Surgical Approach to GASTRIC CANCER

Gilbert SEBBAG, MD Chairman, Surgery B Department Soroka University Medical Center

Gastric Cancer

Epidemiology
Worldwide until 1988 leading
causes of death from cancer today >1 million new GC cases/y

Epidemic Japan, Korea, China,

Central Asia & Middle East, Eastern Europe, part Sth

Gender Male > female (2/1) Race Age

Higher incidence in AA, colored people starts 4th & 5th decades, peak in 60s

America

Lowest incidence Australia, New

Zealand

Gastric Cancer

Epidemiology
Global
- IVth most common cancer - Anatomical pattern change in Western countries
(proximal stomach + distal esophagus > 45% poorer prognosis)

Japan

Incidence 100/100,000/y, leading death from Ca

U.S.A.
Israel

2011 expected 21,200 new cases / deaths 10,800

Early 20th century was # 2 cancer death cause immigrants southern former USSR

Migration

Japan Hawaii: no change

Japan US: lower if western life style

Number of deaths

% all cancer death

Comparison of stomach cancer deaths in

European and Asian countries, 1997

Latvia
Number of deaths % all cancer death

Males

Females

Males

Females

360 526 25 246 32 1057 1571 2588 26343 262 7979

304 334 26 126 15 684 1060 1366 19834 188 5037

12.30 12.51 5.01 14.96 8.27 5.18 13.07 11.44 16.22 9.97 14.43

12.03 10.45 5.53 11.27 5.08 4.09 12.54 8.40 15.28 8.76 12.00

Lithuania Luxembourg

Males

Females

Males

Females

Macedonia Malta Netherlands

Armenia Austria Azerbaijan Belarus Bulgaria Croatia Czech Republic Estonia Germany Greece Hungary Kazakhstan Kyrgyzstan

253 726 609 1859 1064 627 954 216 7356 790 1344 1774 404

155 697 346 1248 710 393 774 168 6859 529 1030 1217 210

12.16 7.54 21.63 15.92 11.40 9.43 6.16 12.00 6.84 5.70 7.08 15.60 25.65

9.85 7.56 17.40 16.05 10.66 8.94 6.27 10.99 6.69 6.06 7.12 13.23 16.33

Portugal Romania Russian Federation Slovenia Ukraine

United Kingdom
England and Wales Northern Ireland Scotland Japan Kuwait Republic of Korea Singapore

4541
4046 104 392 32218 7 7501 254

2953
2567 68 318 17521 7 4303 141

5.70
5.75 5.64 5.20 19.28 2.88 22.44 10.88

3.97
3.93 3.90 4.33 16.17 4.17 22.93 7.86

Gastric Cancer

Epidemiology
Mortality risk
Males Females

10

20

30

40

50

10

20

30

Gastric Cancer

Etiology & Pathogenicity

Predisposing factors
Diet-related

- low intake
- high intake

citrus, raw vegetables, fruit, high fiber, vitamins A & C salted meat & fish, high nitrate

Drinking from wells Way of life

high nitrate

poor food preparation & storing lack refrigeration, smoked food

Gastric Cancer

Etiology & Pathogenicity

Predisposing factors
Occupational

(cont.)

rubber & coal industry globally

Low socioeconomic level Medical

H. Pylori, Gastritis Gastric mucosal atrophy Previous gastric surgery

Etiology & Pathogenicity

Gastric Cancer

Helicobacter pylori gastric infection.

Advanced age. Male gender. Diet low in fruits and vegetables. Diet high in salted, smoked, or preserved foods. Chronic atrophic gastritis. Intestinal metaplasia. Pernicious anemia. Gastric adenomatous polyps Family history of gastric cancer(1-3%). Cigarette smoking. Menetriers disease (giant hypertrophic gastritis). Familial adenomatous polyposis.

Gastric Cancer

Etiology & Pathogenicity

Theory - Pathogenesis
Time scale

Normal mucosa
low acidity diet, environment

Atrophic mucosa
bacterial overgrowth

Mucosal injury ? Cancer

nitrites

Gastric Cancer

Anatomy
Arterial Venous

Vascular supply

Lt gastric, Rt gastric, Rt&Lt Gastroepiploic Vasa brevia Same path portal liver blood borne metastasis invasion path

Lymphatics

First line

Lesser & greater curves, Pyloric, pericardial

IInd line
Distant

Splenic & hepatic A, proximal Lt gastric, celiac A

Peri-esophageal LSC fossa Virshow LN Lt axilla Irishs LN Para-aortic

Histo-Pathology
Types Adenocarcinoma > 95% Lymphoma (1-3%) Other: GIST, carcinoid

Gastric Cancer

Classifications
Borrmann

Staging for prognosis appreciation

type type type type type I II III IV V polypoid, fungating ulcers + borders ulcer + infiltrating diffuse infiltrating unclassifiable

Pathology
Classifications
(cont.)

