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Extent of Lymphadenectomy for Esophageal Cancer

Introduction

  • Controversial extent of lymphadenectomy in esophagectomy for cancer.
  • Aggressive nature of esophageal cancer often leads to both local nodal and distant metastases at presentation.
  • Neoadjuvant treatments frequently used for locally advanced disease.
  • Debate centers on whether radical lymphadenectomy provides:
    • Improved locoregional control.
    • Enhanced survival rates.
  • Extended lymphadenectomy offers better staging, aiding in:
    • Patient counseling.
    • Influencing use of adjuvant treatments.

Lymphatic Drainage of the Esophagus and Patterns of Spread

  • Lymphatic drainage knowledge is crucial for rational lymphadenectomy.
  • The esophagus traverses three body compartments; lymph flow has a wide pattern of spread.
  • Embryologic origin leads to bilateral lymphatic drainage:
    • From branchial arches and pharyngeal pouches (above).
    • From splanchnic mesoderm (below).
    • Demarcation at tracheal bifurcation.

Early Esophageal Cancer

  • Lymph node spread follows anatomical pathways.
  • Tumor location determines likely nodes involved:
    • Above tracheal bifurcation: upper mediastinum and neck nodes.
    • Below tracheal bifurcation: nodes toward the celiac axis.
    • At tracheal bifurcation: may metastasize in either direction.
  • Skipping of lymph node stations is rare.

Advanced Esophageal Cancer

  • Submucosal lymphatic network allows longitudinal spread.
  • Important in advanced tumors with blocked primary pathways.
  • T3 disease associated with up to 85% chance of lymph node involvement.

Here is the table for "Numbers and Naming of Regional Lymph Nodes" from the Japanese Classification of Esophageal Cancer, 12th Edition: Part I:

No. Lymph Node Name Description
Cervical Lymph Nodes
No.100 Superficial lymph nodes of the neck
No.100spf Superficial cervical lymph nodes
No.100sm Submandibular lymph nodes
No.100tr Cervical pretracheal lymph nodes
No.100ac Accessory nerve lymph nodes
No.101 Cervical paraesophageal lymph nodes
No.102 Deep cervical lymph nodes
No.102up Upper deep cervical lymph nodes
No.102mid Middle deep cervical lymph nodes
No.103 Peripharyngeal lymph nodes
No.104 Supraclavicular lymph nodes
Thoracic Lymph Nodes
No.105 Upper thoracic paraesophageal lymph nodes
No.106 Thoracic paratracheal lymph nodes
No.106rec Recurrent nerve lymph nodes
No.106recL Left recurrent nerve lymph nodes
No.106recR Right recurrent nerve lymph nodes
No.106pre Pretracheal lymph nodes
No.106tb Tracheobronchial lymph nodes
No.106tbL Left tracheobronchial lymph nodes
No.106tbR Right tracheobronchial lymph nodes
No.107 Subcarinal lymph nodes
No.108 Middle thoracic paraesophageal lymph nodes
No.109 Main bronchus lymph nodes
No.109L Left main bronchus lymph nodes
No.109R Right main bronchus lymph nodes
No.110 Lower thoracic paraesophageal lymph nodes
No.111 Supradiaphragmatic lymph nodes
No.112 Posterior mediastinal lymph nodes
No.112aoA Anterior thoracic paraaortic lymph nodes
No.112aoP Posterior thoracic paraaortic lymph nodes
No.112pul Pulmonary ligament lymph nodes
No.113 Ligamentum arteriosum lymph nodes (Botallo lymph nodes)
No.114 Anterior mediastinal lymph nodes
Abdominal Lymph Nodes
No.1 Right paracardial lymph nodes
No.2 Left paracardial lymph nodes
No.3a Lesser curvature lymph nodes (left gastric artery) Along the branches of the left gastric artery
No.3b Lesser curvature lymph nodes (right gastric artery) Along the 2nd branches and distal part of the right gastric artery
No.4 Lymph nodes along the greater curvature
No.4sa Lymph nodes along the short gastric vessels
No.4sb Lymph nodes along the left gastroepiploic artery
No.4d Lymph nodes along the right gastroepiploic artery
No.5 Suprapyloric lymph nodes
No.6 Infrapyloric lymph nodes
No.7 Lymph nodes along the left gastric artery
No.8a Lymph nodes along the common hepatic artery (Anterosuperior group)
No.8p Lymph nodes along the common hepatic artery (Posterior group)
No.9 Lymph nodes along the celiac artery
No.10 Lymph nodes at the splenic hilum
No.11 Lymph nodes along the splenic artery
No.11p Lymph nodes along the proximal splenic artery
No.11d Lymph nodes along the distal splenic artery
No.12 Lymph nodes in the hepatoduodenal ligament
No.13 Lymph nodes on the posterior surface of the pancreatic head
No.14 Lymph nodes along the superior mesenteric vessels
No.14A Lymph nodes along the superior mesenteric artery
No.14V Lymph nodes along the superior mesenteric vein
No.15 Lymph nodes along the middle colic artery
No.16 Lymph nodes around the abdominal aorta
No.16a1 Lymph nodes in the aortic hiatus
No.16a2 Lymph nodes around the abdominal aorta (upper margin of celiac trunk to lower margin of the left renal vein)
No.16b1 Lymph nodes around the abdominal aorta (lower margin of the left renal vein to upper margin of inferior mesenteric artery)
No.16b2 Lymph nodes around the abdominal aorta (upper margin of inferior mesenteric artery to aortic bifurcation)
No.17 Lymph nodes on the anterior surface of the pancreatic head
No.18 Lymph nodes along the inferior margin of the pancreas
No.19 Infradiaphragmatic lymph nodes
No.20 Lymph nodes in the esophageal hiatus of the diaphragm

