative care helps ensure complete and uneventful patient recovery. Features of preoperative and postoperative care in patients with GISTs include the following:
• • Fluid resuscitation and transfusion
  • • Patients with GIST-related hemorrhage require intravenous fluid resuscitation. Those with massive hemorrhage may require transfusion of blood products.
    • Postoperatively, resuscitative and maintenance intravenous fluids are provided. Most commonly, a balanced salt solution such as lactated Ringer is used.
  • Correction of electrolyte abnormalities: Specific electrolyte abnormalities can be directly measured and replaced as appropriate.
  • Activity: Early postoperative activity is encouraged.
  • Diet and nutrition
  • • Patients receive nothing by mouth for varying durations, depending on the preference of the operating surgeon.
    • Following nasogastric tube removal, patients can be started on a liquid diet and advanced to a full diet as tolerated. Postgastrectomy diet counseling by a registered dietitian is helpful in patients undergoing subtotal or total gastrectomies.
    • Depending on the patient's preoperative nutritional status, a period of specialized nutritional support might be indicated. This can range from enteral tube feedings to peripheral hyperalimentation to total parenteral nutrition. Multivitamin and iron supplementation may be indicated.
  • Drains
  • • Depending on the type of resection, a nasogastric tube is left in place postoperatively. Ensuring that the tube is continuously functional and remains unclogged is crucial. Criteria for removal of a nasogastric tube vary by clinician.
    • A urinary Foley catheter remains in place in the early postoperative period or during the preoperative resuscitative period in patients who have sustained major hemorrhage or other complications. The catheter aids monitoring of hydration status and serves as a guide for fluid resuscitation. Once the patient is stabilized and no additional major fluid shifts are anticipated, the catheter can be removed.
  • Pulmonary toilet
  • • Instruct patients to cough and to take frequent deep breaths. The incentive spirometer is an important adjunct for this and should be used by the patient every 1-2 hours while awake.
    • Early mobilization of the patient assists with maintaining good pulmonary toilet.
  • Monitoring
  • • Vital signs are monitored per protocol. Intake and output records are kept.
    • Pulse oximetry is used when appropriate to measure oxygen saturation.
  • Antibiotics
  • • Unless bowel perforation or other septic complications have occurred, a single dose of intravenous antibiotic prophylaxis against wound infection is usually sufficient.
    • Patients with abdominal catastrophes such as bowel perforation or infarction require a full therapeutic course of intravenous antibiotics that cover the spectrum of gut flora.
  • Pain control, deep venous thrombosis prophylaxis, and aspiration precautions
  • • An epidural catheter can be placed by anesthesia personnel for postoperative pain control. Alternately, a patient-controlled anesthesia schedule can be ordered.
    • Prophylaxis against deep venous thrombosis is crucial because it and pulmonary embolism are significant sources of postoperative morbidity and mortality. Available modalities include subcutaneous heparin, subcutaneous fractionated heparin preparations, and sequential compression stockings.
    • The head of the bed can be kept elevated 30-45°, or sometimes higher for elderly patients or during sleep, to help prevent aspiration.

Further Outpatient Care

• Comprehensive follow-up is extremely important in all but the smallest and lowest-grade tumors. A follow-up plan should include these measures:
• • Periodic office visits and physical examinations are crucial in the follow-up of patients with GISTs.
  • Periodic CT scanning can be ordered to aid in the detection of locally recurrent disease or distant metastasis. The optimal frequency for CT scan follow-up is not known. This is left to the discretion of the attending physician.
  • Positron emission tomography scanning may be indicated in the follow-up of patients with GISTs, especially those receiving imatinib mesylate for incompletely resected, recurrent, or metastatic disease.

Complications

• Complications can be divided into preoperative and postoperative categories. Preoperative tumor-related complications usually occur with tumors larger than 4 cm.
• • Major preoperative complications include the following:
  • • Hemorrhage
    • Bowel obstruction
    • Volvulus
    • Intussusception
    • Bowel perforation with peritonitis
  • The range of postoperative complications is that typical for major abdominal and GI surgery. The following is a representative but not exhaustive list:
  • • Wound infection
    • Wound dehiscence with or without evisceration
    • Urinary tract infection
    • Atelectasis
    • Pneumonia
    • Anastomotic disruption
    • Anastomotic stricture
    • Marginal ulceration
    • Intra-abdominal abscess formation
    • Cholangitis
    • Delayed gastric emptying or gastroparesis
    • Internal or enterocutaneous fistula
    • Small bowel obstruction
    • Dumping syndrome
    • Alkaline reflux gastritis
    • Cardiac arrhythmias
    • Myocardial infarction
    • Deep venous thrombosis
    • Pulmonary embolism

Prognosis

• The predominant prognostic factors in patients with GISTs include the size of the tumor and the mitotic rate. To these may be added the ability or inability to achieve completely negative resection margins.
• • Reported 5-year disease-specific survival rates are 30-60% according to results reported by many studies (eg, DeMatteo et al, 2000 and 2002; Crosby et al 2001; Carney, 1999; Conlon et al 1995).^{24, 21, 25, 26} The disparity between patients presenting with localized primary disease (median survival of 5 y) and those presenting with metastasis or recurrent disease (median survival of 10-20 mo) is large.
  • Location is also significant. Patients with gastric GISTs tend to fare better than those with extragastric GISTs.
  • The importance of the mitotic count as a prognostic factor and predictor of malignant behavior was illustrated by Dougherty et al in 1991.²⁷ Even after curative resections, patients with a mitotic rate of 10 or greater per 50 high-power fields (HPFs) had a median survival rate of 18 months, compared with an 80%, 8-year disease-free survival rate in patients who had curative resections and tumors with a mitotic rate less than 10/50 HPFs.
  • The 2002 Fletcher et al stratification of the risk of aggressive or malignant behavior in GISTs, based on size and mitotic rate, is as follows:¹⁶
  • • Very low risk - Smaller than 2 cm and less than 5/50 HPFs
    • Low risk - From 2-5 cm and less than 5/50 HPFs
    • Intermediate risk - Either (1) smaller than 5 cm and 6-10/50 HPFs or (2) 5-10 cm and less than 5/50 HPFs
    • High risk - Includes (1) larger than 5 cm and more than 5/50 HPFs, (2) larger than 10 cm and any mitotic rate, or (3) any size and more than 10/50 HPFs

Patient Education

• Patients should be educated about as many aspects of the disease as possible, including diagnostic and therapeutic measures and options. Most importantly, they should be apprised of the need for lifelong close clinical follow-up, even after complete resection of disease. Emphasize that GISTs have a propensity to recur.
• For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Stomach Cancer and Cancer of the Small Intestine.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The standard of care includes resection of the tumor to negative margins whenever possible. Therapy with imatinib mesylate is indicated in many patients, including those with metastatic disease and incomplete resections. Nearly all patients with GISTs, with the potential exception of those with very small low-risk tumors, deserve careful lifelong follow-up with updated histories, physical examinations, and imaging studies. Delayed diagnosis, failure to treat with appropriate adjuvant therapy, and inadequate follow-up are all areas for potential medicolegal pitfalls.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Mazur MT, Clark HB. Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol. Sep 1983;7(6):507-19. [Medline].
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