Gastric Cancer

Gastric Cancer

Ahmet Kilic October 12, 2005 UMMS Surgical Resident Conference

Gastric Neoplasia „

Benign Gastric polyps „ Ectopic pancreas „

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Malignant Gastric Adenocarcinoma „ Gastric Lymphoma „ Gastric Sarcoma „

Gastric Cancer „ „ „ „ „ „ „ „ „

Epidemiology Risk Factors Pathology Clinical Presentation Preoperative Evaluation Staging Treatment Outcomes Surveillance

Epidemiology „ „ „

1980’s – most common CA worldwide Geography (Japan / S. America) United States 10th most common; dec. incidence in past 70 years „ Male : Female = 2:1 „

Pathology „ „ „ „ „ „

Gastric Adenocarcinoma (~ 95%) Squamous Cell Carcinoma Adenoacanthoma Carcinoid Gastrointestinal stromal tumors (GISTs) Lymphoma

Borrmann System

Lauren System „

Intestinal „

Environmental „

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Men > women „

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Gastric atrophy, intestinal metaplasia Increasing inc. w/ age

Gland formation Hematogenous Spread Microsatellite instability APC gene mutations p53, p16 inactivation APC, adenomatous polyposis coli

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Diffuse „ „

Blood type A Women > men „

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Younger age group

Poorly differentiated, signet ring cells Transmural / lymphatic spread Decreased E-cadhedrin p53, p16 inactivation

WHO Classification „

5 main categories „

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Adenocarcinoma – subdivided „

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Adenocarcinoma, Adenosquamous cell carcinoma, squamous cell carcinoma, undifferentiated carcinoma and unclassified carcinoma Papillary, tubular, mucinous, signet ring

Further subdivided based on differentiation

PRIMARY TUMOR (T) TX

Primary tumor cannot be assessed

T0

No evidence of primary tumor

Tis

Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria

T1

Tumor invades lamina propria or submucosa

T2

Tumor invades muscularis propria or subserosa

T2a

Tumor invades muscularis propria

T2b

Tumor invades subserosa

T3

Tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structures

T4

Tumor invades adjacent structures

REGIONAL LYMPH NODES (N) NX

Regional lymph node(s) cannot be assessed

N0

No regional lymph node metastasis

N1

Metastasis in 1 to 6 regional lymph nodes

N2

Metastasis in 7 to 15 regional lymph nodes

N3

Metastasis in more than 15 regional lymph nodes

DISTANT METASTASIS (M) MX

Distant metastasis cannot be assessed

M0

No distant metastasis

M1

Distant metastasis

STAGE GROUPING Stage 0

Tis

N0

M0

Stage 1A

T1

N0

M0

Stage IB

T1

N1

M0

T2a/b

N0

M0

T1

N2

M0

T2a/b

N1

M0

T3

N0

M0

T2a/b

N2

M0

T3

N1

M0

T4

N0

M0

Stage IIIB

T3

N2

M0

Stage IV

T4

N1–3

M0

T1–3

N3

M0

Any T

Any N

M1

Stage II

Stage IIIA

From AJCC Cancer Staging Manual, 6th ed. New York, Springer-Verlag, 2001.

Clinical Presentation „ „

Asymptomatic Early „ „

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More advanced disease „ „ „ „

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Weight loss Anorexia Fatigue Emesis

Symptoms dependent on location „ „ „

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Vague epigastric discomfort / indigestion Pain is constant, nonradiating, unrelieved by food digestion

Proximal Distal Diffuse

GI bleeding, obstruction

Clinical Presentation „

Physical signs – late Assoc. w/ locally advanced or mets „ Palpable abdominal mass „ Palpable supraclavicular (Virchow’s) LN „ Palpable periumbilical (Sister May Joseph’s) LN „ Peritoneal mets palpable by rectal exam (Blumer’s shelf) „ Palpable ovarian mass (Krukenberg’s tumor) „ S/Sx of hepatomegaly „

Pre-operative Evaluation „

Once gastric cancer is suspected „

Flex. Upper endoscopy modality of choice „

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Double contrast barium upper gi cost effective w/ 90% accuracy – however can not distinguish benign from malignant gastric ulcers.

