Comparison of factors and prognosis in transthoracic vs. transthoracic-abdominal surgery for EGJA

Comparison of factors and prognosis in transthoracic vs. transthoracic-abdominal surgery for EGJA | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of factors and prognosis in transthoracic vs. transthoracic-abdominal surgery for EGJA Ying Ji, Fei Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7029813/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background : Esophagogastric junction adenocarcinoma (EGJA) is a malignant tumor with special location and complex condition, mainly occurring at the junction of esophagus and stomach. With the increasing incidence, its surgical treatment has attracted wide attention. At present, the mainstream surgical methods include transthoracic surgery (TET) and transthoracic combined surgery (TAT), and there are significant differences between the two in terms ofoperation path, postoperative recovery and prognosis. The purpose of this study is to retrospectively analyze the therapeutic effect and prognosis of EGJA patients with two surgical methods, in order to provide valuable reference for clinical decision-making. METHODS : The clinical data of 148 patients with EGJA treated by transthoracic (80 cases)or transthoracic (68 cases) operation in our hospital from 2016 to 2018 were collected.. The Kaplan–Meier method and the log-rank test were used for univariate survival analysis. Cox regression model was used for multivariate survival analysis. RESULTS : This study identified gender, neoadjuvant chemotherapy, adjuvant chemotherapy, and T stage as significant prognostic factors influencing overall survival (OS) and disease-free survival (DFS). Transthoracic surgery was associated with a longer operative time (188 vs. 155 minutes, P<0.001), a greater number of dissected lymph nodes (24 vs. 22), and an increased number of positive lymph nodes (3 vs. 2, P=0.022), particularly in type II patients (4 vs. 2, P=0.029). For type I patients, overall survival (OS) rates were 52. 1% for the thoracoabdominal surgery group compared to 53. 1% for the transthoracic surgery group, while disease-free survival (DFS) rates were 41.0% and 65.7%, respectively. However, these differences were not statistically significant. In type II patients, although transthoracic surgery is associated with a longer surgical duration, this does not impact the length of hospital stay or intraoperative blood loss. Furthermore, due to its capacity to dissect a greater number of positive lymph nodes, transthoracic surgery may be more effective in reducing tumor residue. Notably, patients undergoing thoracoabdominal surgery experienced a significant improvement in OS (42% vs. 9.3%, P=0.035), although the change in DFS was not statistically significant (35.4%vs. 21.7%). Conclusions : Patients classified as Type I may be more appropriate candidates for transthoracic surgery, given its shorter operation time. In contrast, both transthoracic and abdominal surgeries may represent more suitable surgical options for Type II patients. esophagogastric junction adenocarcinoma Prognosis Transthoracic surgery Transthoracic approach surgery The results of the surgery Figures Figure 1 Figure 2 Figure 3 Introduction Esophagogastric junction adenocarcinoma (EGJA) is an adenocarcinoma that arises from the junction of the distal esophagus and the proximal cardia, representing a common malignant tumor of the gastrointestinal tract. Recent epidemiological data indicate that the incidence of distal gastric squamous cell carcinoma and esophageal squamous cell carcinoma has been decreasing gradually over the years, whereas the incidence of EGJA has been increasing, with a corresponding decrease in the age of onset [ 1 ] . The Siewert classification of esophagogastric junction adenocarcinoma (EGJA) is currently widely accepted, categorizing EGJA into three types based on the anatomical location of the tumor midpoint [ 2 ]. Type I tumors are defined as those with their center located 1–5 cm from the proximal end of the esophagogastric junction (EGJ). Type II tumors have their midpoint situated within 1 cm of the EGJ, while Type III tumors are found in the proximal part of the stomach, with their midpoint located 1–5 cm from the EGJ. In clinical practice, the treatment approaches for EGJA patients often overlap within the realm of thoracic gastrointestinal surgery. Presently, clinical data indicate that esophagogastrectomy is the preferred treatment for Siewert type I tumors, whereas total gastrectomy is favored for type III tumors [ 3 ]. However, there is currently no discernible treatment trend for type II tumors. Regarding the choice of surgical method, Siewert I type surgical treatment has developed the second edition of esophageal cancer guidelines in reference to the International Union for Cancer Control (UICC). The transthoracic approach can facilitate double-field lymph node dissection; however, some transthoracic surgeons prefer to perform this procedure in conjunction with thoracoabdominal surgery. In contrast, Siewert II's clinical treatment primarily involves combined thoracoabdominal surgery, although experienced transthoracic surgeons may also utilize a simple transthoracic approach for double-field lymph node dissection. Some experts argue that the perioperative incidence associated with the transthoracic approach is higher than that of the thoracoabdominal approach, yet the survival rate of patients undergoing the transthoracic method is significantly improved [ 4 ]. Conversely, other experts contend that the transthoracic approach does not result in higher morbidity or survival rates [ 5 ]. Consequently, substantial controversies persist regarding the surgical approach, surgical method, resection scope, and lymph node dissection in the treatment of EGJA [ 6 ] . This study retrospectively summarizes the clinical data of patients with Siewert I and type II esophagogastric junction adenocarcinoma (EGJA) who underwent thoracotomy. It analyzes the safety of the upper resection margin of the tumor, lymph node dissection, prognosis, and other factors, thereby providing a strong basis for the standardization of surgical treatment. Patients and methods Patient registration We retrospectively collected data from 148 patients diagnosed with esophagogastric junction adenocarcinoma (EGJA) who were treated at the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University between January 2016 and January 2018. All patients underwent R0 radical surgery, and both preoperative endoscopy and postoperative pathological examinations confirmed the diagnosis of Siewert type I or type II EGJA. Inclusion criteria for this study comprised patients diagnosed with EGJA Siewert type I and II, as confirmed by preoperative gastroscopy and postoperative pathology. All patients underwent radical R0 resection, exhibited no significant tumor invasion or distant metastasis, and had no history of other malignancies. Furthermore, participants were required to have no comorbidities related to serious cardiopulmonary diseases and no prior upper gastrointestinal surgeries. Exclusion criteria included the presence of concomitant malignant tumors at other sites, non-EGJA patients, and incomplete clinical or follow-up data. This study has received approval from the Ethics Committee of our hospital. Operation method All patients in this cohort received general anesthesia, double-lumen tracheal intubation, and both intravenous and inhalation anesthesia administered by the same anesthesiology team. Intraoperative lymph node labeling (Fig. 1 ) was conducted in the sequence outlined for the 11 cases according to the Japan Esophageal Association Classification of esophageal cancer. The thoracic region included the subcarina (group 107), inferior accessory thoracic esophagus (group 110), and inferior pulmonary ligaments (group 112). The abdominal cavity encompassed the paracardiac artery (groups 1 and 2), the left gastric artery (7 groups), the common hepatic artery (8 groups), the greater curvature of the stomach (4 groups), the abdominal trunk (9 groups), and the diaphragm (20 groups) [ 7 ]. The transthoracic approach involves a left posterolateral incision at the 7th intercostal space. The lower and middle sections of the esophagus were completely detached and mobilized, with the esophagus being