Prognostic Significance of the Proximal Margin for Esophagogastric Junction Adenocarcinoma With Type II&nbsp;and III Tumors After Surgery

doi:10.21203/rs.3.rs-121091/v1

Download PDF

Research article

Prognostic Significance of the Proximal Margin for Esophagogastric Junction Adenocarcinoma With Type II and III Tumors After Surgery

https://doi.org/10.21203/rs.3.rs-121091/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

The incidence of esophagogastric junction adenocarcinoma (EJA) has increased in recent years, with surgical resection the main choice of treatment. The optimal length of the proximal margin for EJA is still under debate, and the impact of EJA survival and recurrence remains unclear. The aim of the present study was to investigate the influence of the optimal length of the proximal margin on EJA.

Methods

From January 2011 to December 2015, 131 patients who had EJA with type II tumors were included and retrospectively analyzed. All patients underwent radical R0 resection. The proximal margin was measured promptly after resection, and the frozen-section pathological examination was negative for the margin.

Results

There were 3 cases of Siewert type I EJA (2.9 %), 75 cases of Siewert type II EJA (57.9 %), and 53 cases (40.1%) of Siewert type III EJA. The median number of lymph nodes examined was 19 (range: 1–41), and the median number of positive lymph nodes was 2 (range: 0–18). Sixty-three patients underwent total gastrectomy (48.1%), and 68 underwent proximal gastrectomy (51.9%). The median follow-up time was 57.3 months: (range 1.9–174.1); 34 patients (26%) relapsed and 74 (56.5%) died. The 5-year overall survival rate of type II tumor patients was 68.2%, and that of type III tumor patients was 38.5% (P = 0.02). For patients with a proximal margin <2 cm, the median recurrence time was 41.6 months, whereas it was for 42.8 months for patients with proximal margin >2 cm (log–rank: 0.496). Our data analysis found that a proximal margin length of 2 cm was a prognostic variable for type II and type III tumors.

Conclusions

There are a number of factors associated with recurrence and overall survival at 5 years for patients who have EJA with type II and type III tumors, and a proximal margin >2 cm may indicate better prognosis.

Cancer Biology

Oncology

Proximal margin

Siewert type

esophagogastric junction adenocarcinoma(EJA)

prognosis

The incidence of esophagogastric junction adenocarcinoma (EJA) has increased in recent years, particularly in Western and Asian countries.^1–3 According to data from Japan, the incidence of EJA has increased by 7.3% from the 1960s to the beginning of the 21^st century. ⁴ A single-center registration study of gastric cancer in China found that the proportion of esophageal–gastric junction (EGJ) cancer increased from 22.3% to 35.7% between 1988 and 2012.⁵ According to the Siewert classification, there are three types of EJA: Siewert type I is defined as tumors located 1–5 cm above the esophagogastric junction, Siewert type II tumors are located at the upper l–2 cm below the esophagogastric junction, and Siewert type III tumors are located 2–5 cm below the esophagogastric junction.⁶ According to the AJCC Cancer Staging Manual, 8th edition, EJA is categorized and staged as esophageal cancer, as long as the tumor center is within 2 cm of the junction, regardless of whether it invades the esophagus. If it is not within 2 cm of the junction, the tumor is grouped and treated as stomach cancer, even if it has invaded the EGJ.⁷ Currently, surgical resection is regarded as the cornerstone of curative treatment, although the introduction of neoadjuvant/adjuvant chemotherapy and radiotherapy and chemotherapy have been found to improve disease prognosis.⁸ Due to the complexities of EJA tumor location, a consensus has yet to be reached on the best surgical strategy. The appropriate resection range of the esophagus and stomach, the scope and location of lymph node resection, and the best surgical method are still unclear.⁹

The optimal length of the proximal margin for EJA is also still under debate, with only a limited number of studies published on this. In their study, Barbour et al. showed that the proximal margin length might be associated with patient survival in type II–IV tumors, but not in type I tumors, and they found that if the length of the proximal margin was >3.8 cm, then the prognosis of type II+ tumor patients could be significantly improved.¹⁰ However, Mine et al. found that, for patients who have EJA with type II or type III tumors, the length of the proximal margin exceeds 2 cm, which seems to be satisfactory.¹¹ The proximal margin length is key for R0 and R1 resection status, and thus for survival outcome.^12,13 Therefore, it is crucial to determine a safe operation range when performing surgery.

