The Prognostic Significance of Subcarinal Lymph Node Dissection in Esophagectomy for Middle and Lower Thoracic Squamous Cell Carcinoma

doi:10.21203/rs.3.rs-5009603/v1

Background

This retrospective study assesses the prognostic value of subcarinal lymph node dissection (SCLND) in esophageal squamous cell carcinoma (SCC) of the middle and lower thoracic regions.

Methods

Conducted at the Fourth Hospital of Hebei Medical University, the study included 1588 patients with SCC who underwent radical resection from 2008 to 2014. After propensity score matching, 661 patients were analyzed, with 185 without and 476 with SCLND. Kaplan-Meier curves, Log-rank tests, and Cox regression were used for survival analysis, with SPSS 23.0.

Results

SCLN metastasis was found in 10.3% of patients. Factors influencing metastasis included tumor size, invasion depth, positive lymph node count, and smoking and alcohol history. SCLND significantly affected overall survival, with 5-year rates of 47.7% for non-metastatic versus 12.8% for metastatic patients. SCLND improved long-term survival for T3-T4a stage patients but not for T1-T2.

Conclusion

Despite a low SCLN metastasis rate, its presence significantly worsens prognosis. SCLND improves long-term survival, particularly for T3-T4a stage patients, guiding surgical decisions on lymph node dissection.

Esophageal Cancer

Subcarinal Lymph Node Dissection

Prognosis

Propensity Score Matching Analysis

Esophagectomy

China is a high-incidence country for esophageal cancer, with the number of annual cases accounting for approximately half of the global incidence of esophageal cancer [1]. Squamous cell carcinoma is the most common pathological type, and most patients are diagnosed in the advanced stages, often when seeking medical attention [2]. The main treatment method at this stage is surgery, which has the potential to offer a cure for patients with resectable esophageal cancer. However, the prognosis of patients after surgery is poor, and some patients may have lymph node metastasis early after surgery. Lymph node dissection, an essential component of esophageal cancer surgery, can enhance the accuracy of N staging and potentially improve the prognosis if performed reasonably. However, excessive lymph node dissection not only fails to improve patient outcomes but may heighten the risk of complications, especially pulmonary complications [3].

The subcarinal lymph node （SCLN） is located below the bifurcation of the trachea and receives direct ascending lymphatic drainage from the middle and lower esophagus. It is connected to the paratracheal lymphatic chain and the thoracic duct [4]. The SCLN, being classified as a regional lymph node for esophageal cancer and considered crucial for cancer in this region [5], necessitates its dissection during esophagectomy as a routine step. However, there are significant discrepancies in the research results regarding the rate of metastasis to the SCLN, and there is limited research on the impact of dissecting the SCLN on the prognosis of esophageal cancer patients [3,6,7].

Therefore, this retrospective study used propensity score matching analysis to analyze the influencing factors of SCLN involvement in middle and lower esophageal cancer, as well as the impact of SCLN resection on prognosis. The aim was to establish a protocol for lymph node dissection during surgery for middle and lower esophageal cancer, in order to avoid the complications associated with excessive lymph node dissection and the adverse effects of inadequate lymph node staging and prognosis caused by insufficient lymph node dissection.

Inclusion criteria. Our inclusion criteria were as follows: (1) Patients diagnosed with squamous cell carcinoma of the middle and lower thoracic esophagus postoperatively; (2) Having undergone resection for esophageal cancer; (3) Intraoperative lymph node dissection of at least 7 nodes; (4) Postoperative adjuvant therapy including standard chemotherapy, radiotherapy, or chemoradiotherapy. The postoperative adjuvant therapy regimen consisted of platinum-based double-drug chemotherapy for at least 2 courses and/or radiotherapy for at least one course; (5) No preoperative adjuvant therapy (radiotherapy, chemotherapy, or chemoradiotherapy); and (6) No history of other tumor types. This study was approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University. As it was a retrospective study, informed consent was waived.