Gastric Cancer

Broders Differentiation: Well, moderate, poor, anaplastic

Laurens

Intestinal type: epidemic, older, male metaplasia, mucosa atrophy, preCa Diffuse type: submucosal spread,endemic, young, female, A group, genetic?, familial (Bonaparte), early metastasis

Molecular Signet-Ring cell, E-cadherin mutation

All correlate with poor prognosis

Pathology
Ways of Gastric Cancer Spread
LN metastasis
Local extension

Gastric Cancer

early 40-70% @ time of surgery

submucosal through serosa to adjacent organs: colon, pancreas

Hematogenous spread Distant mets to liver, lung,

bone, adrenal, pancreas

Peritoneal seeding Carcinomatosis, Krukenberg, Blummer shelf

Gastric Cancer

Clinical Presentation
Symptoms Nonspecific, ~ weight loss, anorexia,
Fatigue, epigastric discomfort Anemia, acute UGI bleeding rare 10-15% GI signs dysphagia cardia vomiting distal, antrum

Physical Exam

usually normal Invasion to colon, spleen, pancreas

Epigastric mass means locoregional spread Distant seeding ovary (krukenberg), peritoneum pelvis (blummer shelf) LN Virshow, Irish nodes

Gastric Cancer

Clinical Evaluation
Part of pre-treatment assessment H & P, Blood tests anemia, liver tests Endoscopy + Bx diagnosis Imaging for preoperative for staging Sometimes barium swallow true anatomical site CT chest abdomen pelvis , N distant & M EUS T & local N (less performant/esophageal) Laparoscopy + liver IOUS excellent staging Tumor-markers CEA, CA19-9 F/U only

Endoscopic picture of Gastric Ca

Large Ulcerative Lesion

Endoscopic picture of Gastric Ca

Polypoid Lesion

Imaging Evaluation

Gastric Cancer

Barium swallow with distal obstruction of stomach

EUS picture of Gastric Ca

TUMOR

Clinical Evaluation

Gastric Cancer

Screening

Success in Japan & some in Sth Korea significant decrease in Gastric Ca death rate over 35 last y Tests upper GI endoscopy (GP!) double contrast Ba swallow

In Japan

of 40% of early gastric Ca no change in incidence diagnostic & treatment (EMR)

Gastric Cancer

Clinical Evaluation
Classical TNM

Staging

US, Europe (AJCC/UICC)

But Japanese classification based on 18 LN

regions!! Basis of theoretical advantage of LN

resection with gastrectomy LN spread may be strongest predictive factor/survival
N status 5 YS
N0 N1 N2 N3 57-85% 32-51% 9-31% 10%

Gastric Cancer

Treatment
Combined modalities
Neo-adjuvant CXT feeding Jejunostomy Surgery Adjuvant CX-RXT

Surgery

Surgery
Goal complete R0 resection of cancer
GC + locoregional spread ~50% -> R1 Gross dis. (positive margin) R2

LN resection = 15 LN @ min. Unresectable distant mets, peritoneal carcinomatosis (?)

major vasc. structures involvement

Gastric Cancer

Treatment

Surgery

Gastrectomy = only potentially curative tool Endoscopic mucosal resection (EMR) for Early gastric Ca + F/U in Japan + selective lymphadenectomy 2-17% LN + Classical Gastrectomy + Lymphadenectomy Gastrectomy total, subtotal hemigastrectomy proximal

Gastric Cancer

Treatment
Proximal lesion

Surgery strategy

Total gastrectomy + Roux-en-Y reconstruction

Proximal gastrectomy (high morbidity)

Distal lesion
Subtotal gastrectomy + bilroth II reconstruction Hemigastrectomy + bilroth II

Distal gastrectomy + bilroth I

poor oncological safety

Functional result poor in total & proximal gastrectomy Proximal surgical margins at least 6 cm / submucosal spread

Gastric Cancer

Treatment
Lymphadenectomy

Surgery Strategy

N1 lesser curv. (1,3,5) + greater curv. (2,4,6) N2 Lt GA (7) + Com HA (8) + Celiac A (9) + Splenic A (10,11) N3-4 distant + para-Ao LN

D resection of LN
DO fail to remove N1 D1 N1 + omentum D2 N2 + omental bursa, pericardia LN Extended D2 + splenectomy

Survival advantage

> 15 N2 LN removal > 20 N3 LN

Total gastrectomy Roux-en-Y reconstruction

Roux-en-Y reconstruction after total gastrectomy

Subtotal gastrectomy

Bilroth II Reconstruction

Distal gastrectomy

Bilroth I reconstruction

Gastric Cancer

Treatment
Morbidity & Mortality
Surgery extent
Proximal Total Subtotal

Surgery

Morbidity
50% 35% 25%

Mortality
7-10%!! 3-7% 3-5%

Treatment
Neoadjuvant

Gastric Cancer

Non-surgical treatment
Preop 5 FU + Leucovorin + RXT
downstaging ~ CRC GE junction Ca downstaging

Adjuvant Treatments
Systemic Chemotherapy Gastric CA = systemic disease @ diagnosis. Postoperative IV 5 FU, MMC, Doxorubicin, Taxol

Treatment
Adjuvant Treatments (cont.)

Gastric Cancer

Non-surgical treatment
Radiation rationale 30-40% loco-regional failure

+ 5 FU as sensitizer

Novel treatment for Carcinomatosis

Cytoreduction for control of local & peritoneal spread Intraoperative with heat & postoperative Slight survival advantage , 5 FU, MMC, Cisplatin

Other

Immunotherapy, tamoxifen = trials

Treatment
Advanced Gastric Cancer

Gastric Cancer

Surgery

Indication = only palliation when bleeding, obstruction, perforation High morbidity & mortality

CXT
RXT

Single drug, combos: trials

Palliative: pain, bleeding control

Treatment Results

Gastric Cancer

Overall 5Y Survival ~ 20% TxN0M0 5YS >70% cure? Survival by Stage

Stage I II % of pts 6% 9% 5 YS >70% 42%

III
IV

20%
65%

20%
5%

Thank you

Questions?