retracted using a traction band. Dissection of the diaphragm was performed, including the bilateral diaphragmatic horns. The gastrocolic ligament along the upper margin of the transverse colon was excised while preserving the right gastroomental vessel. Both the gastrosplenic and hepatogastric ligaments were dissected. The gastropancreatic ligaments were also addressed. Resection was carried out on the left gastric artery and the surrounding lymph nodes, along with the gastric cardia and the left gastric and hepatic lymph nodes. Dissection of the left side of the stomach was completed, along with the middle and lower sections of the esophagus and approximately two-thirds of the proximal stomach. Additionally, dissection of the subxiphoid and subpulmonary vein lymph nodes was performed, followed by the execution of an esophagogastroaortic subarch anastomosis. The transthoracic approach comprises two main components. The abdominal section primarily involves laparoscopic surgery, which begins with an epigastric midline incision to dissect the gastrocolic ligaments along the upper margin of the transverse colon. The right gastroomental vessel is preserved, while the gastrosplenic and hepatogastric ligaments are excised, along with the gastropancreatic ligaments. Dissection is performed on the abdominal cardia, left stomach, and liver lymph nodes, as well as the left gastric artery. The proximal end of the stomach is then resected, resulting in the formation of a tubular stomach. Following the closure of the abdominal cavity, a small left thoracic incision is made in the back of the chest, allowing for the removal of subprotuberant lymph nodes and subpulmonary vein lymph nodes. Finally, an esophagogastroaortic subarch anastomosis is performed. Observation marker The comparison between Siewert Type I and Type II was conducted with respect to various factors, including age, sex, pathological stage of the tumor, lymph node involvement, TNM classification, depth of tumor invasion, number of lymph nodes dissected, positive rate of lymph node dissection, surgical approach, proximal incisal margin distance, intraoperative blood loss, postoperative anastomotic fistulas, and complications. The TNM staging is based on the esophageal cancer staging criteria outlined in UICC Version 8. Preoperative neoadjuvant chemotherapy was administered to patients with TNM stage II or higher, consisting of two cycles of induction chemotherapy (cisplatin, 20 mg on days 1–5; Tegeo capsule, 60 mg on days 1–14), with surgery considered only after confirming that the tumor had not progressed. Subsequently, 2 to 4 additional cycles of chemotherapy were provided based on the postoperative pathological stage. post-operation follow-up The 5-year overall survival (OS) and disease-free survival (DFS) rates were analyzed using the log-rank test. OS is defined as the duration from the date of surgery to the date of death from any cause, while DFS is defined as the interval between surgery and either cancer recurrence or death from any cause. Follow-up after surgery included outpatient visits, correspondence, phone calls, and home visits. Statistical process Statistical analysis was conducted using SPSS version 21.0. The Kaplan-Meier method was employed for single-factor survival analysis, while the log-rank test was utilized to assess differences in survival rates among the various groups. Univariate survival analysis of prognostic factors was performed using the Cox regression model (reverse Wald method), with a significance threshold set at P < 0.05. Variables demonstrating a significant difference in univariate analysis (P < 0.05) were subsequently selected for further formula variable analysis. Results Patient clinical characteristics The clinical characteristics of patients enrolled in this study are presented in Table 1 . Among the 148 patients, 68 were assigned to the thoracoscopic approach group, while 80 were in the thoracoabdominal approach group. The cohort comprised 120 males and 28 females, with an average age of 61 ± 8 years. A total of 80 patients were classified as Siewert I type, including 35 patients from the thoracoabdominal approach and 45 from the thoracoscopic approach. Additionally, 68 patients were identified as Siewert II type, with 33 patients from the thoracoabdominal approach and 35 from the thoracoscopic approach. The distribution of postoperative pathological stages was as follows: T1 (12 cases), T2 (12 cases), T3 (20 cases), and T4 (104 cases). Among these, patients with TNM stages IIA to IIIA received neoadjuvant chemotherapy, which included oxaliplatin and tegafur/Gemelacil/omelacil. No significant differences were observed in gender, age, Siewert type, neoadjuvant chemotherapy, adjuvant chemotherapy, or T stage between patients undergoing transthoracic or thoracoabdominal surgery. However, significant differences were noted in N stage and the number of lymph node-positive patients between the two surgical approaches (P < 0.001). Comparison of clinical factors of two surgical methods in EGJA patients The operative time for the transthoracic approach group was shorter than that of the thoracoabdominal approach group. As shown in Table 2 , there were no statistically significant differences in intraoperative blood loss or length of stay between the two groups. The number of lymph nodes removed by thoracoabdominal surgery (24 ± 3) was greater than that removed by the transthoracic approach (22 ± 4, P < 0.001) in both Siewert type I (24 ± 3 vs. 22 ± 2, P = 0.009) and type II EGJA patients (24 ± 3 vs. 21 ± 4, P = 0.005). This suggests that superior wall lymph nodes can be effectively dissected via thoracoabdominal surgery. However, in patients with Siewert type I (P = 0.302), there was no significant difference in the number of positive lymph nodes between the two procedures. Conversely, more positive lymph nodes were dissected in patients with Siewert type II using thoracoabdominal surgery (4 ± 3 vs. 2 ± 3, P = 0.029). Comparison of prognostic factors in EGJA patients As shown in Fig. 2 , patients with Siewert I type EGJA have a better prognosis. The 5-year overall survival (OS) rate was 52.3% for patients with Siewert I EGJA and 29.4% for those with Siewert II EGJA (P = 0.076). Additionally, the 5-year disease-free survival (DFS) was lower for Siewert II patients, at 29. 1%, compared to 51.0% for Siewert I patients (P = 0.019). Although there was no significant difference in OS or DFS between the two surgical methods across all cohorts (Figs. 3A and B), for type I patients, the surgical approach did not impact OS or DFS. However, transthoracic and abdominal surgery significantly improved OS in type II patients (42% vs. 9.3%, P = 0.035). The improvement in DFS (35.4% vs. 21.7%, P = 0. 187) was not statistically significant. Based on the survival outcomes, transthoracic abdominal surgery may be more appropriate for patients with Siewert II EGJA. In all patients, stage T and stage N are critical prognostic factors influencing overall survival (OS) and disease-free survival (DFS). However, age and histological differentiation did not demonstrate statistically significant effects on 5-year OS and DFS. Additionally, patients who received neoadjuvant chemotherapy exhibited worse outcomes, with OS at 53.4% versus 10% (P < 0.001) and DFS at 54.6% versus 19. 