This table categorizes lymph nodes by region (Cervical, Thoracic, Abdominal) and provides a comprehensive breakdown based on the Japanese Classification of Esophageal Cancer, 12th Edition: Part I.

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Lymph Node Tiers

  • Lymph node dissection divided into three fields:

    1. Upper abdomen
    2. Mediastinum
    3. Neck

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Variations in Two-Field Lymphadenectomy

  • Squamous Cell Carcinoma (SCC) Regions (e.g., Japan):
    • Two-field includes upper abdomen and both inferior and superior mediastinum, along both recurrent laryngeal nerves.
  • Adenocarcinoma Regions:
    • Two-field includes upper abdomen and inferior mediastinum (up to the carina).

Nodes Resected in Each Field

1. Abdominal Lymph Node Dissection (First Field)

  • Superior gastric nodes:
    • Paracardial nodes (left and right).
    • Lesser curvature nodes.
    • Nodes along the left gastric artery.
  • Celiac trunk nodes:
    • Nodes around the celiac axis at the root of:
      • Left gastric artery.
      • Common hepatic artery.
      • Splenic artery.
  • Common hepatic nodes.

Importance:

  • Commonly involved in lower esophageal tumors.
  • Intramural spread distally is greater with adenocarcinoma (54%) than SCC (10%).

2. Thoracic Lymph Node Dissection (Second Field)

  • Includes:
    • Mediastinal nodes.
    • Thoracic duct.
    • Nodes at both pulmonary hila.
    • Paraesophageal nodes.
    • Nodes at the carina and bronchi.
    • Paratracheal nodes.
  • Extended mediastinal dissection:
    • Nodes on the right side of the trachea.
    • Nodes along the left recurrent laryngeal nerve.
    • Subaortic nodes.

3. Cervical Node Dissection (Third Field)

  • Includes:
    • Brachiocephalic nodes.
    • Deep internal and external cervical nodes.
    • Nodes along the left and right recurrent laryngeal nerves.

Importance:

  • More common involvement in SCC.
  • Deep internal and external nodes are more commonly involved than deep lateral nodes.

Nodes According to Anatomic Region

Cervical Lymph Nodes

  • Deep lateral nodes
  • Deep external nodes
  • Deep internal nodes

Superior Mediastinal Lymph Nodes

  • Recurrent nerve lymphatic chain
  • Paratracheal nodes
  • Brachiocephalic artery nodes
  • Infraaortic-arch nodes

Middle Mediastinal Lymph Nodes

  • Tracheal bifurcation nodes
  • Pulmonary hilar nodes
  • Paraesophageal nodes

Lower Mediastinal Lymph Nodes

  • Paraesophageal nodes
  • Diaphragmatic nodes

Superior Gastric Lymph Nodes

  • Paracardial nodes
  • Lesser curvature nodes
  • Left gastric artery nodes

Celiac Trunk Nodes

  • Common hepatic nodes

Squamous Cell Carcinomas vs. Adenocarcinomas

Squamous Cell Carcinoma (SCC)

  • Commonly in middle and proximal esophagus.
  • Nodal involvement:
    • Rare when confined to mucosa (0–7%).
    • Increases with deeper invasion:
      • Up to 50% in submucosal invasion.
      • Over 73% in transmural tumors.
  • High rate of cervical node involvement, especially with proximal tumors.