We conducted a retrospective, observational study. Based on the classification of the AJCC Cancer Staging Manual, 8th edition, patients diagnosed with EJA type II and type III tumors, treated with surgery between January 2011 and December 2015, were included in the present study, except patients with gastric cancer and/or those undergoing neoadjuvant therapy. The inclusion criteria were: (i) patients undergoing radical surgery, including radical proximal or total gastrectomy; (ii) a negative confirmation of the proximal margin; and (iii) type II and type III tumors without distant metastasis. Patients with incomplete medical information, those undergoing neoadjuvant therapy, those with malignant tumors in other locations, and those who had previously had exploratory or tumor-reduction surgeries were excluded. Fresh specimens were cut longitudinally immediately after resection. The sample was then stretched to the maximum extent and fixed to a plate. The surgeon then measured and recorded the length of the proximal edge. The proximal margin was sent for frozen-section pathological examination to confirm whether the proximal margin length was sufficient. If insufficient, further resection was performed until there was a negative confirmation of the proximal margin. All surgical procedures and the extent of lymph node clearance conformed to the Japanese Gastric Cancer Treatment Guidelines (Japanese Gastric Cancer Association 2011). All procedures were conducted in accordance with the Declaration of Helsinki, as revised in 2013¹⁴.

Data on age, sex, Siewert type, extent of surgery, tumor size, proximal margin, T stage, clinical stage, lymphatic–vascular invasion, neural invasion, differentiation status, total lymph nodes, lymph node metastasis, mediastinal lymph node dissection, Lauren type, human epidermal growth factor 2 status, adjuvant therapy, and relapse or recovery were collected. All patients underwent enhanced chest and abdominal computed tomography every 6 months after discharge to evaluate tumor recurrence and distant metastasis until October 2015. Follow-up was generally conducted through outpatient visits, email, and telephone interviews, and follow-up data were updated until November 1, 2015. The follow-up rate, median follow-up time (months), and overall survival results were included in the study. The main reason that patients could not be followed up was because they declined outpatient visits or changed their telephone numbers and addresses.

All variables were analyzed using descriptive statistics. The results are presented as percentages, means, and dispersion measures. We used the unadjusted Kaplan–Meier method for visualization of the survival curves, and the log–rank test to compare survival curves using SPSS version 22.0. Logistic regression analysis was used for survival identified by univariate analysis were further assessed by multivariate analysis. The P-value was considered to be statistically significant at the 5% level. To better define the surgical margin, we use the receiver–operator curve (ROC). Based on the Declaration of Helsinki and the general research health law.¹⁴ Informed consent was not required for the present study, and patient confidentiality was assured.

We present the following article in accordance with the STROBE reporting checklist.

In total, 168 patients diagnosed with EJA without neoadjuvant chemotherapy were included in the present study, according to our admission and discharge criteria. Thirty-seven patients were excluded; 4 had undergone exploration or tumor-reduction surgery, 10 were diagnosed with T1 tumors according to the final pathological report, and 23 had incomplete information (Figure 1). Finally, 131 patients were included: 100 men (76.3%) and 31 women (23.7%, male-to-female ratio 3.22:1), with a median age of 64 years (range: 38–86). Three patients (2.9%) had Siewert type I tumors, 75 (57.3%) had Siewert type II tumors, and 53 (40.1%) had Siewert type III tumors. For Siewert type I tumors, the median tumor size was 4.5 cm (range: 4–5.5 cm); for Siewert type II tumors, the median tumor size was 4 cm (range: 1–10 cm); and for Siewert type III tumors, the median tumor size was 6 cm (range: 2.5–10 cm). All patients underwent open or laparoscopic surgery. Sixty-three (48.1%) patients underwent total gastrectomy, and 68 (51.9%) underwent subtotal gastrectomy. The median number of lymph nodes examined was 19 (range: 1–41), and the median number of positive lymph nodes was 2 (range: 0–18). The median delay time of adjuvant therapy was 8 weeks (range: 4–13 weeks). Chemotherapy regimens included XELOX, CapeOx, FOLFOX, and capecitabine. The patient clinical characteristics are shown in Table 1.

