Effect of different surgical approaches on the survival and safety of Siewert type II esophagogastric junction adenocarcinoma: a systematic review and meta-analysis
BMC Cancer volume 23, Article number: 1130 (2023)
Whether a transthoracic (TT) procedure by a thoracic surgeon or a transabdominal (TA) by a gastrointestinal surgeon is best for Siewert type II esophagogastric junction adenocarcinoma (EGJA) remains unknown. Survival and perioperative outcomes were compared between the two groups in this meta-analysis to clarify this argument.
We searched 7 databases for eligible studies comparing TT and TA procedures for Siewert type II EGJA. The final analyzed endpoints included intraoperative and hospitalization outcomes, recurrence, complication, and survival.
Seventeen studies involving 10,756 patients met the inclusion criteria. The TA group had higher rates of overall survival (OS) (HR: 1.31 [1.20 ~ 1.44], p < 0.00001) and disease-free survival (DFS) (HR: 1.49 [1.24 ~ 1.79], p < 0.0001). The survival advantage of OSR and DFSR increased with time. Subgroup analysis of OS and DFS suggested that TA remained the preferred approach among all subgroups. More total/positive lymph nodes were retrieved, and fewer lymph node recurrences were found in the TA group. The analysis of perioperative outcomes revealed that the TA procedure was longer, had more intraoperative blood loss, and prolonged hospital stay. Similar R0 resection rates, as well as total recurrence, local recurrence, liver recurrence, peritoneal recurrence, lung recurrence, anastomosis recurrence and multiple recurrence rates, were found between the two groups. The safety analysis showed that the TT procedure led to more total complications, anastomotic leakages, cases of pneumonia, and cases of pleural effusion.
The TA procedure appeared to be a suitable choice for patients with Siewert type II EGJA because of its association with longer survival, fewer recurrences, and better safety.
In Western countries, the incidence of esophagogastric junction adenocarcinoma (EGJA) has increased significantly each year [1, 2]. Compared with esophageal and gastric cancer, its therapeutic effect is unsatisfactory, and one of the important reasons is that the treatment methods are not uniform or standardized, especially the surgical methods . The classification system reported by Siewert et al. has been widely accepted in clinical practice in the past 20 years . Esophagectomy + proximal gastrectomy (transthoracic [TT] or thoracoabdominal) is suitable for Siewert type I EGJA, and extended gastrectomy + distal esophagus resection (transabdominal [TA]) is suitable for type III EGJA . However, for Siewert type II EGJA, whether esophagectomy + proximal gastrectomy performed in the TT procedure is better than extended gastrectomy + distal esophagus resection performed in the TA procedure has been debated by thoracic surgeons and gastrointestinal surgeons for decades.
In clinical studies, there were also notable differences regarding this argument. Chen et al. reported that the TA approach was associated with a longer overall survival (OS) time than the TT approach . Voron et al. reported longer disease-free survival (DFS) in the TA group . The survival advantages of the TA group were also found in some other studies [8, 9]. Longer survival may be associated with better lymph node dissection and fewer complications (anastomotic leakage, pneumonia, etc.) [9,10,11]. However, Blank et al. reported an opposite survival result . In some other studies, no survival differences were found between the two groups [13, 14].
To clarify this clinical debate, the survival rate, recurrence rate, and perioperative outcomes were compared between the two groups in this meta-analysis.
Materials and methods
Throughout the implementation of this study, the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was used as a checklist. (Table S1). (This study has been registered in PROSPERO, ID: CRD42023401527).
PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar were searched to find relevant literature published from their inception to January 2023. We used text and medical subject headings (MeSH) terms as follows: “Transthoracic”, “Transabdominal”, and “esophagogastric junction adenocarcinoma” (details are listed in Table S2). We also hand-searched the references of the included studies for further relevant articles.
Population: Patients with Siewert type II EGJA.
Intervention and comparison: TT (Surgery procedure of digestive tract: esophagectomy, proximal gastrectomy and esophagogastrostomy; Range of lymph node dissection [LND]: two-fields lymphadenectomy. Different transthoracic approaches [Left single incision or thoracoabdominal two incisions], managements of residual stomach [gastric tube or not] and surgical forms [traditional open surgery or minimally invasive surgery] are all acceptable) vs. TA (Surgery procedure of digestive tract: extended gastrectomy with distal esophagus resection, and esophagojejunostomy; Range of LND: D1+ or D2 lymphadenectomy. Different surgical forms [traditional open surgery or minimally invasive surgery] are all acceptable).