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Adenocarcinoma

  • Commonly in lower esophagus and esophagogastric junction.
  • Nodal involvement:
    • Similar low incidence (0–7%) when confined to mucosa.
    • Increases to 15–50% with submucosal invasion.
    • Up to 80% with invasion through the muscularis propria.
  • Greater intramural distal spread, leading to more abdominal node involvement.

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Differences in Recurrence Patterns

  • SCC:
    • Higher rates of extrathoracic recurrences.
    • Common recurrence in cervical and abdominal lymph nodes.
  • Adenocarcinoma:
    • Lower incidence of local recurrence but still significant (9–15%).

Implications of Lymphadenectomy

Arguments for Extensive Lymphadenectomy

  • Improved locoregional control.
  • Provides more accurate staging.

Studies and Findings

  • Lymph Node Yield and Survival:
    • Some studies find no survival benefit with higher lymph node yield.
    • Lymph node ratio (positive nodes/total nodes) is a strong prognostic factor.
      • Higher ratio linked to increased mortality.
      • Adequate sampling is essential.

Micrometastases

  • Present in up to 50% of node-negative patients.
  • Impact on prognosis is inconclusive.

Tailoring Lymphadenectomy

  • Ideally based on disease stage and risk factors.
  • Staging accuracy limitations hinder precise tailoring.
  • Sentinel node techniques are unreliable due to skip metastases.

Neoadjuvant Treatments

  • May sterilize residual disease.
  • Impact on the necessity of extensive lymphadenectomy remains uncertain.

Three-Field Lymphadenectomy

Usage and Rationale

  • Common in Japan due to high prevalence of SCC.
  • Addresses significant cervical lymph node involvement.

Outcomes

  • Some studies show improved survival with three-field dissection in SCC.
  • Adenocarcinoma patients show limited benefit; routine cervical dissection may not be justified.

Considerations

  • Individualized approach based on:
    • Extent of disease.
    • Likelihood of recurrence.
    • Patient fitness.
  • Multidisciplinary discussion is essential for decision-making.

Morbidity of Lymphadenectomy

Potential Complications

  • Respiratory problems (pneumonia, ARDS).
  • Recurrent laryngeal nerve injury.
  • Thoracic duct injury leading to chyle leak.

Contributing Factors

  • One-lung ventilation may increase pulmonary edema.
  • Impaired lymphatic flow due to mediastinal dissection.

Studies and Observations

  • Some studies report no significant increase in morbidity with extensive lymphadenectomy.
  • Quality of life not adversely affected by the number of nodes removed.

Summary

  • TNM Staging System (7th and 8th editions) evaluates N category by the number of positive nodes.
  • Inadequate lymph node yield can lead to understaging and affect prognosis.
  • Debate continues on the extent of lymphadenectomy:
    • Advocates argue for better locoregional control and staging.
    • Critics highlight lack of survival benefit evidence and potential morbidity.
  • Neoadjuvant therapy may reduce the need for extensive lymphadenectomy but is unpredictable.
  • Current Recommendations:
    • En bloc lymphadenectomy is recommended to remove potential positive nodes.
    • An individualized approach is crucial, considering patient-specific factors and multidisciplinary input.

