The different routes of lymph node metastases in esophageal cancer and its significance.
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ABSTRACT:
SUBMITTER: Hutchings H
PROVIDER: S-EPMC10713315 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
The different routes of lymph node metastases in esophageal cancer and its significance.
Hutchings Hollis H Okereke Ikenna C IC
Journal of thoracic disease 20231026 11
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Project description:ObjectivesTo identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer.Summary background dataLimited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics.MethodsData on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques.ResultspN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones.ConclusionsIn esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.
| S-EPMC5405457 | biostudies-literature
Project description:BackgroundMyofibroblasts have an important role in regulating the normal colorectal stem cell niche. While the activation of myofibroblasts in primary colorectal cancers has been previously described, myofibroblast activation in lymph node metastases has not been described before.MethodsParaffin-embedded lymph node sections from patients with macrometastases, micrometastases and isolated tumour cells were stained to identify myofibroblasts and to characterise the distribution of different cell types in tumour-containing lymph nodes. The extent of myofibroblast presence was quantified and compared with the size of the metastasis and degree of proliferation and differentiation of the cancer cells.ResultsWe show substantial activation of myofibroblasts in the presence of colorectal metastases in lymph nodes, which is intimately associated with glandular structures, both in micro- and macrometastases. The degree of activation is positively associated with the size of the metastases and the proportion of Ki67+ve cancer cells, and negatively associated with the degree of enterocyte differentiation as measured by CK20 expression.ConclusionThe substantial activation of myofibroblasts in tumour-containing lymph nodes strongly suggests that these metastatic cancer cells are still significantly dependent on their microenvironment. Further understanding of these epithelial-mesenchymal interactions could lead to the development of new therapies in metastatic disease.
| S-EPMC3670500 | biostudies-literature
Project description:Purpose: Recent studies have highlighted the existence of subclones in tumors. Lymph nodes are generally the first location of metastasis for most solid epithelial tumors, including colorectal cancer. We sought to understand the genetic origin of lymph node metastasis in colorectal cancer by evaluating the relationship between colorectal cancer subclones present in primary tumors and lymph nodes.Experimental Design: A total of 33 samples from seven colorectal cancers, including two or three spatially disparate regions from each primary tumor and one to four matched lymph nodes for each tumor, underwent next-generation whole-exome DNA sequencing, Affymetrix OncoScan SNP arrays, and targeted deep confirmatory sequencing. We performed mapping between SNPs and copy number events from the primary tumor and matched lymph node samples, allowing us to profile heterogeneity and the mutational origin of lymph node metastases. The computational method PyClone was used to define subclones within each tumor. The method Clonality Inference in Tumors Using Phylogeny (CITUP) was subsequently used to infer phylogenetic relationships among subclones.Results: We found that there was substantial heterogeneity in mutations and copy number changes among all samples from any given patient. For each patient, the primary tumor regions and matched lymph node metastases were each polyclonal, and the clonal populations differed from one lymph node to another. In some patients, the cancer cell populations in a given lymph node originated from multiple distinct regions of a tumor.Conclusions: Our data support a model of lymph node metastatic spread in colorectal cancer whereby metastases originate from multiple waves of seeding from the primary tumor over time. Clin Cancer Res; 24(9); 2214-24. ©2017 AACRSee related commentary by Gerlinger, p. 2032.
