Lymphatic Drainage Regional lymphatics (N1) Submocosal plexus Regional (N1) & non-regional lymph nodes (M1a & M1b) Thoracic duct & the systemic venous circulation (M1b) Abundant lymph-capillary network in the submucosal longitudinal lymphatic drainage (vs. segmental in colon ca.) Rice TW, Lancet, 1999, Hosch SB, JCO, 2001, Lerut, Ann Surg, 2004 Lymph-capillary network in submucosal space ☞ Widespread and random patterns of lymph node metastasis Ando N, Ann Surg, 2000 Skip metastasis: 50~60% MatsubaraT, Cancer, 2000
Lymph Node Mapping System
NRegional Lymph Nodes NXRegional lymph nodes cannot be assessed. NONo regional lymph node metastases N1Regional lymph node metastases MDistant Metastasis MXDistant metastases cannot be assessed. M1a:Upper thoracic esophagus metastatic to cervical lymph nodes Lower thoracic esophagus metastatic to celiac lymph nodes M1bUpper thoracic esophagus metastatic to other nonregional lymph nodes or other distant sites Midthoracic esophagus metastatic to either nonregional lymph nodes or other distant sites Lower thoracic esophagus metastatic to other nonregional lymph nodes or other distant sites
Patterns of Metastatic Nodal Spread
Association with tumor location-1 Akiyama H, Ann Surg 1994.Altorki N, Ann Surg 2002 Patterns of Metastatic Nodal Spread ☞ 3-field LN dissection
Association with tumor location-2 Kato H, J Surg Oncol 1991Sharma S, Surg Today 1994 Patterns of Metastatic Nodal Spread ☞ 2-field LN dissection Nodal metastasis is a rare finding three levels away from the location of the tumor. It is most common in the same level as the tumor and one level adjacent to the tumor. The involvement of lymph nodes that are two levels away from the location of the tumor is also very common but to a lesser extent. Patients with carcinoma in the upper thoracic esophagus rarely had metastasis in the abdominal nodes, while those with carcinoma in the lower thoracic esophagus rarely had metastasis in the cervical nodes.
Association with depth of tumor invasion-1 Rice TW, Ann Thorac Surg 1998 Patterns of Metastatic Nodal Spread
Association with depth of tumor invasion-2 Matsubara T, Br J Surg 1999 Patterns of Metastatic Nodal Spread ☞ T stage ↑→ LN Metastasis ↑
Association with tumor cell type Sheids 6 th edition Patterns of Metastatic Nodal Spread ☞ No difference
Axial margin Siu KF, Ann Surg 1986 Law S, Am J Surg 1998 Extent of Resection Taking account shrinkage of the specimen after resection as a guide to surgery, an in-situ margin of 10cm (fresh contracted specimen of ~5cm) should be aimed to, allow a less than 5% chance of anastomotic recurrence.
Lymphadenectomy Pearson, 3 rd edition Extent of Resection Standard 2-field Extended 2-field Total 2-field Mediastinal lymph node dissection Abdominal lymph node dissection Cervical lymph node dissection or
Cervical Esophagus Distant metastasis: 20% Regional metastasis: 63% Median survival: 11~14months 5-year survival: 14~21% 5-year survival was significantly low when regional neck LN involved (8% vs. 38%) However, regional LN involvement was not prognostic parameter in multivariate analysis Marmuse JP, Am J Surg, 1995 Triboulet JP, Arch Surg, 2001
Upper Thoracic Esophagus In resectable T3 squamous cell carcinoma, Manshanden CG Eur J Surg Oncol 2000 Igaki H, Br J Surg 2005 ☞ Although cervical lymph node dissection is important for staging, curative surgery for cervical-upper esophageal cancer combined with extended lymph node dissection is probably only indicated in selected cases without distant lymph node metastasis. Bresadola F, ORL J Otorhinolaryngol Relat Spec 2001 o o No difference Limited resection Extended LN dissection 3-year survival 14%20%
Middle & Lower Thoracic Esophagus In Japan, 70% of the esophageal carcinoma occurs in the middle thoracic esophagus. Ando N, Ann Surg 2000 Tachibana M, Am J Surg 2005 Nine of 141 patients with middle esophageal cancer had cervico-thoracic nodal involvement. → 3-field LN dissection proved to be important for correct staging. In lower thoracic esophageal carcinoma, no patient had cervico-upper thoracic LN involvement. → Patients with negative upper thoracic LN not necessarily have to undergo a 3-field LN dissection. Involved celiac nodes were found in tumors at all three locations. → For esophageal tumors investigation of celiac LN is worthwhile.
