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Two vs. Three Field Lymph Node

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Presentation on theme: "Two vs. Three Field Lymph Node"— Presentation transcript:

1 Two vs. Three Field Lymph Node
Dissection in Surgery for Esophageal Cancer 고려대학교 구로병원 김현구

2 Incision vs. LN Dissection
Ivor-Lewis Two-hole Two-incision Two-field McKweon Three-hole Tri-incision Three-field

3 Case-1 M/61 G-fiber: 39cm from incisor Biopsy: Squamous cell carcinoma
Stage: cT1N0M0 Treatment? Ivor-lewis

4 Case-2 M/63 G-fiber: 25~28cm from incisor
Biopsy: severe dysplasia with leiomyoma Stage: cT1N0M0 Treatment? Ivor-lewis, carinoma in situ

5 Case-3 M/49 G-fiber: 26~28cm from incisor
Biopsy: Squamous cell carcinoma Stage: cT1N0M0 Treatment? 3-field

6 Two-Field or Three-Field ?
Tumor location Depth of tumor invasion Tumor cell type Tumor location Depth of tumor invasion Tumor cell type Substantial morbidity Prognostic benefit Quality of life

7 Optimal Surgical Extent ?
Systemic disease Palliative Advancement of chemotherapy & radiotherapy Minimal operative technique perioperative management Radical 다른 gastrointestinal cancer와 같이 식도암에서도 적절한 lymph node dissection의 범위가 어디까지 인가에 대해서는 여전히 논란이 되고 있다. 식도암은 초기인 경우를 제외하고는 systemic disease이기 때문에 수술은 기본적으로 palliative 목적이다 라는 minimalist attitude를 가진 그룹이 있는 반면1, 명백한 nonregional lymphatic spread가 있는 경우에도 extended radical resection esophagectomy와 lymphadenectomy를 시행하여야 한다는 의견을 가진 그룹도 있다2. 그러나, 수술 기법과 수술 후 환자 관리 기법의 향상으로 extended radical esophagectomy가 비교적 안전하게 시행될 수 있는 여건이 형성된 반면, 항암과 방사선 치료의 발전은 radical esophagectomy의 필요성을 경감시키는 여건이 조성되기도 하였다.

8 Categorization of Esophageal Segment
Cervical Upper thoracic Mid thoracic Lower thoracic Abdominal 식도는 5개의 구역으로 구분되는데, 경부 식도는 cricoid cartilage 하방에서 부터 thoracic inlet (suprasternal notch, 18cm from incisor)) 사이의 5~6cm 길이의 segment이다 (C6 to T1). 상흉부 식도는 thoracic inlet 부터 tracheal bifurcation (24cm from incisor)사이에 위치하며, 중흉부 식도는 incisor로부터 32 cm 까지 이며, 하흉부 식도는 esophagogastric junction (40cm from incisor, T10 or 11)) 까지 이고, 복부 식도는 intraabdominal portion에 0.5~2.5cm길이로 존재한다 (T11 or T12).

9 Lymphatic Drainage Multidirectional lymphatic flow
Human organogenesis동안 lymphatic pathway는 branchiogenic mesenchyme과 body mesenchyme이라는 두 개의 서로 다른 source에 의해 형성되는데, 이로 인해 tracheal bifurcation부위를 중심으로 lymphatic pathway가 서로 반대 방향을 향하고 있고, tracheal bifurcation부위의 lymphatic pathway는 bidirectional flow를 보여 준다

10 Lymphatic Drainage Lymph-capillary network in submucosal space
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 또한, 식도의 lymphatic drainage system은 submucosal space 주로 존재하는 lymph-capillary network의 독특한 구조로 인해 식도암이 림프절을 통해 전이 될 때 segmental spread가 아닌 longitudinal spread를 하게 되고3 (Fig. 3), 이로 인해 skip metastasis의 빈도가 50~60%까지 보고 되고 있다4. ☞Widespread and random patterns of lymph node metastasis Ando N, Ann Surg, 2000 Skip metastasis: 50~60% MatsubaraT, Cancer, 2000

