Comparative study of computed tomography (CT) and pathological diagnosis toward mediastinal lymph node metastasis in esophageal carcinoma

Summary

Objective:

To investigate the diagnostic criteria of mediastinal lymph node metastasis (MLNM) in esophageal carcinoma (EC) by comparing the lymph node sizes measured by computed tomography (CT) and obtained by postoperative pathological examination.

Method:

A total of 305 EC patients were selected. MLNM location, shortest diameter and number were investigated one week before surgery, and then compared with their pathological findings.

Results:

The receiver operating characteristic (ROC) curve analysis revealed that the minimum diameters of MLNM in the thoracic cavity was 8 mm (area under curve [AUC] = 0.766, Youden index = 0.424), 5 mm in supraclavicular fossa (AUC = 0.785, Youden index = 0.494), 6 mm in tracheoesophageal groove (AUC = 0.755, Youden index = 0.405); the sensitivity was increased significantly, and the Youden index was increased significantly when compared with 10 mm.

Conclusion:

The shortest diameter of diagnostic criteria of lymph nodes in EC could be less than 10 mm on CT.

Keywords:
Esophageal Neoplasms; Lymph Nodes; Tomography, X-ray Computed

Introduction

Esophageal carcinoma (EC) is a common gastrointestinal cancer, with about 481,000 new cases worldwide in 2008, and accounts for 3.8% of the total number of cancers. Its incidence has a clear regional distribution, and the morbidity and mortality of EC in developing countries account for more than 80%.¹ The morbidity and mortality of EC in China ranks the first in the world.² EC still has high incidence in China, and in 2012 it ranked the fifth of malignant tumors with its mortality raking the fourth.³ Lymph node metastasis and the number of metastases are important factors that will impact the prognosis of EC.^4-6 Compared with the sixth edition, the seventh edition of tumor-node-metastasis (TNM) staging standards⁷ emphasizes more the impact of the number of lymph node metastasis on the staging. Presently, most Chinese and foreign scholars^8-10 believe that the seventh edition of staging criteria is better than the sixth edition in evaluating the treatment options and prognosis, so, it is very important to accurately diagnose lymph node metastasis. The current standard of positive lymph node set the shortest diameter as 10 mm,¹¹ but this standard is one clinical estimated value while without any pathological evidence; so, there are some controversies, because clinical metastatic lymph nodes in some parts are often smaller. This study compared the features of lymph nodes measured by CT and obtained by postoperative pathology, aiming to investigate the diagnostic criteria of the shortest diameter of EC-MLNM, thus providing guidance for accurate preoperative staging and outlining radiotherapeutic target areas.

Method

Clinical data

A total of 305 patients with thoracic esophageal carcinoma admitted into the Fujian Cancer Hospital from January 2012 to December 2014 were collected, including 236 males and 69 females; aging 34-82 years, with the mean as 58.3±8.2 years. This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Fujian Medical University. Written informed consent was obtained from all participants.

Inclusion criteria: newly diagnosed, without distant metastasis or other malignant tumor, without any anticancer treatments before surgery and performed surgery within one week of CT scanning. The basic pathological situations of the patients are shown in Table 1.

Table 1
General pathological information of the patients.

Pathological information	n
Site
Upper thoracic segment	15
Middle thoracic segment	206
Lower thoracic segment	84
T staging
T0-1	57
T2	59
T3	142
T4	47
Pathological type
Poorly differentiated SqCa	25
Moderately differentiated SqCa	254
Highly differentiated SqCa	15
Other	11

Methods and parameters of CT scanning

PHILIPS Brilliance 256-slice spiral CT scanner (Eindhoven, Holland) was used for the scanning with the parameters as: tube voltage 120 kV, tube current 300-350 mA, scanning collimator 1 mm, pitch 0.9, scanning layer thickness 5 mm, layer spacing 5 mm, reconstruction layer thickness 2.5 mm, and layer spacing 2 mm. The enhanced scanning used one high-pressure syringe to rapidly inject 100 mL of non-ionic contrast agent (iodohydrin) from the elbow vein (injection rate 3 mL/s). Each patient was placed in the supine position when scanning, and the scanning area started from the supraclavicular fossa to the superior mesenteric artery level, the data of which was then transmitted into the Vitrea 2 workstation for multi-window and multi-planar reconstruction.

