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Classification of lymph node stations.
Source publication
Background:
An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depend...
Contexts in source publication
Context 1
... classification systems are used in different countries to classify lymph node stations around the esophagus: the AJCC 8th edition esophageal cancer staging and the JES 11th edition esophageal cancer staging. In Fig. 1 and Table 1 these classifications have been combined for the purpose of this ...
Context 2
... study parameter(s) Numbers and percentages of resected lymph nodes and lymph node metastases will be given per lymph node station ( Fig. 1). Tumor location and invasion depth will be categorized. Patients with adenocarcinoma and squamous cell carcinoma and patients with and without neoadjuvant therapy will be analyzed ...
Similar publications
Background
We analyzed the pathological characteristics and recurrence pattern of cN0 submucosal esophageal cancer after esophagectomy and conducted risk stratification to determine the feasibility of performing endoscopic resection for cN0pT1b esophageal squamous cell malignancies.Methods
We retrospectively enrolled 167 patients who underwent righ...
Citations
... 6 To overcome this problem, Schuring et al. 6 proposed one uniform TIGER-study classification system with defined anatomic landmarks based on the 11th edition of the 'Japanese Classification of Esophageal Cancer' (JES) and the 8th edition of the 'American Joint Committee on Cancer/Union for International Cancer Control' (AJCC/UICC) classification. 7 Even when consensus has been reached on which LNSs to dissect (the extent of LND), it is expected that discrepancies remain in the definition of anatomic boundaries of each LNS. This became apparent during the development of the procedure-specific competency assessment tool (MIE-CAT) by Ketel et al. 8 to assess the surgical performance of minimally invasive esophagectomy (MIE) and to determine where most discrepancies were present in assessing the LND phases during MIE. ...
... This largely corresponds to the two-field or abdominal and mediastinal LND 3 (except for the higher thoracic LNSs 6, 7 and 8 and the abdominal LNSs 17, distal, and 19. 7 Surprisingly, the upper mediastinal paraoesophageal LNS (no. 10) was indicated to be routinely dissected by almost all the surgeons, with most of the surgeons performing Ivor-Lewis esophagectomy. ...
Background
The optimal extent of lymph node dissection (LND) and the anatomic boundaries per lymph node station (LNS) during minimally invasive esophagectomy (MIE) for esophageal cancer remain a topic of debate. This study investigated the opinion of Dutch esophageal cancer surgeons on their routine LND extent and anatomic boundaries per LNS during MIE.
Methods
In April 2023, an English web-based cross-sectional survey was conducted. In each of the 15 Dutch hospitals performing MIE, two MIE surgeons were asked to participate. The routine LND extent (quantity, specific LNS) for distal esophageal adenocarcinoma, (dis)agreement with the TIGER definition, and anatomic boundaries for each LNS in six directions were queried.
Results
The survey was completed by 24 Dutch MIE surgeons (80% response rate). Consensus on the routine LND extent ( ≥ 85% of the participating surgeons) included the left and right paracardial, left gastric artery, celiac trunk, proximal splenic artery, common hepatic artery, subcarinal middle mediastinal paraoesophageal, lower mediastinal paraoesophageal, pulmonary ligament, and upper mediastinal paraoesophageal LNSs. Other LNSs were not widely considered routine. Although, certain anatomic boundaries were consistent among the surgeons, the majority varied, even when they agreed on the TIGER definition.
Conclusion
Significant variations in surgical practice among Dutch esophageal surgeons regarding their routine extent of LND and anatomic boundaries of LNSs during MIE were demonstrated. Variation may have an impact on clinical outcomes, hampering uniform treatment strategies and hindering comparison of performance assessments. This study highlighted the need for an international follow-up study toward one uniform defined LND during MIE for esophageal cancer.
... These results are expected to strengthen the evidence related to lymphatic flow in EGJC and contribute to developing consensus between the East and West countries. 26) Surgical approach Two important randomized controlled trials (RCTs) from the Netherlands and Japan examined the surgical approach for EGJC ( Table 3). The Dutch trial compared the right transthoracic approach with the transhiatal approach for Siewert type I or II EGJC. ...
Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.
... In this research study, the three assessors guided the content of the tool and duration of training prior to using the tool, whereas a more formal approach and training strategy may be required to ensure objectivity and standardization of ratings. This improved approach is already being implemented in ongoing trials including the TIGER Study [23]. ...
Background
Despite its recognized importance, there is currently no reliable tool for surgical quality assurance (SQA) of gastrectomy in surgical oncology. The aim of this study was to develop an SQA tool for gastrectomy and to apply this tool within the ADDICT Trial in order to assess the extent and completeness of lymphadenectomy.
Methods
The operative steps for D1+ and D2 gastrectomy have been previously described in the literature and ADDICT trial manual. Two researchers also performed fieldwork in the UK and Japan to document key operative steps through photographs and semi-structured interviews with expert surgeons. This provided the steps that were used as the framework for the SQA tool. Sixty-two photographic cases from the ADDICT Trial were rated by three independent surgeons. Generalizability (G) theory determined inter-rater reliability. D-studies examined the effect of varying the number of assessors and photographic series they rated. Chi-square assessed intra-rater reliability, comparing how the individual assessor’s responses corresponded to their global rating for extent of lymphadenectomy.
