Cancer of Esophago-Gastric Junction

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Cancer of Esophago-Gastric Junction -AEG
(adenocarcinomas of esophagogastric junction)-
Jong Ho Park
Department of Thoracic Surgery
Korea Cancer Center Hospital
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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
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Gastroesophageal (GE) junction
Z-line(squamo-columnar junction) moving with
age as a result of reflux esophagitis
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Siewerts Classification
5cm
endoscopic cardia
5cm
approved at the consensus conference during the
2nd International Gastric Cancer Congress, 1997
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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.

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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.

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TREND in USA
Cancer 1998832049-53
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TREND in JAPAN
III
II
10.0
2.3
I
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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

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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
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TREATMENTS
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The management of ADC of EGJ continue to be a
debate. Definition, surgical approach, outcome
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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
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Extent of Lymphadenectomy for AEG II and III

• Distribution of LN metastases after surgery

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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
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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
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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.

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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

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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
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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)

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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.

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Outcomes in Germany
5YSR(R0) 43.2 , 10 YSR(R0) 32.7
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Outcomes in Japan
Overall 5YSR 52.83 Type I 134, Type II 1129
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Outcomes in China
5YSR (R0) 37.5 in type I (29) , 34.5 in type
II (80), 33.3 in type III (94)
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MULTIMODAL TREATMNET
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• 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
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• Neoadjuvant radiotherapy
• 40 Gy / 4 weeks by 2 Gy qd x 20

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

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• 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
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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.

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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
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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
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Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Survival (R0) Median 44.8
5YSR 40.1
10YSR 28.3
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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
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Adenocarcinoma of Esophago-Gastric Junction in
KCCH
Grade
28
117
92
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Extended total gastrectomy with transhiatal
resection of the distal esophagus