Gastric Cancer

Steven H. Lin and Salma Jabbour

Background

What is the incidence of gastric cancer in the U.S. and worldwide?

U.S: 21,130 cases/yr (in 2009), with 10,620 deaths (7^th leading)
Worldwide: ~875,000 new cases/yr; 2^nd-leading cause of death (behind lung cancer)

Where are the high-incidence areas in the world?

The highest incidences are found in East Asia (Japan and China) > South America > Eastern Europe.

What are some acquired and genetic risk factors for developing gastric cancer?

Acquired factors: Helicobacter pylori infection, high intake of smoked and salted foods, nitrates, diet low in fruits/vegetables, smoking, RT exposure, obesity, Barrett esophagus/GERD, prior subtotal gastrectomy
Genetic factors: E-cadherin (CDH-1 gene) mutation, type A blood group, pernicious anemia, HNPCC, Li-Fraumeni syndrome

How does tumor location relate to the underlying etiology of gastric adenocarcinoma?

Body and antral lesions are associated with H. pylori infection and chronic atrophic gastritis, whereas proximal gastric lesions (gastroesophageal [GE] junction, gastric cardia) are associated with obesity, GERD, and smoking.

Which has poorer prognosis: proximal or distal gastric cancer?

Stage for stage, proximal gastric cancer has a poorer prognosis.

What are the 2 histologic types of gastric adenocarcinoma? How do these 2 types differ in terms of etiology of the gastric cancer?

Intestinal and diffuse are the 2 histologic types of adenocarcinomas. Intestinal type are differentiated cancers with a tendency to form glands, occur in the distal stomach, and arise from precursor lesions seen mostly in endemic areas and in older people, more commonly men, suggesting an environmental etiology. Diffuse type are less differentiated (signet ring cells, mucin producing), have extensive submucosal/distant spread, and tend to be proximal. They do not arise from precancerous lesions, are more common in low-incidence areas, and are more common in women and younger people, suggesting a genetic etiology.

What is the the Borrmann classification of gastric cancer?

The Borrmann classification is based on the gross morphologic appearance. It is divided into 5 types:

Type I: polypoid/fungating
Type II: ulcerating
Type III: ulcerating/infiltrative
Type IV: diffusely infiltrating (linitis plastica)
Type V: cannot be classified (most aggressive)

What are the lymphatic drainages of the stomach? Please also include the Japanese Research Society (JRS) classification of nodal designation.

1^st echelon: N1–perigastric nodes (lesser and greater curvature) and periesophageal nodes (proximal gastric)
2^nd echelon: N2–celiac axis, common hepatic, splenic
More distant: N3–hepatoduodenal, peripancreatic, mesenteric root; N4–portocaval, PA nodes, middle colic
JRS N1–N4 are not the same as AJCC staging.

What are the patterns of spread for gastric cancer?

Local extension to adjacent organs, lymphatic mets, peritoneal spread, or hematogenous (liver, lung, bone). Liver/lung mets are generally for proximal/GE junction tumors.

What are the anatomic boundaries and organs for the stomach?

Superior: diaphragm, left hepatic lobe
Inferior: transverse colon, mesocolon, greater omentum
Anterior: abdominal wall
Posterior and lateral: spleen, pancreas, left adrenal, left kidney, splenic flexure of colon

What is the most important prognostic factor for gastric cancer?

TNM stage is the most important factor, with the histologic grade and Borrmann types not being independently prognostic apart from tumor stage. However, in general, Borrmann type I and II are more favorable compared to type IV.

Is all nodal involvement equally prognostic for gastric cancer?

No. The # and location of nodes are important. Min LN involvement adjacent to the primary lesion is more favorable.

Workup/Staging

How do pts with gastric cancer generally present?

Anorexia, abdominal discomfort, weight loss, fatigue, n/v, melena, and weakness from anemia

What aspects of the physical exam are relevant for evaluating a pt for a possible gastric malignancy?

General physical with focus on abdominal mass (local extension), liver mets, ovarian mets (Krukenberg tumor), distant LN mets (Virchow: left SCV; Irish: left axillary; Sister Mary Joseph: umbilical), ascites, Blumer shelf (rectal peritoneal involvement)

What is important in the workup for gastric cancer?

Gastric cancer workup: H&P (onset, duration, Hx of risk factors), CBC, CMP, esophagogastroduodenoscopy + Bx, EUS +/− FNA of regional LN mets, CT C/A/P, and diagnostic laparoscopy to r/o peritoneal seeding

How many layers are seen on EUS when imaging the GI tract?

5 layers are seen on EUS: layers 1, 3, and 5 are hyperechoic (bright), and layers 2 and 4 are hypoechoic (dark). Layer 1 is superficial mucosa, layer 2 is deep mucosa, layer 3 is submucosa, layer 4 is muscularis propria, and layer 5 is subserosa fat and serosa.

What is the rate of upstaging to stage IV using diagnostic laparoscopy?

35%–40% of pts are found to have mets using diagnostic laparoscopy.

Why is PET imaging not routinely used in staging gastric cancer?

In 1 study, only approximately two thirds of primary tumors are FDG avid (Shah et al., Proc ASCO 2007), with GLUT-1 transporter rarely present on the common subtypes of gastric cancer (signet ring and mucinous). Therefore, there are too many false negatives.

What is the AJCC 7^th edition (2009) T-staging classification for gastric cancer?

Tis: confined to mucosa without invasion to lamina propria
T1a: invades lamina propria or muscularis mucosae
T1b: invades submucosa
T2: invades muscularis propria
T3*: penetrates subserosa without invasion of visceral peritoneum (serosa)
T4a*: invades serosa
T4b: invades adjacent structures
*Tumor is classified as T3 if it penetrates through the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum without perforation of the visceral peritoneum covering these structures. Tumor is classified as T4 if it penetrates the visceral peritoneum covering the gastric ligaments or the omentum.