Cervical LN Metastasis in Esophageal Cancer 1.14~30% patients: metastasis to cervical lymph nodes 40% for upper third tumors 20% for lower third tumors 2.Frequency of nodal metastasis: increased with depth of tumor penetration Intramucosa < submucosa < muscularis propria < adventitia 30% < 50% < 60% < 80% 3.LNs in both recurrent laryngeal nerves frequently have metastasis. Isono K, 1991, Oncology ☞ Extended radical esophagectomy with 3-field LN dissection ☞ Improving accuracy of staging & better local control
5 –Year Survival in 2- vs. 3-Field LN Dissection Akiyama H, Am J Surg Field3-Fieldp - Node55%84% Node28%43%0.008
Skeptical Views to 3-Field LN Dissection-1 1.Systemic disease Replaced by neoadjuvant chemotherapy or intraoperative radiotherapy 2.Hospital mortality: 4% Increased morbidity: 44.8% Recurrent laryngeal nerve palsy: 16~58% Pulmonary complication: 21.3% Anastomotic leak: 19~30% Septic complication: 27% Decreased QOL Severe hoarseness, restricted food intake, reduced exercise tolerance: 20%
Skeptical Views to 3-Field LN Dissection-2 3.No prognostic benefit Recurrence rate in cervical LN: 11% Isolated cervical nodal recurrence: 4% vs. Mediastinum(21%), systemic organ metastasis(26%) ☞ Minimal role of cervical LN dissection 4.Prospective Randomized study 2-Field3-Fieldp Nishihira T, Am J Surg, %65%NS National cancer hospital in Tokyo 33%48%0.3
LN Dissection along Recurrent Laryngeal Nerve Recurrent laryngeal LN + cervical LN → Cervicothoracic group
Selective 3-Field LN Dissection
Sentinel Lymph Node The first lymph node within the lymphatic basin reached by lymph draining from the primary lesion
Limited Reports Complicated compared to gastric cancer Limited No. of early esophageal cancer The frequency of metastasis in SLN was significantly higher LN involvement was found in only 2% of the non-SLN Kitagawa Y, Surg Clin North Am 2000 The preoperative mapping of SLN based on the lymphoscintigraphy Improved the accuracy of the intraoperative gamma probing Baciewicz FA, Jr., J Invest Surg 2000
Procedure Preoperation 1 day before surgery Radioisotope injection 4 hours after injection Lymphoscintigram Kitagawa, Gen Thorac Cardiovasc Surg, 2008
Procedure Intraoperation Percutaneous gamma probing Gamma probing through thoracotomy or thoracoscopy Dual tracer method Radioisotope Blue dye: endoscopically injection right before surgery
SLN Mapping in Esophageal Cancer 1.Predict overall lymph node status 2.Tailored extent of lymphadenectomy Avoid unnecessery morbidity and mortality for node- negative patients More radical treatment for node-positive patients 3.More detailed examination to optimize disease staging of target specific nodal tissue Step sectioning Immunochemistry RT-PCR 4.Determination of the radiation field during CCTR
SLN Mapping in EMR Organ preservation treatment : EMR, PDT, Argon plasma coagulation
KUGH Experiences SexAgeLocationCCRTC-StageP-StageOperationSLNNo. of SLNMetastasis M65LowerNoT1N0M0T3N1M0Ivor-Lewis8, 17, F56LowerNoT1N0M0T3N0M0Ivor-Lewis91no M64LowerNoT1N0M0 Ivor-Lewis7, 8, 10, 174no M64MiddleYesT1N0M0T0N0M0McKeown3p1no M65LowerNoT1N0M0T3N0M0Left thoracotomy17, 182no M61LowerNoT1N0M0T2N0M0Ivor-Lewis201no M48MiddleYesT3N0M0T0N0M0Ivor-Lewis41no M60UpperYesT2N0M0 McKeown1, 8, 93no M70MiddleNoT2N0M0T3N1M0McGweon1, 2, 4, 7, 852 M65MiddleNoT1N0M0T2N0M0McGweon1, 72no M46MiddleNoT2N0M0 McGweon7, 82no M50LowerNoT2N0M0T2N1M0Ivor-Lewis7, 8, 9, 16, M58LowerNoT2N0M0T3N1M0Ivor-Lewis7116 Duration: November 2007 ~ March 2009 Patients: T1~3 N0M0 squamous esophageal cancer Radioisotope: 99mTc-neomannosyl human serum albumin ( 99m Tc-MSA)
Conclusions Curative surgery for cervical-upper esophageal cancer combined with extended LN dissection is probably only indicated in selected cases without distant LN metastasis. 3-field LN dissection proved to be important for correct staging in middle esophageal cancer. In lower thoracic esophageal carcinoma, patients with negative upper thoracic LN not necessarily have to undergo a 3-field LN dissection. No statistical difference in survival was found in randomized trials comparing an extensive LN dissection with a limited lymphadenectomy. Selective LN dissection using sentinel lymph node mapping have to be further evaluated before it can be applied widely.