Exclusion criteria. Exclusion criteria: This study excluded (1) patients with upper thoracic esophageal cancer; (2) patients with non-squamous cell carcinoma postoperatively; (3) those with lymph node dissection of less than or equal to 6 nodes; and (4) patients at M1 stage.

Patients. This study collected information on patients who underwent radical resection for esophageal cancer at the Fourth Hospital of Hebei Medical University, China, from January 2008 to January 2014. All patients had complete clinical and pathological data. The patients were staged following the 8th edition of the AJCC/UICC TNM classification system for esophageal cancer [8].

A total of 198 patients in the non-dissected SCLN group and 1390 patients in the dissected SCLN group were analyzed using SPSS 23.0 for 1:3 propensity score matching analysis. Among them, 185 cases in the non-dissected group were successfully matched with 476 cases in the dissected group, resulting in a total of 661 cases included in this study. All patient medical records and follow-up data were complete (see table 1).
Surgery. All patients underwent esophagectomy under double-lumen intubation and intravenous-inhalation combined general anesthesia. The approach for esophagectomy was selected as either a left or right thoracotomy based on the location of the cancer. The tubed stomach was used as an esophageal substitute. For lower thoracic esophageal cancer, radical esophagectomy, lymph node dissection, mobilization of the stomach, and anastomosis in the thorax were all completed through a left thoracotomy (Sweet operation). For cancer located in the middle third of the esophagus, the tubed stomach was constructed through a midline incision in the abdomen, and then radical resection of the esophagus and lymph nodes, followed by anastomosis in the upper thorax, were performed through a right thoracotomy (Ivor Lewis esophagectomy) or in the neck (McKeown operation). Some Ivor-Lewis and McKeown operations were completed using minimally invasive esophagectomy (MIE) techniques.

Postoperative adjuvant therapy. Postoperative adjuvant therapy adhered to the guidelines set by the Chinese Society of Clinical Oncology (CSCO), which recommended chemoradiotherapy for patients with T4aN0M0 and T1-4aN+M0 staging [9]. The administration of chemotherapy and radiotherapy could be either sequential or synchronous, depending on the patient's tolerability.

Typically, chemotherapy was administered for 3 to 4 cycles after surgery, and included regimens such as paclitaxel and platinum (TP) or fluorouracil and platinum (FP). For the TP regimen, paclitaxel (China Shiyao Pharmaceutical Group Co., Ltd., Shijiazhuang, China) in a dose of 175 mg/m²(days 1-2) and cisplatin (Qilu Pharmaceutical Group Co., Ltd., Jinan, China) in a dose of 15 mg/m²(days 1–5) were administered intravenously, with a repeat cycle after 3 weeks. For the FP regimen, 5-fluorouracil in a dose of 75 mg/m² (days 1-5) and cisplatin (Qilu Pharmaceutical Group Co., Ltd., Jinan, China) in a dose of 15 mg/m²(days 1–5) were administered intravenously, with a repeat cycle after 3 weeks.

The postoperative radiotherapy field encompassed the tumor bed and high-risk lymphatic drainage area, with a total dose of 54 Gy, delivered at 2.0 Gy per day, five times per week.

Follow-up study. The follow-up study was conducted through phone interviews, email communication, outpatient clinic visits, and utilizing the hospital's follow-up system. The follow-up assessments included evaluations of clinical symptoms, signs, CT scans, gastroscopy, and pathological biopsy to determine postoperative recurrence and/or metastasis. Follow-up assessments were conducted every six months until the date of death or February 5th, 2019. Two consecutive losses to follow-up were considered as indicating death, with the date of death recorded as the time of the first loss to follow-up. Overall survival (OS) was defined as the time between the date of surgery and either the date of death or the last date of follow-up.

