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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.jpg8/11/2019 Gastric Cancer 2012
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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 77.9Female 33.3
Male 10.8Female 4.9
Male 43.6Female 19.0
Male 5.9Female 2.6
Male 11.5Female 4.3
Male 18.6Female 13.3
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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A. Macroscopic findings
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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A. Macroscopic findings
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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A. Macroscopic findings
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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A. Macroscopic findings
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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A. Macroscopic findings
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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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
Macroscopic findings
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Macroscopic findings
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
Recommended