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Gastric Cancer

- Helicobacter pylori infection is primary risk in 65-80%. - Smoking/tobacco abuse is second leading risk factor. - Diet rich in additives (e.g., smoked, pickled, or salted foods; highly spiced foods), nitrates, and nitrites have been implicated. - Atrophic gastritis/intestinal metaplasia - Pernicious anemia - Preexisting diabetes mellitus - Overweight and obesity: strength of association increases with increasing body mass index (BMI) - Familial polyposis - Barrett esophagus - Patients in lower socioeconomic status have higher risk of gastric cancer. - Low consumption of fruits and vegetables - Ethnicity: Hispanic, Japanese, Chilean, Costa Rican - Migrants from high-incidence areas (e.g., Iceland, Chile, or Japan) to low-incidence areas maintain an increased risk, whereas their offspring have an occurrence rate that corresponds to that of the new location.

- Assess risk factors (tobacco use; H. pylori infection, dietary history; family history of upper GI cancers or genetic syndromes). - Anorexia; unintentional weight loss (70-80%) - Early satiety - New onset dyspepsia - Nausea and vomiting - Change in bowel habits - Chronic noncolicky abdominal pain (especially in epigastrium) - Postprandial fullness to severe steady pain - Unrelieved by antacids - Exacerbated by food - Relieved by fasting

- Abdominal palpation for masses and/or ascites - Palpation for lymph nodes - Left supraclavicular node (Virchow) - Sister Mary Joseph nodule at umbilicus

- Radical subtotal gastrectomy with gastrojejunostomy or gastroduodenostomy is the usual treatment. - Removal of a large part of the stomach along with the greater and lesser omentum en bloc - Splenectomy or distal pancreatectomy done in certain situations - Excise direct tumor extensions at the time of surgery

para>Rare

Pregnancy Considerations

EPIDEMIOLOGY

  • Predominant age: >55 years (2/3 are >65 years)
  • Predominant gender: male > female (1.7:1)
  • Incidence is decreasing globally but it is still the third leading cause of cancer death worldwide.

Incidence

  • 5.9/100,000 males (North America)
  • 2.5/100,000 females (North America)
  • 21,130 new cases per year (United States)

ETIOLOGY AND PATHOPHYSIOLOGY

Unknown

Genetics

  • More common in people with blood group A
  • 2 to 4 times more common in first-degree relatives
  • 1-3% of gastric cancers are associated with inherited gastric cancer predisposition syndromes (hereditary diffuse gastric cancer [CDH1] gene).
  • Amplification or overexpression of the HER2 protein is associated with some gastric cancers.

RISK FACTORS

  • Helicobacter pylori infection is primary risk in 65-80%.
  • Smoking/tobacco abuse is second leading risk factor.
  • Diet rich in additives (e.g., smoked, pickled, or salted foods; highly spiced foods), nitrates, and nitrites have been implicated.
  • Atrophic gastritis/intestinal metaplasia
  • Pernicious anemia
  • Preexisting diabetes mellitus
  • Overweight and obesity: strength of association increases with increasing body mass index (BMI)
  • Familial polyposis
  • Barrett esophagus
  • Patients in lower socioeconomic status have higher risk of gastric cancer.
  • Low consumption of fruits and vegetables
  • Ethnicity: Hispanic, Japanese, Chilean, Costa RicanMigrants from high-incidence areas (e.g., Iceland, Chile, or Japan) to low-incidence areas maintain an increased risk, whereas their offspring have an occurrence rate that corresponds to that of the new location.

GENERAL PREVENTION

  • Avoid tobacco, engage in regular exercise, maintain optimal body weight, and maintain a healthy diet.Diets that include 5 to 20 servings of both fruits and vegetables each week reduce the risk of gastric malignancy by ~50%.
  • Insufficient data to recommend routine gastric cancer screening
  • Screening to identify and eradicate H. pylori may be of benefit in high-prevalence areas.

COMMONLY ASSOCIATED CONDITIONS

  • Giant hypertrophic gastritis (M ©n ©trier disease)
  • Intestinal metaplasia
  • Atrophic gastritis
  • H. pylori infection

DIAGNOSIS

ALERT

Symptoms often present late in the disease course.

HISTORY

  • Assess risk factors (tobacco use; H. pylori infection, dietary history; family history of upper GI cancers or genetic syndromes).
  • Anorexia; unintentional weight loss (70-80%)
  • Early satiety
  • New onset dyspepsia
  • Nausea and vomiting
  • Change in bowel habits
  • Chronic noncolicky abdominal pain (especially in epigastrium)Postprandial fullness to severe steady painUnrelieved by antacidsExacerbated by foodRelieved by fasting
  • GI bleeding (10%)
  • Dysphagia (rare)

PHYSICAL EXAM

  • Abdominal palpation for masses and/or ascites
  • Palpation for lymph nodesLeft supraclavicular node (Virchow)Sister Mary Joseph nodule at umbilicus
  • Assess for jaundice.