The classification criteria of intrathoracic lymph nodes referred to the standards revised by the American Joint Committee on Cancer-Union for International Cancer Control (AJCC-UICC) in 2009. Because partial surgical lymph node distribution methods are inconsistent with imaging methods, this study was based on the CT findings and compared with the pathological findings. In order to produce a better comparison, we requested that the surgeons divided the patients into different groups according to the locations of their individual lymph nodes resected surgically, namely the supraclavicular fossa group (SCF), the tracheoesophageal groove group (TEG), the paratrachea group (pT), the paraesophagus group (pE), the subcarina group (sC) and the lung hilum group (LH). Patients who could not be confirmed were excluded, and the biggest lymph node was calculated if more were in the same CT region. Other cases that cannot be concluded into corresponding areas were excluded.

Imaging data acquisition

The best window width and position were adjusted and enlarged appropriately, targeting the grouping positions of the lymph nodes. Position, shortest diameter and number of the lymph nodes in the visual field were recorded and determined jointly by two physicians to obtain a consensus as the final result; at the same, one senior physician was arranged to be in charge of the quality control.

Pathological examination

The lymph nodes were dissected by EC radical correction as well as intraoperative thoracic + abdominal or cervical + thoracic + abdominal lymph node dissection, followed by pathological examination according to the grouping.

Statistical analysis

SPSS for windows 19.0 software package was used for the data entry and analysis; the diagnostic tests used the receiver operating characteristic (ROC) curve for the analysis, and the area under the curve, corresponding sensitivity, specificity, accuracy and the Youden index were also calculated.

Results

General information

Among the 305 patients with thoracic esophageal cancer enrolled into our study, the total number of the lymph nodes found by CT and confirmed pathologically was 1,043, including 203 with positive pathological confirmation and 840 with negative pathological confirmation. The lymph nodes of different zones are shown in Table 2.

Table 2
Lymph nodes found by CT in different zones (mm).

Distribution	SCF	TEG	pT	pE	sC	LH
Number of pathological positive	13	47	30	50	45	18
Min short diameter of pathological positive	3.5	3.0	4.4	4.2	4.2	5.2
Max short diameter of pathological positive	8.0	14.1	14.1	16.5	17.2	15.1
Number of pathological negative	40	132	191	146	245	86
Min short diameter of pathological negative	3.0	3.0	3.0	3.3	3.5	3.5
Max short diameter of pathological negative	9.3	12.8	17.7	10.1	22.8	12.4

• SCF: supraclavicular fossa; TEG: tracheoesophageal groove; pT: paratrachea; pE: paraesophagus; sC: subcarina; LH: lung hilum.

Minimum diameter for diagnosing intrathoracic MLNM in esophageal carcinoma-mediastinal lymph node metastasis (EC-MLNM)

ROC curve analysis revealed that the shortest diameter of lymph node ≥ 8 mm can be set as the best standard for diagnosing intrathoracic EC-MLNM, with area under curve (AUC) as 0.766 (Figure 1A), sensitivity as 54.5%, specificity as 87.9%, accuracy as 82.0% and the Youden index as 0.424. When the shortest diameter was set ≥ 10 mm, the sensitivity, specificity, accuracy and Youden index were 19.6%, 95.8%, 82.4% and 0.154, respectively; when the shortest diameter was set ≥ 5 mm, the sensitivity, specificity, accuracy, and Youden index were 93.7%, 21.4%, 34.2% and 0.151, respectively.

FIGURE 1
ROC curve of shortest diameter of lymph nodes in different areas.

Minimum diameter for diagnosing EC-MLNM at supraclavicular fossa

The ROC curve analysis revealed that the shortest diameter of lymph node ≥ 5 mm can be set as the best standard for diagnosing EC-MLNM at supraclavicular fossa, with AUC as 0.785 (Figure 1B), sensitivity as 76.9%, specificity as 72.5%, accuracy as 73.6%, and the Youden index as 0.494. When the shortest diameter was set ≥ 10 mm, the sensitivity, specificity, accuracy, and Youden index were 0, 1, 75.4% and 0.000, respectively.

Minimum diameter for diagnosing EC-MLNM at tracheoesophageal groove

The ROC curve analysis revealed that the shortest diameter of lymph node ≥ 6 mm can be set as the best standard for diagnosing intrathoracic EC-MLNM at tracheoesophageal groove, with AUC as 0.755 (Figure 1C), sensitivity as 61.7%, specificity as 78.8%, accuracy as 74.3% and the Youden index as 0.405. When the shortest diameter was set ≥ 10 mm, sensitivity, specificity, accuracy and the Youden index were 8.5%, 97.7%, 74.3% and 0.062, respectively; when the shortest diameter was set ≥ 5 mm, sensitivity, specificity, accuracy, and the Youden index were 72.3%, 65.2%, 67.0%, and 0.375, respectively.