The median length of the proximal margin was 1 cm (range: 0.5–2.5) in patients with Siewert type I tumors, 1 cm (range: 0.4–5) in Siewert type II tumors, and 1.2 cm (range: 0.4–5) in patients with Siewert type III tumors (Table 1). The impact of the proximal margin length on overall survival was analyzed. A proximal margin length of 2 cm was found to be a prognostic variable for patients with type II and type III tumors in both the univariate (Kaplan–Meier method, P = 0.02) and multivariable analyses (hazard ratio: 2.00, 95% confidence interval: 0.54 –7.41, P = 0.25, Cox method) (Tables 2 and 3).

The length of the proximal edge in the surgical specimens and its relationship with recurrence and the 5-year overall survival rate, which is sorted by centimeters (from nearest to farthest), is shown in Figures 1 and 2.

In the univariate analysis, patients with poorly differentiated tumors (P = 0.005), late clinical stage (P = 0·008), and neural invasion (P = 0.044) were at higher risk of recurrence. Patients with higher pT category tumors (P = 0·028), more lymph node metastasis (P = 0·013), poorly differentiated tumors (P = 0·005), proximal margins of <2 cm (P = 0·019), late clinical stage (P = 0.012), and postsurgical recurrence had significantly worse survival (Table 2).

The median follow-up time was 57.3 months (range: 1.9–174.1); 34 patients (26%) relapsed and 74 patients (56.5%) died. The median overall survival time of patients with a tumor proximal margin of <2 cm was 55.5 months, and that of patients with a proximal margin of >2 cm was 68 months (log–rank: 0.019). The median recurrence time for patients with a proximal margin of <2 cm was 41.6 months, whereas it was 42.8 months for patients with a proximal margin of >2 cm (log–rank: 0.496) (Table 1).

In the multivariate analysis, only tumor differentiation status was found to be the prognostic factor for recurrence. The variables related to the 5-year overall survival rate were tumor infiltration (type II vs. III), proximal margin, tumor differentiation status, and recurrence. However, in the ROC analysis, we did not find that a definitive margin showed better tumor outcomes (Tables 3 and 4).

Type II tumor patients had a 5-year overall survival of 68.2%, and type III tumor patients had a 5-year overall survival of 38.5% (P = 0.02) (Figure 4).We observed an 18.2% recurrence in type II tumor patients, and a 27.5% recurrence in type III tumor patients (P = 0.19) (Figure 5). Patients with type II and type III tumors had a 5-year overall survival of 43.5%. The recurrence rate was 26%; 11 patients had local–regional relapse (32.4%), 23 (67.6%) had distant metastasis, 5 had relapse at 1 distant site (21.7%), 10 had relapse at 2 distant sites (43.5%), 6 had relapse at 3 distant sites (26.1%), and 2 patients had relapse at 4 or more sites (17.4%). No patients died post surgery.

An increase in EJA has been observed globally in recent years, particularly in Western and Asian countries. According to previous literature, the most common tumor types are types II and III.^1–3,15,16 Our retrospective study showed a slight increase in the prevalence of EJA in our hospital (data not shown) during the past 10 years, which is similar to findings reported in the literature. Our data revealed that patients with EJA had poorer survival outcomes than patients with distal gastric cancer because of the different tumor characteristics.^17,18 The optimal length of the proximal margin for EJA is still under debate, and the impact of EJA survival and recurrence remains unclear. Compared with subtotal esophagectomy, the proximal margin of patients undergoing extended gastrectomy should be shorter. Barbour et al. found that proximal margin length was a more significant prognostic factor in types II–IV tumors with N0–2 (P<0.01). However, the same cannot be said for patients with types II–IV N3 tumors (P = 0.48). A proximal length of 3.8 cm in resected specimens is considered an independent prognostic factor according to analyses limited to R0 or R1 resection. The proximal margin length was considered a prognostic factor between the esophagectomy group (5 cm) and the gastrectomy group (2 cm) and influenced the survival of patients with Siewert type I tumors.¹⁰ Mine et al. found that, for patients with EJA with types II–IV tumors, a proximal margin length >2 cm seemed to be associated with better survival (P = 0.008). Type IV tumor patients are more likely to require neoadjuvant therapy. Thus, different surgical strategies can influence the proximal margin length. Barbour et al. performed used esophagectomy (69.7%), whereas Mine et al. exclusively used transhiatal extended gastrectomy.^10,11 Our research mainly focused on the effect of the proximal margin length on patients with EJA type II and III tumors, and we found that a gross proximal margin of >2 cm was an independent prognostic factor for patients with EJA type II and III tumors undergoing radical surgery. Gross proximal margin lengths of 1.5, 2.5, 3, and 3.5 cm had no statistically significant impact on survival. Patients with poor differentiation status seemed more prone to relapse and had a worse prognosis, according to our analysis, which was similar to previous literature.^10,11,17,18 However, Feng et al. and Ohe et al. found that a sufficient proximal margin was not an absolute factor related to survival and recurrence, and in the case of R0 resection, the distance between the free margin and tumor did not affect prognosis.^19,20 Squires et al. also demonstrated there are other pathological factors that affect survival other than the proximal margin.²¹

