1. Review on Management of Gastro-esophageal Junction Cancer
14/4/2018
Review on Management of Gastro-esophageal Junction Cancer
 joint hospital surgical grand round   
Dr. Vincent Chan  Pamela Youde Nethersole Eastern Hospital

2. content Definition Latest Trend Surgical Approach Resection extent
Adjuvant/ neoadjuvant therapy

3. definition GEJ SCJ (Z-line) Upper limit of the gastric folds/
Lower limit of the palisade longitudinal vessels (Japan)  
SCJ (Z-line)
Where squamous mucosa of the esophagus and columnar mucosa of the stomach meet 
Distance between GEJ and SCJ: 3 to 11mm
large veins exceeding 100 mm in diameter are observed much more frequently in the lamina propria of the lower oesophageal sphincter (LOS)

4. GEJ tumor Siewert classification (Siewert 1996) Type I
1 to 5 cm proximal to GEJ
Type II
Between 1 cm proximal and cm distal to GEJ
Type III
2 to 5 cm distal to GEJ
center

5. GEJ tumor Siewert classification (Siewert 1996) Type I
Male predominance
Predominant intestinal-type pathology (similar to Esophageal adenocarcinoma)
Arisen from Barrett's intestinal metaplasia
Type II
Mixed etiology
Type III
Similar proportion of diffuse and intestinal histologic types as Gastric Cancer
Might be associated with Helicobacter pylori and atrophic gastritis

6. GEJ tumor Siewert classification- Lymph node metastases Type
Mullen JT, et al. What's the Best Way to Treat GE Junction Tumors? Approach Like Gastric Cancer. Ann Surg Oncol 2016; 23:3780.
GEJ tumor
Siewert classification- Lymph node metastases
Type
Percent of tumors with lymph node metastases
Location of nodal metastases I 65
Upper abdominal nodes (54%) Mediastinum (46%) II 70
Abdominal nodes (paracardial, lesser curvature, left gastric) (71%) Mediastinum (30%)
III 90
Abdominal nodes (91%) Mediastinum (9%)
Type 1: upper mediastinum

7. 8th edition AJCC/UICC staging 2017 cancers of the esophagus and esophagogastric junction
Upper edge of cancer in distal thoracic esophagus/EGJ/ within the proximal 5 cm of stomach that extend into EGJ
Esophageal cancer
Epicenter <2 cm into the proximal stomach
Epicenter >2 cm involvement into the proximal stomach
Stomach cancer
7th edition
epicenter is determined from upper and lower border measurements, which also provide cancer length
 epicenter is more than 2 cm distal from the EGJ = Stomach Cancer even if the EGJ is involved.
8th edition

8. 8th edition AJCC/UICC staging 2017 cancers of the esophagus and esophagogastric junction
Staging grouping by histopathology
Adenocarcinoma
Squamous cell carcinoma
Staging grouping by clinical status
before treatment decision (clinical)
after esophagectomy alone (pathologic)
after preresection therapy followed by esophagectomy (postneoadjuvant pathologic)
ideally, cancer stage grouping and survival should be connected.

9. 8th edition AJCC/UICC staging 2017 cancers of the esophagus and esophagogastric junction
SCC Adenocarcinoma
Survival of patients with early-stage and intermediate-stage disease was worse for those who had squamous cell carcinomas than
for those who had similarly staged adenocarcinomas

10. Liu et al. Changes of Esophagogastric Junctional Adenocarcinoma and
Gastroesophageal Reflux Disease Among Surgical Patients
During 1988–2012. Ann Surg 2016;263:88–95
latest trend
Worldwide: Increasing number of adenocarcinoma of esophagus and GEJ
China: Increasing proportion of GEJ tumor    
Retrospective cohort in China for 25 years (>5000 cases)  proportion of EGJA was increased from 22.3% in period 1

11. latest trend
China: Increasing proportion of Type I and III GEJ tumor   Positive correlation with increase in GERD for Type I tumor
The proportion of Siewert type III (35.9% vs 47.0%) (P<0.001) and type I (8.7% vs 15.8%)
(P?0.002) tumors of EGJA increased

12. workup OGD CT thorax + abdomen EUS +/- FNA PET/ PET-CT
Exploratory laparoscopy
EUS allows assessment of both perigastric and mediastinal lymph node
PET detect 15 to 20% of cases metastasis non visible on the Ct-

13. surgical approach (Type I)
Ann Surg 2017;266:232–236
surgical approach (Type I)
Transthoracic esophagectomy with partial gastrectomy & two- field lymphadenectomy 
Minimally invasive?
Two field = mediastinal, upper abdomen

14. surgical approach (Type I)
Ann Surg 2017;266:232–236
surgical approach (Type I)
Randomized Controlled Trial
115 patients with resectable intrathoracic esophageal carcinoma
54.7% (distal esophagaus/ Siewert Type I)
Randomized between open and minimally invasive esophagectomy
Overall 3-year survival 40.4% (open) VS 50.5% (minimally invasive)  (P=0.207)
Disease-free 3-year survival 35.9% (open) VS 40.2% (minimally invasive) [HR (0.389 to 1.239)]
Right thoracoscopy in the prone position with single-lumen tracheal intubation,
upper abdominal laparoscopy, and cervical incision  bronchus blocker was placed in the right bronchus to help with 1-lung ventilation during anastomosis