Statistical analysis. Using SPSS 23.0 software package (IBM Corporation, Armonk, USA), we included 13 covariates in the propensity score matching analysis, including gender, age, tumor location, lesion length, T staging, N staging, differentiation degree, total number of lymph node dissections, smoking history, alcohol consumption history, positive stump, vessel tumor thrombus, and postoperative adjuvant therapy. We used the 1:3 nearest neighbor propensity score matching method with a tolerance value set to 0.05 to match patients in the group without SCLN dissection with patients in the group with dissection of this level of lymph node. Kaplan-Meier survival curves and Log-rank tests were used for univariate survival analysis, and Cox regression analysis was used for multivariate survival analysis. Count data were analyzed using the chi-square test and logistic regression analysis. Kaplan-Meier curves were created using R 4.1.2 (The R Foundation, www.r-project.org ). A P value less than 0.05 was considered statistically significant.

Postoperative complications. According to the data in Table 1, the difference in pleural effusion between the dissecting and non-dissecting groups of subcarinal LNs after matching was statistically close to significant (P=0.059), while the other complications show no significant difference in distribution between the two groups before and after matching, as indicated by P-values greater than 0.05.

SCLN metastasis rate and degree. A total of 661 patients were included in the study, with 476 patients undergoing SCLN dissection and 49 patients with metastasis of the node, resulting in a SCLN metastasis rate of 10.3%. A total of 1592 SCLNs were harvested, with 70 positive nodes, indicating a metastasis degree of 4.4%.

Factors affecting SCLN metastasis. The application of chi-square test for univariate analysis showed that gender (χ²=1.168, P=0.280), age (P=0.689, χ²=0.160), tumor location (χ²=0.078, P=0.779), differentiation degree (χ²=0.237, P=0.626), and vascular tumor thrombus (χ²=1.282, P=0.258) were not risk factors for SCLN metastasis. However, tumor diameter (χ²=8.310, P=0.004), tumor invasion depth (χ²=24.809, P=0.000), number of positive lymph nodes (χ²=26.341, P=0.000), smoking history (χ²=5.088, P=0.024), and alcohol consumption history (χ²=4.074, P=0.044) were related factors for lymph node metastasis in middle and lower esophageal squamous cell carcinoma.
The T stage was highly correlated with the rate of SCLN metastasis, with a 0% for T1 stage, 2.3% for T2 stage (2 out of 86), 11.4% for T3 stage (42 out of 299), and 27.8% for T4a stage (5 out of 18) (χ²=24.809, P=0.000).

Multivariate logistic regression analysis showed that tumor invasion depth (P=0.003) and the number of positive lymph nodes (P=0.000) were independent risk factors for SCLN metastasis in middle and lower esophageal squamous cell carcinoma.

Factors affecting overall Survival. A total of 661 patients were enrolled, and as of the follow-up date, 265 patients were alive and 396 patients had died. The 3-year and 5-year OS rates were 57.0% and 44.3%, respectively. The median survival time was 49 months (range: 1-117 months).

Univariate analysis for OS. The results revealed that factors that influenced postoperative OS included gender (χ²=8.249, P=0.004), tumor length (χ²=25.708, P=0.000), tumor invasion depth (χ²=70.772, P=0.000), number of positive lymph nodes (χ²=149.077, P=0.000), postoperative adjuvant therapy (χ²=21.279, P=0.000), number of dissected lymph nodes (χ²=8.557, P=0.003), smoking status (χ2=4.115, P=0.006), residual tumor status (χ²=6.634, P=0.010), and presence of tumor thrombus in the vessel (χ²=6.634, P=0.010). However, factors like age (χ²=1.211, P=0.269), tumor location (χ²=0.195, P=0.659), degree of differentiation (χ²=0.177, P=0.674), and SCLN dissection (χ²=2.041, P=0.153) did not show any statistically significant difference in influencing OS (Table 2).

Multivariate Analysis for OS: Multiple factors including gender (P=0.025<0.05), tumor length (P=0.047<0.05), invasion depth (P=0.000), number of positive lymph nodes (P=0.000), number of dissected lymph nodes (P=0.024), and presence or absence of postoperative adjuvant therapy (P=0.000) were identified as independent factors affecting OS in patients with thoracic esophageal squamous cell carcinoma in multivariate Cox regression analysis (Table 2).