1% (P < 0.001). Similarly, those who underwent adjuvant chemotherapy had poorer outcomes, with OS at 78% versus 21.8% (P < 0.001) and DFS at 68.8% versus 27.6% (P < 0.001). These findings may be attributed to the fact that these patients often present with more severe disease conditions. The same patterns regarding these factors are also observed when stratified by Siewert types I and II, with data presented in Tables 3 and 4 . Multivariate analysis In all patients, both T stage and N stage are critical factors. A Cox proportional hazards regression model was employed for analysis, with variables exhibiting statistically significant differences in univariate analysis identified as independent variables. The results indicated that T stage (T3: HR = 5.927, [95% CI: 1.567–22.418], P = 0.009; T4: HR = 6.198, [95% CI: 1.710-22.469], P = 0.006) and N stage (N2: HR = 3.039 [95% CI: 1.096–8.427], P = 0.033; N3: HR = 2.855 [95% CI: 1.070–7.622], P = 0.036) were independent factors influencing overall survival (OS) in patients with EGJA cancer (Table 5 ). When stratified into Siewert I and Siewert II groups, only sex emerged as an independent factor affecting patient outcomes (Table 5 ). Discussion EGJA is a prevalent malignant gastrointestinal tumor that arises at the esophagogastric junction [ 8 ]. Due to its location at the interface of the esophagus and stomach, EGJA exhibits characteristics of both esophageal and gastric malignancies, leading to distinct differences in surgical treatment approaches in clinical practice. Consequently, there is considerable controversy and ongoing discussion regarding the optimal surgical method and the extent of lymph node dissection. Surgery remains the primary treatment method for esophagogastric junction adenocarcinoma (EGJA), and it is crucial to select appropriate surgical techniques based on the different Siewert stages [ 9 , 10 ]. An effective surgical choice should fulfill the following criteria: (1) complete resection of the primary tumor; (2) preservation of a safe upper incisal margin; (3) thorough lymph node dissection; (4) attainment of a higher postoperative long-term survival rate; and (5) minimization of surgical trauma, reduction of postoperative complications, and facilitation of rapid recovery following the procedure. The esophagogastric junctional adenocarcinoma (EGJA) is located at the thoracoabdominal junction, necessitating a careful selection of surgical approach based on tumor location prior to surgery to ensure complete exposure and removal. Siewert Type I tumors, which are primarily situated in the chest cavity, require a reconstructive esophagogastric anastomosis in the chest to achieve a satisfactory upper incisal margin, regardless of the surgical technique employed. Conversely, Siewert Type III tumors, predominantly located near the stomach, generally allow for thoracoabdominal surgery to attain an adequate upper incision margin [ 11 ]. In the case of Siewert Type II tumors, which are positioned at the thoracoabdominal junction, there remains considerable debate regarding the optimal surgical method to secure a satisfactory superior incisal margin [ 9 , 12 , 13 ]. Research [ 14 ] indicates that transthoracic resection in Siewert Type II patients is associated with a lower rate of positive upper margins. A positive upper margin is correlated with significantly reduced long-term survival rates compared to a negative margin, with median survival times of 11. 1 months and 36.3 months, respectively [ 15 ]. Currently, there is no consensus regarding the ideal upper incisal margin for EGJA, although studies suggest that a safe incision margin distance of 5–8 cm from the esophagus is recommended [ 15 , 16 ]. Furthermore, the safety and efficacy of transthoracic surgical approaches have been confirmed [ 17 ]. In this study, Siewert Type I and II EGJA patients exhibited a significantly improved 5-year overall survival rate when the upper incisal margin was ≥ 5 cm. However, for Siewert Type III EGJA patients, the 5-year overall survival rate was higher in the thoracoabdominal surgery group compared to the transthoracic surgery group when the upper incisal margin was ≥ 5 cm (53.3% vs. 83.3%). Therefore, the transthoracic approach is deemed more suitable for patients with advanced Siewert Type II cancer. In this study, the 5-year overall survival rate for patients with Siewert type I EGJA was 53. 1% in the thoracic surgery group and 52. 1% in the thoracic and abdominal surgery group. There was no significant difference in prognosis between the two surgical methods for Siewert type I EGJA. However, the operation time in the transthoracic surgery group was shorter than that in the thoracoabdominal surgery group. Therefore, transthoracic surgery is recommended for patients with Siewert type I cancer. In patients with Siewert type II EGJA, significant differences were observed in operation time, the number of lymph nodes, and the number of positive lymph nodes between the transthoracic and thoracoabdominal surgery groups. The 5-year overall survival rate was 9.3% in the thoracoabdominal surgery group and 42% in the transthoracic surgery group. The prognosis for patients in the transthoracic surgery group was significantly better than that for those in the thoracoabdominal surgery group (P = 0.035). Therefore, the transthoracic approach is more suitable for patients with Siewert type II advanced cancer. The AICC and UICC 8th Edition regulations for esophageal and gastric cancer specify that Siewert Type I and II EGJA lymph nodes are categorized under esophageal cancer, whereas Type III lymph nodes are classified under gastric cancer. In the case of Siewert Types I and II EGJA, the lymph node dissection in the lower mediastinum and abdominal cavity follows the same protocol as that for esophageal cancer. In assessing the N stage, specific requirements exist regarding the total number of lymph nodes removed; however, there are no established criteria for lymph node score. According to some studies [ 18 ], the number of lymph nodes excised serves as an independent factor influencing the prognosis of esophagogastric junction adenocarcinoma (EGJA). Furthermore, another study [ 19 ] indicated that the number of lymph nodes removed during radical EGJA surgery is typically limited to 15, with patients who had more than 15 lymph nodes removed demonstrating a better prognosis compared to those with fewer than 15. In our study, we observed that as the number of lymph node metastases in Siewert types I and II increased, the N stage also heightened, leading to a decrease in the 5-year survival rate of patients. Notably, there was no significant difference in the 5-year survival rates between Siewert type II patients with more than 15 lymph nodes and those with fewer than 15. Conversely, among Siewert type I patients, those who had more than 15 lymph nodes removed exhibited lower 5-year survival rates compared to those with fewer than 15 lymph nodes removed. It has been reported [ 20 ] that the lymph node metastasis of esophagogastric junction adenocarcinoma (EGJA) predominantly occurs within the abdominal cavity, particularly in the lymph nodes associated with the paracardial and left gastric arteries. Consequently, all patients in this study underwent lymph node dissection in both groups. When assessing intrathoracic mediastinal lymph nodes, patients with Siewert type I exhibited the highest rate of mediastinal lymph node metastasis among all subtypes [ 21 ], with a reported incidence ranging from 25–35%. Sasako et al. [ 22 ] indicated that the incidence of mediastinal lymph node metastasis in Siewert type II patients varied between 7% and 32%. Additionally, another study reported that 16% of Siewert type II patients had lymph node metastases in both the chest and abdomen, while 19% exhibited mediastinal lymph node metastases [ 23 ]. The study results of Kakeji et al. [ 24 ] indicated that laparoscopic surgery combined with radical esophagogastric junction adenocarcinoma (EGJA) is an optimal approach for mediastinal and abdominal lymph node dissection, as it not only facilitates thorough dissection but also minimizes bleeding. Noshiro et al.'s study further confirmed the safety and feasibility of thoracic laparoscopic treatment for EGJA [ 25 ]. It has been observed that an increased incision length in transthoracic surgery correlates with heightened intraoperative bleeding, while intraoperative procedures such as transposition and tracheal intubation for lung isolation contribute to prolonged operative time [ 26 ]. In recent years, compared to the traditional long posterolateral thoracic incision, endoscopic EGJA surgery utilizing both thoracoscopy and laparoscopy has resulted in shorter thoracic incisions, reduced stimulation of the intercostal nerves, and significant advantages in minimizing intraoperative bleeding and the risk of lung infection [ 27 ]. In this study, the operative steps for mediastinum procedures were identical between the two approaches, and all patients were treated by the same surgeon. Consequently, The differences between the two surgical methods and procedures were not considered statistically significant., the position and level of the anastomosis were consistent, and the same trophic vessels—the gastric diaphragm and the right gastroepiploic vessel—were preserved during the surgery. This approach facilitated early