11 Lymph Node Mapping System
현재 두 개의 lymph node mapping system이 사용되고 있다. Guidelines for Clinical and Pathological Studies on Carcinoma of the Esophagus advocated by the Japanese Society for Esophageal Disease7에서는 1번 에서 16번까지 gastric cancer lymph node map을 abdominal lymph node map에 사용하고, 나머지 cervical과 mediastinum에는 100에서 112까지 번호를 정하였고, station은 primary tumor로 부터의 거리에 기초해 N1-4로 구분하였다. American Joint Committee on Cancer8는 Lung cancer map을 modified 한 것으로, 3p (upper paraesophageal LN), 8M, 그리고 8L를 구분하고, 15에서 20까지 복부 lymph node를 추가하였고, M1a/b를 구분하여 stage를 정하였다

12 Lymph Node Mapping System
Regional Lymph Nodes NX Regional lymph nodes cannot be assessed. NO No regional lymph node metastases N1 Regional lymph node metastases M Distant Metastasis MX Distant metastases cannot be assessed. M1a: Upper thoracic esophagus metastatic to cervical lymph nodes Lower thoracic esophagus metastatic to celiac lymph nodes M1b Upper 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

13 Patterns of Metastatic Nodal Spread

14 Association with tumor location-1
Patterns of Metastatic Nodal Spread Association with tumor location-1 Akiyama2는 전체적으로 cervical LN에 30%의 전이가 있고, 식도암의 위치에 따라 upper, mid, lower에 각각 46%, 29%, 27%의 cervical LN 전이를 보인다고 하였고, adenocarcinoma9에서도 이와 비슷한 결과를 보여 주어 3-field LN dissection을 정당화 하였다. Akiyama H, Ann Surg 1994. Altorki N, Ann Surg 2002 ☞ 3-field LN dissection

15 Association with tumor location-2
Patterns of Metastatic Nodal Spread Association with tumor location-2 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. Kato10와 Sharma11는 3-field LN dissection를 시행한 결과 upper esophageal cancer는 abdominal LN에 전이가 거의 없고, lower esophageal cancer는 cervical LN에 전이가 거의 가지 않는다고 하면서, 5 level로 나누었을 때, 임파선 전이가 3 level이상을 건너가지는 않는다고 하여, 3-field LN dissection의 역할에 의문을 제기하였다. Kato H, J Surg Oncol 1991 Sharma S, Surg Today 1994 ☞ 2-field LN dissection

16 Association with depth of tumor invasion-1
Patterns of Metastatic Nodal Spread Association with depth of tumor invasion-1 Rice12는 T2, T3, T4 stage의 regional LN 전이율이 T1 stage에 비해 6배, 23배, 35배라고 하였고, Matsubara6 13는 primary tumor가 lamina propria, muscularis mucosa, submucosa에 각각 침범시 LN 전이율이 0%, 23%, 49%라고 보고하였다. Rice TW, Ann Thorac Surg 1998

17 Association with depth of tumor invasion-2
Patterns of Metastatic Nodal Spread Association with depth of tumor invasion-2 Matsubara6 13는 primary tumor가 lamina propria, muscularis mucosa, submucosa에 각각 침범시 LN 전이율이 0%, 23%, 49%라고 보고하였다. Reccurrent laryngeal nerve와 perigastric LN에 주로 전이 된다. Matsubara T, Br J Surg 1999 ☞ T stage ↑→ LN Metastasis↑

18 Association with tumor cell type
Patterns of Metastatic Nodal Spread Association with tumor cell type Adenocarcinoma와 squamous cell cancer 간의 LN 전이 pattern에 대한 systemic paper는 없지만 같은 부위cancer의 두 논문을 비교시 lymph node spread에 별 차이는 없다. ☞ No difference Sheids 6th edition