Flex. Upper Endo w/ multiple biopsies (>7) around ulcer crater for histo Biopsy of ulcer crater → necrotic debris „ Accuracy (98%) → inc. w/ direct-brush cytology „

Pre-operative Evaluation „

Esophagogastroduodenoscopy – palliation Laser ablation „ Dilation „ Tumor stenting „

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EUS „

Aid in staging gastric wall tumor invasion „ LN status „

Diagnosis: Gastric Cancer „ „ „

CBC, CMP, Coags CXR, CT scan of abdomen Women „

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CT chest for proximal gastric cancer Limitations „ „

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< 5 mm mets on liver/peritoneum Staging for LN mets 25 – 86 %

Laparoscopy „

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Pelvic CT / US

23 – 37 % mets

Cytology of peritoneal fluid / peritoneal lavage „

+ finding → poor prognosis

Staging „

TNM system „

1997 „

Nodal status „

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Location → number of positive nodes

Cardia vs distal - ? Survival R status „ „ „

R0 – microscopically negative margin R1 – micro +, gross – R2 – gross residual disease

Staging

Surgical Treatment „ „

Absence of distant mets Resection margin w/ neg. microscopic margins Gastric tumors char. by extensive intramural spread „ Line of resection at least 6 cm from the tumor mass to decrease recurrence at anastomosis „

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App surgery based on location / pattern of spread

Surgical Treatment „

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

Proximal / Cardia „

Proximal Gastrectomy– increased morbidity / mortality „

Buhl, et al. „

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Dumping, heartburn, reduced appetite

Norwegian Stomach Ca Trial Prox. gastrectomy morbid / mortal 52% 16% „ Total gastrectomy morbid / mortal 38% 8% „

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Total gastrectomy considered procedure of choice for proximal gastric lesions

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 „

Extended Lymphadenectomy „

Controversial „

Japanese system D1 – group 1 LN „ D2 – groups 1 & 2 „ D3 – D2 plus para-aortic LN „ To remove station 10 & 11 LN – splenectomy „ D2 resection – partial pancreatectomy „

Extended Lymphadenectomy „

No longer routine „ „

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Used for tumor extension Removal of station 10 LN

Dutch „

D1 vs D2 resection „

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Japan „

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Increased intra-hosp mortality

D2 improved survival over D1

West „

No improvement

Palliation „

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20 – 30% of gastric cancer presents w/ stage IV disease Relief of symptoms w/ minimal morbidity Surgical palliation Percutaneous, endoscopic, radiotherapuetic techniques Nonoperative tx „

Laser recanalization, endoscopic dilatation (+/- stent)

Adjuvant Therapy „

1999 „

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~ 29% of gastrectomy pts underwent some type of adjuvant tx (71% sx alone)

Southwest Cancer Oncology Group trial „

5-FU, Leucovorin w/ chemorad for R0 Sx – 27 mos 3 yr survival 41% „ Chem/Rad – 36 mos 3 yr survival 50% „

Outcomes

Recurrence „

After gastrectomy quite high 40 – 80 % „ Most occur w/in first 3 years „ Locoregional failure 38 – 45% „

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Anastomosis, gastric bed and regional nodes

Peritoneal dissemination – 54%

Surveillance „

Recurrence high first 3 years „

Complete H&P every 4 mos for 1 year Then every 6 mos for 2 years „ Annually after „

CBC, LFT – as clinically indicated „ CXR, CT abd/pel - ? Routinely „ Annual endoscopy for subtotal gastrectomy „

Gastric Lymphomas „ „ „ „ „

Epidemiology Pathology Evaluation Staging Treatment

Epidemiology „

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Stomach most common site for lymphomas in GI system Primary gastric lymphoma – uncommon „

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~ 15 % of gastric CA, ~ 2 % of lymphomas

Vague symptoms „ „

Epigastric pain, early satiety and fatigue Bleeding uncommon

50% have anemia on presentation „ 6th and 7th decade (M:F is 2:1) „

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Most commonly in antrum

Pathology „

Multiple classification systems Most common diffuse large B-cell ~ 55% „ Extranodal marginal cell lymphoma (MALT) ~ 40% „ Burkitt’s lymphoma ~3% „ Mantel cell ~1% „ Follicular lymphoma ~1% „