recovery of respiratory function postoperatively. The analysis revealed no significant difference in the 5-year survival rates for Siewert type I patients who underwent transthoracic versus thoraco-abdominal surgery; thus, transthoracic surgery is recommended. In contrast, for Siewert type II patients, the 5-year survival rate and prognosis associated with thoraco-abdominal surgery were superior to those of transthoracic surgery. Therefore, transthoracic surgery is also recommended for this group, with simultaneous mediastinal and abdominal lymph node dissection advised to minimize residual tumor cells at the incisal margin. In addition to surgical treatment, neoadjuvant chemotherapy for esophagogastric junction adenocarcinoma (EGJA) has gained acceptance among clinicians due to its benefits in enhancing surgical resection rates and extending patient survival in select cases, particularly for Siewert type II patients. Research indicates that preoperative neoadjuvant chemotherapy decreases both the recurrence and metastasis rates in cancer patients, resulting in a higher 5-year survival rate [ 28 ]. Notably, in this study, Siewert type I and II patients who did not receive neoadjuvant chemotherapy exhibited a higher 5-year survival rate compared to those who underwent the treatment. However, it is important to note that preoperative neoadjuvant chemotherapy is not appropriate for all advanced EGJA patients. Some studies have revealed that P53 and Ki-67 expression levels are negatively correlated with the sensitivity and effectiveness of neoadjuvant chemotherapy, potentially due to their interference with tumor cell apoptosis and metabolic processes [ 29 , 30 ] . This study compared the surgical outcomes of various methods concerning the safety of the upper incisal margin, lymph node dissection, postoperative complications, and the 5-year postoperative survival rate, thereby providing a theoretical foundation for the judicious selection of surgical techniques. However, this retrospective study exhibited some selection bias, and the influence of varying tumor invasion depths was not accounted for in the comparison, which presents certain limitations. In conclusion, the primary factors influencing the postoperative outcomes of Siewert type I and Siewert type II esophagogastric junction adenocarcinoma (EGJA) were the surgical method employed and the extent of lymph node dissection. Transthoracic surgery is deemed suitable for patients with Siewert type I lesions, while it is also appropriate for patients with Siewert type II progression. Nevertheless, the degree of lymph node metastasis in Siewert type I and Siewert type II EGJA remains a significant factor that restricts the prognosis of this condition. Declarations Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions Two authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Fei Li. The first draft of the manuscript was written by Ying Ji and two authors commented on previous versions of the manuscript. Two authors read and approved the final manuscript. Consent to participate Informed consent was obtained from all individual participants included in the study. 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Supplementary Files Tables.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 26 Nov, 2025 Reviewers agreed at journal 12 Nov, 2025 Reviews received at journal 30 Sep, 2025 Reviewers agreed at journal 26 Sep, 2025 Reviewers invited by journal 16 Sep, 2025 Editor assigned by journal 16 Jul, 2025 Submission checks completed at journal 16 Jul, 2025 First submitted to journal 02 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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13:22:34","extension":"html","order_by":63,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":153923,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7029813/v1/a8cee67ac12748b19984dc75.html"},{"id":92088620,"identity":"6a761f76-4552-4189-9788-495f52de8b25","added_by":"auto","created_at":"2025-09-24 13:14:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":774347,"visible":true,"origin":"","legend":"\u003cp\u003eNaming and numbers of lymph node stations in Japanese Classification of EsophagealCancer, 11th Edition [4].\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7029813/v1/048e44100e2f8381c9433174.png"},{"id":92087109,"identity":"55638d19-be0d-4ce7-b3e7-0664d18a3013","added_by":"auto","created_at":"2025-09-24 13:06:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":397381,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier plot of overall survival(OS, A) and disease-free survival (DFS, B) in EGJA patients stratified by Siewert type.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7029813/v1/3d4334795675bbdb92818414.png"},{"id":92087121,"identity":"7a3f2a02-c1c2-465b-ab6d-6c051a126413","added_by":"auto","created_at":"2025-09-24 13:06:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":879443,"visible":true,"origin":"","legend":"\u003cp\u003eThe Kaplan-Meier plot of overall survival (OS) and disease-free survival (DFS) in EGJA patients who accepted different kinds of surgery.\u003c/p\u003e\n\u003cp\u003eA (OS) and B (DFS) in all of the AEG patients; C (OS) and D (DFS) in Siewert type I AEG patients; E (OS) and F (DFS) in Siewert type II AEG patients.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7029813/v1/3a2a69fed7b0bad5fd7dedc1.png"},{"id":92189087,"identity":"7d25340f-3b8c-4971-b408-0d23cc1fac98","added_by":"auto","created_at":"2025-09-25 14:57:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3604893,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7029813/v1/d7bea6e8-54bf-44ac-8c9f-a226dc12cadb.pdf"},{"id":92087107,"identity":"4773b3fc-7da4-43fa-9d8c-22216337b938","added_by":"auto","created_at":"2025-09-24 13:06:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":99377,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7029813/v1/8d6f682ac9ab4c6675c321be.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of factors and prognosis in transthoracic vs. transthoracic-abdominal surgery for EGJA","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEsophagogastric junction adenocarcinoma (EGJA) is an adenocarcinoma that arises from the junction of the distal esophagus and the proximal cardia, representing a common malignant tumor of the gastrointestinal tract. Recent epidemiological data indicate that the incidence of distal gastric squamous cell carcinoma and esophageal squamous cell carcinoma has been decreasing gradually over the years, whereas the incidence of EGJA has been increasing, with a corresponding decrease in the age of onset [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] .\u003c/p\u003e\u003cp\u003eThe Siewert classification of esophagogastric junction adenocarcinoma (EGJA) is currently widely accepted, categorizing EGJA into three types based on the anatomical location of the tumor midpoint [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Type I tumors are defined as those with their center located 1–5 cm from the proximal end of the esophagogastric junction (EGJ). Type II tumors have their midpoint situated within 1 cm of the EGJ, while Type III tumors are found in the proximal part of the stomach, with their midpoint located 1–5 cm from the EGJ. In clinical practice, the treatment approaches for EGJA patients often overlap within the realm of thoracic gastrointestinal surgery. Presently, clinical data indicate that esophagogastrectomy is the preferred treatment for Siewert type I tumors, whereas total gastrectomy is favored for type III tumors [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, there is currently no discernible treatment trend for type II tumors.