Results
The tool comprised 20 items, including 19 anatomical landmarks and a global rating score. Overall reliability had G-coefficient of 0.557. Internal consistency was measured with a Cronbach’s alpha score of 0.869 and Chi-square confirmed intra-rater reliability for each assessor as < 0.05.
Conclusions
A photographic surgical quality assurance tool is presented for gastrectomy. Using this tool, the assessor can reliably determine not only the quality but also the extent of the lymphadenectomy performed based on remaining anatomy rather than the excised specimen.
... This means that active brain surveillance following treatment with curative intent for oesophageal cancer would require substantial resources, including time as well as financial investment, and is therefore not recommended based on the present results. A future international cohort study on recurrence patterns after neoadjuvant chemoradiotherapy and oesophagectomy is being planned with the TIGER study database, to further investigate the unexpected and somehow counterintuitive observation of more brain recurrences in patients with TRG1-ypN0 33 . The current standard for assessing prognosis after the surgical removal of oesophageal malignancies is the eighth edition of the TNM classification 24 . ...
Background
This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG>1-ypN0, TRG1-ypN+ and TRG>1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.
Methods
This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival.
Results
Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P < 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P < 0.001) than those with TRG>1. The TRG>1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG>1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P < 0.001) and worse mean overall survival (33 versus 41 months; P < 0.001).
Conclusion
Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG>1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.
... évi eredményei [29] során is látható volt, hogy a preoperatív kezelés a felső és középső mediastinalis nyirokcsomók érintettségét 10% alá csökkentette (5,1% és 7,5%). Az optimális nyirokcsomó-dissectio jelenleg sincs meghatározva, talán a folyamatban lévő TIGER-tanulmány sok kérdésre választ ad majd [34]. ...
A felső gastrointestinalis traktus daganatai nagy mortalitású betegségek. Az elmúlt évtizedekben bekövetkezett technikai fejlődésnek köszönhetően a betegek túlélése jelentősen javult, de az átlagos 5 éves túlélés sem gyomor-, sem nyelőcsőtumorok esetén nem haladja meg a 35%-ot. A szűrőprogramot bevezető országokban a betegek gyakran korai stádiumban kerülnek felfedezésre, és ellátásuk endoszkópos úton is lehetséges. Az onkológia fejlődésével a tumorok terápiájának a multimodális megközelítés lett az alapja, ezzel mód nyílt az előrehaladott állapotú betegek mind nagyobb arányú kuratív célú kezelésére. A minimálisan invazív technikák térhódítása megfelelő onkológiai radikalitás mellett csökkentette a műtéti megterhelést és javította a posztoperatív felépülést. Az utóbbi években egyre nagyobb hangsúlyt kapott a betegek komplex előkészítése, így tovább javultak a műtéttel kapcsolatos morbiditási mutatók. Írásunkban összefoglaljuk a felső tápcsatorna daganatainak ellátásában az utóbbi évtizedekben bekövetkezett változásokat. Orv Hetil. 2024; 165(6): 203–210.
... 46 In 2019, the TIGER study protocol was published, an ongoing observational cohort study investigating the distribution of lymph node metastases in esophageal cancer. 47 This protocol contains a classification for lymph node stations in esophageal cancer in the context of the TIGER study. In this classification system, the AJCC 8th edition and the JES 11th edition are combined and simplified for research purposes. ...
... Recently, a match for the two established classification systems and the TIGER classification has been proposed, which aimed to contribute to more uniformity and to better comparison of studies about the distribution of lymph node metastasis in esophageal cancer patients (Supplementary Table 1 and Supplementary Figs 1-3). 18,47 During the IGSC Joint Meeting in Munich in 1994, the extent of lymphadenectomy was discussed between esophageal cancers specialists and defined as 'standard', 'extended', 'total mediastinal' and a 'threefield' lymphadenectomy. The 3-field lymphadenectomy includes at least the following stations according to the JES classification system: cervical esophagus (Ce); station 101 and 104, mediastinal; station 106rec, 106pre, 106tbL and 107-112, upper abdominal; station 1-2, 3, 7, 9 and 19-20. ...
... The standard 2-field does not include the dissection of the upper paratracheal nodes. 48,49 A summary of which TIGER lymph node stations are resected for the different fields of lymphadenectomy extents is given in Figure 2. 18,47 ...
The current curative multimodal treatment of advanced esophageal cancers consists of neoadjuvant or perioperative chemo(radio)therapy followed by a radical surgical resection of the primary tumor and a 2- or 3-field lymphadenectomy. One of the most important predictors of long-term survival of esophageal cancer patients is lymph node involvement. The distribution pattern of lymph node metastases in esophageal cancer is unpredictable and depends on the primary tumor location, histology, T-stage and application of neoadjuvant or perioperative treatment. The optimal extent of the lymphadenectomy remains controversial; there is no global consensus on this topic yet. Some surgeons advocate an aggressive and extended lymph node dissection to remove occult metastatic disease, to optimize oncological outcomes. Others promote a more restricted lymphadenectomy, since the benefit of an extended lymphadenectomy, especially after neoadjuvant chemoradiotherapy, has not been clearly demonstrated, and morbidity may be reduced. In this review, we describe the development of lymphadenectomy, followed by a summary of current evidence for lymphadenectomy in esophageal cancer treatment.