19 Extent of Resection Axial margin
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. Resection margin을 in-situ 로는 10cm, fresh contracted specimen인 경우에는 5cm (in-situ 길이의 44%이다14)를 목표로 한다. 이 경우 anastomotic recurrence는 5%미만으로 나타난다15. Siu KF, Ann Surg 1986 Law S, Am J Surg 1998

20 Extent of Resection Lymphadenectomy Mediastinal lymph node dissection
Standard 2-field Extended Total Standard mediastinal LN dissection은 carina하방의 periesohpageal tissue와 celiac axis 주위의 LN dissection을 하는 경우이고, superior mediastinum (right apical, recurrent laryngeal, paratracheal)을 포함하는 경우에는 extended 2-field LN dissection이라 하며, left recurrent laryngeal, paratracheal LN, total 2-field LN dissection이고, 양측 cervical LN가 포함된 경우를 3-field LN dissection이라 한다 (Fig. 6) . 그러나, 일본에서는 2-field LN dissection을 thyroid grand의 하방 부터 양측 recurrent laryngeal chain이 포함되어 있는 superior mediastinum을 포함한다. Abdominal lymph node dissection or Cervical lymph node dissection Pearson, 3rd edition

21 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 Cervical esophageal cancer환자 40명을 대상으로 한 보고에 의하면, 20%에서는 distant metastasis가 있고, 63%에서 regional lymph node metastasis가 있었으며, 이들의 median survival은 11~14개월, 5년 생존율은 14%~21%로 보고되었다. Regional lymph node 전이가 있는 경우가 (8% vs. 38%)없는 경우에 비해 예후가 나빴지만, multivariate analysis상에서는 예후인자는 아니었다16. Marmuse JP, Am J Surg, 1995 Triboulet JP, Arch Surg, 2001

22 Upper Thoracic Esophagus
In resectable T3 squamous cell carcinoma, o 3-year survival No difference Limited resection 14% 20% Extended LN dissection Manshanden CG Eur J Surg Oncol 2000 Igaki H, Br J Surg 2005 Resectable한 T3 stage의 upper esophageal cancer에 대한 limited resection과 extended resection의 3년 생존율이 각각 14%와 20%로 차이가 없다17, 18. Cervical-upper thoracic esophageal cancer에 대한 cervical lymph node dissection은 staging에는 중요하나, extended lymph node dissection을 포함한 curative surgery는 distant lymph node metastasis가 없는 경우에만 예후에 도움이 된다19. ☞ 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

23 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.

24 Cervical LN Metastasis in Esophageal Cancer
14~30% patients: metastasis to cervical lymph nodes 40% for upper third tumors 20% for lower third tumors Frequency of nodal metastasis: increased with depth of tumor penetration Intramucosa < submucosa < muscularis propria < adventitia 30% < % < % < 80% 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

25 5 –Year Survival in 2- vs. 3-Field LN Dissection
p Node 55% 84% 0.004 + Node 28% 43% 0.008 Akiyama H, Am J Surg. 1984

26 Skeptical Views to 3-Field LN Dissection-1
Systemic disease Replaced by neoadjuvant chemotherapy or intraoperative radiotherapy 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%

27 Skeptical Views to 3-Field LN Dissection-2
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 Prospective Randomized study 식도암 수술 후 경부에서의 재발율은 11% 이고, 이중 isolated cervical nodal recurrence는 4%인 반면, mediastinum과 systemic organ 전이율이 21%와 26%로 neck dissection이 예후에 별 영향을 끼치지 못함을 알 수 있다21. 2-Field 3-Field p Nishihira T, Am J Surg, 1998 48% 65% NS National cancer hospital in Tokyo 33% 0.3

28 LN Dissection along Recurrent Laryngeal Nerve
Recurrent laryngeal LN + cervical LN → Cervicothoracic group Superior mediastinal area의 recurrent laryngeal LN와 cervical LN를 cervicothoracic group으로 명명하고 one entity로 생각, 2-field로 recurrent Laryngeal nerve주위의 superior mediastinal LN dissection의 completeness하면 cervical phase를 추가할 필요가 없다는 보고가 있다30, 31

29 Selective 3-Field LN Dissection
일부에서는 paratracheal lymph node에 대해 frozen biopsy하여, RT-PCR을 시행하여 전이가 있는 경우에만 cervical lymph node dissection을 시행하기도 하였다32, 33.