\u003c/p\u003e\u003cp\u003e Regarding the choice of surgical method, Siewert I type surgical treatment has developed the second edition of esophageal cancer guidelines in reference to the International Union for Cancer Control (UICC). The transthoracic approach can facilitate double-field lymph node dissection; however, some transthoracic surgeons prefer to perform this procedure in conjunction with thoracoabdominal surgery. In contrast, Siewert II's clinical treatment primarily involves combined thoracoabdominal surgery, although experienced transthoracic surgeons may also utilize a simple transthoracic approach for double-field lymph node dissection. Some experts argue that the perioperative incidence associated with the transthoracic approach is higher than that of the thoracoabdominal approach, yet the survival rate of patients undergoing the transthoracic method is significantly improved [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Conversely, other experts contend that the transthoracic approach does not result in higher morbidity or survival rates [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Consequently, substantial controversies persist regarding the surgical approach, surgical method, resection scope, and lymph node dissection in the treatment of EGJA [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] .\u003c/p\u003e\u003cp\u003eThis study retrospectively summarizes the clinical data of patients with Siewert I and type II esophagogastric junction adenocarcinoma (EGJA) who underwent thoracotomy. It analyzes the safety of the upper resection margin of the tumor, lymph node dissection, prognosis, and other factors, thereby providing a strong basis for the standardization of surgical treatment.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003ePatient registration\u003c/p\u003e\u003cp\u003eWe retrospectively collected data from 148 patients diagnosed with esophagogastric junction adenocarcinoma (EGJA) who were treated at the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University between January 2016 and January 2018. All patients underwent R0 radical surgery, and both preoperative endoscopy and postoperative pathological examinations confirmed the diagnosis of Siewert type I or type II EGJA.\u003c/p\u003e\u003cp\u003eInclusion criteria for this study comprised patients diagnosed with EGJA Siewert type I and II, as confirmed by preoperative gastroscopy and postoperative pathology. All patients underwent radical R0 resection, exhibited no significant tumor invasion or distant metastasis, and had no history of other malignancies. Furthermore, participants were required to have no comorbidities related to serious cardiopulmonary diseases and no prior upper gastrointestinal surgeries. Exclusion criteria included the presence of concomitant malignant tumors at other sites, non-EGJA patients, and incomplete clinical or follow-up data. This study has received approval from the Ethics Committee of our hospital.\u003c/p\u003e\u003cp\u003e\u003cb\u003eOperation method\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll patients in this cohort received general anesthesia, double-lumen tracheal intubation, and both intravenous and inhalation anesthesia administered by the same anesthesiology team. Intraoperative lymph node labeling (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) was conducted in the sequence outlined for the 11 cases according to the Japan Esophageal Association Classification of esophageal cancer. The thoracic region included the subcarina (group 107), inferior accessory thoracic esophagus (group 110), and inferior pulmonary ligaments (group 112). The abdominal cavity encompassed the paracardiac artery (groups 1 and 2), the left gastric artery (7 groups), the common hepatic artery (8 groups), the greater curvature of the stomach (4 groups), the abdominal trunk (9 groups), and the diaphragm (20 groups) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe transthoracic approach involves a left posterolateral incision at the 7th intercostal space. The lower and middle sections of the esophagus were completely detached and mobilized, with the esophagus being retracted using a traction band. Dissection of the diaphragm was performed, including the bilateral diaphragmatic horns. The gastrocolic ligament along the upper margin of the transverse colon was excised while preserving the right gastroomental vessel. Both the gastrosplenic and hepatogastric ligaments were dissected. The gastropancreatic ligaments were also addressed. Resection was carried out on the left gastric artery and the surrounding lymph nodes, along with the gastric cardia and the left gastric and hepatic lymph nodes. Dissection of the left side of the stomach was completed, along with the middle and lower sections of the esophagus and approximately two-thirds of the proximal stomach. Additionally, dissection of the subxiphoid and subpulmonary vein lymph nodes was performed, followed by the execution of an esophagogastroaortic subarch anastomosis.\u003c/p\u003e\u003cp\u003eThe transthoracic approach comprises two main components. The abdominal section primarily involves laparoscopic surgery, which begins with an epigastric midline incision to dissect the gastrocolic ligaments along the upper margin of the transverse colon. The right gastroomental vessel is preserved, while the gastrosplenic and hepatogastric ligaments are excised, along with the gastropancreatic ligaments. Dissection is performed on the abdominal cardia, left stomach, and liver lymph nodes, as well as the left gastric artery. The proximal end of the stomach is then resected, resulting in the formation of a tubular stomach. Following the closure of the abdominal cavity, a small left thoracic incision is made in the back of the chest, allowing for the removal of subprotuberant lymph nodes and subpulmonary vein lymph nodes. Finally, an esophagogastroaortic subarch anastomosis is performed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eObservation marker\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe comparison between Siewert Type I and Type II was conducted with respect to various factors, including age, sex, pathological stage of the tumor, lymph node involvement, TNM classification, depth of tumor invasion, number of lymph nodes dissected, positive rate of lymph node dissection, surgical approach, proximal incisal margin distance, intraoperative blood loss, postoperative anastomotic fistulas, and complications. The TNM staging is based on the esophageal cancer staging criteria outlined in UICC Version 8. Preoperative neoadjuvant chemotherapy was administered to patients with TNM stage II or higher, consisting of two cycles of induction chemotherapy (cisplatin, 20 mg on days 1–5; Tegeo capsule, 60 mg on days 1–14), with surgery considered only after confirming that the tumor had not progressed. Subsequently, 2 to 4 additional cycles of chemotherapy were provided based on the postoperative pathological stage.\u003c/p\u003e\u003cp\u003e\u003cb\u003epost-operation follow-up\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe 5-year overall survival (OS) and disease-free survival (DFS) rates were analyzed using the log-rank test. OS is defined as the duration from the date of surgery to the date of death from any cause, while DFS is defined as the interval between surgery and either cancer recurrence or death from any cause. Follow-up after surgery included outpatient visits, correspondence, phone calls, and home visits.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStatistical process\u003c/b\u003e\u003c/p\u003e\u003cp\u003eStatistical analysis was conducted using SPSS version 21.0. The Kaplan-Meier method was employed for single-factor survival analysis, while the log-rank test was utilized to assess differences in survival rates among the various groups. Univariate survival analysis of prognostic factors was performed using the Cox regression model (reverse Wald method), with a significance threshold set at P \u0026lt; 0.05. Variables demonstrating a significant difference in univariate analysis (P \u0026lt; 0.05) were subsequently selected for further formula variable analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003ePatient clinical characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe clinical characteristics of patients enrolled in this study are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among the 148 patients, 68 were assigned to the thoracoscopic approach group, while 80 were in the thoracoabdominal approach group. The cohort comprised 120 males and 28 females, with an average age of 61\u0026thinsp;\u0026plusmn;\u0026thinsp;8 years. A total of 80 patients were classified as Siewert I type, including 35 patients from the thoracoabdominal approach and 45 from the thoracoscopic approach. Additionally, 68 patients were identified as Siewert II type, with 33 patients from the thoracoabdominal approach and 35 from the thoracoscopic approach. The distribution of postoperative pathological stages was as follows: T1 (12 cases), T2 (12 cases), T3 (20 cases), and T4 (104 cases). Among these, patients with TNM stages IIA to IIIA received neoadjuvant chemotherapy, which included oxaliplatin and tegafur/Gemelacil/omelacil. No significant differences were observed in gender, age, Siewert type, neoadjuvant chemotherapy, adjuvant chemotherapy, or T stage between patients undergoing transthoracic or thoracoabdominal surgery. However, significant differences were noted in N stage and the number of lymph node-positive patients between the two surgical approaches (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cb\u003eComparison of clinical factors of two surgical methods in EGJA patients\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe operative time for the transthoracic approach group was shorter than that of the thoracoabdominal approach group. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, there were no statistically significant differences in intraoperative blood loss or length of stay between the two groups. The number of lymph nodes removed by thoracoabdominal surgery (24\u0026thinsp;\u0026plusmn;\u0026thinsp;3) was greater than that removed by the transthoracic approach (22\u0026thinsp;\u0026plusmn;\u0026thinsp;4, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in both Siewert type I (24\u0026thinsp;\u0026plusmn;\u0026thinsp;3 vs. 22\u0026thinsp;\u0026plusmn;\u0026thinsp;2, P\u0026thinsp;=\u0026thinsp;0.009) and type II EGJA patients (24\u0026thinsp;\u0026plusmn;\u0026thinsp;3 vs. 21\u0026thinsp;\u0026plusmn;\u0026thinsp;4, P\u0026thinsp;=\u0026thinsp;0.005). This suggests that superior wall lymph nodes can be effectively dissected via thoracoabdominal surgery. However, in patients with Siewert type I (P\u0026thinsp;=\u0026thinsp;0.302), there was no significant difference in the number of positive lymph nodes between the two procedures. Conversely, more positive lymph nodes were dissected in patients with Siewert type II using thoracoabdominal surgery (4\u0026thinsp;\u0026plusmn;\u0026thinsp;3 vs. 2\u0026thinsp;\u0026plusmn;\u0026thinsp;3, P\u0026thinsp;=\u0026thinsp;0.029).\u003c/p\u003e\u003cp\u003e\u003cb\u003eComparison of prognostic factors in EGJA patients\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, patients with Siewert I type EGJA have a better prognosis. The 5-year overall survival (OS) rate was 52.3% for patients with Siewert I EGJA and 29.4% for those with Siewert II EGJA (P\u0026thinsp;=\u0026thinsp;0.076). Additionally, the 5-year disease-free survival (DFS) was lower for Siewert II patients, at 29. 1%, compared to 51.0% for Siewert I patients (P\u0026thinsp;=\u0026thinsp;0.019). Although there was no significant difference in OS or DFS between the two surgical methods across all cohorts (Figs.\u0026nbsp;3A and B), for type I patients, the surgical approach did not impact OS or DFS. However, transthoracic and abdominal surgery significantly improved OS in type II patients (42% vs. 9.3%, P\u0026thinsp;=\u0026thinsp;0.035). The improvement in DFS (35.4% vs. 21.7%, P\u0026thinsp;=\u0026thinsp;0. 187) was not statistically significant. Based on the survival outcomes, transthoracic abdominal surgery may be more appropriate for patients with Siewert II EGJA.\u003c/p\u003e\u003cp\u003eIn all patients, stage T and stage N are critical prognostic factors influencing overall survival (OS) and disease-free survival (DFS). However, age and histological differentiation did not demonstrate statistically significant effects on 5-year OS and DFS. Additionally, patients who received neoadjuvant chemotherapy exhibited worse outcomes, with OS at 53.4% versus 10% (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DFS at 54.6% versus 19. 1% (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, those who underwent adjuvant chemotherapy had poorer outcomes, with OS at 78% versus 21.8% (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DFS at 68.8% versus 27.6% (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). These findings may be attributed to the fact that these patients often present with more severe disease conditions. The same patterns regarding these factors are also observed when stratified by Siewert types I and II, with data presented in Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMultivariate analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn all patients, both T stage and N stage are critical factors. A Cox proportional hazards regression model was employed for analysis, with variables exhibiting statistically significant differences in univariate analysis identified as independent variables. The results indicated that T stage (T3: HR\u0026thinsp;=\u0026thinsp;5.927, [95% CI: 1.567\u0026ndash;22.418], P\u0026thinsp;=\u0026thinsp;0.009; T4: HR\u0026thinsp;=\u0026thinsp;6.198, [95% CI: 1.710-22.469], P\u0026thinsp;=\u0026thinsp;0.006) and N stage (N2: HR\u0026thinsp;=\u0026thinsp;3.039 [95% CI: 1.096\u0026ndash;8.427], P\u0026thinsp;=\u0026thinsp;0.033; N3: HR\u0026thinsp;=\u0026thinsp;2.855 [95% CI: 1.070\u0026ndash;7.622], P\u0026thinsp;=\u0026thinsp;0.036) were independent factors influencing overall survival (OS) in patients with EGJA cancer (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). When stratified into Siewert I and Siewert II groups, only sex emerged as an independent factor affecting patient outcomes (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEGJA is a prevalent malignant gastrointestinal tumor that arises at the esophagogastric junction [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Due to its location at the interface of the esophagus and stomach, EGJA exhibits characteristics of both esophageal and gastric malignancies, leading to distinct differences in surgical treatment approaches in clinical practice. Consequently, there is considerable controversy and ongoing discussion regarding the optimal surgical method and the extent of lymph node dissection.\u003c/p\u003e\n\u003cp\u003eSurgery remains the primary treatment method for esophagogastric junction adenocarcinoma (EGJA), and it is crucial to select appropriate surgical techniques based on the different Siewert stages [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. An effective surgical choice should fulfill the following criteria: (1) complete resection of the primary tumor; (2) preservation of a safe upper incisal margin; (3) thorough lymph node dissection; (4) attainment of a higher postoperative long-term survival rate; and (5) minimization of surgical trauma, reduction of postoperative complications, and facilitation of rapid recovery following the procedure.\u003c/p\u003e\n\u003cp\u003eThe esophagogastric junctional adenocarcinoma (EGJA) is located at the thoracoabdominal junction, necessitating a careful selection of surgical approach based on tumor location prior to surgery to ensure complete exposure and removal. Siewert Type I tumors, which are primarily situated in the chest cavity, require a reconstructive esophagogastric anastomosis in the chest to achieve a satisfactory upper incisal margin, regardless of the surgical technique employed. Conversely, Siewert Type III tumors, predominantly located near the stomach, generally allow for thoracoabdominal surgery to attain an adequate upper incision margin [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. In the case of Siewert Type II tumors, which are positioned at the thoracoabdominal junction, there remains considerable debate regarding the optimal surgical method to secure a satisfactory superior incisal margin [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. Research [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e] indicates that transthoracic resection in Siewert Type II patients is associated with a lower rate of positive upper margins. A positive upper margin is correlated with significantly reduced long-term survival rates compared to a negative margin, with median survival times of 11. 