cancer of esophago-gastric junction -aeg (adenocarcinomas of esophagogastric junction)- jong ho park...
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CancerCancer of Esophago-Gastric of Esophago-Gastric JunctionJunction
-AEG (adenocarcinomas of -AEG (adenocarcinomas of esophagogastric junction)-esophagogastric junction)-
Jong Ho Park
Korea Cancer Center HospitalDepartment of Thoracic Surgery
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□ 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
approved at the 2nd IGCA, 1997 ISDE & IGCA, 1998
J.R. Siewert & H.J.Stein
DEFINITION of AGE
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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
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Siewert’s Classification
approved at the consensus conference during the 2nd International Gastric Cancer Congress, 1997
endoscopic cardia
5cm
5cm
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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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□ 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.
STAGING AJCC 6th edition
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Cancer 1998;83:2049-53
0.7
3.22.1
3.3
TREND in USA
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2.3 %
10.0 %
I
II
III
TREND in JAPAN
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Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota.
Gastroenterology 1997 May;112(5):1448-56
□2200 Olimsted County, Minnesota : 19.8% GE reflux
□730 Sydney residents (random sample): 17.5% GE reflux
□2243: 8.5% GE reflux
□6035: 6.6% GE reflux
GASTROESOPHAGEAL REFLUX
AUS
JPN
USA
KOR
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Am J Gastroenterol 2000;95:914-920
□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.
HELICOBACTER PYLORI
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TREATMENTS
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The management of ADC of EGJ continue to be a debate.; Definition, surgical approach, outcome…
Surgical resection is the mainstay of treatment of EGJ tumor of all resectable tumor stage
□1982-2005, 1602 AEG resected (290 women,1312 men)
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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
□ AEG II / III tumors; cardia carcinomas and subcardiac gastric cancers
Transthoracic en bloc esophagectomy with resection of the proximal stomach with 2-field lymphadenectomy
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): 353–361
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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)
Gastric cancer. 1998;1:1-15
□ D2-lymphadenectomy(1-11)□ Pancreas-preserving splenectomy ; only in infiltration in splenic hilum
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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. (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.
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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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5YSR(R0) 43.2 %, 10 YSR(R0) 32.7 %
Outcomes in Germany
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Overall 5YSR 52.83 %Type I 134, Type II 1129
Outcomes in Japan
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5YSR (R0) 37.5 % in type I (29) , 34.5% in type II (80), 33.3% in type III (94)
Outcomes in China
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MULTIMODAL TREATMNET
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Neoadjuvant chemotherapy 3 preop+3 postop ECF (epirubicin,cisplatin, fluorouracil)
MAGIC(Medical Research Coucil Adjuvant Gastric Infusional Chemotherapy) trial
UK Perioperative chemotherapy vs surgery alone for resectable gastroesophageal cancer
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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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Germany Phase III preop CT vs CRT in locally advanced ADC of EGJ
Neoadjuvant CT vs. CCRT 2.5 PLF (cisplatin+fluorouracil+leucovorin) vs. 2 PLF + cisplatin+etoposide+30 Gy, 2 Gy fr. /week
Early closed due to low accrual
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•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.
Neoadjuvant therapy
Recommendations of the ISDE/ IGCA consensus conference
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AdenocarcinomaAdenocarcinoma of Esophago-Gastric Junction of Esophago-Gastric Junction
in KCCHin 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
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AdenocarcinomaAdenocarcinoma of Esophago-Gastric Junction of Esophago-Gastric Junction
in KCCHin 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 5
Brain 4
Neck node 4
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AdenocarcinomaAdenocarcinoma of Esophago-Gastric Junction of Esophago-Gastric Junction
in KCCHin KCCH
Survival (R0) Median 44.8
5YSR 40.1 %
10YSR 28.3 %
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AdenocarcinomaAdenocarcinoma of Esophago-Gastric Junction of Esophago-Gastric Junction
in KCCHin KCCH
Stage
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AdenocarcinomaAdenocarcinoma of Esophago-Gastric Junction of Esophago-Gastric Junction
in KCCHin KCCH
Invasion depth
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AdenocarcinomaAdenocarcinoma of Esophago-Gastric Junction of Esophago-Gastric Junction
in KCCHin KCCH
Node metastasis
61
204
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AdenocarcinomaAdenocarcinoma of Esophago-Gastric Junction of Esophago-Gastric Junction
in KCCHin KCCH
Grade
28
117
92
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Extended total gastrectomy with transhiatal resection of the distal esophagus