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Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma.

ABSTRACT: BACKGROUND:Lymph node metastasis (LNM) is a standard mechanism of cancer progression in esophageal squamous cell carcinoma (ESCC). We aimed to clarify the anatomical mechanism of skip nodal metastasis to mediastinal zones by analyzing the relationship between LNM to sentinel zones and lymphatic vessel counts in the muscle layer adjacent to the outer esophagus. METHODS:We examined the surgical records of 287 patients with ESCC who underwent potentially curative surgery (three-field lymphadenectomy) and whole esophagi, including pharynges and stomachs from 10 cadavers, to determine the number of lymphatic vessels in the intra-outer longitudinal muscle layer adjacent to the outer esophagus of the cervical (Ce), upper thoracic, middle thoracic (Mt), lower thoracic (Lt), and abdominal esophagi (Ae). RESULTS:The frequency of LNM to the middle mediastinal and supraclavicular zones, including the Mt and Ce, respectively, was lower than to the upper and lower mediastinal and abdominal zone in patients with superficial and advanced thoracic ESCC. In cadavers, the lymphatic vessel counts of the intra-outer longitudinal muscle layer in the Mt and Ce were significantly lower than those of the Lt and Ae, suggesting that lymphatic flow toward the outside of the Mt and Ce was not more abundant than to other sites. CONCLUSION:Our anatomical data suggested that the absence of intra-muscle lymphatic vessels in the middle mediastinal and supraclavicular zones causes skip LNM in patients with thoracic ESCC. Thus, standard esophagectomy with lymph node dissection, including distant zones, may be appropriate for treating patients with superficial thoracic ESCC.

SUBMITTER: Kumakura Y

PROVIDER: S-EPMC5891562 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma.

Kumakura Yuji Y Yokobori Takehiko T Yoshida Tomonori T Hara Keigo K Sakai Makoto M Sohda Makoto M Miyazaki Tatsuya T Yokoo Hideaki H Handa Tadashi T Oyama Tetsunari T Yorifuji Hiroshi H Kuwano Hiroyuki H

Annals of surgical oncology 20180223 5

<h4>Background</h4>Lymph node metastasis (LNM) is a standard mechanism of cancer progression in esophageal squamous cell carcinoma (ESCC). We aimed to clarify the anatomical mechanism of skip nodal metastasis to mediastinal zones by analyzing the relationship between LNM to sentinel zones and lymphatic vessel counts in the muscle layer adjacent to the outer esophagus.<h4>Methods</h4>We examined the surgical records of 287 patients with ESCC who underwent potentially curative surgery (three-field ...[more]

PMID: 29476296

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Project description:The lymphovascular invasion (LVI) status facilitates the determination of the optimal therapeutic strategy for superficial esophageal squamous cell carcinoma (SESCC), but in clinical practice, LVI must be confirmed by postoperative pathology. However, studies of the risk factors for LVI in SESCC are limited. Consequently, this study aimed to identify the risk factors for LVI and use these factors to establish a prediction model. The data of 516 patients who underwent radical esophagectomy between January 2007 and September 2019 were retrospectively collected (training set, n=361, January 2007 to May 2015; validation set, n=155, June 2015 to September 2019). In the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate analyses were utilized to identify predictive factors for LVI in patients with SESCC. A nomogram was then developed using these predictors. The area under the curve (AUC), calibration curve, and decision curve were used to evaluate the efficiency, accuracy, and clinical utility of the model. LASSO regression indicated that the tumor size, depth of invasion, tumor differentiation, lymph node metastasis (LNM), sex, circumferential extension, the presence of multiple lesions, and the resection margin were correlated with LVI. However, multivariate analysis revealed that only the tumor size, depth of invasion, tumor differentiation, and LNM were independent risk factors for LVI. Incorporating these four variables, model 1 achieved an AUC of 0.817 in predicting LVI. Adding circumferential extension to model 1 did not appreciably change the AUC and integrated discrimination improvement, but led to a significant increase in the net reclassification improvement (p=0.011). A final nomogram was constructed by incorporating tumor size, depth of invasion, tumor differentiation, LNM, and circumferential extension and showed good discrimination (training set, AUC=0.833; validation set, AUC=0.819) and good calibration in the training and validation sets. Decision curve analysis demonstrated that the nomogram was clinically useful in both sets. Thus, it is possible to predict the status of LVI using this nomogram scoring system, which can aid the selection of an appropriate treatment plan.

Project description:BackgroundAccurate prediction of tumor invasion depth in superficial esophageal squamous carcinoma (SESC) is essential for deciding the appropriate treatment strategy. We proposed novel endoscopic criteria to differentiate between mucosal and submucosal esophageal cancers and to evaluate the diagnostic accuracy and usefulness of the criteria.MethodsA total of 352 patients who underwent endoscopic or surgical resection for SESC between 1991 and 2010 were included. First, the novel endoscopic criteria were created based on the endoscopic features of 60 randomly selected patients as follows: for T1m cancers, I. flat or slightly elevated or depressed lesion with smooth/even surface of any size, II. slightly elevated lesion of ≤ 1 cm with granular or uneven surface, III. hyperemic flat lesion of ≤ 3 cm with granular or uneven surface, IV. slightly depressed lesion of ≤ 2 cm with uneven surface and for T1sm cancers, I. irregularly (unevenly) nodular or protruded lesion of any size, II. slightly elevated lesion of > 1 cm with granular or uneven surface, III. hyperemic flat lesion of > 3 cm with granular or uneven surface, IV. irregularly (unevenly) depressed lesion of > 2 cm, and V. ulcerative lesion of any size. Next, the endoscopic findings of the remaining 292 patients were reviewed according to the criteria.ResultsThe accuracy of novel endoscopic criteria was 79.5% (232/292). The sensitivity and specificity of mucosal cancers were 78.4% and 81.0%, respectively, whereas those for submucosal cancers were 81.0% and 78.4%, respectively. The accuracy for mucosal cancers was high (97.3%, 72/74) when the lesions were flat or slightly elevated/depressed with smooth/even surface regardless of size, whereas that for submucosal cancers was high (85.7%, 18/21) when the lesions were irregular/nodular protrusions regardless of size. In multivariate analysis, macroscopic type IIb lesion was identified as an independent factor affecting accuracy (P < 0.05). The difference in recurrence-free survival rates between endoscopically mucosal and submucosal cancers was significant (P = 0.026).ConclusionThe novel endoscopic criteria appear to be accurate and useful in predicting invasion depth in SESC. Our criteria might help not only to decide the treatment strategy between surgery and endoscopic resection but also to predict the outcomes of SESC.

Dataset Information

Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma.

Publications

Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma.

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