1 months and 36.3 months, respectively [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. Currently, there is no consensus regarding the ideal upper incisal margin for EGJA, although studies suggest that a safe incision margin distance of 5\u0026ndash;8 cm from the esophagus is recommended [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. Furthermore, the safety and efficacy of transthoracic surgical approaches have been confirmed [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this study, Siewert Type I and II EGJA patients exhibited a significantly improved 5-year overall survival rate when the upper incisal margin was \u0026ge;\u0026thinsp;5 cm. However, for Siewert Type III EGJA patients, the 5-year overall survival rate was higher in the thoracoabdominal surgery group compared to the transthoracic surgery group when the upper incisal margin was \u0026ge;\u0026thinsp;5 cm (53.3% vs. 83.3%). Therefore, the transthoracic approach is deemed more suitable for patients with advanced Siewert Type II cancer.\u003c/p\u003e\n\u003cp\u003eIn this study, the 5-year overall survival rate for patients with Siewert type I EGJA was 53. 1% in the thoracic surgery group and 52. 1% in the thoracic and abdominal surgery group. There was no significant difference in prognosis between the two surgical methods for Siewert type I EGJA. However, the operation time in the transthoracic surgery group was shorter than that in the thoracoabdominal surgery group. Therefore, transthoracic surgery is recommended for patients with Siewert type I cancer. In patients with Siewert type II EGJA, significant differences were observed in operation time, the number of lymph nodes, and the number of positive lymph nodes between the transthoracic and thoracoabdominal surgery groups. The 5-year overall survival rate was 9.3% in the thoracoabdominal surgery group and 42% in the transthoracic surgery group. The prognosis for patients in the transthoracic surgery group was significantly better than that for those in the thoracoabdominal surgery group (P\u0026thinsp;=\u0026thinsp;0.035). Therefore, the transthoracic approach is more suitable for patients with Siewert type II advanced cancer.\u003c/p\u003e\n\u003cp\u003eThe AICC and UICC 8th Edition regulations for esophageal and gastric cancer specify that Siewert Type I and II EGJA lymph nodes are categorized under esophageal cancer, whereas Type III lymph nodes are classified under gastric cancer. In the case of Siewert Types I and II EGJA, the lymph node dissection in the lower mediastinum and abdominal cavity follows the same protocol as that for esophageal cancer.\u003c/p\u003e\n\u003cp\u003eIn assessing the N stage, specific requirements exist regarding the total number of lymph nodes removed; however, there are no established criteria for lymph node score. According to some studies [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e], the number of lymph nodes excised serves as an independent factor influencing the prognosis of esophagogastric junction adenocarcinoma (EGJA). Furthermore, another study [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e] indicated that the number of lymph nodes removed during radical EGJA surgery is typically limited to 15, with patients who had more than 15 lymph nodes removed demonstrating a better prognosis compared to those with fewer than 15. In our study, we observed that as the number of lymph node metastases in Siewert types I and II increased, the N stage also heightened, leading to a decrease in the 5-year survival rate of patients. Notably, there was no significant difference in\u003c/p\u003e\n\u003cp\u003ethe 5-year survival rates between Siewert type II patients with more than 15 lymph nodes and those with fewer than 15. Conversely, among Siewert type I patients, those who had more than 15 lymph nodes removed exhibited lower 5-year survival rates compared to those with fewer than 15 lymph nodes removed.\u003c/p\u003e\n\u003cp\u003eIt has been reported [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e] that the lymph node metastasis of esophagogastric junction adenocarcinoma (EGJA) predominantly occurs within the abdominal cavity, particularly in the lymph nodes associated with the paracardial and left gastric arteries. Consequently, all patients in this study underwent lymph node dissection in both groups. When assessing intrathoracic mediastinal lymph nodes, patients with Siewert type I exhibited the highest rate of mediastinal lymph node metastasis among all subtypes [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e], with a reported incidence ranging from 25\u0026ndash;35%. Sasako et al. [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e] indicated that the incidence of mediastinal lymph node metastasis in Siewert type II patients varied between 7% and 32%. Additionally, another study reported that 16% of Siewert type II patients had lymph node metastases in both the chest and abdomen, while 19% exhibited mediastinal lymph node metastases [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe study results of Kakeji et al. [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e] indicated that laparoscopic surgery combined with radical esophagogastric junction adenocarcinoma (EGJA) is an optimal approach for mediastinal and abdominal lymph node dissection, as it not only facilitates thorough dissection but also minimizes bleeding. Noshiro et al.\u0026apos;s study further confirmed the safety and feasibility of thoracic laparoscopic treatment for EGJA [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. It has been observed that an increased incision length in transthoracic surgery correlates with heightened intraoperative bleeding, while intraoperative procedures such as transposition and tracheal intubation for lung isolation contribute to prolonged operative time [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. In recent years, compared to the traditional long posterolateral thoracic incision, endoscopic EGJA surgery utilizing both thoracoscopy and laparoscopy has resulted in shorter thoracic incisions, reduced stimulation of the intercostal nerves, and significant advantages in minimizing intraoperative bleeding and the risk of lung infection [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eIn this study, the operative steps for mediastinum procedures were identical between the two approaches, and all patients were treated by the same surgeon. Consequently, The differences between the two surgical methods and procedures were not considered statistically significant., the position and level of the anastomosis were consistent, and the same trophic vessels\u0026mdash;the gastric diaphragm and the right gastroepiploic vessel\u0026mdash;were preserved during the surgery. This approach facilitated early recovery of respiratory function postoperatively. The analysis revealed no significant difference in the 5-year survival rates for Siewert type I patients who underwent transthoracic versus thoraco-abdominal surgery; thus, transthoracic surgery is recommended. In contrast, for Siewert type II patients, the 5-year survival rate and prognosis associated with thoraco-abdominal surgery were superior to those of transthoracic surgery. Therefore, transthoracic surgery is also recommended for this group, with simultaneous mediastinal and abdominal lymph node dissection advised to minimize residual tumor cells at the incisal margin.\u003c/p\u003e\n\u003cp\u003eIn addition to surgical treatment, neoadjuvant chemotherapy for esophagogastric junction adenocarcinoma (EGJA) has gained acceptance among clinicians due to its benefits in enhancing surgical resection rates and extending patient survival in select cases, particularly for Siewert type II patients. Research indicates that preoperative neoadjuvant chemotherapy decreases both the recurrence and metastasis rates in cancer patients, resulting in a higher 5-year survival rate [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]. Notably, in this study, Siewert type I and II patients who did not receive neoadjuvant\u003c/p\u003e\n\u003cp\u003echemotherapy exhibited a higher 5-year survival rate compared to those who underwent the treatment. However, it is important to note that preoperative neoadjuvant chemotherapy is not appropriate for all advanced EGJA patients. Some studies have revealed that P53 and Ki-67 expression levels are negatively correlated with the sensitivity and effectiveness of neoadjuvant chemotherapy, potentially due to their interference with tumor cell apoptosis and metabolic processes [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e] .