3. Description of Lymph Nodes

3.1 Name, Number, and Extent of Lymph Node Stations in Esophageal Cancer

  • Classification of Lymph Nodes
    • Names and Numbers: Defined in Table 5 and Figure 23.
    • Abdominal Lymph Nodes: Follow the Japanese Classification of Gastric Carcinoma.
  • Recording Lymph Node Stations
    • Use "No." plus the lymph node number (e.g., No.106recR).
  • Imaging Criteria for Lymph Node Metastasis
    • CT Diagnosis
      • Slice size should be ≀2.5 mm on contrast-enhanced CT.
      • Short Diameter Criterion: 6 mm is recommended as the cutoff.
      • Limitation: About 1/3 of metastatic lymph nodes have a short diameter of <5 mm.
    • PET/CT Diagnosis
      • Superior to CT in positive predictive value.
      • Diagnostic Criteria Not Standardized: Affected by factors like blood sugar level, machine type, and protocol.
      • False Positives: Mediastinal lymph nodes may accumulate FDG due to inflammation or sarcoidosis.
  • Recording Metastatic and Resected Nodes
    • Record as No.[Number] (Metastatic Nodes/Resected Nodes) (e.g., No.104R (0/10)).
  • Extralymph Node Metastasis
    • Definition: Cancer nests without lymphatic tissue in fat tissue outside the esophagus or stomach.
    • Recording: Note the number and station as extralymph node metastasis.
  • Extranodal Involvement
    • Includes direct or vascular invasion.
    • Should be recorded separately.

3.2 Regional Lymph Nodes

  • Definition Based on Tumor Location
    • Ce: Cervical esophagus
    • Te: Thoracic esophagus
    • Jz: Esophagogastric junction
    • Refer to Table 6 and Figures 24-26 for detailed mapping.
  • Special Cases
    • Multiple Esophageal Cancers: Determine regional lymph nodes based on the deepest tumor invasion or main tumor location.
  • Classification Changes
    • The 12th edition shifts N classification to the number of metastatic lymph nodes per UICC TNM classification.
    • Aims to reflect survival benefits from lymph node dissection.
  • Concept of Regional Lymph Nodes
    • M1a Lymph Nodes:
      • No.104 in thoracic esophageal cancer.
      • No.101, 104, and 16 in Jz cancer.
      • Recognized as M1a due to potential dissection benefits.
    • M1b Lymph Nodes:
      • Other extra-regional lymph nodes not included in regional count.
    • Excluded Nodes:
      • No.102, 106pre, 106tbR, and 112aoP in thoracic esophageal cancer are classified as M1b.

3.3 Grading of Lymph Node Metastasis (N)

  • N Classification
    • NX: Regional lymph node metastasis cannot be assessed.
    • N0: No regional lymph node metastasis.
    • N1: Metastasis to 1-2 regional lymph nodes.
    • N2: Metastasis to 3-6 regional lymph nodes.
    • N3: Metastasis to 7 or more regional lymph nodes.
  • Preferred Lymphadenectomy
    • Cervical and Thoracic Esophageal Cancer: D2 or more lymphadenectomy.
    • Esophagogastric Junction Cancer: D1 + α or more lymphadenectomy.

4. Distant Organ and Lymph Node Metastasis (M)

  • M Classification
    • MX: Distant organ or extra-regional lymph node metastasis cannot be assessed.
    • M0: No distant organ or extra-regional lymph node metastasis.
    • M1a: Metastasis to lymph nodes outside the region with potential dissection efficacy.
    • M1b: Metastasis to lymph nodes not regional nor M1a, or distant organ metastasis.
  • Assessment of Distant Metastasis
    • Consider operative findings, intraoperative imaging, pathological diagnosis, and final findings.
    • Record whether metastases are resected.
  • Recording Sites of Metastasis
    • LYM: Lymph node
    • SKI: Skin
    • HEP: Liver
    • PUL: Lung
    • MAR: Bone marrow
    • OSS: Bone
    • PER: Peritoneum
    • PLE: Pleura
    • BRA: Brain
    • MEN: Meninx
    • ADR: Adrenal
    • OTH: Others
  • Intramural Metastasis
    • Metastasis to the stomach wall is considered distant metastasis and recorded as M1b (IM1-St).

5.3 Degree of Lymph Node Dissection and Residual Tumor

5.3.1 Lymph Node Dissection

  • Two-Field Dissection
    • Regions: Thoracic and abdominal lymph nodes.
    • Mandatory Nodes: No.101, 105, 106rec, 106tbl, 107, 108, 109, 110, 111, 112aoA, 112pul, 1, 2, 3, 7, 8a, 9, 11p.
    • Optional: Dissection of No.106tbl, 111, 8a, and 11p may be omitted.
  • Three-Field Dissection
    • Regions: Cervical, thoracic, and abdominal lymph nodes.
    • Equivalent to: Two-field dissection plus cervical lymph node dissection.
    • Cervical Lymph Node Dissection:
      • Bilateral resection of No.101, 102, and 104.
      • Note: Dissection of No.102 can be omitted.
      • No.101 can be resected from the thorax.