| S-EPMC5932232 | biostudies-literature
Project description: Not available
| S-EPMC6944331 | biostudies-literature
Project description:IntroductionTumor-targeted imaging is a promising technique for the detection of lymph node metastases (LNM) and primary tumors. It remains unclear which biomarker is the most suitable target to distinguish malignant from healthy tissue in esophageal adenocarcinoma (EAC).ObjectiveWe performed an immunohistochemistry study to identify viable tumor markers for tumor-targeted imaging of EAC.MethodsWe used samples from 72 patients with EAC to determine the immunohistochemical expression of ten potential tumor biomarkers for EAC (carbonic anhydrase IX [CA-IX], carcinoembryonic antigen [CEA], hepatic growth factor receptor, epidermal growth factor receptor, epithelial membrane antigen [EMA], epithelial cell adhesion molecule [EpCAM], human epidermal growth factor receptor 2 [HER-2], urokinase plasminogen activator receptor, vascular endothelial growth factor-A [VEGF-A], and VEGF receptor 2). Immunohistochemistry was performed on tissue microarrays of LNM (n = 48), primary EACs (n = 62), fibrotic tissues (n = 11), nonmalignant lymph nodes (n = 24), and normal esophageal and gastric tissues (n = 40). Tumor marker staining was scored on intensity and percentage of positive cells.ResultsEMA and EpCAM showed strong expression in LNM (> 95%) and primary EACs (> 95%). Significant expression was also observed for LNM and EAC using VEGF-A (85 and 92%), CEA (68 and 54%), and CA-IX (4 and 34%). The other tumor biomarkers showed expression of 0-15% for LNM and primary EAC. Except for VEGF-A, nonmalignant lymph node staining was scored as slight or absent.ConclusionsHigh expression rates and correlation between LNM in EAC combined with low expression rates in healthy lymph nodes and esophagus tissues were observed for EpCAM and CEA, meaning these are promising targets for tumor-targeted imaging approaches for lymph nodes in patients with EAC.
| S-EPMC7113228 | biostudies-literature
Project description:BackgroundThe incidence of lymph node metastases is closely related to the T-stage, and therefore Eastern guidelines advice a D1 lymphadenectomy for early gastric cancer and a D2 lymphadenectomy for advanced gastric cancer. The aim of this study was to compare the lymph node metastases rate in the stations dissected with a D2-lymphadenectomy (stations 8-12) yet spared with a D1-lymphadenectomy, between different T-stages in a Western patient cohort.MethodsFor this retrospective study, patients who underwent a gastrectomy in the Amsterdam University Medical Center (UMC), location Academic Medical Center (AMC), between 2011 and 2016 were identified from a prospectively maintained database. The primary outcome was to compare the rate of lymph node metastases in station 8-12 between different cT-stages.ResultsOne hundred twelve patients met our inclusion criteria. There were no positive lymph nodes in the lymph nodes stations 8-12 in cT1 and (y)pT1-stage tumors. The more advanced cT2-4 and (y)pT2-4 stage tumors show a high metastases rate (11.1% to 40.0%) in the lymph node stations 8-12.ConclusionsThe results from this study endorse the Japanese Gastric Cancer Guideline; in early gastric cancer, a D1 lymphadenectomy is sufficient, while in advanced gastric cancer a D2 lymphadenectomy should be performed.
| S-EPMC9459217 | biostudies-literature
Project description:PurposeLateral lymph node metastases in rectal cancer remain a clinical challenge. Different treatment regimens have been suggested. This retrospective regional cohort study examines outcome after combined oncological and surgical treatment of MRI-positive lateral lymph nodes (LLN).MethodsData from the Swedish Colorectal Cancer Registry (SCRCR) and patient records were used for retrospective analysis of resected high-risk rectal cancers between 2009 and 2014. The aim was to compare tumour characteristics, neoadjuvant therapy, recurrence and outcome after lateral lymph node dissection.ResultsOne thousand and one hundred nineteen cases were identified and after exclusion 344 patients with cT3-T4 ≤ 10 cm from the anal verge were analysed. Thirty (8.7%) patients with MRI-positive LLN were identified. Synchronous distant metastases were associated with MRI-positive LLN (p-value 0.019). Long-course chemoradiotherapy was clinical practice in cases of MRI-positive LLN. No differences in local (p-value 0.154) or distant (p-value 0.343) recurrence rates between MRI-positive LLN patients and MRI-negative patients were detected. Only four patients underwent lateral lymph node dissection (LLND). There was no significant difference in overall survival during follow-up between the MRI-negative (CI at 95%; 99-109 months) and MRI-positive group (CI at 95%; 69-108 months; p-value 0.14).ConclusionLateral lymph node metastases present a challenging clinical situation. The present study shows that combination of neoadjuvant therapy and selective LLND is an applicable strategy in cases of MRI-positive LLN.
