1. Cancer of Esophago-Gastric Junction
-AEG (adenocarcinomas of esophagogastric junction)-
Jong Ho Park
Department of Thoracic Surgery
Korea Cancer Center Hospital

2. Endoscopic point of view:
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
Typical longitudinal gastric mucosa folds as endoscopic cardia
classification

4. Siewert’s 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.
These observations indicate a possible heterogeneity in the pathogenesis and biologic behavior of adenocarcinoma arising in the EGJ.

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 Barrett’s esophagus is present, adenocarcinoma in both the gastric cardia and lower esophagus is most likely to be esophageal in origin.

7. TREND in USA
2.1
3.3
0.7
3.2
Cancer 1998;83:

8. TREND in JAPAN
III II
10.0 %
2.3 % I

9. GASTROESOPHAGEAL REFLUX
USA
Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota.
2200 Olimsted County, Minnesota : % GE reflux
Gastroenterology 1997 May;112(5):
AUS
730 Sydney residents (random sample): % GE reflux
KOR
2243: % 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 1997;41:279-80
Need prospective, randomized, placebo-controlled trials.
Am J Gastroenterol 2000;95:

11. TREATMENTS

12. The management of ADC of EGJ continue to be a debate.
; Definition, surgical approach, outcome…
, AEG resected
(290 women,1312 men)
Surgical resection is the mainstay of treatment of EGJ tumor of all resectable tumor stage

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 September; 232(3): 353–361

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. 1998;1:1-15

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. (1~4s)
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. (1~11)
D3 dissection; resection extended to the nodes in position 12~16.

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)
~ 0.3

19. Treatment Algorithm for EGJ Cancer
Stage
Good performance
Poor performance
Stage 0
Surgery alone
PDT, mucosal ablation
Stage I
RT +/- chemo
Stage IIA, IIB, III, IVA
Surgery +/- chemo/RT
Or Chemo/RT alone
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)
; 5-FU + cisplatin + Taxol (alternative regimen #1)
; 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) %, 10 YSR(R0) %

23. Outcomes in Japan
Overall 5YSR %
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 preop+3 postop ECF (epirubicin,cisplatin, fluorouracil)
UK Perioperative chemotherapy vs surgery alone for resectable gastroesophageal cancer
250 vs 253 patients
Postop. Complication; 46% vs 45%
DFS; p < 0.001
Overall survival; p=0.009
MAGIC(Medical Research Coucil Adjuvant Gastric Infusional Chemotherapy) trial

27. Neoadjuvant radiotherapy
40 Gy / 4 weeks by 2 Gy qd x 20
China Ramdomized clinical trial on preop RT + S vs S of adenocarcinoma of gastric cardia
5YSR 30.1% vs 19.7%
N Engl J Med 1996;335:462-7
5YSR 30.1% vs 19.7%

28. Neoadjuvant CCRT
2 /week Chemo (fluorouracil + cisplatin) + 40 Gy ,15/3week
Ireland Comparison of multimodal therapy and surgery for esophageal adenocarcinoma
5YSR 30.1% vs 19.7%
N Engl J Med 1996;335:462-7
3YSR 32% vs 6%

29. Neoadjuvant CT vs. CCRT 2.5 PLF (cisplatin+fluorouracil+leucovorin)
vs. 2 PLF + cisplatin+etoposide+30 Gy, 2 Gy fr. /week
Germany Phase III preop CT vs CRT in locally advanced ADC of EGJ
Early closed due to low accrual
2009년 report
119 patients
Complete tumor resection (69.5% vs 71.5%)
Pathologic complete response (15.6% vs 2.0%)
Tumor free L/N (64.4% vs 37.7%)
3-year SR (27.&% vs 47.4%, p=0.07)
Postop mortality (10.2% vs 3.8%)

30. Recommendations of the ISDE/ IGCA consensus conference
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.
Meta-analysis including 20 randomized trials have demonstrated decent survival benefits. But these are esophageal cancers.
Response rate of preoperative antineoplastic regimen; 30-60%
Early response group with FDG-PET.

31. Adenocarcinoma of Esophago-Gastric Junction
in KCCH
December 1987-August 2008 , 265 complete resection
M / F 193 / 72
3 distal esophageal adenocarcinoma
1 Barrett’s 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%
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
Brain 4
Neck node

33. Adenocarcinoma of Esophago-Gastric Junction
in KCCH
Survival (R0)
Median 44.8
5YSR %
10YSR %

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