We observed a 26% (34/131) recurrence rate, and tumor differentiation status was found to be the only significant prognostic factor of recurrence. Most recurrences were distant (23/34, 67.6%), and local–regional recurrences were relatively lower (11/34, 32.4%). According to Patrão et al., tumor differentiation status, pT stage were the strongest prognostic factors for poor outcome and relapse.²² In their study, the relapse rate was 61% (108/177), with only 9 (8.3%) isolated cases of local–regional relapse with symptoms, whereas the majority of cases (99/108, 91.7%) presented with distant metastasis. In their study, Suh et al. had a recurrence rate of 30% after excluding type I cancers; distant metastasis was found to be more prevalent (14%), and only 4.1–0.6% of patients had local–regional recurrence²³. This could be due to only suspicious clinical or laboratory findings undergoing more advanced imaging examinations, such as computed tomography, magnetic resonance imaging, and gastrointestinal endoscopy, and thus many asymptomatic local recurrences are missed due to a lack of timely imaging examinations. Therefore, we may be underestimated and cannot reliably describe the overall local recurrence rate. Almost all recurrences are only diagnosed when there are symptoms, which could be at a relatively late stage, and could explain why the incidence of isolated local metastases was relatively lower. These results suggest that effective systemic treatment is important, and to a large extent, represents the unmet needs of EJA. If we consider that our study only covers type II and type III tumor patients during the 5-year follow-up period, our data are different from those reported in the literature to some extent.

Our specimens were cut longitudinally and lymph nodes were removed for pathological examination, stretched to the maximum extent, and placed on plates. The total length of the proximal edge was determined by vision and touch, and was measured and recorded by the surgeon. If insufficient and additional distal esophagus was removed, we measured the total length of the proximal edge. Because of shrinkage of the specimens, these measured lengths did not true reflect the corresponding in situ lengths before the conclusion of the operation. In 1986, Siu et al. found that esophageal specimens shrunk to approximately half their length after resection, and the upper margin was reduced to a greater extent than the lower edge (44% vs 54% of in situ length, respectively) after resection and before fxation.¹⁸ Thus, based on their findings, a proximal margin of 2 cm would be 4 cm, and the cited minimal proximal margin ranging between 2 and 5 cm would be between 4 and 10 cm in situ.

Limitations

The present retrospective study had several limitations. First, we did not have accurate measurements of the proximal margin length due to shrinkage of the esophagus after resection, and due to the difference between observers; therefore, the lack of a centralized examination of pathological specimens may have led to deviation in the results. Second, the sample size used in the present study was small and was limited to a single institution; thus, more prospective studies are needed to verify our findings in the Chinese population. Finally, we did not evaluate the risk factors for the positive proximal margin, nor did we evaluate the effect of neoadjuvant therapy on the state of the proximal margin after resection.

There are a number of factors associated with recurrence and overall survival at 5 years for patients who have EJA with type II and type III tumors, and a proximal margin of >2 cm may indicate a better prognosis.

esophagogastric junction adenocarcinoma (EJA)

American Joint Committee on Cancer(AJCC)

receiver–operator curve (ROC)

Ethics approval and consent to participate

This retrospective study was approved by the Ethics Committee of Guangdong Provincial People’s Hospital and was carried out in adherence with the Declaration of Helsinki [No. GDREC2016296H(R1)].

