Gastric Cancer 2012

8/11/2019 Gastric Cancer 2012

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Gastric cancer


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Gastric cancer

Eberspapyrus1600 BC

Hippocrates460-377 BCKarkinos, karkinoma.


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Gastric cancer

Claudius Galenus (131-201 AD)from Pergamum (present Turkey)

Avicenna(Abn Ali Al Hosain Ibn Abdallah Ibn Sina)

(980-1037) from Kharmaithen

(Bokhara province, Persia)
http://images.google.lt/imgres?imgurl=http://clendening.kumc.edu/dc/rm/a_172pa.jpg&imgrefurl=http://clendening.kumc.edu/dc/rm/major_ancient.htm&h=435&w=347&sz=49&tbnid=Av-kW8FGpowJ:&tbnh=123&tbnw=98&hl=lt&start=13&prev=/images%3Fq%3DAvicenna%26svnum%3D10%26hl%3Dlt%26lr%3D%26sa%3DNhttp://en.wikipedia.org/wiki/Image:Galen.jpg


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Gastric cancer is one the most common cancer,also one of the most common causes of overallcancer-related mortality worldwide.

Geographic areas of highest incidence: Japan,

Korea, South America, and Eastern Europe Prognosis depends on the developmental stage at

diagnosis; 5-year survival rate is low (~20%).

At early stage, GC is a treatable disorder, with 5-year survival rate >90%.Kikuchi et al.Survival after surgical treatment of early gastric cancer: surgical techniquesand long-term survival. Langenbecks Arch Surg 2004; 389:69-74

Gastric cancer. What is the problem?


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The Ten Most Common Cancers in 1984,

2007 and projected to 2030Number of Cases, UK

Cancer Site 1984 Cancer Site 2007 Cancer Site 2030

Lung 43.049 Breast 45.758 Prostate 61.090

Colorectum* 29.216 Lung 39.490 Colorectum* 58.176

Breast 26.600 Colorectum* 38.442 Breast 57.442

Stomach 13.329 Prostate 36.083 Lung 57.201

Prostate11.714

Uterus15.062

Malignant Melanoma21.824

Bladder11.629

Non-Hodgkin

Lymphoma 10.928Uterus

21.443

Uterus 9.112 Malignant Melanoma 10.723

Non-Hodgkin

Lymphoma 15.386

Pancreas 6.811 Bladder 10.151 Kidney 14.815

Ovary 5.500 Kidney 8.205 Bladder 14.092

Leukaemia 5.443 Oesophagus 7.969 Pancreas 11.927

Prepared by Cancer Research UK using data sourced from M Mistry et al. Cancer incidence in the

UK: Projections to the year 2030, Br J Cancer, 2011. (Vol 105) page 17951803


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Overall epidemiology of oncologyIncidence of gastric cancer worldwide*

*Incidence: new cases / 100,000 population / year

Parkin DM, et al. CA Cancer J Clin.1999;49:33-64.

Male 16.4Female 8.2

Male 36.3Female 16.9


Male 10.8Female 4.9


Male 5.9Female 2.6

Male 11.5Female 4.3


Male 8.4Female 4.0

EasternEuropea

Japan

Australia/N. Zealand

China

NorthAfrica

SouthAfrica

CentralAmerica

WesternEurpoe

NorthAmerica

798 000 new cases in1990


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Stomach Cancer (ICD-10 C16), Males,

World Age-Standardised Incidence and

Mortality Rates, Regions of the World, 2008

Estimates

http://info.cancerresearchuk.org


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Stomach Cancer (ICD-10 C16), Females,

World Age-Standardised Incidence and

Mortality Rates, Regions of the World, 2008

Estimates

http://info.cancerresearchuk.org


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Overall epidemiology of oncology

Incidence of gastric cancer in USA


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0 5 10 15 20 25 30 35 40

DenmarkSweden

BelgiumFinlandFrance

NetherlandsMalta

UK

AustriaIreland

LuxembourgSpain

CyprusCzech

GermanyEU

Greece

ItalySlovakiaBulgariaHungarySloveniaPortugal

LatviaRomaniaEstonia

PolandLithuania

Males

Females

Age-standardised cancer incidence rate per 100,000 population,

stomach cancer, by sex, EU countries, 2006 estimates

http://www.cancerresearchuk.org


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Age-related incidence of gastric cancer in USA

Overall epidemiology of oncology

Hohenberg P and Gretschehel S. Lancet. 2003,362:305-315


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Our situation:

Incidence of gastric cancer in Lithuania:

39.2/100 000 in 1982

27.4/100 000 in 1994E.Stratilatovas, E.Sangaila.-Medicina.- 1996, 32 tomas, 10 priedas, p.137

28.9 (28.4)/100 000 in 1999 (2004)

(male 36.7, female 21.1)Pagrindiniai onkologins pagalbos rezultatai Lietuvoje. 1999 metai (2004).

