Gastric Carcinoma

Incidence/Prevalence Adenocarcinoma - 90% intestinal (decreasing trend) diffuse (increase trend) Non-Hodgkin's lymphoma - 6% GIST Carcinoid Squamous cell Ca

Incidence/Prevalence 3rd most common GI malignancy (after colorectal and pancreatic) Second causes of death from cancer lung (17.8 %), gastric (10.4 %), and liver (8.8 %) The worldwide incidence of gastric cancer has declined rapidly over the recent few decades Part of the decline may be due to the recognition of certain risk factors such as H. pylori and other dietary and environmental risks Despite the decline, the absolute number of new cases per year is increasing

GEOGRAPHICAL VARIATION The incidence of gastric cancer varies with different geographic regions. Approximately 60 percent of gastric cancers occur in developing countries The highest incidence rates are in Eastern Asia, the Andean regions of South America, and Eastern Europe Japan & S. America  75 & 150 / 100,000 US & W.Europe  8 & 15 / 100,000

Incidence/Prevalence Early Gastric Carcinoma Japan  40 % United States  6 -10 %

Incidence/Prevalence Slowly developing Usually discovered in advanced stages Men>Women Occurs between the ages of 50-70

ENVIRONMENTAL RISK FACTORS  Emigrants from high-incidence to low-incidence countries often experience a decreased risk of developing gastric carcinoma. Diet  Foods such as pickled vegetables, salted fish and meat, smoked foods and salt Salt — High salt intake damages stomach mucosa and increases the susceptibility to carcinogenesis in rodents Dietary nitrates (bacteria in stomach breaks down nitrites to compounds that are carcinogenic in animals)

ENVIRONMENTAL RISK FACTORS People who smoke cigarettes or use alcohol are 1.5 times more likely Socioeconomic status  -The risk of distal gastric cancer is increased by approximately twofold in populations with low socioeconomic status - By contrast, proximal gastric cancers have been associated with higher socioeconomic class

ENVIRONMENTAL RISK FACTORS H. pylori: Important in the etiology of peptic ulcers and gastric cancer Found in 60 percent of gastric carcinomas Gastric surgery  increased risk of gastric cancer after gastric surgery Billroth II procedure , with the risk being greatest 15 to 20 years after surgery

RISK FACTORS Gastric polyps Gastric ulcer Genetic factors include: First degree relatives Type A blood Pernicious anemia

Anatomy of Stomach Cardia Pylorus Body Antrum

Stomach-normal histology Parietal cells - in body produce HCl Chief cells - in body - pepsinogen Mucous cells - all over - mucus G cells-in antrum - gastrin

Anatomy of the stomach

Location 37% in the proximal third of the stomach 30% in the distal stomach 20% in the midsection Remaining 13% in the entire stomach

Gastric Carcinoma Lauren Classification There are two main histologic variants of gastric adenocarcinoma. The most frequent is the "intestinal type", so called because of its morphologic similarity to adenocarcinomas arising in the intestinal tract. The less common diffuse type gastric cancers

Gastric Carcinoma Lauren Classification Intestinal patients greater than 50, male>female arises from metaplastic glands in chronic gastritis; associated with H. pylori incidence decreasing in USA Diffuse (signet ring cell, linitis plastica) younger patients, no gender preference not associate with H. pylori incidence increasing

Intestinal type One model for the "intestinal type" of gastric cancer describes a progression from chronic gastritis to chronic atrophic gastritis, to intestinal metaplasia, dysplasia, and eventually to adenocarcinoma

Morphologic types of Carcinoma Stomach Fungating Ulcerating Diffuse

Ulcerated gastric adenocarcinoma

Thickened “linitis plastica” type adenocarcinoma infiltrating gastric wall

Physical Assessment Early gastric cancer Abdominal discomfort initially relieved with antacids Feeling of fullness Epigastric, back, or retrosternal pain NOTE: most people will show no clinical manifestations

Symptoms of Gastric Disorders Heartburn Epigastric pain Dyspepsia (upset stomach) Vomiting Hematemesis Frequently “coffee-ground” emesis Melena

Physical Assessment Advanced stage: Nausea/vomiting Obstructive symptoms Iron deficiency/anemia Palpable epigastric mass Enlarged lymph nodes Weakness/fatigue Progressive weight loss