5.3.3 Definition of Extent of Lymph Node Dissection (D)

  • Cervical Esophageal Cancer (Ce)
    • DX: Extent cannot be assessed.
    • D1: Less than D2 dissection performed.
    • D2:
      • Dissection of No.100, 101, 102 mid, 104, 105, 106rec.
      • Note:
        • Nodes 105, 106recR, 106recL acceptable if resected from the neck.
        • Dissection without No.102 still considered D2.
    • D3: Not applicable.
  • Thoracic Esophageal Cancer (Te)
    • DX: Extent cannot be assessed.
    • D1: Incomplete two-field dissection.
    • D2: Complete two-field dissection.
    • D3: Complete three-field dissection.
  • Esophagogastric Junctional Cancer (Jz)
    • D1:
      • Dissection of No.1, 2, 3a, and 7.
      • Nodes with β‰₯20% incidence of metastasis.
    • D1+:
      • Dissection of No.1, 2, 3a, 7, 8a, 9, and 11p.
      • Nodes with β‰₯10% incidence of metastasis.
    • D2:
      • Dissection of No.1, 2, 3a, 7, 8a, 9, 11p, 19, 20, and 110.
      • Recommended for esophageal invasion length of 2.1–4.0 cm.
    • D3:
      • Dissection of No.1, 2, 3a, 7, 8a, 9, 11p, 19, 20, 105, 106recL, 106recR, 107, 108, 109L, 109R, 110, 111, 112aoA, 112pul.
      • Recommended for esophageal invasion length >4.0 cm.
    • Additional Notes:
      • Total Gastrectomy: Include No.3b, 4sa, 4sb, 4d, 5, and 6.
      • Classification D is based on surgical procedure.
      • Nodes 4sa and 4sb are excluded due to low metastasis frequency.

5.3.4 Residual Tumor After Endoscopic and Surgical Resection (R)

  • R Classification
    • RX: Presence of residual tumor cannot be assessed.
    • R0: No residual tumor.
    • R1: Microscopic residual tumor at resection margin or radial margin.
      • Includes cases suspected of microscopic residuals based on frozen sections or cytology.
    • R2: Macroscopic residual tumor.
  • Evaluation Notes
    • Residual Tumor Assessment:
      • Evaluate for both primary tumor and metastatic lesions.
    • Multiple Lesions:
      • Determine R classifications separately for each lesion.
    • Piecemeal Resection:
      • R0 confirmed only when restructuring is possible and non-cancerous tissue is at resection margins.
      • RX assigned if restructuring is impossible or margins cannot be assessed.
  • Criteria for RX Classification
    • Non-assessable Margins:
      • Due to crushed or burned tissue effects.
    • Impossible Restructuring:
      • From piecemeal resection.
    • Suspected Residual Tumor:
      • Non-continuous tumor extension in the basal layer.
      • Possible residuals in vertical margin due to intraductal spread.
    • Other Reasons:
      • Any factors preventing determination of residual tumor.

Key Points to Remember

  • Standardized Recording: Always use the designated numbering system (e.g., No.106recR) for clarity.
  • Imaging Limitations: Be cautious with CT and PET/CT diagnostics due to size limitations and potential false positives.
  • Classification Updates: The shift to number-based N classification aligns with UICC standards and focuses on survival benefits.
  • Dissection Guidelines: The extent of lymph node dissection varies with cancer location and invasion length.
  • Residual Tumor Assessment: Accurate classification is essential for treatment planning and prognosis.

Notes on Preferred Practices

  • Lymphadenectomy Recommendations:
    • D2 or more for cervical and thoracic esophageal cancer.
    • D1 + α or more for esophagogastric junction cancer.
  • Dissection Benefit:
    • M1a nodes, though extra-regional, may provide survival benefits when dissected.
  • Recording Metastasis:
    • Detailed recording helps in staging and treatment decisions.

By focusing on these core concepts and guidelines, healthcare professionals can ensure accurate diagnosis, effective treatment planning, and improved patient outcomes in esophageal cancer management.