Outcomes: Intraoperative and hospitalization outcomes, recurrence, complication, and survival.
Study design: Cohort study (CT) or RCT.
Exclusion criteria: basic/animal-based study, review, meta-analysis, abstract only, and study lacking the data of the above outcomes.
The following data were extracted by two independent investigators (HYZ and YMY): participant characteristics, intraoperative and hospitalization outcomes (operating time, intraoperative blood loss, etc.), recurrence (total, local, lymph node recurrence, etc.), complications (total complication, complication [Clavien-Dindo classification III–IV], postoperative mortality, etc.) , and survival (OS, DFS, etc.). Disagreements were resolved by the above two investigators through recheck and discussion.
As a supplement to survival data (OS, PFS), we also analyzed the survival rate at 1, 2, 3, and 5 years. Subgroup analysis of OS and DFS was performed according to published year, region, TT group, surgical volume, and study design.
Quality assessment of the included studies
The Jadad Scale (5 points) was used to assess the RCTs. The assessment tool focused on three main items: accountability of patients, randomization, and masking. Studies of high quality scored three or more .
The Newcastle–Ottawa Scale (NOS, 9 points) was used to assess the CTs. The assessment tool focused on the following criteria: selection (four points), comparability (two points), and exposure (three points). Studies of high quality scored eight or nine points, and studies of medium quality scored six or seven points .
The evidence level of the results was assessed by the Grades of Recommendations Assessment, Development and Evaluation (GRADE) system based on publication bias, inconsistency, indirectness, risk of bias, and imprecision .
All statistical analyses were performed using STATA 12.0 software and Review Manager 5.3. The pooled risk ratio (RR) was used to analyze dichotomous variables (recurrences, complications, etc.). The mean difference (MD) was used to analyze continuous variables (intraoperative blood loss, operating time, etc.). The hazard ratio (HR) was used to analyze survival data (OS and DFS). In the analysis of advantageous outcomes (OS, number of lymph nodes retrieved, etc.), RR > 1, MD > 0, or HR < 1 suggested that it was beneficial to the TT group. In the analysis of disadvantageous outcomes (recurrences, intraoperative blood loss, etc.), RR > 1 or MD > 0 suggested that it was beneficial to the TA group. I2 and Cochran’s Q test were used to assess interstudy heterogeneity. When the p value was > 0.1 and the I2 value was ≤ 50%, a fixed-effects model was used; otherwise, a random-effects model was applied. Funnel plots were conducted to assess publication bias. A p value < 0.05 indicated that the results were significantly different.
Study identification and characteristics
After screening 2459 relevant publications, we included 17 studies for the meta-analysis, of which 15 studies were CTs and the other 2 studies were RCTs (Fig. 1) [6,7,8,9,10,11,12,13,14, 19,20,21,22,23,24,25,26]. These 17 studies included 10,756 patients in total, including 8026 in the TA group and 2730 in the TT group. Table 1 summarizes the characteristics of the 17 studies. Table S3 summarizes the quality assessments of the included studies, in which 9 studies were of high quality and 8 studies were of medium quality. Table 2 summarizes the evidence level assessments of the results, in which all evidence levels were very low or low.
Longer OS was achieved in the TA group (HR: 1.31 [1.20 ~ 1.44], p < 0.00001, Fig. 2). In the analysis of OSR, the survival rate of the TA group was higher than that of the TT group in all years (1, 2, 3, and 5 years) (Fig. 3). The survival advantage of OSR increased with time (RR increased from 0.96 to 0.79) (Fig. 4A).
Longer DFS was achieved in the TA group (HR: 1.49 [1.24 ~ 1.79], p < 0.0001, Fig. 2). In the analysis of DFSR, the survival rate of the TA group was higher than that of the TT group in all years (1, 2, 3, and 5 years) (Fig. 5). The survival advantage of DFSR increased with time (RR increased from 0.87 to 0.71) (Fig. 4B).
Subgroup analysis of survival
A subgroup analysis of OS and DFS was performed according to publication year (earlier than 2017 or 2017–2023), region (East Asia or Europe), TT group (thoracoabdominal or left transthoracic), surgical volume (> 20 per year or < 20 per year), and study design (RCT or CT). In the analysis of OS and DFS, there was no change in the preferred procedure among all subgroups. However, in the subgroups of region (Europe), TT group (left transthoracic), surgical volume (< 20 per year), and study design (RCT), there was no significant difference in OS associated with TA procedures. In subgroups of surgical volume (> 20 per year) and study design (RCT), there was no significant difference in the DFS advantage of the TA group (Table 3).