| S-EPMC8589806 | biostudies-literature
Project description:BackgroundLower thoracic esophageal cancer (LTEC) with celiac node metastasis and upper thoracic esophageal cancer (UTEC) with supraclavicular node metastasis were previously categorized as M1a diseases. Our study aimed to investigate whether the clinical significance of supraclavicular and celiac lymph node metastasis should be reevaluated in thoracic esophageal cancer.MethodsA total of 6178 patients with thoracic esophageal cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database during 2004-2015. Treatment strategies and outcomes (OS, overall survival; CSS, cancer-specific survival) of patients with different nodal status were reviewed. The Cox proportional hazards regression model was applied to evaluate the prognostic factors. Statistical analyses were performed in all subgroups.ResultsMultivariate analysis identified supraclavicular node metastasis but not celiac node metastasis as an independent predictor of both OS and CSS in LTEC. However, metastasis to supraclavicular or celiac nodes was not an independent predictor of OS and CSS in UTEC. Surgery was not associated with increased OS and CSS for UTEC with celiac or supraclavicular node metastasis but was favored as a predictor of better OS and CSS for LTEC with celiac or supraclavicular node metastasis. Radiotherapy benefited OS and CSS in LTEC involving celiac or supraclavicular nodes and in UTEC involving celiac nodes, while only OS benefited from radiotherapy in UTEC involving supraclavicular nodes.ConclusionsThese results provide preliminary evidence that the clinical significance of supraclavicular and celiac lymph node metastasis should be reevaluated in thoracic esophageal cancer with different prognostic information according to the primary sites.
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Project description:Knowing the anatomical lymphatic drainage of the esophagus is crucial to understanding the dissemination pattern of esophageal tumor. During the embryonal growth, the middle and lower part of the esophagus stretches as the lymphatic networks develop in the submucosal layer. The abundant submucosal lymphatics drain in a longitudinal fashion directly to their proximal and distal ends. The lymphatic route from the proximal esophagus through recurrent nerve nodes to supraclavicular nodes are a component of the mesentery of the proximal esophagus. The lower esophagus mostly drains its lymph into paracardial nodes related to celiac nodes through the mesentery of the distal esophagus. Lymphatic routes to mid and lower paraesophageal nodes usually originate from the intermuscular area of the muscularis propria. The lymphatic communication between the submucosa and intermuscular area is limited. The anatomical concept was confirmed clinically by a large series of single institution and the nationwide registry in Japan. The clinical data for the incidence of involved nodes verified the anatomical observations that long longitudinal extension of lymphatic drainage in the submucosa connected to the upper mediastinum lymphatics and paracardial lymphatics. The extent of dissection should be not tailored according to the anatomical distance from the tumor but according to the incidences of metastasis of each area, those were differed by tumor location. The areas for node dissection should be modified according to the tumor location. Although in patients with tumor limited to within the submucosal layer, even with tumors located in the mid- and lower esophagus, lymphatic metastasis was frequent in the upper mediastinum and perigastric area via the abundant submucosal lymphatics in a longitudinal fashion. When tumor invades or penetrates the muscle layer, the incidence of paraesophageal lymph node metastasis in the middle and lower mediastinum increases.
| S-EPMC5538982 | biostudies-other
Project description:Although multidisciplinary treatment has improved the prognosis of esophageal cancer, it is commonly associated with one of the worse prognoses. Since lymph node (LN) metastases can primarily occur from the cervical to the abdominal field, a strategy for extended LN dissection has been established. The three field LN dissection (3FD) during a transthoracic esophagectomy which is defined as a procedure for cervico-thoraco-abdominal LN dissection, was established in the 1980s' in Japan, and is currently widely accepted throughout the world. To date, various comparative trials between 3FD and two field LN dissections (2FD) have been reported and show that a transthoracic esophagectomy with 3FD is superior to 2FD for prognosis. However, in 3FD, postoperative complications, such as recurrent laryngeal nerve palsy and postoperative gastrointestinal dysfunction can be induced. Furthermore, there are few prospective trials that have compared between 2FD and 3FD. Therefore, to determine the ideal range of LN dissection, various factors (e.g., location of the primary tumor, disease progression, tumor histology, and perioperative treatment) must be considered. Recently, the efficacy of intense perioperative treatment for esophageal cancer has been reported, and the significance of minimally invasive surgical procedures are being verified. The ideal combination of perioperative treatment and feasible surgery must be established to improve the oncological outcome of esophageal cancer patients further.
| S-EPMC5538994 | biostudies-other