Consent for publication

Not applicable.

Availability of data and materials section

All data generated or analysed during this study are included in this published article.

Competing interests

The authors declare that they have no competing interests.

Funding

Guangdong Provincial People's Hospital "Guangdong Outstanding Young Medical Talents" supporting research funds, KJ012019439.

The cost of the project was supported by the funding such as data entry and follow-up.

Author information

Affiliations

Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

Qian Yan, Weixian Hu, Jiabin Zheng,Zejian Lv, Junjiang Wang, Yong Li

The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China;

Qian Yan,Yong Li

Authors Contributions：

(I) Conception and design: Y Li, Q Yan; (II) Administrative support: The Ethics Committee of Guangdong Provincial People’s Hospital;(III) Provision of study materials or patients: Q Yan, W Hu, J Zheng; (IV) Collection and assembly of data:Q Yan, W Hu, J Zheng,Z Lv;J Wang(V) Data analysis and interpretation: Q Yan, W Hu, J Zheng; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Corresponding author

Correspondence to Yong Li.

Acknowledgments

None

Devesa SS, Blot WJ, Fraumeni JF Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States.hCancer. 1998;83(10):2049, Frau
Bollschweiler E, Wolfgarten E, Gutschow C, H patterns in the incidence of esophageal and gastric carcinoma in the United States.he lower marginollowCancer. 2001;92(3):549 Wolfg
Steevens J, Botterweck AA, Dirx MJ, van den Brandt PA, Schouten LJ. Trends in incidence of oesophageal and stomach cancer subtypes in Europe. Eur J Gastroenterol Hepatol. 2010;22(6):669rol He
Kusano C, Gotoda T, Khor CJ, et al. Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan.eJ Gastroenterol Hepatol. 2008;23(11):1662patolr
Liu K, Yang K, Zhang W, et al. Changes of Esophagogastric Junctional Adenocarcinoma and Gastroesophageal Reflux Disease Among Surgical Patients During 1988-2012: A Single-institution, High-volume Experience in China.rAnn Surg. 2016;263(1):88hang
Maric R, Cheng KK. Classification of adenocarcinoma of the oesophagogastric junction.nBr J Surg. 1999;86(8):1098. Class
Rice TW, Ishwaran H, Ferguson MK, et al. Cancer of the esophagus and esophagogastric junction: an eigth edition staging primer. J Thorac Oncol.2017( 12):36ease
van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer.aN Engl J Med. 2012;366(22):2074junctio
Mariette C, Piessen G, Briez N, et al. Oesophagogastric junction adenocarcinoma: which therapeutic approach?.eLancet Oncol. 2011;12(3):296sen G
Barbour AP, Rizk NP, Gonen M, et al. Adenocarcinoma of the gastroesophageal junction: influence of esophageal resection margin and operative approach on outcome.oAnn Surg. 2007;246(1):1k NP
Mine S, Sano T, Hiki N, et al. Proximal margin length with transhiatal gastrectomy for Siewert type II and III adenocarcinomas of the oesophagogastric junction.aBr J Surg. 2013;100(8):1050ki N,
Mattioli S, Di Simone MP, Ferruzzi L, et al. Surgical therapy for adenocarcinoma of the cardia: modalities of recurrence and extension of resection. Dis Esophagus.2001( 14):104–109
Mariette C, Castel B, Balon JM,et al. Extent of oesophageal resection for adenocarcinoma of the oesophagogastric junction.hEur J Surg Oncol. 2003;29(7):588phage
Hasegawa S, Yoshikawa T. Adenocarcinoma of the esophagogastric junction: incidence, characteristics, and treatment strategies.eGastric Cancer. 2010;13(2):63hika
Zhang LH, Huang Q . Changes in incidences of gastric cardiac gastroesophageal junctional and sub-cardiac carcinomas in Nanjing of China:20-year retrospective study from a single tertiary medical center. N Am J Med Sci.2009( 2): 35–
Dexter SP, Sue-Ling H, McMahon MJ,et al. Circumferential resection margin involvement: an independent predictor of survival following surgery for oesophageal cancer. Gut. 2001;48(5):667er. se
Shen JG, Cheong JH, Hyung WJ, et al. Influence of a microscopic positive proximal margin in the treatment of gastric adenocarcinoma of the cardia.pWorld J Gastroenterol. 2006;12(24):3883rolosco
Siu KF, Cheung HC, Wong J. Shrinkage of the esophagus after resection for carcinoma. Ann Surg. 1986;203(2):173, Wong
Feng F, Tian Y, Xu G, et al. The length of proximal margin does not influence the prognosis of Siewert type II/III adenocarcinoma of esophagogastric junction after transhiatal curative gastrectomy. Springerplus. 2016;5:588. Published 2016 May 11.
Ohe H, Lee WY, Hong SW,et al. Prognostic value of the distance of proximal resection margin in patients who have undergone curative gastric cancer surgery.mWorld J Surg Oncol. 2014;12:296.
Squires MH 3rd, Kooby DA, Pawlik TM, et al. Utility of the proximal margin frozen section for resection of gastric adenocarcinoma: a 7-Institution Study of the US Gastric Cancer Collaborative.aAnn Surg Oncol. 2014;21(13):4202oby DA,
G,Kordatou Z,et al.Prognostic significance of positive circumferential resection margin post neoadjuvant chemotherapy in patients with esophageal or gastro-esophageal junction adenocarcinoma.Eur J Surg Oncol 2019;45:439-445.
Suh YS,Lee KG,Oh SY,et al.Recurrence Pattern and Lymph Node Metastasis of Adenocarcinoma at the Esophagogastric Junction.Ann Surg Oncol 2017;24:3631-3639.