The impact of SCLN metastasis on OS. The 5-year survival rate among patients with non-metastatic SCLN had reached a noteworthy 47.7%, significantly surpassing the 12.8% observed in the metastatic SCLN group. The statistical contrast between these two cohorts was marked, with a chi-square value of 27.611 and a corresponding P-value of 0.000, which denoted a highly significant and statistically validated disparity (Figure 1).

The impact of SCLN dissection on OS. The 5-year OS rates in the non-dissection group was 44.3%, while the corresponding rates in the dissection group were 48.8% (P=0.153, χ²=2.041) (Figure 2A). Stratified analysis revealed no statistically significant difference in OS between the non-dissection and dissection groups for patients with T1 and T2 stages. However, there was a significant difference in the T3+T4a stage between the two groups (χ² = 6.016, P=0.014), with five-year survival rates of 27.4% and 34.3%, respectively. The SCLN dissection group had a superior survival rate compared to the non-dissection group (Figure 2B-D).

Comment

Lymph node metastasis is a critical aspect of esophageal cancer progression, portending a less favorable prognosis. The esophageal submucosa harbors a dense longitudinal lymphatic network, facilitating lymph node skipping metastasis in early esophageal cancer. Conversely, the esophageal muscularis contains a transverse lymphatic system that drains into periesophageal lymph nodes or connects directly with the paratracheal lymphatic chain or thoracic duct. Notably, the SCLN plays a pivotal role in the lymphatic drainage of middle and lower esophageal cancer [4].

Lymph node dissection, a crucial component of esophageal cancer surgery, ensures more precise postoperative pathological staging and even enhances long-term survival when performed appropriately. However, overzealous cleaning can lead to postoperative complications, such as the increase in postoperative pneumonia resulting from the dissection of SCLNs [3]. In this study, although there was no increase in major postoperative complications, the additional subcarinal lymph node dissection did indeed have a trend of increasing pleural effusion, thereby increasing the drainage volume. Therefore, it is essential to have a thorough understanding of the metastatic status of SCLNs, their impact on long-term survival, and the appropriate criteria for resection of this lymph node level.

In the literature, the metastatic rate of SCLNs is relatively low, with an incidence ranging from 7.0-22.9% [6,7]. Furthermore, several studies have evaluated the risk factors for metastatic diseases in the subcarinal region. Niwa and colleagues reported a rate of 7.0% SCLN metastasis in thoracic esophageal cancer. In multivariate analysis, clinical T stage (T2–T4) was the independent predictive factor for pathological SCLN metastasis (p = 0.021) [6]. Feng et al. reported the rate of subcarinal LN metastasis was 22.9% (116/507). A logistic regression analysis indicated that factors such as tumor length (>3cm vs ≤3cm), tumor location (lower vs upper/middle), vessel involvement (Yes vs No), and depth of invasion (T3-4a vs T1-2) were associated with an increased risk of SCLN metastasis [7]. In the present study, we found that the metastatic rate of SCLNs was 10.3%. This rate was strongly associated with T stage, with a significant P value of less than 0.001. When analyzing patients with stage T1-4 esophageal cancer, we observed a varying metastatic rate in the SCLNs, ranging from 0% to 27.8%. Notably, as the invasion depth to esophageal layers increased, the metastatic rate of SCLNs also increased, with significant P values less than 0.001. These findings suggest that the metastatic potential of SCLNs is influenced by invasion depth. This also suggests that, for patients diagnosed with stage T1 and T2 esophageal cancer, the procedure of SCLN dissection may not be necessary. The study's findings indicate a promising practical application. Nonetheless, further research is warranted to validate this conclusion, particularly concerning the long-term survival implications of lymph node dissection.

In this study, we only focused on the metastasis of SCLNs from lower and middle thoracic esophageal cancer, not upper thoracic esophageal cancer, as metastasis from upper thoracic esophageal cancer is very rare. Shibamoto et al. reported a 0% rate of SCLN metastasis from upper thoracic esophageal cancer[10]. The corresponding figure from the study of Shang et al was 8.6%, which was relative lower than that from middle (19.1%) and lower (16.2%) thoracic esophageal cancer[11]. Therefore, dissection of SCLN was not suggested when performing esophagectomy for cancer arising from upper thoracic esophagus in these studies.