15. surgical approach (Type II and III)
Total gastrectomy + D2 lymphadenectomy +/- distal esophagectomy
At least 15 lymph node
R0 Resection
At least 5 cm proximal (esophageal) margin
> 4cm distal margin
D1: station 1-7
D2: station 1-12

16. surgical approach (Type II and III)
British Journal of Surgery 2013; 100: 1050–1054
surgical approach (Type II and III)
Proximal margin

17. surgical approach (Type II and III)
Retrospective cohort
140 patients with Siewert type II and III tumor (pT2–4 N0–3 M0)
Transhiatal gastrectomy + R0 resection
Multivariable analysis : Gross proximal margin of 20mm or less is an independent prognostic factor (hazard ratio (HR) 3.56)

18. surgical approach (Type II and III)
World J Gastroenterol 2017 April 21; 23(15):
surgical approach (Type II and III)
Lymph node dissection
single-center, retrospective, cohort

19. surgical approach (Type II and III)
 Index of estimated benefit from LN dissection (IEBLD):  frequency of metastasis to the station x 5year survival rate of patients with metastases to that station

20. lymph node dissection (Siewert Type II/III)
LN along the lesser curvature (3), the left gastric artery (7) ; right and left paracardial LN (2,1) should be dissected
Tumors affecting ≤ 3 cm of esophagus achieved no benefit from lower mediastinal LN dissection

21. surgical approach (Type II and III)
Y. Kurokawa. Ten-year follow-up results of a randomized clinical trial comparing left thoracoabdominal and abdominal transhiatal approaches to total gastrectomy for adenocarcinoma of the
oesophagogastric junction or gastric cardia. BJS 2015; 102: 341–348
surgical approach (Type II and III)
Trans-hiatal VS Thoracoabdominal
Randomized clinical trial (JCOG9502)
167 patients
10-year overall survival rate of TH VS LTA (left thoracoabdominal approach)
Hazard ratio for death 1.42 for the LTA technique
No significant survival benefit for LTA

22. surgical approach (Summary)
Type I
Transthoracic esophagectomy with partial gastrectomy & two-field lymphadenectomy  (Open/ minimal invasive)
Type II and III
Transhiatal total gastrectomy + D2 lymphadenectomy +/- distal esophagectomy
(2cm proximal margin)

23. Adjuvant therapy Indication: Previous trials focus on two subgroups:
margin-positive disease
node-positive disease
pT3 or above
Previous trials focus on two subgroups:
distal esophagus/EGJ
EGJ/ gastric
More favorable towards neo-adjuvant
lack of trials that focus on the EGJ

24. perioperative treatment
MAGIC trial (N Engl J Med 2006)
Patient with distal esophageal, EGJ, and gastric adenocarcinoma
Perioperative chemotherapy (ECF) decrease tumor size and stage and significantly improved progression-free and overall survival

25. neoadjuvant therapy CROSS trial (N Engl J Med 2012)
366 patients with potentially resectable esophageal or EGJ cancers (T1N1/ T2-3N0-1)
75% EGJ tumor
5 week Carboplatin + Paclitaxel + concurrent radiotherapy
Neoadjuvant chemoradiotherapy improved survival compared with surgery alone (Hazard ratio 0.65; 95% C.I to 0.87)
Significant benefit for SCC, marginal benefit for adenocarcinoma
Majority adenocarcinoma

26. neoadjuvant therapy Systemic review (Eur J Cancer 2013)
Eight RCTs (1049 patients with gastro/esophageal adenocarcinoma)
Preoperative chemotherapy associated with longer overall survival (hazard ratio [HR] 0.81; p<0.0001)
Appeared larger survival advantages in GEJ tumours, but subgroup differences not statistically significant

27. conclusion Increasing prevalence of GEJ tumor New staging system
Role of minimally invasive approach
Shorter proximal resection margin might be appropriate

28. Q&A

29. Thank you

30. Integrated genomic characterization of oesophageal carcinoma
Nature January 12;
pathogenesis
Barrett’s esophagus and Esophageal adenocarcinoma might originate from proximal gastric cells or embryonic remnant cell populations at the GEJ
molecular similarity between EACs and CIN gastric cancers

31. surgical approach (Summary)
Type I
8cm proximal margin
Type II
Proximal gastrectomy might be acceptable
(IEBLD for distal perigastric LN = 0)
Type III
Total gastectomy

32. neoadjuvant therapy POET trial (Journal of Clinical Oncology 2009)
First randomized study limited exclusively to EGJ tumor
Locally advanced tumor (T3-4 NXM0)
Arm A: Induction chemotherapy > Surgery
Arm B: Chemotherapy > Chemoradiotherapy > Surgery
Significant higher probability of showing pathologic complete response and tumor-free lymph nodes
Closed prematurely because of poor accrual