Table. 1 Population characteristics.

Variables	Scale	No. of patients
sex ratio(M:F)		100:31
Age(year)		64（38-86）
Siewert type	I	3（2.3）
	II	75（57.3）
	III	53（40.4）
Resection	Total gastrectomy	63（48.1）
Resection	Subtotal gastrectomy	68（51.9）
Size(cm)		4.5（1-10）
Proximal margin(cm)		1.0（0.4-5.5）
Lauren type	intestinal	77（58.8）
Lauren type	diffuse	54（41.2）
Differentiation status	Poor	67(51.1)
Differentiation status	Median-high	64（48.9）
Invasion	T2	22（16.8）
Invasion	T3	109（83.2）
Total lymph nodes		19（1-47）
Positive lymph nodes		2（0-18）
Mediastinal lymph node dissection	Yes	53(49.5)
Mediastinal lymph node dissection	No	78(59.5)
Neural invasion	Yes	71（54.2）
Neural invasion	No	60（45.8）
Lymphatic–vascular invasion	Yes	69（52.7）
Lymphatic–vascular invasion	No	62（47.3）
Adjuvant treatment	Yes	91（69.5）
Adjuvant treatment	No	40（30.5）
HER-2 stastus	Positive	19（14.5）
HER-2 stastus	Negative	112（85.5）
Recurrence	Yes	34（26.0）
Recurrence	No	97（74.0）
Clinical stage	I	1（0.8）
	II	29（22.1）
	III	73（55.7）
	IV	28（21.4）