Lymph node involvement is a significant factor that impacts the prognosis of patients with esophageal cancer. Nevertheless, there is limited information regarding the connection between SCLN metastasis and the prognosis of patients with ESCC. Feng et al. revealed that the occurrence rate of SCLN metastasis in patients was 22.9%. Furthermore, patients with SCLN metastasis had a significantly lower 5-year cumulative survival rate compared to those without metastasis (26.7% vs. 60.9%; P < 0.001)[7]. Niwa and colleagues found that the 5-year disease-free survival rate was significantly lower in patients with pathological SCLN metastasis compared to those without (23.1% vs. 67.5%, respectively; log-rank p < 0.0001) [6]. In the present study, the 5-year-survival rate for patients with SCLN metastasis was 47.7% compared to 12.8% in those without (P<0.001). It appears that the findings from various studies are rather consistent in indicating that the metastasis of SCLNs in esophageal cancer has a negative impact on patient prognosis.

Until now, there has been limited knowledge regarding the impact of SCLN dissection on long-term survival, and the findings have been inconsistent. Hu and his colleagues conducted a PSM analysis on 128 patients with thoracic esophageal cancer, revealing that the 5-year survival rates for the non-dissection and dissection groups were 38.9% and 34.3%, respectively (P>0.05). Based on these findings, their study did not recommend the dissection of SCLNs. However, the study lacked a stratified analysis, thus limiting its ability to identify specific candidate populations that would have benefited from SCLN dissection [3]. Niwa et al. conducted a retrospective study involving 342 consecutive patients with thoracic esophageal squamous cell carcinoma (ESCC) who underwent R0 subtotal esophagectomy. Their analysis suggested that SCLN dissection may not provide significant value for patients with upper and lower thoracic ESCC and could potentially be omitted, particularly in cases of superficial carcinoma, based on their calculated efficacy index of lymph node dissection [6]. Similarly, Shang and his colleagues proposed that, based on their calculated efficacy index, SCLN dissection can be omitted for patients with upper thoracic esophageal squamous cell carcinoma (ESCC). However, for patients with middle and lower thoracic esophageal cancer, SCLN dissection is still recommended [11]. Therefore, there is a relatively consistent view that subcarinal lymphadenectomy can be omitted in upper thoracic esophageal cancer. However, there remains no consensus on the necessity of subcarinal lymphadenectomy for middle and lower esophageal cancer. In this study, we stratified the middle and lower esophageal cancer patients based on T staging. The results demonstrated that subcarinal lymphadenectomy had no significant impact on the long-term survival of T1-2 esophageal cancer patients, whereas it significantly improved the long-term survival of T3-4a esophageal cancer patients. Consequently, we recommend omitting subcarinal lymphadenectomy for T1-2 esophageal cancer patients, but it should be performed for T3-4a esophageal cancer patients. The results of this analysis are highly operable and can guide decisions on whether to perform SCLN dissection during surgery.

However, following limitations should be taken into account when interpreting the study's results and when considering the applicability of the findings to broader patient populations or different clinical contexts. 1. Retrospective Study Design: As a retrospective study, it is subject to selection bias and information bias, which may affect the accuracy and generalizability of the findings. 2. Single-Center Data: The study is based on data from a single medical center, which may limit the diversity of the patient population and the applicability of the results to different healthcare settings. 3. Follow-Up Completeness: The study's long-term follow-up may be affected by loss to follow-up, which could introduce bias if the reasons for loss to follow-up are related to the study outcomes. 4. Surgical Technique Variability: Variations in surgical techniques and practices among surgeons may influence the outcomes, and these variations were not controlled for in the study. 5. Potential for Residual Confounding: Despite the use of propensity score matching to adjust for potential confounders, there may still be residual confounding factors that were not measured or could not be adjusted for in the analysis.

In summary, while the metastatic rate of SCLNs (LN) is relatively low among patients with thoracic esophageal squamous cell carcinoma (ESCC), their metastasis can significantly worsen the prognosis. However, dissection of subcarinal LN can significantly enhance long-term survival for patients, particularly those with T3-4a staging.