DIAGNOSIS Esophagogastroduodenoscopy - Polypoid mass - Ulcer crater - Thickened fibrotic gastric wall

Preoperative evaluation Abdominopelvic CT scan  Endoscopic ultrasonography  Chest CT For patients with a proximal gastric cancer PET scan Sensitivity of PET scans for the detection of peritoneal carcinomatosis is only about 50 percent.  Staging laparoscopy  Between 20 and 30 % of patients who have disease that is beyond T1 stage on EUS will be found to have peritoneal metastases despite having a negative CT scan

Gastric carcinoma Tumor Node Metastasis T1 invades lamina propria or submucosa N0 no mets in LN M0 no distant mets T2 invades muscularis propria or subserosa N1 mets in perigastric LN 1-6 LN M1 Distant mets T3 penetrates serosa N2 mets in perigastric LN 7 – 15 LN T4 invades adjacent organs N3 mts to > 15 LN

STAGE GROUPING Stage 0 Tis N0 M0 Stage 1A T1 Stage IB N1 T2a/b Stage II N2 T3 Stage IIIA T4 Stage IIIB Stage IV N1–3 T1–3 N3 Any T Any N M1 From AJCC Cancer Staging Manual, 6th ed. New York, Springer-Verlag, 2001.

Spread of Gastric Ca Spreads through stomach into the gastric wall to the Lymph nodes Pancreas Transverse colon Omentum Through portal vein into Liver Through systemic circulation into lungs, and bone Peritoneum Ovaries Pelvic cul-de-sac Distant Lymph nodes

Spread of Gastric Ca

Clinical Presentation Physical signs – advanced or mts Palpable abdominal mass Palpable supraclavicular (Virchow’s) LN Palpable periumbilical (Sister Mary Joseph’s) LN Peritoneal mets palpable by rectal exam (Blumer’s shelf) Palpable ovarian mass (Krukenberg’s tumor) Hepatomegaly

Surgical Treatment Absence of distant mts Patient with distant mts but with complicated tumor Line of resection at least 6 cm from the tumor mass to decrease recurrence at anastomosis

Carcinoma of Stomach Surgical options Total gastrectomy Proximal tumours Mid-body tumours Subtotal gastrectomy Distal tumours Omentectomy

Distal Tumors Account for ~ 35 % of all gastric cancers No 5-year survival difference b/n subtotal vs total gastrectomy Subtotal appropriate if negative margins Recurrence vs nonrecurrence depends on margin of 3.5 cm vs 6.5 cm margins 4 – 6 cm  10% involvement margins 2 cm  30 %

Cardia / proximal ~ 35-50% of gastric adenocarcinomas Proximal Proximal Tumors Cardia / proximal ~ 35-50% of gastric adenocarcinomas Proximal More advanced at presentation Curative resection is rare Total gastrectomy

Palliation 20 – 30% of gastric cancer presents as stage IV disease Surgical palliation Percutaneous, endoscopic, radiotherapuetic techniques Nonoperative tx Laser recanalization, endoscopic dilatation (+/- stent)

Carcinoma of Stomach Surgical treatment Overall 5 year survival rate 10 – 21% in western series Japanese series 50% Adjuvant therapy (postoperative) Neoadjuvant therapy (preoperative) Response rates vary from 21 –31% clinical response rate to complete response rate of 0-15%

Adjuvant Therapy Southwest Cancer Oncology Group trial 5-FU, Leucovorin w/ chemorad for R0 3 yr survival 41% Chem/Rad 3 yr survival 50% 28% benefit in survival

Gastric Carcinoma - Natural History 2/3 of patients have locally advanced or metastatic disease at diagnosis 50% recurrence following curative surgery Adjuvant Chemo + R/T improves survival

Recurrence After gastrectomy quite high 40 – 80 % Most occur w/in first 3 years Locoregional failure 38 – 45% Anastomosis, gastric bed and regional nodes Peritoneal dissemination – 54% Annual endoscopy for subtotal gastrectomy

Gastric Carcinoma Prognosis invasion is most important factor early: limited to mucosa and submucosa; 90-95% survival at 5 years late: beyond submucosa; less than 10 - 30% survival at 5 years Five-year survival 95 % for patients with superficial T1 tumors and negative lymph nodes (stage IA disease) 7 - 8 % for patients with N3 nodes or any distant metastases LN Dissection