Table.2 Univariate analysis of potential risk factors for T2-3 AEJ cancers

Variables	Scale	Survived 57 (%)	No survived 74 (%)	P value	Recurrence 34 (%)	No recurrence 97 (%)	P value
Gender	Male	44 (77.2)	56 (75.7)	0.989	27 (79.4)	73 (75.3)	0.618
Gender	Female	13 (22.8)	18 (24.3)	0.989	7 (20.6)	24 (24.7)	0.618
Age	<65	24(42.1)	29 (39.2)	0.259	13(38.2)	40(41.2)	0.941
Age	≥65	33 (57.9)	45 (60.8)	0.259	21 (61.8)	57 (58.8)	0.941
Siewert type	I	2(3.5)	1 (1.4)	0.682	1(2.9)	2 (2.1)	0.769
	II	30 (52.6)	45(60.8)		20 (58.8)	55 (56.7)
	III	25 (43.9)	28 (37.8)		13 (38.2)	40 (41.2)
Resection	Total gastrectomy	30 (52.6)	33 (44.6)	0.409	15 (44.1)	48 (49.5)	0.606
Resection	Subtotal gastrectomy	27 (47.4)	41(55.4)	0.409	19 (55.9)	49 (50.5)	0.606
Size	<4 cm	27(47.4)	27 (36.5)	0.359	12 (35.3)	42 (43.3)	0.388
Size	≥4 cm	30 (52.6)	47(63.5)	0.359	22(64.7)	55 (56.7)	0.388
Proximal margin	<2.0cm	42(73.7）	67(90.5)	0.019	28(82.4)	81(83.5)	0.497
Proximal margin	≥2.0cm	15 (16.8)	7 (9.5)	0.019	6(17.6)	16(16.5)	0.497
Lauren type	intestinal	40 (70.2)	37 (50.0)	0.075	19 (55.9)	58 (59.8)	0.581
Lauren type	diffuse	17 (29.8)	37 (50.0)	0.075	15(44.1)	39 (40.2)	0.581
Differentiation status	Poor	21 (36.8)	46(62.2)	0.005	23(67.6)	44 (45.4)	0.010
Differentiation status	Median-high	36(63.2)	28(37.8)	0.005	11(32.4)	53(54.6)	0.010
Invasion	T2	15 (16.8)	7 (9.5)	0.028	4 (11.8)	18(18.6)	0.194
Invasion	T3	42 (73.7)	67 (90.5)	0.028	30 (88.2)	79(81.4)	0.194
Total lymph nodes	<16	24(42.1)	26(35.1)	0.803	14 (41.2)	36 (37.1)	0.865
Total lymph nodes	≥16	33(57.9)	48(64.9)	0.803	20 (58.8)	61 (62.9)	0.865
Positive lymph nodes	<5	44(77.2)	42(56.8)	0.013	21(61.8)	65(67.0)	0.159
Positive lymph nodes	≥5	13 (22.8)	32 (43.2)	0.013	13 (38.2)	32(33.0)	0.159
Mediastinal Lymph node dissection	Yes	21(36.8)	32 (43.2)	0.622	19 (55.9)	34(35.1)	0.056
Mediastinal Lymph node dissection	No	36(63.2)	42 (56.8)	0.622	15(44.1)	63(64.9)	0.056
Neural membrame	Yes	29 (50.9)	42 (56.8)	0.342	23 (67.6)	48 (49.5)	0.044
Neural membrame	No	28(49.1)	32 (43.2)	0.342	11 (32.4)	49(50.5)	0.044
Vascular thrombus	Yes	27(47.4)	42 (56.8)	0.135	21(61.8)	49(50.5)	0.059
	No	30 (52.6)	32 (43.2)	0.135	13 (38.2)	48 (49.5)	0.059
	I	1 (1.8)	0(0.00)	0.012	0(0.0)	1 (1.0)	0.008
	II	19 (33.3)	10(13.5)		4(11.8)	25 (25.8)
	III	28(49.1)	45 60.8)		21 (61.8)	52 (53.6)
	IV	9 (15.8)	19(25.7)		9(26.5)	19(19.6)
Adjuvant treatment	Yes	39 (68.4)	52 (70.3)	0.517	25(73.5)	66 (68.0)	0.480
Adjuvant treatment	No	18(31.6)	22 (29.7)	0.517	9(26.5)	31(32.0)	0.480
HER-2	positive	9 (15.8)	10 (13.5)	0.727	7 (20.6)	12(12.4)	0.392
HER-2	negtive	48(84.2)	64 (86.5)	0.727	27 (79.4)	85 (87.6)	0.392
Recurrence	Yes	8 (14.0)	26(35.1)	0.001	N/A	N/A
Recurrence	No	49(86.0)	48 (64.9)	0.001	N/A	N/A

Table.3 Cox regression of the factors associated with 5-OS

	B	Hazard ratio(95% CI)	P
Proximal margin	-0.935	0.393(0.179-0.86)	0.019
Recurrence	0.717	2.048(1.254-3.343)	0.004
Differentiation status	-0.489	0.614(0.379-0.992)	0.046

Table .4 Cox regression of the factors associated with recurrence

	B	Hazard ratio(95% CI)	P
Differentiation status	0.744	2.105(1.008-4.395)	0.048

Download PDF

Version 1

posted

You are reading this latest preprint version

Prognostic Significance of the Proximal Margin for Esophagogastric Junction Adenocarcinoma With Type II and III Tumors After Surgery

Status:

Version 1

Abstract

Figures

Background

Methods

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Status:

Version 1