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Cancer of Esophago-Gastric Junction

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Title: Cancer of Esophago-Gastric Junction


1

Cancer of Esophago-Gastric Junction -AEG
(adenocarcinomas of esophagogastric junction)-
Jong Ho Park
Department of Thoracic Surgery
Korea Cancer Center Hospital
2
DEFINITION of AGE
  • Adenocarcinomas which have their center within
    5cm proximal or distal of the anatomic cardia.
  • Endoscopic point of view
  • the upper end of the typical longitudinal fold of
    the gastric mucosa is defined as the so called
    endoscopic cardia rather than the Z-line

J.R. Siewert H.J.Stein
approved at the 2nd IGCA, 1997 ISDE IGCA,
1998
3
Gastroesophageal (GE) junction
Z-line(squamo-columnar junction) moving with
age as a result of reflux esophagitis
4
Siewerts Classification
5cm
endoscopic cardia
5cm
approved at the consensus conference during the
2nd International Gastric Cancer Congress, 1997
5
Backgrounds
  • Incidence change in white men
  • 10/yr increase during last decade, in
    contrast to the decreasing prevalence of gastric
    cancer.
  • A preponderence of the male sex in Type I than
    Type II or III.
  • Hx. Of a hiatal hernia, obesity and GE reflux in
    Type I than Type II or III.
  • Reflux related intestinal epithelial metaplasia
    in Type I and H. pylori and
    intestinal metaplasia in Type II III.
  • The prevalence of undifferentiated tumors and
    tumors with a non-intestinal growth pattern in
    rather low in AGE Type I and increase
    significantly from Type II III cytokeratins,
    cell adhesion molecules, p53 genomic pattern.
  • Different lymphographic studies and
    micrometastasis pattern to L/N.
  • pT3 (visceral peritoneum) in UICC classification
    partial extraperitoneal location and lymphatic
    spread into retroperitoneum.

6
STAGING AJCC 6th edition
  • If more than 50 of the cancer involves the
    esophagus, the cancer is classified as
    esophageal.
  • If more than 50 of the tumor is below the GE
    junction, as gastric .
  • If the tumor is located equally above and below
    the GE junction, squamous cell, small cell, and
    undifferentiated carcinoma are classified as
    esophageal and
  • adenocarcinoma and signet ring cell carcinomas
    as gastric.
  • When Barretts esophagus is present,
    adenocarcinoma in both the gastric cardia and
    lower esophagus is most likely to be esophageal
    in origin.


7
TREND in USA
Cancer 1998832049-53
8
TREND in JAPAN
III
II
10.0
2.3
I
9
GASTROESOPHAGEAL REFLUX
Prevalence and clinical spectrum of
gastroesophageal reflux a population-based study
in Olmsted County, Minnesota.
USA
  • 2200 Olimsted County, Minnesota 19.8 GE
    reflux

Gastroenterology 1997 May112(5)1448-56
AUS
  • 730 Sydney residents (random sample) 17.5
    GE reflux

KOR
  • 2243 8.5 GE reflux

JPN
  • 6035 6.6 GE reflux

10
HELICOBACTER PYLORI
  • The decrease in H. pylori infection has
    paralleled the increasing rate of ADC of the
    esophagus
  • Gut
    199741279-80
  • Need prospective, randomized, placebo-controlled
    trials.

Am J Gastroenterol 200095914-920
11
TREATMENTS
12
The management of ADC of EGJ continue to be a
debate. Definition, surgical approach, outcome
13
Surgical strategies (based on tumor location)
Complete removal of the primary tumor with its
lymphatic drainage
  • Adenocarcinoma of esophagogastric junction (AEG)
    I tumors
  • distal esophageal adenocarcinoma

Transthoracic en bloc esophagectomy with
resection of the proximal stomach with 2-field
lymphadenectomy
  • AEG II / III tumors
  • cardia carcinomas and subcardiac gastric
    cancers

Total gastrectomy with transhiatal resection of
the distal esophagus (transhiatally extended
gastrectomy) Wide splitting of the
diaphragmatic hiatus, Transhiatal resction of
the distal esophagus, En bloc lymphadenctomy
of the lower posterior mediastinum, D2
lymphadenectomy
Ann Surg. 2000 September 232(3) 353361
14
Extent of Lymphadenectomy for AEG II and III
  • Distribution of LN metastases after surgery

15
Radioisotope Lymphography-Gastric Cancer 1998-
  • Lymphatic pathways are mainly directed toward the
    abdomen.

Siewert Type I Siewert Type II Siewert Type III
Abdominal tier 53.8 70.5 90.7
Chest L/N 46.2 29.5 9.3
16
Extent of Lymphadenectomy for AEG II and III
Lymph node station of Japanese Gastric Cancer
Association(JGCA)
  • D2-lymphadenectomy(1-11)
  • Pancreas-preserving splenectomy
  • only in infiltration in splenic hilum

Gastric cancer. 199811-15
17
D1 Vs. D2 Lymphadenectomy-Guidelines of the
Japanese Research Society of the Study of Gastric
Cancer-
  • D1 dissection removal of the involved part of
    the stomach (distal or total), including greater
    and lesser omentum. The spleen and pancreas tail
    are only resected when necessitated by tumor
    invasion. (14s)
  • D2 dissection the omental bursa is removed with
    the frontal leave of the transverse mesocolon,
    and the (Lt. gastric, common hepatic, celiac,
    splenic A.) vascular pedicles of the stomach are
    cleared completely. Standard resection of the
    spleen and pancreatic tail was only done in
    proximal tumors to achieve adequate removal of D2
    lymph node stations 10 and 11. (111)
  • D3 dissection resection extended to the nodes in
    position 1216.

