gastric cancer matt white am report april 19, 2010

Gastric Cancer

Matt White

AM Report

April 19, 2010

Objectives

Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

Objectives

Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

Epidemiology

Incidence: 21,260 cases in 2007 – ~7 per 100,000

11,210 cancer deaths in 2007 Mortality significantly decreased in past 75

years (unknown reasons)

Gastric tumors

85% adenoocarcinomas 15% lymphomas and gastrointestinal stromal

tumors (GIST)

Adenocarcinoma Cancer types

“Intestinal type” (more common)– Morphologically similar to intestinal

adenocarcinomas.

Diffuse-type– Lack of intercellular adhesions (germline mutation

in protein E-cadherin)

Spectrum of gastric cancer

Proposed progression: chronic gastritis -->

– chronic atrophic gastritis --> intestinal metaplasia -->

– dysplasia --> adenocarcinoma

Risk Factors for gastric cancer

Diet– nitroso compounds– low fruit/vegetable, high fried foods/processed meat– High salt intake

Obesity Smoking (HR 2-3) ? Alcohol H. Pylori Low socioeconomic status Hereditary diffuse gastric cancer

– 40-67% lifetime risk for men, 60-83% for women Immigrants from endemic areas

– maintain native country risk, risk to offspring similar to new homeland

Objectives

Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

Presentation

Approximately 50% of cases present with symptoms and have disease extending beyond locoregional confines

Of locoregional cases, only ½ can undergo a potentially curative resection

Symptoms at presentation

Symptoms (cont’d)

Dysphagia: more common with proximal gastric tumors

Occult GI bleeding very common, overt bleeding <20%.

Less Common Symptoms

Pseudoachalasia: if Auerbach’s plexus involved

Colonic obstruction: if cancer spreads (direct extension) to colonic wall

Signs

Palpable abdominal mass: most common physical finding

If cancer spreads via lymphatics…– Left supraclavicular node (Virchow’s)– Periumbilical node (Sister Mary Joseph)– Left axillary node (Irish)– Enlarged ovary (Krukenberg's tumor)– Ascites

Objectives

Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

Diagnosis

EGD– Gold standard– Single biopsy from ulcer -> sensitivity ~ 70%– Seven biopsies from ulcer -> sensitivity >98%– Brush cytology increases sensitivity of single

biopsies, aid in multiple biopsies unclear

Barium studies

False negative in as many as 50% of cases Sensitivity as low as 14% in early cases May be superior to EGD for linitis plastica

– EGD may be normal while “leather-bottle” will be apparent on radiograph

Linitis Plastica

Diffuse-type gastric cancer Tumor often infiltrates the submucosa and

muscularis propria Superficial biopsies may be falsely negative Combination of strip and bite biopsy needed

if suspicious for linitis plastica

Linitis Plastica, “leather bottle stomach”

Objectives

Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

Staging of Gastric Cancer

Two systems: – Japanese classification (more elaborate and

anatomic based)– Western: developed by American Joint Committee

on Cancer (AJCC) and International Union Against Cancer (UICC) -- more widely used

Tumors at GE junction of in cardia of stomach within 5cm of GE junction– Classified using esophageal staging

Other caveats

T stage: dependent on depth of tumor invasion NOT size of lesion

Nodal stage: based on # of positive LN rather than location of LNs (proximity to tumor)

Staging workup

Biopsy Imaging

– CT: evaluates for metastases (M stage) 20-30% with negative CT have intraperitoneal disease at

laparatomy Accuracy of 50-70% for T stage Slightly worse accuracy for N stage compared to EUS

– EUS: most reliable nonsurgical method to evaluate depth of invasion

More accurate than CT for T stage 65-90% accurate for N stage

Staging workup

PET– More sensitive than CT for detection of distant

metastases. – Also useful for detecting LNs– Negative PET not helpful- even large tumors can

be falsely negative if metabolic activity low. Most diffuse gastric cancers (signet ring) are not FDG

avid

Staging workup

Serologic markers– CEA, CA-125, CA 19-9, CA 72-4 may be elevated

but have low sensitivity/specificity– None are diagnostic– Preoperative elevation in markers usually

pretends high risk of adverse outcome– No serologic finding should exclude surgical

consideration

AJCC Staging System

AJCC Staging System

Objectives

Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening

Treatment

Locoregional (stage I-III) disease– Potentially curable– Refer for multidisciplinary evaluation and

consideration of surgery

Advanced (stage IV) disease– Palliative therapy– Studies indicate longer survival and better quality

of life with systemic treatment

Treatment

Complete surgical resection with removal of LNs (only chance of cure)– Possible in < 1/3 of cases

Subtotal gastrectomy for distal carcinomas, total or near-total for proximal masses

Reduction of tumor bulk (palliative)– Chemotherapy (cisplatin + 5-FU or irinotecan)

Partial response in 30-50% of patients

– Radiation (for pain control, no mortality benefit with XRT alone)

Data from SEER. Patients diagnosed from 1991-2000 (n=14,097). Stage IA (n=1194), stage IB (n=655), stage IIA (n=1161) stage IIB (n=1195), stage IIIA (n=1031), stage IIIB (n=1660), stage IIIC (n=1053), stage IV (n=6148).

PrognosisStage TNM Features

% of Cases*

% 5-year survival*

0 TisN0M0 Node negative; limited to mucosa 1 90

IA T1N0M0Node negative; invasion of lamina propria or

submucosa 7 59

IB T2N0M0Node negative; invasion of muscularis

propria 10 44

II

T1N2M0 Node positive; invasion beyond mucosa but within wall 17 29T2N1M0

T3N0M0 Node negative; extension through wall

IIIAT2N2M0 Node positive; invasion of muscularis propria

or through wall 21 15T3N1-2M0

IIIB T4N0-1M0Node negative; adherence to surrounding

tissue 14 9

IV T4N2M0Node negative; adherence to surrounding

tissue 30 3Any M1 Distant Metastases

** Data from American Cancer Society

Objectives

Epidemiology Clinical Presentation Diagnosis Staging Treatment Screening/Follow-up

Screening

Currently screening programs in Japan, Venezuela, Chile due to high incidence

– Mostly barium studies, EGD is concerning findings– Some use serum pepsinogen testing for high risk with EGD

confirmation– H. pylori: sensitivity 88%, specificity 41% (Japan)– Japan study: 5-year survival 74-80 in screened group, 46-

56% for non-screened group. Not cost effective in US due to relatively low

incidence (<10 per 100,000)– Preventing incidence of 1 gastric cancer death estimated to

cost $247,600

Gastric Ulcers

25% of patient with gastric cancer have history of a gastric ulcer

American Society of Gastrointestinal Endoscopy recommendations:

– Follow-up EGD in 8-12 weeks to verify healing. – Non-healing ulcers need repeat biopsies

Question of cost-effectiveness of repeat endoscopies; however, small (curable) lesions may be missed without follow-up.

Take Home Points

Most cases present in advanced stage Staging workup (CT vs PET vs EUS) to

evaluate extent of disease Staging laparoscopy indicated for medically

fit patients with >T1 lesion and without stage IV disease

Ensure follow-up of ulcers seen on EGD No effective screening in US patients

References

Harrison’s Principles of Internal Medicine Up to Date