Adenocarcinoma of Gastroesophageal Junction Joint Hospital Surgical Grand Round 8th November, 2014 Prepared by Dr. Rain So Kwong Wah Hospital

Outline of Presentation Definitions Classification of adenocarcinoma of OGJ Surgical approach Neoadjuvant therapy in locally advanced disease

Definitions Gastric cardia OGJ The squamocolumnar junction (Z-line) Zone of the stomach adjacent to the orifice of the tubular esophagus OGJ Endoscopically: The proximal margin of longitudinal gastric mucosal folds Anatomically: At the level of the angle of His The squamocolumnar junction (Z-line) The visible line formed by the juxtaposition of squamous and columnar epithelia, 3-10mm proximal to OGJ

Classification of OGJ tumour Described by Dr. Siewert OGJ tumor: All tumours that have their center within 5 cm proximal or distal to the anatomical OGJ. The classification was approved at the consensus meetings of the 7th International Society of Diseases of the Esophagus in 1995 and the 2nd International Gastric Cancer Congress in Munich 1997

Classification 1cm to 5cm above OGJ 1cm above to 2 cm below OGJ 2cm to 5cm below OGJ

Lymphatic spread Later in type I than type II/III Chronic inflammatory process leads to a degeneration of lymphatic vessel Lymph node involvement Type I: Upper mediastinum, the tracheal bifurcation and above. Type II/III: lower mediastinum, celiac trunk. P.M. Schneider (ed.), Adenocarcinoma of the Esophagogastric Junction, Recent Results in Cancer Research 182, DOI: 10.1007/978-3-540-70579-6_2, © Springer-Verlag Berlin Heidelberg 2010

Surgical treatment Primary Aim: R0 resection Adequate lymphadenectomy Complete resection of primary tumour Type I: Intramural spread, multiple satellite tumours Reported incidence of residual tumour at the resection margin: 5-35%* Adequate lymphadenectomy Stipa S, Di Giorgio A, Ferri M. Surgical treatment of adenocarcinoma of the cardia.Surgery 1992; 111:386–93. Bozzetti F, Bignami P, Bertario L, Fissi S, Eboli M. Surgical treatment of gastric cancer invading the oesophagus. Eur J Surg Oncol 2000;26: 810–4.

Topic to be discussed Optimal proximal resection and surgical approach in esophagectomy for type I Surgical approach for Type II/III Optimal lymph node dissection in type II/III

Extent of oesophageal resection No infiltration was observed in patients whose proximal margin exceeded 7 cm. Median survival rate in PPRM 11.1 months Vs NPRM 36.3 months (p<0.02) No difference in postoperative mortality and morbidity rates, in anastomotic leakage or recurrence rates. Conclusion: 8cm proximal margin is considered to be adequate. C. Mariette, et al (2003), Extent of oesophageal resection for adenocarcinoma of the oesophagogastric junction, EJSO 2003; 29: 588–593