Lietuvos Kancerregistras. Vilnius, 2000 (2005),

Spain: 16.1 /100 000 in 1994Monferrer-Guardiola-R et al.- An-Med-Interna. -1996 Feb; 13(2): 68-72


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Our situation:

82% of GC is diagnosed at stage III and IV, justaround 2 % at stage I.

J.Umbrasas, A.Bubnys, S.Jureviius. -Medicina.- 1996, 32 tomas, 10 priedas, p.144.

60% patients exit wiithin the first year from

diagnosis.

Only 65% of all diagnosed GC cases are

confirmed histologically.E.Stratilatovas, E.Sangaila.-Medicina.- 1996, 32 tomas, 10 priedas, p.137.


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Etiology

Genetic factors (5-10%): Blood group A

CDH1 gene mutations (E-cadherin)

Exogenous factors (nutrition):

High concentration of nitrates in smoked and salted productsnitrates nitrites nitrozamines

Endogenous factors (infection):

achlorhydria promotes bacterial propagation in the stomach HP

Chromic atrophic gastritis

Status following gastric resection

Adenomatous gastric polyposis (malignancy in 20%)


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Risk factors for gastric cancer (US)

H. Pylori infection

Age

Male

Vegetable-free and fruit-free diet

Smoked, marinated and salted products in the diet

Atrophic gastritis

Intestinal metaplasia

Pernicious anaemia (Addison-Biermer anaemia)

Adenomatous gastric polyposis

Family history of cancer

Smoking

Hypertrophic gastritis

Familial adenomatous polyposis


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Optimal treatment of gastric cancer requires

precise diagnosis of the developmental stage as

the stage strictly determines the surgical

approach:

depending on the outspread of the process, the

decision is made for a surgical intervention(either radical or palliative), or for a palliative

non-surgical therapy.

Diagnosis


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Principles of decision-making

In cases with multiple primary neoplasticlocuses, the deepest invasion into the gastric wall

is taken into account.

When providing information on cancer, three

major sources are being used:

clinical datasurgical findings

final data


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Principles of decision-making

Once diagnosed, no findings can ever be

changed or deleted

Any finding that cannot be ascertained

unambiguously should be marked as

undetermined.


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Practical points in the diagnosis of

gastric cancer


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A. Macroscopic findings

1. Position of the tumour

Stomach can be divided into

3 distinct parts:

Cupper 1/3

M- intermediate 1/3A - lower 1/3

E - oesophagus

D - duodenum

E

C

MAD

MMA

CMA

CE

AD


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2.Position of the tumour

In the transverse section, the stomach can be

divided into 4 parts:

Less- lesser curvature

Gregreater curvature

Antanterior wall

Post- posterior wall

Ant

PostLess

Gre


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Location:

Antrum - 35%

Lesser curvature - 30%

Cardia - 25%

Other - 10%


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A. Macroscopic findingsAdenocarcinoma of the esophago-gastric junction

Tumours 5 cm above and 5 cm below

The esophago-gastric junction

Are classified by Siewert JRand Stein HJ (1998):

Type Idistal esophageal;

Type IIcentrum within the

junction;

Type IIIsubcardiac tumour.


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TNM Classification(7th Edition, 2010)

Depth of tumor invasion (T) Tis: Carcinoma in situ- intraepithelial tumor without

invasion of the lamina propria

T1a : tumor invades lamina propriaor muscularis

mucosae T1b : tumor invades submucosa

T2 : tumor invades muscularis propria

T3 : tumor penetrates subserosal connective tissue withoutinvasion of visceral peritoneum or adjacent structures

T4a : tumor invades serosa (visceral peritoneum)

T4b : tumor invades adjacent structures


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Structure of the stomach wall


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Early cancer - T1 cancer: infiltration of just

the mucosa and submucosa layers,

Muscularis propria intact. Advanced cancer: outspread of tumour

beyond the submucosa layer.


