Gastric Cancer 09.

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Gastric tumors: Benign: Polyps Lieomyoma (Gastrointestinal stromal tumor GIST ) Malignant: Adenocarcinoma 85% Lymphoma 5% GIST Sarcoma Carcinoid Others

description

Gastric cancer: 2009 update.

Transcript of Gastric Cancer 09.

Page 1: Gastric Cancer 09.

Gastric tumors:

Benign:

Polyps

Lieomyoma (Gastrointestinal stromal tumor GIST )

Malignant:

Adenocarcinoma 85%

Lymphoma 5%

GIST Sarcoma

Carcinoid

Others

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Gastric polyps:

Hyperplastic –

Benign, inflammatory,hamartomas 75%

Adenomatous –

Premalignant

Mixed

Part of FAP syndrome

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Gastric Cancer

• Gastric cancer– Adenocarcinoma– GIST (gastro-intestinal stromal tumour)– Carcinoid– Lymphoma– other

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Pathohistologic classification

• Histology• Adenocarcinoma 90%• Lymphoma 5%• GI Stromal tumor 2%• Carcinoid <1%• Metastasis <1%• Adenosquamous/squamous <1%• Miscellaneous <1%

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Adenocarcinoma – Lauren classification

• Diffuse– Linitis plastica type– Poorer prognosis

• Intestinal– Localised– Better prognosis– Distal stomach

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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

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Risk Factors

• Diet• Genetics• H. Pylori infection: very important cause.• Pernicious anemia• Pts with partial gastrectomy• Vagotomy.• Atrophic gastritis• Menetrier’s disease

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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

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Risk Factors

• Partial gastrectomy- slightly increased risk

• Menetrier’s Disease- rugal fold hypertrophy, hypochlorhydria and protein-losing enteropathy

• Adenomatous Gastric Polyps

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Gastric Cancer

Environmental factors

H. pylori Genetic factors

Etiological Factors of Gastric Cancer

Precancerous changes

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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

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Gastric Cancer

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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.

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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%

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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%

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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

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Laboratory tests

Iron deficiency anemia

Fecal occult blood test (FOBT)

Tumor markers (CEA, Ca19-9)

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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

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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

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T stage (UICC TNM 2002)

T1T1

T3

T2b

T2a

T1Adjacentstructure

T4

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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

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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

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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.

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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

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Gastric lymphoma:

• Most of B-cell origin

• Primary gastric lymphoma rare

• Non-Hodgkin’s most common type

• 5 year survival rate is 50%

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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.

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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.

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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.

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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

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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

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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

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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

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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.

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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

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• 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.

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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.

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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.

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Gastric cancers

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Endoscopic features of gastric cancer

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EUS-Stomach