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
2DEFINITION 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
3Gastroesophageal (GE) junction
Z-line(squamo-columnar junction) moving with
age as a result of reflux esophagitis
4Siewerts Classification
5cm
endoscopic cardia
5cm
approved at the consensus conference during the
2nd International Gastric Cancer Congress, 1997
5Backgrounds
- 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.
6STAGING 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.
7TREND in USA
Cancer 1998832049-53
8TREND in JAPAN
III
II
10.0
2.3
I
9GASTROESOPHAGEAL 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
JPN
10HELICOBACTER 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
11TREATMENTS
12The management of ADC of EGJ continue to be a
debate. Definition, surgical approach, outcome
13Surgical 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
14Extent of Lymphadenectomy for AEG II and III
- Distribution of LN metastases after surgery
15Radioisotope 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
16Extent 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
17D1 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.
18Prognostic 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
19Treatment 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
20Specific 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)
21Radiation 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.
22Outcomes in Germany
5YSR(R0) 43.2 , 10 YSR(R0) 32.7
23Outcomes in Japan
Overall 5YSR 52.83 Type I 134, Type II 1129
24Outcomes in China
5YSR (R0) 37.5 in type I (29) , 34.5 in type
II (80), 33.3 in type III (94)
25MULTIMODAL 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
30Neoadjuvant 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.
31Adenocarcinoma 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
32Adenocarcinoma 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
33Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Survival (R0) Median 44.8
5YSR 40.1
10YSR 28.3
34Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Stage
35Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Invasion depth
36Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Node metastasis
61
204
37Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Grade
28
117
92
38Extended total gastrectomy with transhiatal
resection of the distal esophagus