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3. Macroscopic type

Type 1 : Polypoid tumors, sharply demarcated from thesurrounding mucosa, usually attached on a wide base.

Type 2 : Ulcerated carcinomas with sharply demarcatedand raised margins.

Type 3 : Ulcerated carcinomas without definite limits,infiltrating into the surrounding wall.

Type 4 : Diffusely infiltrating carcinomas in whichulceration is usually not a marked feature.

Type 5 : Non-classifiable carcinomas that cannot beclassified into any of the above types.


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3. Macroscopic type (Bormann)

Type 1

Type 2

Type 3

Type 4


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Histological forms

Adenocarcinoma:

Papillary adenocarcinoma Tubular adenocarcinoma:

Well-differentiated type

Moderately differentiated type

Poorly differentiated adenocarcinomaSolid type

Non-solid type

Signet-ring cell carcinoma

Mucinous adenocarcinoma

Special types

Adenosquamous carcinoma

Squamous cell carcinoma

Carcinoid tumor


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Histological forms

Adenocarcinoma: Papillary adenocarcinoma

Tubular adenocarcinoma:

Well-differentiated typeModerately differentiated type

Poorly differentiatedadenocarcinoma

Solid type

Non-solid type

Signet-ring cell carcinoma

Mucinousadenocarcinoma

Special types Adenosquamous

carcinoma

Squamous cell carcinoma Carcinoid tumor


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Grading

Grading refers to the appearance of the cancer cellsunder the microscope.

Grade 1 (low-grade) - The cancer cells tend to growslowly, look quite similar to normal cells (are welldifferentiated) and are less likely to spread than higher

grades. Grade 2 (moderate-grade) - The cells look more

abnormal and are slightly faster growing.

Grade 3 (high-grade) - The cancer cells tend to grow

more quickly, look very abnormal (are poorlydifferentiated) and are more likely to spread than low-grade cancer cells.

Grade 4undifferentiated cells


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Growth patterns

Laurensclassification by growth patterns (1965):

Intestinal: expansively (polypoid-like)growing

tumour with clear-cut borders

Diffuse: infiltrating growth, without clear-cutborders. Peculiar form:Linitis plastica;prognosis

unfavourable due to metastases to lymphatic nodes.


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Laurens classification

Intestinal Diffuse

More common in endemic

regions

More common in regions of

low incidence

Related to gastric atrophy Related to blood group A

Glandular formation,

intestinal metaplasia

Poorly differentiated, signet-

ring-type

Male>female Female>male

Hematogenic spread Lymphogenic spread

In relation with the age More common at young age


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Diffuse type signet-ringcancer

A M i fi di


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A. Macroscopic findings4. Lymphatic nodes

4.1. Regional lymphatic nodes (stations)

No. 1 Right paracardial LN

No. 2 Left paracardial LN

No. 3 LN along the lesser curvature

No. 4sa LN along the short gastric vessels

No. 4sb LN along the left gastroepiploic

vessels No. 4d LN along the right gastroepiploic

vessels

No. 5 Suprapyloric LN

No. 6 Infrapyloric LN

No. 7 LN along the left gastric artery

No. 8 LN along the common hepatic artery(Anterosuperior and poeterior group)

No. 9 LN around the celiac artery

No. 10 LN at the splenic hilum

No. 11 LN along the splenic artery

No. 12 LN in the hepatoduodenal ligament

No. 13 LN on the posterior surface of thepancreatic head

No. 14v LN along the superior mesentericvein

No. 14a LN along the superior mesentericartery

No. 15 LN along the middle colic vessels

No. 16a1 LN in the aortic hiatus No. 16a2 LN around the abdominal aorta(from the upper margin of the celiac trunkto the lower margin of the left renal vein)

No. 16b LN around the abdominal aorta(to the aortic bifurcation)

No. 17 LN on the anterior surface of the

pancreatic head No. 18 LN along the inferior margin of the

pancreas

No. 19 Infradiaphragmatic LN

No. 20 LN in the esophageal hiatus of thediaphragm

A M i fi di


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A. Macroscopic findings4. Lymphatic nodes

4.1. Regional lymphatic nodes

Grouping (Compartments) of lymph nodes

The regional lymph nodes are classified into three

groups depending upon the location of the primarytumor

This grouping system is based on the results ofstudies of lymphatic flow at various tumor sites,together with the observed survival associated with

metastasis at each nodal station.