30 Sentinel Lymph Node The first lymph node within the
lymphatic basin reached by lymph draining from the primary lesion SLN란 종양이 임파선을 통해 직접 전이 되는 경우 가장 처음 도달하는 임파절 말한다. Morton34등이 하지에 발생한 흑색종 환자에 대한 수술 시 불필요한 서혜부 절제를 줄이고자 하는 목적에서 SLN mapping이란 개념을 도입하였다. 먼저 작은 피부 절개를 통해 lymphotropic dye를 암 조직 주위에 주입하고, 파란색으로 변한 blue node를 SLN로 추정하여 이를 절제한 후 면역조직화학적 검사를 하게 된다. 이 SLN에 암세포의 전이가 발견되면 기존의 방법대로 광범위한 임파선 절제술을 시행하게 되지만, 전이가 없다면 더 이상의 수술을 진행하지 않는다. 이 방법은 수술 전 lymphoscintigraphy를 통해 SLN를 미리 확인하여 이 부분에만 피부 절개를 하는 등 좀더 기술적인 발전을 하여 왔다. 현재 SLN mapping은 초기 유방암과 흑색종에서는 표준적인 수술 기법으로 사용되고 있는데, 흑색종에서는 림프부종과 신경손상을 줄이고35, 유방암에서는 상지 부종과 같은 이환율을 줄 일수 있다36. 또한, 대장암, 위암, 폐암, 그리고, 식도암과 같은 다른 일차암에서도 활발한 연구가 진행되고 있다.

31 Limited Reports 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 Complicated compared to gastric cancer Limited No. of early esophageal cancer

32 Procedure Preoperation
1 day before surgery Radioisotope injection 4 hours after injection Lymphoscintigram Kitagawa, Gen Thorac Cardiovasc Surg, 2008

33 Procedure Intraoperation
Percutaneous gamma probing Gamma probing through thoracotomy or thoracoscopy Dual tracer method Radioisotope Blue dye: endoscopically injection right before surgery

34 SLN Mapping in Esophageal Cancer
Predict overall lymph node status Tailored extent of lymphadenectomy Avoid unnecessery morbidity and mortality for node- negative patients More radical treatment for node-positive patients More detailed examination to optimize disease staging of target specific nodal tissue Step sectioning Immunochemistry RT-PCR Determination of the radiation field during CCTR

35 SLN Mapping in EMR Organ preservation treatment
: EMR, PDT, Argon plasma coagulation

36 KUGH Experiences Duration: November 2007 ~ March 2009
Patients: T1~3 N0M0 squamous esophageal cancer Radioisotope: 99mTc-neomannosyl human serum albumin (99mTc-MSA) Sex Age Location CCRT C-Stage P-Stage Operation SLN No. of SLN Metastasis M 65 Lower No T1N0M0 T3N1M0 Ivor-Lewis 8, 17, 20 3 17 F 56 T3N0M0 9 1 no 64 7, 8, 10, 17 4 Middle Yes T0N0M0 McKeown 3p Left thoracotomy 17, 18 2 61 T2N0M0 20 48 60 Upper 1, 8, 9 70 McGweon 1, 2, 4, 7, 8 5 1, 7 46 7, 8 50 T2N1M0 7, 8, 9, 16, 18 16 58 7

37 Results No. of sentinel lymph node 2.4±1.50 (1~5) Detection rate 100%
False-negative SLN 1/ 13 (7.7%)

38 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.

39 THANK YOU !


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