... Treating regional LNs via resection forms the basis for modern surgical oncologic treatment approaches. Regional LNs are removed and often trigger the implementation of systemic therapies when they harbour cancer (Hagens et al., 2019). The commonality of LN metastasis among cancers presents a broadly applicable opportunity for treatment. ...
Lymph nodes (LNs) are frequently the first sites of metastasis. Currently, the only prognostic LN assessment is determining metastatic status. However, there is evidence suggesting that LN metastasis is facilitated by the formation of a pre-metastatic niche induced by tumour derived extracellular vehicles (EVs). Therefore, it is important to detect and modify the LN environmental changes. Earlier work has demonstrated that neutrophil extracellular traps (NETs) can sequester and promote distant metastasis. Here, we first confirmed that LN NETs are associated with reduced patient survival. Next, we demonstrated that NETs deposition precedes LN metastasis and NETs inhibition diminishes LN metastases in animal models. Furthermore, we discovered that EVs are essential to the formation of LN NETs. Finally, we showed that lymphatic endothelial cells secrete CXCL8/2 in response to EVs inducing NETs formation and the promotion of LN metastasis. Our findings reveal the role of EV-induced NETs in LN metastasis and provide potential immunotherapeutic vulnerabilities that may occur early in the metastatic cascade.
... Recently, the TIGER study was conducted to evaluate the distribution of lymph node metastases in EC specimens following transthoracic esophagectomy with two-or three-field lymphadenectomy [15]. They combined the classification of JES 11th edition and the AJCC 8th edition as the TIGER classification. ...
Lymph node (LN) metastasis is recognized to be an important prognostic factor for esophageal cancer (EC). However, there is no worldwide uniform classification system, and no consensus exists on the extent of the lymphadenectomy. Recently, an international observational cohort study was conducted to evaluate the distribution of LN metastasis in EC patients. Moreover, this could be a milestone to establish a standard classification system and provide new insights to determine the extent of LNs that should be target for treatment. With regard to surgical procedures, three-field lymphadenectomy seems to be promising to improve the prognosis with EC patients. However, extended lymphadenectomy could lead to postoperative complications. The development of minimally invasive esophagectomy (MIE) has allowed us to retrieve cervical paraesophageal nodes without cervical incision and reduce the incidence of postoperative complications. Therefore, it may be possible that the era of MIE could propose the modern extent of LN dissection in the future. Additionally, one of the key components in lymphadenectomy for EC was thoracic duct and surrounding tissues. Although there is some evidence of LN metastasis surrounding the TD, the survival benefit of TD resection is still debatable. With regard to esophagogastiric junction cancer, the extent of LN dissection could be determined by the length of esophageal involvement. We believe further understanding of LN metastasis of EC patients will contribute to establish a global standard of treatment and improve their prognosis.
... Regional LNs are removed and often trigger the implementation of systemic therapies when they harbour cancer 75 . The commonality of LN metastasis among cancers presents a broadly applicable opportunity for treatment. ...
Lymph nodes (LNs) are frequently the first sites of metastasis. Currently, the only prognostic LN assessment is determining metastasis status. However, there is evidence suggesting that LN metastasis is facilitated by a pre-metastatic niche induced by tumour derived extracellular vehicles (EVs). Therefore, it is important to detect and modify the LN environmental changes. We have previously reported that neutrophil extracellular traps (NETs) can sequester and promote distant metastasis. Here, we first confirmed that LN NETs are associated with reduced patient survival. Next, we demonstrated that NETs deposition precedes LN metastasis and NETs inhibition abolishes LN metastases in animal mode. Furthermore, we discovered that EVs are essential to the formation of LN NETs. Lymphatic endothelial cells secrete CXCL8/2 in response to EVs inducing NETs formation and the promotion of LN metastasis. Our findings are the first to reveal the role of EV induced NETs in LN metastasis and provide potential immunotherapeutic vulnerabilities.
Graphic Abstract
Illustrative demonstration of the LNs premetastatic niche formation induced by EVs and NETs. Primary tumour constantly secretes EVs, which were actively uptaken by LECs. LECs subsequently secretes CXCL8 or CXCL2 upon EV reception. CXCL8 and CXCL2 are both neutrophil chemoattractants and potent NETs inducers. The following neutrophil recruitment and NETs formation lead to increased LN metastasis burden.
... The incongruence between the 2 classifications (JES vs. AJCC) for EC classification and treatment guidelines causes communication difficulties between researchers. In 2019, Hagens et al. [27,28] conducted the TIGER study, a multinational observational study on the distribution of LNMs in EC. In this study, renowned EC centers worldwide collaborated and hoped that the 2 existing classification systems could be combined. ...