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4.2.Location of regional lymphatic nodes


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4.2. Location of regional lymphatic nodes


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TNM Classification

(7th

Edition, 2010)Extent of lymph node metastasis (N)

N0: no regional lymph node metastasis. (A designationof pN0 should be used if all examined lymph nodes are

negative, regardless of the total number removed andexamined)

NX: regional lymph nodes cannot be assessed

N1 : metastasis in 1-2 regional lymph nodes

N2 : metastasis in 3-6 regional lymph nodes N3a : metastasis in 7-15 regional lymph nodes

N3b: metastases in 16 or more regional lymph nodes

i


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Metastasis

Direct invasion

Lymph node dissemination

Blood spread

Intraperitoneal colonization


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Macroscopic findings

5. Metastatic spread of gastric cancer

Liver 38-54%

Peritoneum 17-24%

Omentum 13-21%

Lungs 12-22%

Mesenterion 9%

Pancreas 7-29%

Adrenal glands 5-15%

Karpeh MS, et al. Cancer: Principles & Practice of Oncology. 6th ed.

2001:1092-1126.


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TNM Classification

(7th Edition, 2010)

Distant metastases (M) M0 : No distant metastases,

M1 : Distant metastases

Sister Mary Joseph nodle, Blumers shelf,

Krukenburg tumour



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Surgical classification of stages

(7

th

edition, 2010)Stage IIIA

T4a N1 M0

T3 N2 M0

T2 N3 M0

Stage IIIBT4b N0-1 M0

T4a N2 M0

T3 N3 M0

Stage IIIC

T4a N3 M0T4b N2-3 M0

Stage IV

Any T Any N M1

Stage 0Tis N0 M0

Stage I A

T1 N0 M0

Stage IB

T2 N0 M0T1 N1 M0

Stage IIA

T3 N0 M0

T2 N1 M0

T1 N2 M0Stage IIB

T4a N0 M0

T3 N1 M0

T2 N2 M0

T1 N3 M0

Cli i l if i


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Clinical manifestation

Signs and Symptoms

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


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Signs and Symptoms

Advanced Gastric CancerWeight 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


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Laboratory tests

Iron deficiency anemia

Fecal occult blood test

(FOBT)

Tumor markers (CEA, Ca19-9)


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Endoscopic diagnosis

In patients with signs and symptoms suggestive of

GC, and/or with compatible risk factors or paraneoplastic

conditions, the diagnostic procedure of choice could bean endoscopic examination

The diagnostic criteria for early or advanced gastriccancer under endoscopy are based on the JRSGC and

Bormanns classification


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Radiologic diagnosis

For reasons of cost and availability, radiography may

sometimes be the first diagnostic procedure performed

Classic radiography signs of malignant gastric ulcer

asymmetric/distorted ulcer crater

ulcer on the irregular mass

irregular/distorted mucosal foldsadjacent mucosa with obliterated /distorted area gastricae

nodularity, mass effect, or loss of distensibility


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Radiologic diagnosis

Distal GC Proximal GC Linitis plastica

D t ti f l t i


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Detection of early gastric cancer

Endoscopic screening

general population or high risk persons

Careful observation

Japan is the only country that had conducted large

nationwide mass population screening of asymptomatic

individuals for gastric malignancy

S i l


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Surgical treatmentApproaches

Intraluminal endoscopy

Laparoscopy

Laparotomy

Thoraco-laparotomy

Others

T t t


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Treatment

Surgical resection

EMR

Adjuvant therapy

Palliative therapy


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Surgical treatmentOperative procedures

Mucosectomy

Wedge resection

Segmental resection

Proximal gastrectomy

Pylorus preserving gastrectomy

Distal (subtotal) gastrectomy

Total gastrectomy

Combined resection

S rgical inter entions


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Surgical interventions

Gastrectomy


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Surgical treatment

R0 resection

Which is the sufficient extent of gastrectomy

(resection)?

How extensive should be the lymphadenoctomy?


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Surgical treatment. Radicality

R0 resection indicates a microscopically margin-negative

resection, in which no gross or microscopic tumor remains in

the primary tumor bed.

R1 resection indicates the removal of all macroscopicdisease, but microscopic margins are positive for tumor.