18
Prognostic Factors after Surgery
  • En bloc resection
  • R0 resection
  • Total involved L/N number
  • - 4 or less (AJCC 6)
  • Node ratio (Involved L/N / Total resected L/N)
  • - 0.1 0.3

19
Treatment Algorithm for EGJ Cancer
Stage Good performance Poor performance
Stage 0 Surgery alone PDT, mucosal ablation
Stage I Surgery alone RT /- chemo
Stage IIA, IIB, III, IVA Surgery /- chemo/RT Or Chemo/RT alone RT /- chemo
Stage IVB Chemo /- RT/stents RT/stent
20
Specific Drug Regimens
  • Locoregionally advanced stage (T3,4, N1, or
    M1a)-alternative to surgery
  • 5-FU cisplatin RTx. (50.4 Gy)
  • Investigational for locoregionally advanced stage
    (T3,4, N1, or M1a)-alternative to surgery alone
    or chemoradiation Tx. Alone
  • 5-FU cisplatin RTx. (50.4 Gy) followed
    by surgery
  • Advanced stage (M1b, systemic micrometastases)
  • 5-FU cisplatin (standard regimen)
  • Advanced stage (M1b, systemic micrometastases)
  • 5-FU cisplatin Taxol (alternative
    regimen 1)
  • Advanced stage (M1b, systemic micrometastases)
  • cisplatin CPT-11 (alternative regimen 2)

21
Radiation Therapy
  • T1-2, No cannot tolerate surgery
  • - RTx.(50.4 Gy over 5.5 weeks) /- chemo
    (cisplatin 5-FU)
  • Locoregional advanced stage (T3,4, N1 or M1a)
  • - can be treated with RTx. with chemoTx.
    alone (or surgery alone)
  • but poor result
  • - recommend neoadjuvant RTx. with chemoTx.
    or postop. Adjuvant
  • RTx. with chemoTx.
  • Metastatic (M1b) with obstructive symptom
  • - can be treated with RTx. alone (30Gy over
    2 weeks) or
  • in combination with chemoTx.

22
Outcomes in Germany
5YSR(R0) 43.2 , 10 YSR(R0) 32.7
23
Outcomes in Japan
Overall 5YSR 52.83 Type I 134, Type II 1129
24
Outcomes in China
5YSR (R0) 37.5 in type I (29) , 34.5 in type
II (80), 33.3 in type III (94)
25
MULTIMODAL TREATMNET
26
  • Neoadjuvant chemotherapy
  • 3 preop3 postop ECF (epirubicin,cisplatin,
    fluorouracil)

UK Perioperative chemotherapy vs surgery alone
for resectable gastroesophageal cancer
MAGIC(Medical Research Coucil Adjuvant Gastric
Infusional Chemotherapy) trial
27
  • Neoadjuvant radiotherapy
  • 40 Gy / 4 weeks by 2 Gy qd x 20

28
  • Neoadjuvant CCRT
  • 2 /week Chemo (fluorouracil cisplatin) 40
    Gy ,15/3week

29
  • Neoadjuvant CT vs. CCRT
  • 2.5 PLF (cisplatinfluorouracilleucovorin)
  • vs. 2 PLF cisplatinetoposide30 Gy, 2 Gy
    fr. /week

Germany Phase III preop CT vs CRT in locally
advanced ADC of EGJ
Early closed due to low accrual
30
Neoadjuvant therapy Recommendations of the ISDE/
IGCA consensus conference
  • A general application of multimodal treatment
    protocols in patients with potentially resectable
    adenocarcinoma of the esophagogastric junction
    was not recommanded.
  • Restrict neoadjuvant therapy to locally advanced
    tumors at the esophagogastric junction to
    patients in whom an R0-resection appears
    questionable.

31
Adenocarcinoma of Esophago-Gastric Junction in
KCCH
December 1987-August 2008 , 265 complete resection
M / F 193 / 72
3 distal esophageal adenocarcinoma
1 Barretts esophagus
257 Total gastrectomy (91 thoracoabdominal incision)
8 Ivor Lewis operation
Stage IA 13, IB 19, II 35, IIIA 104, IIIB 45, IV 49
32
Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Recurrence 80/265, 30.1 Recurrence 80/265, 30.1
Abdominal LN 26 (9.8)
Liver 18 (6.8)
Lung 12 (4.5)
Mesentery seeding 11 (4.2)
Anastomosis site 7 (2.7)
Mediastinal LN 5
Ovary 5
Brain 4
Neck node 4
33
Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Survival (R0) Median 44.8
5YSR 40.1
10YSR 28.3
34
Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Stage
35
Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Invasion depth
36
Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Node metastasis
61
204
37
Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Grade
28
117
92
38
Extended total gastrectomy with transhiatal
resection of the distal esophagus
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