Ethics Approval and Consent to Participate：This study was conducted in accordance with the ethical standards of the Ethics Committee of the Fourth Hospital of Hebei Medical University, and it adhered to the principles of the Declaration of Helsinki. As a retrospective study analyzing existing medical records and data, informed consent from individual participants was not required. The study was approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University, and the need for written informed consent was waived due to the nature of the study, which involved no intervention or interaction with patients beyond the collection of anonymized, de-identified data. All patient data were handled and stored in compliance with the regulations and guidelines for the protection of personal health information.

Consent for Publication：For this retrospective study, which involves the analysis of de-identified patient data, individual consent for publication was not required as the data were anonymized and presented in an aggregate form without any personal identifiers. The study was conducted in compliance with the ethical standards of the Ethics Committee of the Fourth Hospital of Hebei Medical University, and all procedures followed were in accordance with the Helsinki Declaration. Given the nature of the data and the analysis, which does not include any individual details, images, or videos that could potentially reveal the identity of the participants, no additional consent for publication beyond the approval from the Ethics Committee was sought or required. The manuscript adheres to the Editorial Policies regarding the presentation of case reports and the protection of individual privacy.

Availability of Data and Materials：The datasets generated and analyzed during the current study are not publicly available due to privacy and confidentiality restrictions but are available from the corresponding author on reasonable request. To ensure the protection of patient information and in compliance with ethical standards, data sharing will be conducted under strict guidelines and only after receiving approval from the Ethics Committee of the Fourth Hospital of Hebei Medical University. Researchers interested in accessing the data should contact the corresponding author, Dr. Jun Feng Liu, by email at [email protected], outlining the research objectives and data requirements. Access to the data will be granted after a review and approval process by the relevant institutional authorities to confirm the legitimacy of the request and the intended use of the data.

Competing Interests tatement:： The authors declare that there are no conflicts of interest, including but not limited to financial interests, activities, relationships, or affiliations, that could influence the work presented in this manuscript. No funding was received for this study, and the authors have not received any financial support or benefits from commercial sources for the work reported in this paper. The views and opinions expressed in this publication are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency or organization.

Funding statement: No funding was received for this study. The authors have not received any financial support or benefits from commercial sources for the work reported in this paper.

Authors' Contributions: Si Wei Xu, the primary author, was responsible for the conception and design of the study, data acquisition, analysis, and drafting the manuscript. Jun Feng Liu, the corresponding author, contributed to the study design, provided critical revisions to the manuscript, and supervised the overall research project. Xin Bo Liu participated in the data analysis and interpretation, and assisted in drafting the manuscript. Zhi Hua Shi was involved in the data collection and provided valuable input on the surgical procedures described in the study. Bing Ji Cao contributed to the statistical analysis and interpretation of the results. Shao Wei Zhang assisted in the acquisition and organization of the clinical data used in the study.

All authors have read and approved the final version of the manuscript for submission. Each author has participated sufficiently in the work and takes public responsibility for appropriate portions of the content. The authors confirm that the contributions detailed above are accurate and that there are no other individuals who have met the criteria for authorship but are not listed.

Acknowledgements： The authors would like to express their sincere gratitude to the follow-up staff at the Fourth Hospital of Hebei Medical University for their diligent assistance in conducting the follow-up work, which was integral to the successful completion of this study. Their efforts in tracking patient outcomes and collecting essential data have significantly contributed to the accuracy and reliability of the study's findings. We also acknowledge the support and cooperation of all the patients who participated in this study. Their willingness to share their medical information has been invaluable to advancing our understanding of esophageal cancer treatment and outcomes.

Dr. Si Wei Xu is currently working in the First Hospital of Hebei Medical University.

