gastric cancer 09
DESCRIPTION
Gastric cancer: 2009 update.TRANSCRIPT
Gastric tumors:
Benign:
Polyps
Lieomyoma (Gastrointestinal stromal tumor GIST )
Malignant:
Adenocarcinoma 85%
Lymphoma 5%
GIST Sarcoma
Carcinoid
Others
Gastric polyps:
Hyperplastic –
Benign, inflammatory,hamartomas 75%
Adenomatous –
Premalignant
Mixed
Part of FAP syndrome
Gastric Cancer
• Gastric cancer– Adenocarcinoma– GIST (gastro-intestinal stromal tumour)– Carcinoid– Lymphoma– other
Pathohistologic classification
• Histology• Adenocarcinoma 90%• Lymphoma 5%• GI Stromal tumor 2%• Carcinoid <1%• Metastasis <1%• Adenosquamous/squamous <1%• Miscellaneous <1%
Adenocarcinoma – Lauren classification
• Diffuse– Linitis plastica type– Poorer prognosis
• Intestinal– Localised– Better prognosis– Distal stomach
Gastric Cancer: Adenocarcinoma
• 750,000 cases annually. 22,000 new cases in the US each year
• Rise in cancer of the proximal stomach and GEJ
Risk Factors
• Diet• Genetics• H. Pylori infection: very important cause.• Pernicious anemia• Pts with partial gastrectomy• Vagotomy.• Atrophic gastritis• Menetrier’s disease
Risk Factors
• Dietary Factors- foods rich in nitrates, nitrites, preserved meat & vegetables(smoked/salted).
• Genetic Factors- Lynch syndrome II. Microsatellite instability (MSI) is present in up to 33% of gastric cancers
• Pernicious Anemia- auto-immune atrophic gastritis increased risk by 2-3x
Risk Factors
• Partial gastrectomy- slightly increased risk
• Menetrier’s Disease- rugal fold hypertrophy, hypochlorhydria and protein-losing enteropathy
• Adenomatous Gastric Polyps
Gastric Cancer
Environmental factors
H. pylori Genetic factors
Etiological Factors of Gastric Cancer
Precancerous changes
Pathologic Features
• Distal cancer- H. Pylori related
• Proximal cancer- GERD/Barrett’s dz
• Chronic gastritis Atrophic Gastritis Intestinal Metaplasia Dysplasia/Cancer
• Intestinal type vs diffuse type
Gastric Cancer
Clinical Features
• Vague symptoms- early satiety, abdominal pain, bloating, dyspepsia, wt loss, anorexia
• GI bleeding, microcytic anemia, vomiting if GOO present• Associated paraneoplastic syndromes-
• Acanthosis Nigricans• Venous Thrombi (Trousseau’s syndrome)
• Metastasis:• Sister Mary Joseph’s node• Virchow’s node • Liver secondaries.
Clinical manifestation
• Signs/Symptoms of Early Gastric Cancer
• Asymptomatic or silent 80%• Peptic ulcer symptoms 10%• Nausea or vomiting 8%• Anorexia 8%• Early satiety 5%• Abdominal pain 2%• Gastrointestinal blood loss <2%• Weight loss <2%
• Dysphagia <1%
Signs and Symptoms• Advanced Gastric Cancer• Weight loss 60%• Abdominal pain 50%• Nausea or vomiting 30%• Anorexia 30%• Dysphagia 25%• Gastrointestinal blood loss 20%• Early satiety 20%• Peptic ulcer symptoms 20%• Abdominal mass or fullness 5%• Asymptomatic or silent <5%
Duration of symptoms
Less than 3 month 40%
3-12 months 40%
Longer than 12 month 20%
Special signs & terms
• Linitis plastica: diffusely infiltrating with a rigid stomach
• Virchow’s node: supraclavicular lymphadenopathy (left)
• Irish’s node: axillary lymphadenopathy
• Sister Mary Joseph’s node: umbilical
lymphadenopathy
Laboratory tests
Iron deficiency anemia
Fecal occult blood test (FOBT)
Tumor markers (CEA, Ca19-9)
Diagnostic Studies
• Contrast radiograpy( Barium)- may be initial test for vague symptoms.
• Endoscopy: the usual diagnostic method with the use of image enhancing methods as chromo endoscopy for early detection of small lesions.
• CT- cannot determine depth of invasion. Good for detecting distant disease
• EUS- more accurate for T / N staging than CT
Staging/Prognosis
• Early gastric cancer- 5-yr survival rate of 80-90%
• Survival for Stage III or IV disease is 5-20% at 5 years
T stage (UICC TNM 2002)
T1T1
T3
T2b
T2a
T1Adjacentstructure
T4
N & M stage (UICC TNM 2002)
• N stage– N0 - no nodes– N1 - 1-6 nodes– N2 - 7-15 nodes– N3 > 15 nodes
• M stage– M0 – no distant metastases– M1 – distant metastases (includes distant
nodes
Early GC:– Incidence of EGC increased from 1-15%
Due to Open access endoscopy• For early diagnosis urgent (<2 weeks) specialist referral for
endoscopic investigation indicated when dyspepsia with:– Chronic GI bleeding– Progressive unintentional wt loss– Progressive dysphagia– Persistent vomiting– Iron deficiency anaemia– Epigastric mass– Suspicious barium meal
Early GC:• Mostly Japanese.• Confined to the mucosa &submucosa, irrespective of nodal state, • Surgical resection may be curative &definitely improves the 5-
year survival rate to > 50%. • When early gastric cancer is confined to the mucosa, endoscopic
mucosal resection (EMR) may be an alternative.
