Gastric Cancer

para>Rare
Pregnancy Considerations

Rarely diagnosed during pregnancy
Prognosis is poor.

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 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.

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 pain
- Unrelieved by antacids
- Exacerbated by food
- Relieved by fasting
GI bleeding (10%)
Dysphagia (rare)

PHYSICAL EXAM

Abdominal palpation for masses and/or ascites
Palpation for lymph nodes
- Left 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
- Albumin <3 g/dL
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 (â‰¤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 therapy
- Used in combination with surgery and/or chemotherapy
- Little benefit when used alone because gastric tumors have relatively high radiation resistance
- Has 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 bloc
- Splenectomy or distal pancreatectomy done in certain situations
- Excise 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 preferred
- Consider 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.

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.

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