Type I Phase III trial in Netherlands (Dutch trial) Right thoracic approach Vs Transhiatal esophagectomy in type I More pulmonary complications and chylous leakage (57% vs 27%, P<0.001; 10% vs 2%, p=0.002) Longer ICU/Hospital stay (6 vs 2 days, p<0.01 and 19 vs 15 days, p<0.001) 14% survival benefit in RTA group in Type I patients (51% Vs 37%, p=0.33) 5 years locoreginal disease-free survival was better in RTA group (1-8 + nodal mets) (64% Vs 23%, p=0.02) THE -During THE, the esophagus was dissected under direct vision through the widened hiatus of the diaphragm, at least up to the inferior pulmonary vein. The tumor and its adjacent lymph nodes were dissected en bloc. -A 3-cm-wide gastric tube was constructed. The left gastric artery was transected at its origin, with resection of local lymph nodes. Celiac lymph nodes were dissected only when there was clinical suspicion of involvement. -After right-sided mobilization of the cervical esophagus, the intrathoracic, normal esophagus was bluntly resected from the neck to the abdomen with use of a vein stripper. -Esophagogastrostomy was performed in the neck, without cervical/upper/middle lymphadenectomy.   TTE -Posterolateral thoracotomy was the first step in transthoracic resection with extended en bloc lymphadenectomy. The thoracic duct, azygos vein, ipsilateral pleura, and all periesophageal tissue in the posterior mediastinum were dissected en bloc. The specimen included the lower and middle mediastinal, subcarinal, and right-sided paratracheal lymph nodes (dissected en bloc). The aortapulmonary-window nodes were dissected separately. -Through a midline laparotomy, the paracardial, lesser curvature, left-gastric-artery (along with lesser curvature), celiac trunk, common-hepatic-artery, and splenic-artery nodes were dissected, and a gastric tube was constructed. The cervical phase of the transthoracic procedure was identical to the transhiatal procedure, but a left-sided approach was used. C. Mariette, et al (2003), Extent of oesophageal resection for adenocarcinoma of the oesophagogastric junction, EJSO 2003; 29: 588–593

Type II/III Phase III trial in Japan (JCOG 9502) Type II/III tumour Left thoracoabdominal Vs transhiatal extended total gastrectomy Total gastrectomy with D2 Lymphadenectomy (including splenectomy) + para-aortic node dissection (lateral to aorta and above the left renal vein) TH: periesophageal lymph node dissection LTA: mediastinal nodal dissection Sasako M, et al; Japan Clinical Oncology Group (JCOG9502) (2006) Left thoracoabdominal approach versus abdominal-transhiatal approach for gastric cancer of the cardia or subcardia: a randomised controlled trial. Lancet Oncol 7:644–651

Type II/III Transhiatal extended total gastrectomy was superior to thoracoabdominal approach in treating type II/III tumour. Sasako M, et al; Japan Clinical Oncology Group (JCOG9502) (2006) Left thoracoabdominal approach versus abdominal-transhiatal approach for gastric cancer of the cardia or subcardia: a randomised controlled trial. Lancet Oncol 7:644–651

Summary of two major trials Conclusions: Type I tumour: Transthoracic en bloc esophagectomy including mediastinal lymphadenectomy. Type II/III: Transhiatal extended total gastrectomy.

Type II/III Difference in lymph node dissection? IEBLD=index of estimated benefit of LN dissection Frequency (+LNmet) x 5-year survival rate of pts with +LNs Type II: IEBLD =0 in distal perigastric LNs Proximal gastrectomy can be a feasible option for type II tumour Type III: IEBLD =2.6-3.8 in 4b, 4d, 5 Total gastrectomy H Goto et al, The optimal extent of lymph node dissection for adenocarcinoma of the oesophagogastric junction differs between siewert tyoe II and siewert type III patient, Gastric cancer, DOI 10.1007/S10120-014-0364-0

Locally advanced tumour T3/4, node-positive disease Failure of surgery to obtain locoregional control and early systemic dissemination of disease 5-year survival after potentially curative resection is only up to 20% How about neoadjuvant therapy? Hulscher JBF, van Sandick JW, de Boer AGEM, et al.: Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 2002, 347:1662–1669. Kelsen DP, Ginsberg R, Pajak TF, et al.: Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 1998, 339:1979–1984.

Neoadjuvent therapy Review on phase III clinical trials (1991-2011) Conclusion: neoadjuvant chemotherapy or CRT improves survival Branislav et al.: Optimal therapeutic strategies for resectable oesophageal or oesophagogastric junction cancer. Drugs 2011:71 (5): 541-555

Summary Siewert classification of OGJ tumour bears a good correlation with lymphatic spread. Type I: Transthoracic en bloc esophagectomy including mediastinal lymphadenectomy. Type II/III: Transhiatal extended total gastrectomy. Proximal gastrectomy can be a feasible option for Type II. Results of neoadjuvant therapy in managing locally advanced cancer is promising and shown to improve survival.

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