Intraoperative and hospitalization indicators
Operating time (MD: 35.75 [3.08 ~ 68.42] minutes, p = 0.03, Fig. 6A), intraoperative blood loss (MD: 32.16 [4.83 ~ 59.49] mL, p = 0.02, Fig. 6B), number of lymph nodes retrieved (MD: -4.17 [4.83 ~ 59.49], p = 0.02, Fig. 6C), number of positive lymph nodes retrieved (MD: -3.07 [-0.74~-0.01], p = 0.04, Fig. 6D), and length of hospital stay (MD: 2.47 [0.60 ~ 4.35] days, p = 0.01, Fig. 6F) were better in the TA group. The R0 resection rate (RR: 0.99 [0.95 ~ 1.03], p = 0.64, Fig. 6E) was similar between the two groups.
Fewer lymph node recurrences (RR: 2.90 [1.12 ~ 7.52], p = 0.03) were found in the TA group. The total recurrence, local recurrence, liver recurrence, peritoneal recurrence, lung recurrence, anastomosis recurrence and multiple recurrence rates were similar between the two groups (Figure S1).
In summary, more total complications (RR: 1.39 [1.10 ~ 1.74], p = 0.005) were found in the TA group. Complications (Clavien‒Dindo classification III–-IV) and postoperative mortality were similar between the two groups (Fig. 7).
Fewer anastomotic leakages (RR: 1.58 [1.10 ~ 2.27], p = 0.01), pneumonia (RR: 1.71 [1.30 ~ 2.25], p = 0.0001) and pleural effusion (RR: 1.92 [1.04 ~ 3.52], p = 0.04) were found in the TA group. Similar incidences of postoperative hemorrhage, anastomotic bleeding, intraperitoneal bleeding, anastomotic leakage, reoperation, wound infection, peritonitis, pneumothorax, jejunal stump leakage, duodenum stump leakage, wound rupture, esophago-bronchial fistula, gastric tube perforation, necrosis of gastric tube, pancreatic fistula, gastroparesis, anastomotic stricture, pyothorax, bowel obstruction and dumping syndrome were found between the two groups (Table 4, Figure S2).
In the analysis of intraoperative blood loss, operating time, number of lymph nodes retrieved, number of positive lymph nodes retrieved, and length of hospital stay, significant heterogeneity was found. After removal of each study, the tendency of the results did not change, which confirmed the stability and reliability of these results (Figure S3).
EGJA is one of the major cancers with high morbidity and mortality rates worldwide; however, its treatment is not standardized, and the therapeutic effect is unsatisfactory . Whether a transthoracic (TT) procedure by a thoracic surgeon or a transabdominal (TA) by a gastrointestinal surgeon is best for Siewert type II esophagogastric junction adenocarcinoma (EGJA) remains unknown [8, 12, 13]. We first conducted this meta-analysis to answer this question. In this study, the TA procedure achieved longer OS and DFS than the TT procedure. The OSR and the DFSR increased with time. More total/positive lymph nodes were retrieved, and fewer lymph node recurrences were found in the TA group. In the analysis of perioperative outcomes, a longer operating time, more intraoperative blood loss, and a longer hospital stay were found in the TA group. In the analysis of complications, more total complications, anastomotic leakage, pneumonia, and pleural effusion were found in the TT group.
In this analysis, longer OS and DFS were the strongest supporting evidence for the TA group. Better survival results were also reported by Voron et al.’s and Xing et al.’s studies [7, 8]. Two results in our study might explain this advantage: (1) More total lymph nodes and positive lymph nodes were retrieved in the TA group, which directly led to a lower rate of lymph node recurrence after surgery. We believed that the insufficient dissection of lymph nodes is mainly related to the increased difficulty of abdominal lymph node dissection in TT procedures and thoracic surgeons’ lack of understanding of abdominal lymph node dissection [9, 10, 28]. (2) Another explanation for this advantage is the safety of the surgery. In our analysis, a longer operating time, more intraoperative blood loss, a longer hospital stay, and more complications were found in the TT group, which directly led to the higher perioperative mortality rate and indirectly affected the long-term survival of patients . In subgroup analysis of survival, TA procedures remained the preferred choice among all subgroups. The OSR (RR increased from 0.96 to 0.79) and DFSR (RR increased from 0.87 to 0.71) increased with time. In summary, we believe that TA procedures had survival advantages over TT procedures.