Pathology „

Diffuse large B-cell Usually primary „ May occur from progression of less aggressive lymphomas (chronic lymphocytic leukemia / small lymphocytic lymphoma, follicular lymphoma or MALT) „ Risk factors „

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Immunodeficiencies, H. pylori

Gastric MALT

“extranodal marginal zone lymphomas of MALT type” „

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Commonly preceded by H. pylori associated gastritis t(1;14) (p22;q32) and t(11;18)(q21;q21) Impaired response to apoptotic singaling „ Increased NF-κB „

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t(11;18)(q21;q21) „

Predicts responsiveness to tx by H. pylori eradication

Burkitt’s Lymphoma „ „ „ „

EBV virus Highly aggressive Younger population Cardia / body of stomach (rather than antrum)

Staging „ „

Controversial TNM like gastric adenocarcinoma

Treatment „

Multimodality – early stage Resection – controversial „ Chemo/rads alone „

Perforation w/ chemo ~5% „ CHOP – cyclophosphamide, hydroxy- daunomycin, oncovin, predinose) „

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5 year survival Sx/Chemo/Rad 82 % „ Chemo/Rad 84.4 % „

Treatment „

Radiation „

Limited in large tumors Local control 100% < 3 cm „ 60 – 70 % if > 6 cm „

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Risk of complications 30% at 10 years

Treatment „

Late-stage „

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Not amenable to sx; chemo

MALT/very limited diffuse large B-cell „

H. pylori eradication alone 75% „ Repeat endo in 2 mos. ; biannual endo for 3 years „

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Failure of above increased if „

Transmural, node +, transformation Bcl-10

Gastric Sarcoma „ „ „ „ „

Epidemiology Pathology Staging Clinical Manifestation / Evaluation Treatment

Epidemiology „

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Arise from mesenchymal components of gastric wall ~3% of all gastric CA GIST most common „

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Stomach (60-70%)

After 4th decade Mean age 60

GIST - Pathology „

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Initially thought to arise from smooth muscle cells – previously classified as leiomyoma / leiomyosarcoma Histo „

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GIST „ „ „

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Muscularis propria – likely from cells of Cajal Cellular Spindle cell Pleomorphic mesenchymal tumors

Kit protein, CD34+

Staging „ „

No current system Prognosis „

Mitotic frequency „

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Low – benign; High – malignant

Other signs of malignancy „

Size > 5 cm; cellular atypia, necrosis or local invasion, c-kit,

Clinical „

Most common presentation „

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Endoscopy – first diagnostic test „

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GI bleeding, pain dyspepsia w/ biopsy ~50%

CT best – since neoplasm grows intramurally Double-contrast UGI – smooth edged filling defect

Treatment „

Surgery „ „ „

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Most recurrences in first 2 years „

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Negative margin (en-bloc if adjacent organs) Avoid rupture of tumor to prevent peritoneal seeding LN mets rare (<10%) – no added benefit Local disease w/ assoc. liver mets

5 year survival 48% (19 – 56%) Adjuvant tx „ „ „

Radiation – no proven benefit 5% respond to doxorubicin Glivic/Gleevec – 54% partial response „

Approved fro CD117+ unresectbale, mets

Questions A patient has an 8 mm lesion on the lesser curvature of the stomach near the gastroesophageal junction. CT of the abdomen is negative. Gastric biopsy is returned as mucosal associated lymphoid tumor (MALToma). The most appropriate initial treatment would be: A. Radical gastrectomy, roux-en-Y esophagojejunostomy B. Proximal gastrectomy, esophagogastrostomy C. Metastatic work-up; treatment for H. pylori; chemotherapy; radiotherapy D. Treatment for H. pylori E. Wedge resection