R2 indicates gross residual disease with gross residual tumor

that was not resected (primary tumor, regional nodes, and

macroscopic margin involvement).


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Surgical interventionsHarvesting of lymphatic nodes

D1: 1stcompartment of lymph nodes

D2: 1stand 2d compartments of lymph nodes

D3: all stations of lymph nodes should be removed

Regional lymph node group according to the location of tumor


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Regional lymph node group according to the location of tumor.

Sasako M et al. Jpn. J. Clin. Oncol. 2010;40:i28-i37

The Author (2010). Published by Oxford University Press. All rights reserved

Nodal dissection for patients with gastric cancer: a randomized controlled trial.


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Nodal dissection for patients with gastric cancer: a randomized controlled trial.

Sasako M et al. Jpn. J. Clin. Oncol. 2010;40:i28-i37

The Author (2010). Published by Oxford University Press. All rights reserved


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B. Surgical interventions

2. Combined resections

All resections performed in combination withthe main tumour (spleen, liver, colontransversum and its mesenterion, gall-bladder,pancreas, adrenal glands, ovarian, etc.) arecalled combined resections

*Resections of omentum major or minor, anterior

mesenterion of the large intestine, abdominal part ofesophagus, or the initial part of duodenum are not included inthis category.


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Surgical results

Mean 5-year survival is 25% - 38.2%.

Dietl F., Rumpf K.D. Zentralbl-Chir. 1995; 120(10): 800-3

Oertli D. et al. Schweiz-Med-Wochenschr. 1994 Jun 4; 124(22): 945-52

Surgical results


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Surgical results

Early cancer

N*=1137, N*=126,N*=294 In cases of mucosal cancer invasion (T1a), l/n mts can

be found in 2.6-3.1-4%of cases.

In cases of submucosal invasion (T1b), l/n mts can be

found in 9,5-16.4-18,4% of cases. Mucosal cancer


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Surgical resultsEarly cancer: 5-year survival rate

67% of operated casesCohen M.M., Zoeter M.A., Loar C. Surg-Endosc. 1994 Aug; 8(8): 862-6

82%of operated cases

Dietl F., Rumpf K.D. Zentralbl-Chir. 1995; 120(10): 800-3

96% (mucose invasion), 86% (submucose invasion)-Austria!

Jatzko G., Lisborg P.H., Klimpfinger M. Jpn-J-Clin-Oncol. 1992 Feb; 22(1): 26-9

98% (n0), 92% (n+) N=621; 10 years - 97,4% (n0),

87,2% (n+) Seto Y. et al. World J.Surg. , 1997, 21, 186-190


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Surgical resultsEarly cancer

L/n metastases have been found in 63 (10.1%) out of621 patients.

In cases of invasion into 1, 2, 3, 4 and more l/n, 5 (10)-year survival change as folows:

90.0% (70.7%)

92.9% (84.8%)

92.3% (83.1%)

74.0% (55.2%)

Seto Y. et al. World J.Surg. , 1997, 21, 186-190


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Early gastric cancer (EGC)

EGCmucosal and submucosal cancer, regardlessthe invasion to regional l/n or distant metastases.

T1cancer according to TNM classification: tumour

invasion to mucose and/or muscularis mucosa(M),or submucose (SM) layer.

SM1 is defined as invasion = 0,5 mm frommuscularis mucosae


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Morphologic EGC classificationJapanese Research Society for Gastric Cancer

Type Iprotruded (polypoid)type

Type II - superficial type

Type II a - elevated lesion

Type IIb - flat lesion

Type II c - superficiallydepressed lesion

Type III - excavated lesion

Strategy of gastric cancer treatment


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Strategy of gastric cancer treatment

Gotoda T.Gastric Cancer. 2007, 10: 1-11

Gastric cancer Lymphatic nodes Peritoneum,

blood circulation

Localised disorder Systemic disorder

Early stage Advanced cancer

Endoscopic m/sbm resection Adjuvant chemoterapy

Surgical treatment

Gastrectomy + L/n resection

Laparoscopic surgery

Guidelines for endoscopic EGC resection.


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Gotoda T et al. Incidence of lymph node metastasis from early gastric cancer: estimation

with a large number of cases at two large centers. Gastric Cancer 2000; 3:219-25

Depth

Histology

Mucose cancer

ulcer (+) ulcer(-)

20 20< 30 30

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Gastric Cancer 2012

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