\u003c/p\u003e\n\u003cp\u003eThis study compared the surgical outcomes of various methods concerning the safety of the upper incisal margin, lymph node dissection, postoperative complications, and the 5-year postoperative survival rate, thereby providing a theoretical foundation for the judicious selection of surgical techniques. However, this retrospective study exhibited some selection bias, and the influence of varying tumor invasion depths was not accounted for in the comparison, which presents certain limitations. In conclusion, the primary factors influencing the postoperative outcomes of Siewert type I and Siewert type II esophagogastric junction adenocarcinoma (EGJA) were the surgical method employed and the extent of lymph node dissection. Transthoracic surgery is deemed suitable for patients with Siewert type I lesions, while it is also appropriate for patients with Siewert type II progression. Nevertheless, the degree of lymph node metastasis in Siewert type I and Siewert type II EGJA remains a significant factor that restricts the prognosis of this condition.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Fei Li. The first draft of the manuscript was written by Ying Ji and two authors commented on previous versions of the manuscript. Two authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors affirm that human research participants provided informed consent for publication of the images in all tables and Figures.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eManabe, N., K. Matsueda, and K. Haruma, Epidemiological Review of Gastroesophageal Junction Adenocarcinoma in Asian Countries. Digestion, 2022. \u003cstrong\u003e103\u003c/strong\u003e(1): p. 29-36.\u003c/li\u003e\n\u003cli\u003eSiewert, J.R., et al., [Cardia cancer: attempt at a therapeutically relevant classification]. 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Lancet Oncol, 2006. \u003cstrong\u003e7\u003c/strong\u003e(8): p. 644-51.\u003c/li\u003e\n\u003cli\u003eLi, S.M., Z.Y. Li, and X. Ji, [Clinical characteristics of lymph node metastasis in Siewert type II adenocarcinoma of the gastroesophageal junction]. Zhonghua Zhong Liu Za Zhi, 2013. \u003cstrong\u003e35\u003c/strong\u003e(4): p. 288-91.\u003c/li\u003e\n\u003cli\u003eKakeji, Y., et al., Lymph node metastasis from cancer of the esophagogastric junction, and determination of the appropriate nodal dissection. Surg Today, 2012. \u003cstrong\u003e42\u003c/strong\u003e(4): p. 351-8.\u003c/li\u003e\n\u003cli\u003eNoshiro, H., et al., Minimally invasive esophagogastrectomy for esophagogastric junctional cancer. Ann Thorac Surg, 2012. \u003cstrong\u003e93\u003c/strong\u003e(1): p. 214-20.\u003c/li\u003e\n\u003cli\u003eZhu, T.Y., et al., Comparison of short-term surgical outcomes between complete mesenteric resection and traditional transhiatal laparoscopic surgery for Siewert type II/III esophagogastric junction adenocarcinoma. Langenbecks Arch Surg, 2022. \u003cstrong\u003e407\u003c/strong\u003e(8): p. 3811-3818.\u003c/li\u003e\n\u003cli\u003eLI Yuan, SHI Haoming, ZHANG Cheng, CHEN Dan, WU Qingchen. Thoracolaparoscopic esophagectomy and open surgery for different pathological stages of esophageal cancer: a comparison of short-term efficacy[J]. Journal of Third Military Medical University, 2020, 42(24): 2419-2425.\u003c/li\u003e\n\u003cli\u003e. Andrew R. Davies et al.,Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction. JCO 32, 2983-2990(2014).DOI:10.1200/JCO.2014.55.9070\u003c/li\u003e\n\u003cli\u003eGrizzi, G., et al., Preferred neoadjuvant therapy for gastric and gastroesophageal junction adenocarcinoma: a systematic review and network meta-analysis. Gastric Cancer, 2022. \u003cstrong\u003e25\u003c/strong\u003e(5): p. 982-987.\u003c/li\u003e\n\u003cli\u003eChevallay, M., et al., Cancer of the gastroesophageal junction: a diagnosis, classification, and management review. Ann NY Acad Sci, 2018. \u003cstrong\u003e1434\u003c/strong\u003e(1): p. 132-138.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"esophagogastric junction adenocarcinoma, Prognosis, Transthoracic surgery, Transthoracic approach surgery, The results of the surgery","lastPublishedDoi":"10.21203/rs.3.rs-7029813/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7029813/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground : \u003c/strong\u003eEsophagogastric junction adenocarcinoma (EGJA) is a malignant tumor with special location and complex condition, mainly occurring at the junction of esophagus and stomach. With the increasing incidence, its surgical treatment has attracted wide attention. At present, the mainstream surgical methods include transthoracic surgery (TET) and transthoracic combined surgery (TAT), and there are significant differences between the two in terms ofoperation path, postoperative recovery and prognosis. The purpose of this study is to retrospectively analyze the therapeutic effect and prognosis of EGJA patients with two surgical methods, in order to provide valuable reference for clinical decision-making.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMETHODS\u003c/strong\u003e: The clinical data of 148 patients with EGJA treated by transthoracic (80 cases)or transthoracic (68 cases) operation in our hospital from 2016 to 2018 were collected.. The Kaplan–Meier method and the log-rank test were used for univariate survival analysis. Cox regression model was used for multivariate survival analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRESULTS\u003c/strong\u003e: \u0026nbsp;This study identified gender, neoadjuvant chemotherapy, adjuvant chemotherapy, and T stage as significant prognostic factors influencing overall survival (OS) and disease-free survival (DFS). Transthoracic surgery was associated with a longer operative time (188 vs. 155 minutes, P\u0026lt;0.001), a greater number of dissected lymph nodes (24 vs. 22), and an increased number of positive lymph nodes (3 vs. 2, P=0.022), particularly in type II patients (4 vs. 2, P=0.029).\u003c/p\u003e\n\u003cp\u003eFor type I patients, overall survival (OS) rates were 52. 1% for the thoracoabdominal surgery group compared to 53. 1% for the transthoracic surgery group, while disease-free survival (DFS) rates were 41.0% and 65.7%, respectively. However, these \u0026nbsp;differences were not statistically significant. In type II patients, although transthoracic surgery is associated with a longer surgical duration, this does not impact the length of hospital stay or intraoperative blood loss. Furthermore, due to its capacity to dissect a greater number of positive lymph nodes, transthoracic surgery may be more effective in reducing tumor residue. Notably, patients undergoing thoracoabdominal surgery experienced a significant improvement in OS (42% vs. 9.3%, P=0.035), although the change in DFS was not statistically significant (35.4%vs. 21.7%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Patients classified as Type I may be more appropriate candidates for transthoracic surgery, given its shorter operation time. In contrast, both transthoracic and abdominal surgeries may represent more suitable surgical options for Type II patients.\u003c/p\u003e","manuscriptTitle":"Comparison of factors and prognosis in transthoracic vs. transthoracic-abdominal surgery for EGJA","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-24 13:06:27","doi":"10.21203/rs.3.rs-7029813/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-11-26T07:07:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"180587170332839588641944006782516036976","date":"2025-11-12T13:09:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-30T11:46:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336913238172169247394272580412391667060","date":"2025-09-26T13:19:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-16T09:05:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-16T07:52:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-16T04:32:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Medical Research","date":"2025-07-02T13:19:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ee3a7c4a-c875-418a-9d1e-7e1efa7ba91e","owner":[],"postedDate":"September 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-24T13:06:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-24 13:06:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7029813","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7029813","identity":"rs-7029813","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}