Questions A patient has an 8 mm lesion on the lesser curvature of the stomach near the gastroesophageal junction. CT of the abdomen is negative. Gastric biopsy is returned as mucosal associated lymphoid tumor (MALToma). The most appropriate initial treatment would be: A. Radical gastrectomy, roux-en-Y esophagojejunostomy B. Proximal gastrectomy, esophagogastrostomy C. Metastatic work-up; treatment for H. pylori; chemotherapy; radiotherapy D. Treatment for H. pylori E. Wedge resection

Questions Regarding gastric anatomy, physiology, and pathology, which of the following statements is correct? A. Helicobacter pylori, a gram-negative bacteria that produces urease, has

been implicated in the genesis of gastric carcinoma B. The right and left gastroepiploic arteries – branches of the gastroduodenal and left gastric arteries, respectively – are responsible for the blood supply of the greater curvature of the stomach C. Truncal vagotomy accelerates emptying of solids and delays emptying of liquids D. In patients with Zollinger-Ellison syndrome, the treatment of choice for multiple ulcers is total gastrectomy E. Gastric cancers are the most common tumors in the GI tract to present with sub-mucosal spreading, needing at least 5 cm of resection margins

Questions Regarding gastric anatomy, physiology, and pathology, which of the following statements is correct? A. Helicobacter pylori, a gram-negative bacteria that produces urease, has

been implicated in the genesis of gastric carcinoma B. The right and left gastroepiploic arteries – branches of the gastroduodenal and left gastric arteries, respectively – are responsible for the blood supply of the greater curvature of the stomach C. Truncal vagotomy accelerates emptying of solids and delays emptying of liquids D. In patients with Zollinger-Ellison syndrome, the treatment of choice for multiple ulcers is total gastrectomy E. Gastric cancers are the most common tumors in the GI tract to present with sub-mucosal spreading, needing at least 5 cm of resection margins

Questions Which of the following statements about the clinical evaluation of gastric lymphoma is MOST accurate?

A. Best diagnosed by abdominal computed tomographic (CT) scan with oral contrast B. Accounts for approximately 20% of gastric malignancies C. Usually detected by upper gastrointestinal endoscopy and biopsy D. Abdominal pain is an infrequent presenting complaint E. Usually presents urgently with hemorrhage, perforation, or obstruction

Questions Which of the following statements about the clinical evaluation of gastric lymphoma is MOST accurate?

A. Best diagnosed by abdominal computed tomographic (CT) scan with oral contrast B. Accounts for approximately 20% of gastric malignancies C. Usually detected by upper gastrointestinal endoscopy and biopsy D. Abdominal pain is an infrequent presenting complaint E. Usually presents urgently with hemorrhage, perforation, or obstruction

Questions A 42 year old physician has three month history of dark stools, vague abdominal pain, and early satiety. PE demonstrates heme positive stool. The patient is anemic. Upper endoscopy shows a 4.9 cm polypoid mass located in the distal antrum. Endoscopic biopsies of this lesion are inconclusive. At exploration, a gastric lymphoma confined to the stomach and regional nodes is confirmed. The most appropriate management is: A. B. C. D. E.

Chemotherapy Radiation therapy Chemotherapy and radiation Curative resection Resection plus adjuvant chemoradiation

Questions A 42 year old physician has three month history of dark stools, vague abdominal pain, and early satiety. PE demonstrates heme positive stool. The patient is anemic. Upper endoscopy shows a 4.9 cm polypoid mass located in the distal antrum. Endoscopic biopsies of this lesion are inconclusive. At exploration, a gastric lymphoma confined to the stomach and regional nodes is confirmed. The most appropriate management is: A. B. C. D. E.

Chemotherapy Radiation therapy Chemotherapy and radiation Curative resection Resection plus adjuvant chemoradiation

Questions The most common symptoms present at initial diagnosis of gastric carcinoma are A. Weight loss and vague abdominal pain B. Ulcer-type pain and early satiety C. Anorexia and vomiting D. Melena and lower abdominal pain E. Nausea and dysphagia

Questions The most common symptoms present at initial diagnosis of gastric carcinoma are A. Weight loss and vague abdominal pain B. Ulcer-type pain and early satiety C. Anorexia and vomiting D. Melena and lower abdominal pain E. Nausea and dysphagia