Fewer postoperative complication was another advantage of the TA approach. The addition of thoracotomy and thoracic lymph node dissection will increase the incidence of complications, which is also in line with the actual clinical situation. In our study, more total complications, anastomotic leakages, pneumonia cases, and pleural effusion cases were found in the TT group. Anastomotic leakage is the most troublesome complication after the resection of esophageal and cardiac tumors and one of the main causes for perioperative death. In our study, the probability of anastomotic leakage was 5.41% in the TT group and 5.08% in the TA group; the tendency of favoring TA was confirmed in the 8/11 relevant studies [8, 12, 13, 19, 20, 22, 23, 25]. Xing et al. reported a similar result and suggested that a prolonged operation and difficult reinforcement of the anastomosis might be the cause of this difference . We believe that better blood supply and higher probability of incarceration of the cardiac hole may also explain the higher probability of anastomotic leakage in the TT group. Pneumonia is highly prevalent in patients who undergo the TT approach and may endanger the patient’s life during the perioperative period. The tendency to favor TA was confirmed in all 8 relevant studies [9, 11, 12, 19, 20, 22, 23, 26]. The higher rate of pneumonia in the TT group was mainly due to a chest wall injury caused by thoracotomy and the collapse and expansion of the lung during operation . Based on the above reasons, for the EGJA patients in poor physical condition who cannot tolerate thoracotomy, the TA surgery is a good choice.
Although this study systematically analyzed all relevant studies with large size samples and all the involved outcomes, there were still some deficiencies that need to be considered. First, not all the included studies (2/17) were RCTs, which might decrease the evidence level of the results. Second, there were differences in the surgical volume, surgical methods, and criteria for determining the outcomes in different research centers, especially in the TT group. Although subgroup analysis and sensitivity analysis were conducted, there was still heterogeneity in the combined analysis of the outcomes. Third, some meta-analyses involved relatively few or even only one study, which may have affected the reliability of the results. Fourth, the patients were enrolled at different time points in these 17 studies, possibly leading to major changes in surgical methods and surgical requirements that might affect the consistency of outcomes. Fifth, due to insufficient data provided, there might be differences between the two groups regarding tumor size, staging, and lymph node metastasis, which might affect the comparability of the data between the groups.
For patients with Siewert type II EGJA, the TA procedure was a better choice because of its ability to prolong OS and DFS when compared with the TT procedure. The OSR and DFSR increased with time. More complete lymph node dissection and fewer lymph node recurrences were the main reasons for the survival advantage seen in the TA group. In terms of safety, more total complications, anastomotic leakages, pneumonia cases, and pleural effusion cases were found in the TT group. However, due to the above deficiencies, the conclusions of this study still need to be verified in large sample RCTs in the future.
Availability of data and materials
The data sets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Disease-free survival rate
Esophagogastric junction adenocarcinoma
Grading of Recommendations Assessment, Development and Evaluation
Medical subject headings
Overall survival rate
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Randomized clinical trial
Tumor Node Metastasis
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This study was supported by National Natural Science Foundation of China (NSFC), number of grants (81560349). Role of the Funding: The funding had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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Forest plots of recurrences associated with transthoracic surgery and transabdominal surgery. Figure S2 Forest plots of complications associated with transthoracic surgery and transabdominal surgery. Figure S3Sensitivity analysis ofintraoperative blood loss(A), operating time(B), number of lymph node retrieved(C), number of positive lymph node retrieved (D) and hospital stay(E). Figure S4 Funnel plots of survival (overallsurvivalanddisease-free survival, A), overallsurvivalrate (1, 2, 3, 5 years, B) and disease-free survival rate (1, 2, 3, 5 years, C). Table S1PRISMA 2009 Checklist. Table S2 Search strategy. Table S3 Methodological quality assessments of the included studies.
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Zheng, H., Yin, X., Pan, T. et al. Effect of different surgical approaches on the survival and safety of Siewert type II esophagogastric junction adenocarcinoma: a systematic review and meta-analysis. BMC Cancer 23, 1130 (2023). https://doi.org/10.1186/s12885-023-11640-5