Treatment• The only chance for cure is surgical resection, possible in 25-30%.
• If confined to the distal stomach, subtotal gastrectomy with resection of lymph nodes in the porta hepatis & pancreatic head.
• In tumors of the proximal stomach total gastrectomy to obtain an adequate margin & to remove lymph nodes+ distal pancreatectomy &splenectomy, but with higher mortality/ morbidity.
• Limited gastric resection is necessary for patients with excessive bleeding or obstruction& If cancer recurs in the gastric remnant.
• 66% present with advanced disease incurable by surgery alone
• Resistant to radiotherapy- used mostly for palliation
• Chemo- decreases tumor burden in 15% of patients at best
Gastric lymphoma:
• Most of B-cell origin
• Primary gastric lymphoma rare
• Non-Hodgkin’s most common type
• 5 year survival rate is 50%
Gastric lymphoma:• 5% of all malignant gastric tumors.
• Increasing in incidence.
• The majority are non-Hodgkin’s lymphomas & the stomach is the most common extranodal site for non-Hodgkin’s lymphomas.
• Generally younger than those with gastric adenocarcinoma,also male predominance.
• Commonly present with symptoms & signs similar to adenoca.
• Lymphoma in the stomach can be a primary tumor or can be due to disseminated lymphoma.
• B-cell lymphomas of the stomach are most commonly large cell with a high-grade type.
• Low-grade variants are noted in the setting of chronic gastritis called mucosa-associated lymphoid tissue (MALT) lymphomas. strongly associated with H. pylori infection.
Gastric lymphoma: diagnosis• Ba: usually ulcers or exophytic masses; a diffusely infiltrating
lymphoma is more suggestive of secondary lymphoma. • Primary gastric lymphoma, Barium usually show multiple
nodules& ulcers.• Secondary lymphoma typically have the appearance of linitis
plastica. • UGI endoscopy with biopsy/cytology are required for diagnosis
with accuracy of 90%. • Conventional histopathology& immunoperoxidase staining for
lymphocyte markers is helpful in diagnosis. • Proper staging of gastric lymphoma involves EUS, chest&
abdominal CT scans& bone marrow biopsy.
Gastric lymphoma: Treatment• Treatment of gastric diffuse large B-cell lymphoma is best
pursued with combination chemotherapy with or without radiotherapy with 5-year survival rates of 40-60%.
• For MALT lesions, eradication of H. pylori with antibiotics induces regression of the tumor, but longer term follow-up is needed.
• Radiotherapy can be curative for localized MALT lymphomas.
MALTomas
• Low grade B-cell lymphoma associated with chronic H. Pylori infection
• EUS is most reliable method for staging
• Treatment of H. Pylori eradicates the tumor
Other Gastric Tumors
• GIST- originate usually from the muscularis propria.
• Carcinoid Tumors- 0.3% of all gastric tumors. Produce 5-HIAA and can cause carcinoid syndrome. May lead to hyper-gastrinemia
GIST:
• Gastro Intestinal Stromal Tumors• Around 5,000 to 6,000 new cases each year• Tends to occur in middle aged persons with a slight male
predilection • Occur throughout the GI tract
GIST:• Stomach 50-60%• Small bowel 20-30%• Large bowel 10%• Esophagus 5%• Else where in abdomen 5%• Symptoms depend on the site& size of the tumor:
– Abdominal pain – Dysphagia– Gastrointestinal bleeding – Symptoms of bowel obstruction – Small tumors may be asymptomatic– Diagnosis: Light microscopy with Immuno-histochemistry
GIST:• Features favoring benign lesions in general like:– Size less than 5 cm– Low number of mitosis per HPF– No mucosal invasion– Low cellularity– Low markers of cell proliferation
• The above have shown to be associated with malignant behavior in some but not in other studies.
• With prolonged follow up any GIST has the potential to behave in a malignant fashion.
• 50% of primary localized tumors that are resected relapse after 5 years of follow up.
Malignant Versus Benign
Size Mitotic count
Very Low risk <2 cm <5/50 HPF
Low risk 2-5 cm <5/50 HPF
Intermediate risk
<5 cm
5-10 cm
6-10/50 HPF
<5/50 HPF
High risk >5 cm>10 cmAny size
>5/50 HPF Any count>10/50 HPF
• Since activation of Kit played a crucial role in the pathogenesis of GIST, inhibition of Kit would be therapeutic.
• Imatinib was found to be effective in GIST.
• Indicated for large tumors pre or postoperative.
Prognosis:
• The 5-year survival for malignant GIST varies widely from 28 to 80%.
• Median survival of patients in whom complete surgical resection is not possible is 10–23 months.
• The median survival from the time of diagnosis of metastatic or recurrent disease has been reported from 12 to 19 months.
Gastric carcinoids:– Relatively uncommon.
– They are grouped into three categories
– Type 1: gastric carcinoids are associated with chronic atrophic gastritis and often pernicious anemia they account for 70 to 80 percent of all gastric carcinoids.
– Type 2 occur in association with gastrinomas (Zollinger-Ellison syndrome) MEN type 1.
– They account for <5% of gastric carcinoids. Similar to carcinoids in atrophic gastritis, the tumors are thought to arise from ECL cells.
– Type 3 known as sporadic carcinoids occur in the absence of atrophic gastritis or ZES or MEN-1 syndromes.
– Account for 20 % of gastric carcinoids, are the most aggressive; local or hepatic metastases are present in up to 65 % who come to resection.
Gastric cancers
Endoscopic features of gastric cancer
EUS-Stomach