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Table 1 Clinicopathologic features before and after matching

Variates	Before matching					After matching
Variates	SCLND 1383	SCLNnonD 204	²	P	SCLND 476		SCLNnonD 185	²	P
Sex
Female	421	56	1.183	0.277	133		348	0.100	0.752
Male	926	148	1.183	0.277	52		128	0.100	0.752
Age
＜60	601	89	0.151	0.698	80		201	0.056	0.812
≥60	782	115	0.151	0.698	105		275	0.056	0.812
Smoking
No	691	92	1.919	0.166	122		323	0.107	0.744
Yes	692	112	1.919	0.166	63		153	0.107	0.744
Drinking
No	920	92	0.139	0.710	122		323	0.211	0.638
Yes	463	112	0.139	0.710	63		153	0.211	0.638
Tumor site
Middle	1064	114	59.586	0.000	107		312	3.411	0.065
Lower	319	90	59.586	0.000	78		164	3.411	0.065
Length of tumor
＜4cm	428	76	2.389	0.122	67		155	0.797	0.372
≥4cm	955	128	2.389	0.122	118		321	0.797	0.372
Tumor stump
Negative	1305	185	0.051	0.821	172		444	0.019	0.889
Positive	78	19	0.051	0.821	13		32	0.019	0.889
T stage
T1	223	36	5.765	0.217	36		73	5.288	0.152
T2	276	33			30		86
T3	819	120			106		299
T4a	65	15			143		18
N stage
N0	909	128	2.040	0.546	118		300	1.182	0.757
N1	290	44			41		112
N2	152	28			24		54
N3	32	4			2		13
Lymph nodes
＜15	874	177	50.834	0.000	158		403	0.057	0.811
≥15	509	27	50.834	0.000	27		73	0.057	0.811
Differenciation
Well and moderate	1083	165	1.268	0.737	386		68	0.574	0.902
Poor	300	39	1.268	0.737	148		37	0.574	0.902
Hemangioma thrombus
No	1340	197	0.051	0.821	179		460	0.006	0.939
Yes	43	7	0.051	0.821	6		16	0.006	0.939
Postoperative complications
Rep failure	3	25	0.166	0.683	4		6	0.727	0.349
Pneunonitis	0	8	1.145	0.285	0		4	1.573	0.210
Pleural effusion	0	14	1.998	0.159	0		9	3.565	0.059

Table 2. The univariate and multivariate analysis results of overall survival (OS) in this group of non-small cell lung cancer patients.

	Univariate analysis	Multivariate analysis
	HR（95%CI） P	HR（95%CI） P
Sex（M vs F）	1.404（1.111-1.774）0.004	1.251（0.924-1.693）0148
Age (＜60 vs ≥60）	1.118（0.916-1.366）0.273
Site (M vs L）	0.955（0.778-1.173）0.661
Length (＜4cm vs≥4cm）	1.760（1.408-2.200）0.000	0.822（0.650-1.040）0.102
T stage（T1 vs T2 vs T3 vs T4）	1.737（1.518-1.987）0.000	1.008（0.705-1.677）0.000
N stage (N0 vs N1 vs N2 vs N3）	1.931（1.728-2.158）0.000	0.286（0.148-0.553）0.000
Adjuvant cheo（Yes vs No）	1.645（1.326-2.039）0.000	0.508（0.408-0.632）0.000
Differentiation (Well+Med VS Poor)	0.993（0.771-1.279）0.957
Alcohol (Yes vs No）	0.735（0.602-0.897）0.002	1.078（0.846-1.375）0.543
Smoking (Yes vs No）	0.763（0.622-0.937）0.010	1.016（0.776-1.331）0.906
LNs dissected (＜15vs≥15）	0.634（0.465-0.865）0.004	1.426（1.042-1.951）0.027
SCLN metastasis (Yes vs No）	1.115（0.898-1.386）0.323
Stump(Positive vs Negative）	0.484（0.346-0.676）0.000	1.381（0.972-1.960）0.071
Vesel invasion (Yes vs No）	0.545（0.339-0.875）0.011	0.905（0.548-1.494）0.697

No competing interests reported.

The Prognostic Significance of Subcarinal Lymph Node Dissection in Esophagectomy for Middle and Lower Thoracic Squamous Cell Carcinoma

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