DIFFERENTIAL DIAGNOSIS

  • Angiodysplasia of the colon
  • Carcinoma of body or tail of the pancreas
  • Carcinoma of the colon
  • Crohn disease
  • Eosinophilic gastroenteritis
  • Functional dyspepsia
  • Gastric lymphoma
  • GI sarcoidosis
  • Peptic ulcer with or without hemorrhage
  • Small intestinal lymphoma

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • CBC and platelet count:Hemoglobin <12 g/dL (1.86 mmol/L)Hematocrit <35 g/dL (0.35 mmol/L)
  • Serum chemistry analysis
  • Coagulation studies
  • H. pylori testing
  • Stool guaiac
  • Upper endoscopy is the diagnostic test of choice. Allows for direct visualization, biopsy, and cytology:Minimum of six biopsies should be done to confirm a diagnosis of malignancy (1)[C].
  • CT scan of chest, abdomen, and pelvis with contrast and gastric distension for staging (1)[C]

Follow-Up Tests & Special Considerations

  • Pentagastrin test (stomach pH <6)Pernicious anemia may cause a false-positive pentagastrin test.
  • Consider pelvic ultrasound (US) in females.

Diagnostic Procedures/Other

  • Endoscopic US is most accurate preoperative staging tool to identify extent of tumor (2)[C].
  • Laparoscopy with peritoneal washing may be useful for staging in select patients (3)[C].

Test Interpretation

  • Adenocarcinomas: 90% (intestinal [well-differentiated] and diffuse [undifferentiated/linitis plastica])
  • Gastric lymphomas, sarcomas, other rare types: 10%

TREATMENT

GENERAL MEASURES

  • Multidisciplinary approach
  • Surgical excision of the tumor is the only potentially curative option:Extent of lymph node resection is controversial.Endoscopic mucosal resection for early gastric mucosal cancers (≤2 cm in size, histologically differentiated, and nonulcerated) and high-grade dysplasia may be curative (2)[B].Patients with advanced (incurable) disease should discuss surgical reduction, which offers the best form of palliation and improves the likelihood of benefit for chemotherapy and/or radiation therapy.
  • Adjuvant chemotherapy may provide benefit compared to surgery alone (4)[A].
  • Patients with inoperable, locally advanced disease should be offered chemotherapy and reassessed for surgery if response is favorable (2)[A].
  • Patients with stage IV disease should be offered chemotherapy, which improves survival compared with supportive care (2)[A].
  • Radiation therapyUsed in combination with surgery and/or chemotherapyLittle benefit when used alone because gastric tumors have relatively high radiation resistanceHas role in palliation of pain, reducing risk of bleeding, and mitigating obstruction

MEDICATION

First Line

Combination chemotherapy improves survival compared to single-agent 5-FU (4)[A]:

  • Highest survival achieved with regimens containing a fluoropyrimidine (5-FU), anthracyclines, and a platinum compound (cisplatin).
  • In this category, epirubicin, cisplatin, and continuous-infusion 5-FU are tolerated best.

Second Line

  • Ondansetron (Zofran), dronabinol (Marinol), metoclopramide (Reglan), and others for nausea control
  • Pain control with opioids

ISSUES FOR REFERRAL

Refer to a high-volume surgery-oncology center

ADDITIONAL THERAPIES

  • Trastuzumab in combination with cisplatin or 5-FU should be considered in patients with HER2-positive tumors (1)[A].
  • The neoadjuvant use of radiotherapy is not recommended outside clinical trials.

SURGERY/OTHER PROCEDURES

  • Radical subtotal gastrectomy with gastrojejunostomy or gastroduodenostomy is the usual treatment.Removal of a large part of the stomach along with the greater and lesser omentum en blocSplenectomy or distal pancreatectomy done in certain situationsExcise direct tumor extensions at the time of surgery
  • Total gastrectomy is indicated only if necessary to remove the local lesion.
  • Local excision, endoscopic laser therapy, or electrocautery for palliation of incurable lesion by resection of bleeding area or area of obstruction

COMPLEMENTARY & ALTERNATIVE MEDICINE

Commonly used but with little supportive evidence

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

  • Depends on stage at time of diagnosis
  • Most follow-up treatment is outpatient.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Symptom-driven follow-up visits to monitor disease state, assess treatments, monitor for recurrence/metastasis, and assess nutritional status (2)[B].

