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Distrubution of Lymph Node Metastases in Esophageal Adenocarcinoma After Neoadjuvant Chemoradiation Therapy: A Prospective Cohort Study
Hannah T. Künzli*2,1, Anne-Sophie van Rijswijk3, Sybren L. Meijer4, Debby Geijsen5, Mark I. van Berge Henegouwen3, Suzanne S. Gisbertz3
1Gastroenterology and Hepatology, St. Antonius Hospital Nieuwegein, Amsterdam, Netherlands; 2Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands; 3Surgery, Academic Medical Center, Amsterdam, Netherlands; 4Pathology, Academic Medical Center, Amsterdam, Netherlands; 5Radiotherapy, Academic Medical Center Amsterdam, Amsterdam, Netherlands
Introduction: The distribution of lymph node metastases (LNM) in esophageal adenocarcinoma (EAC) is not well studied. Distribution of metastatic lymph nodes (LNs) may be influenced by tumor location, invasion depth and neoadjuvant chemoradiation therapy (CRT). For the extent of the radiation field, as well as the extent of the lymphadenectomy it is essential to elucidate the distribution pattern of LNM.
Aim: To evaluate the distribution pattern of LNM in patients with an esophageal adenocarcinoma after neoadjuvant CRT, and to evaluate the location of LNM in relation to the Clinical Target Volume (CTV) of the neoadjuvant radiation field.
Methods: Between April 1st, 2014 and August 8th 2015, all patients with an EAC undergoing minimally invasive esophagectomy in combination with a 2-field lymphadenectomy were included. Lymph node stations according to the 7th edition of the AJCC classification were excised and separately sent for histopathological examination. The relation between the location of LNM and the CTV was documented by a radiation oncologist dedicated in the field of gastrointestinal oncology, who was blinded for the location of LNM. Patients were excluded if they were diagnosed with an esophageal squamous cell or cardia carcinoma, when no neoadjuvant CRT was administered, or when a salvage or transhiatal resection was performed.
Results: 50 patients (41 male, median age 64 years) were included. A distal and mid EAC was diagnosed in 47 and 3 patients, respectively. A total of 1794 lymph nodes were resected, with a median of 36 (IQR 26-43) lymph nodes per patient. LNM were found in 30 patients (60%) with a median of 3 tumor-positive LNs per patient (range 1-54). Of the 30 patients with LNM, lymph node stations containing LNM were located in the CTV in 44/72 (58%) of cases. Of the total of 164 tumor-positive lymph nodes, 107 (65%) were located in the CTV.
LNM were observed most frequently in the lymph nodes around the left gastric artery (40%, 12/30 patients), celiac trunk lymph nodes (30%, 9/30), in the paraesophageal lymph nodes (27%, 8/30), in the left paracardial lymph nodes (27%, 8/30), and in the high paratracheal lymph nodes (23%, 7/30). Twelve out of 30 patients (40%) diagnosed with LNM, had tumor-positive lymph nodes both above and below the diaphragm.
Conclusion: Esophageal adenocarcinoma frequently metastasizes to both the mediastinal and abdominal lymph node stations. Left gastric artery and celiac trunk lymph nodes have the highest risk for LNM in patients with a distal EAC. Distant nodal metastasis to high paratracheal lymph nodes were also frequently observed in distal EAC, which confirms that LNM distribution pattern in EAC is unpredictable. After neoadjuvant CRT a high percentage of positive lymph nodes are found in and outside the radiation field.
Location lymph node metastases in patients with an EAC
| | N with LNM (%)
of total group of patients with LNM | Number of tumor-positive LNs
median, IQR | LN station located in CTV
N (%) | ypN1 | ypN2 | ypN3 | | Thoracic LN stations | | High paratracheal, right side (2R) | 7 (23) | 1 (1-1) | 2/7 (29) | 2 | 1 | 4 | | Paratracheal, right side (4R) | 2 (7) | 1 (0-x) | 0/2 (0) | 1 | 0 | 1 | | Paratracheal, left side (4L) | 2 (7) | 3 (1-x) | 0/2 (0) | 1 | 0 | 1 | | Aortopulmonary window (5) | 1 (3) | 1 | 0/2 (0) | 0 | 0 | 1 | | Subcarinal (7) | 4 (13) | 1 (1-1) | 2/4 (50) | 0 | 0 | 4 | | Paraesophageal (8) | 8 (27) | 2 (1-2) | 8/8 (100) | 0 | 4 | 4 | | Pulmonary ligament, right side (9R) | 3 (10) | 2 (1-x) | 3/3 (100) | 0 | 0 | 3 | | Pulmonary ligament, left side (9L) | 3 (10) | 2 (1-x) | 2/3 (67) | 0 | 0 | 3 | | Abdominal LN stations | | Paracardial, right side | 7 (23) | 1 (1-3) | 6/7 (86) | 1 | 2 | 4 | | Paracardial, left side | 8 (27) | 2 (1-2) | 7/8 (88) | 2 | 2 | 4 | | Celiac trunk | 9 (30) | 2 (1-3) | 6/9 (67) | 0 | 2 | 7 | | Left gastric artery | 12 (40) | 2 (1-3) | 10/12 (83) | 1 | 5 | 6 | | Splenic artery | 6 (20) | 1 (1-2) | 0/5 (0) | 0 | 4 | 2 | | Common hepatic artery | 3 (10) | 1 (1-x) | 1/3 (33) | 1 | 1 | 1 | | Hepatoduodenal ligament | 0 (0) | N/A | N/A | N/A | N/A | N/A |
Legend: LNM = lymph node metastases LN = lymph node IQR = interquartile range CTV = clinical target volume of radiation field 
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