Discussion

The main clinical diagnostic methods against EC currently include:¹² esophageal barium contrast, chest CT scan, ultrasound or endoscopy; however, all these methods, except for CT, have obvious limitations in diagnosing esophageal carcinoma-lymph node metastasis (EC-LNM). Studies have shown that^13,14 CT can clearly show the existence of lymph node metastasis with high sensitivity, specificity and accuracy, so it can be used effectively to diagnose EC-LNM. Glazer et al.¹⁵ proposed for the first time in 1984 that the shortest diameter of lymph nodes on CT is much more sensitive than the long and short diameters, which can avoid spatial errors. A shortest diameter of lymph node ≥ 10 mm is often used as the standard of CT to diagnose LNM; however, normal and metastatic lymph nodes overlap in size, so the accuracy of this diagnostic criterion is still controversial. Clinically, CT can reveal metastatic lymph nodes with shortest diameter of less than 10 mm. Takemura et al.¹⁶ measured the shortest diameter of metastatic lymph nodes surgically dissected from patients with esophageal squamous cell carcinoma (ESCC) and found 65% of the samples had the shortest diameter less than 1 cm and 27% was less than 5 mm. A certain study has shown that¹⁷ 63% of EC patients have the shortest diameter of metastatic lymph nodes measuring less than 10 mm. The results of our study showed that, compared with 10 mm, the shortest diameter set as 8 mm can effectively diagnose intrathoracic lymph node metastasis, and the sensitivity was increased from 19.6% to 54.5%, while the specificity and accuracy did not change much. So, 8 mm as the standard can exhibit more diagnostic value, and appropriately reducing the shortest diameter standard on CT toward EC-LNM is more rational.

Studies about the diagnostic criteria of CT in EC-LNM are many, while fewer studies are accompanied by pathological evidence, and recent studies just included mediastinal lymph nodes as part of their results for the sake of statistics.^18,19 Our study took into account the unique features of the lymph nodes at the supraclavicular fossa and tracheoesophageal groove, and performed statistical analysis toward them, respectively. Compared with simple intrathoracic lymph node metastasis, the prognosis of the patients with thoracic esophageal carcinoma, which metastasized toward the supraclavicular fossa, was significantly worse. At present, there is no related report about the CT diagnostic criteria targeting supraclavicular lymph nodes in EC. In our study, we considered that shortest diameter of EC-supraclavicular fossa LNM which can be diagnosed by CT is 5 mm. Patients with tracheoesophageal groove lymph node metastasis can present hoarseness, drinking cough, difficulty to breath or even death by asphyxia in severe cases, so it has become an independent risk factor of death. Kato et al.²⁰ considered that EC-tracheoesophageal groove lymph node metastasis can occur in any locations, lesions and tumor cell invasion ranges of primary tumor. Li et al.²¹ believed that the rate of lymph node metastasis to cervical tracheoesophageal groove and medial supraclavicular zone from middle thoracic section of esophageal cancer was increased with later T stages. Schmidt et al.²² considered that general people have lymph nodes in their tracheoesophageal groove, with an average of 3.24 and 5.52 lymph nodes in the left and right tracheoesophageal grooves, respectively. Clinically, lymph nodes at the tracheoesophageal grooves are often found with a shortest diameter significantly less than 10 mm on CT also confirmed on pathological examination. In our study, the shortest diameter for diagnosing EC-tracheoesophageal groove lymph node metastasis was 6 mm.

Lymphadenectasis may be caused by tumor metastasis as well as inflammatory enlargement, proliferative enlargement, or histiocytic hyperplasia-induced enlargement; some tumor cells may enter lymph nodes causing pathological features to take place despite any perceptible changes in nodal size. So, it will easily result in false-positive and false-negative conclusions if determining LNM only based on the lymph node size.^23,24 In addition to the sizes on CT, metastatic lymph nodes may also reveal changes in density, edge or shape to prompt the metastasis, so how to diagnose EC-LNM with both size standards and other diagnostic methods remains a unsolved problem that needs further studies. However, clinically, the shortest diameter is more practical and intuitive to be used as the standard.

Conclusion

The shortest diameters for diagnosing MLNM in the thoracic cavity, supraclavicular fossa and tracheoesophageal groove were 8 mm, 5 mm and 6 mm, respectively, and it is reasonable to reduce the CT diagnostic criteria of the shortest diameter of positive lymph nodes in EC.

• Study conducted at Fujian Provincial Cancer Hospital, Fuzhou, China

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Publication Dates

• Publication in this collection
  Feb 2018

History

• Received
  24 Apr 2017
• Accepted
  26 June 2017