Patient Monitoring

Monitor vitamin B12 and iron levels following surgical resection; supplement if needed.

DIET

  • Maximize preoperative nutritional state.
  • All patients undergoing surgery should be considered for early postoperative nutritional support:Enteral route preferredConsider placement of jejunostomy feeding tube.

PATIENT EDUCATION

  • American Cancer Society: http://www.cancer.org
  • Cancer Research Institute Helpbook: What to Do If Cancer Strikes. FDR Station, Box 5199, New York, NY 10150-5199

PROGNOSIS

  • Because most lesions do not produce symptoms until late in course, gastric carcinomas are usually advanced at the time of diagnosis.
  • Overall 5-year relative survival rate is 24% (if local disease 61%, regional spread 24%, distant spread 3%).
  • Early detection usually occurs when performing screening endoscopy in endemic areas or as an otherwise incidental finding.
  • Primary gastric lymphoma is more treatable than gastric adenocarcinoma.5-year survival rate is 40-60% with subtotal gastrectomy followed by combination chemotherapy.

COMPLICATIONS

  • Early lymphatic spread
  • Aggressive metastatic disease (especially hepatic, cerebral, peritoneum, and pulmonary)
  • Anemia (especially pernicious)
  • Pyloric stenosis
  • Dumping syndrome may occur following gastric surgery.

REFERENCES

11 Allum WH, Blazeby JM, Griffin SM, et al. Guidelines for the management of oesophageal and gastric cancer. Gut. 2011;60(11):1449-1472.22 Okines A, Verheij M, Allum W, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):v50-v54.33 Smith HG, Allum WH. Gastric tumours. Medicine. 2015;43(4):230-233.44 Wagner AD, Unverzagt S, Grothe W, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2010;(3):CD004064.

ADDITIONAL READING

  • Chen WW, Wang F, Xu RH. Platinum-based versus non-platinum-based chemotherapy as first line treatment of inoperable, advanced gastric adenocarcinoma: a meta-analysis. PLoS One. 2013;8(7):e68974.
  • Choi IJ. Current evidence of effects of Helicobacter pylori eradication on prevention of gastric cancer. Korean J Intern Med. 2013;28(5):525-537.
  • Karpeh MSJr. Palliative treatment and the role of surgical resection in gastric cancer. Dig Surg. 2013;30(2):174-180.
  • Khushalani N. Cancer of the esophagus and stomach. Mayo Clin Proc. 2008;83(6):712-722.

SEE ALSO

Multiple Endocrine Neoplasia (MEN) Syndromes

CODES

ICD10

  • C16.9 Malignant neoplasm of stomach, unspecified
  • C16.8 Malignant neoplasm of overlapping sites of stomach
  • C16.2 Malignant neoplasm of body of stomach
  • C16.1 Malignant neoplasm of fundus of stomach
  • C16.0 Malignant neoplasm of cardia
  • C16.5 Malignant neoplasm of lesser curvature of stomach, unsp
  • C16.3 Malignant neoplasm of pyloric antrum
  • C16.4 Malignant neoplasm of pylorus
  • C16.6 Malignant neoplasm of greater curvature of stomach, unsp

ICD9

  • 151.9 Malignant neoplasm of stomach, unspecified site
  • 151.8 Malignant neoplasm of other specified sites of stomach
  • 151.4 Malignant neoplasm of body of stomach
  • 151.3 Malignant neoplasm of fundus of stomach
  • 151.0 Malignant neoplasm of cardia
  • 151.2 Malignant neoplasm of pyloric antrum
  • 151.6 Malignant neoplasm of greater curvature of stomach, unspecified
  • 151.5 Malignant neoplasm of lesser curvature of stomach, unspecified
  • 151.1 Malignant neoplasm of pylorus

SNOMED

  • Malignant tumor of stomach (disorder)
  • adenocarcinoma of stomach (disorder)
  • Malignant tumor of body of stomach
  • Malignant tumor of fundus of stomach
  • Malignant tumor of greater curve of stomach
  • Malignant tumor of lesser curve of stomach
  • Malignant tumor of cardia
  • Malignant tumor of pylorus
  • Primary malignant neoplasm of stomach
  • Malignant neoplasm of pyloric canal of stomach

CLINICAL PEARLS

  • Consider gastric malignancy in patients presenting with epigastric pain and early satiety.
  • Accurate preoperative staging is necessary to determine approach to treatment and optimize survival.
  • Endoscopic US is the most accurate preoperative staging tool.
  • Treatment generally involves a combination of surgery, chemotherapy, and radiation therapy.