Stomach cancer is the fourth most common cancer in the world [1]. Among all stomach cancers, the relative rate of remnant gastric cancer is 1% to 8% [2]. The original definition of remnant gastric cancer was stomach cancer that was discovered at least 5 years after distal gastrectomy for benign disease [3,4]. Recently it has been used to define any cancer that develops in the remnant stomach that remains after partial gastrectomy irrelevantly of the initial diagnosis or surgery [5].

Optimal surgical treatment for remnant gastric cancer has not been determined [6]. Although completion total gastrectomy is the only surgical treatment for remnant gastric cancer, secondary surgery is never straightforward for reasons such as anatomical alteration and adhesions in the abdominal cavity [7]. The frequent resection of other organs and dissection of lymph nodes also make surgery difficult [8].

According to previous studies, patients with metastases of splenic hilar lymph nodes in patients with gastric cancer have a poor prognosis even after therapeutic surgery [9]. In remnant gastric cancer, lymphatic flow and the incidence of lymph node metastasis are ambiguous [10]. Therefore, the lymph node metastasis pattern of remnant gastric cancer may be different from that of primary gastric cancer and surgery for this may require a modified lymph node dissection to include all important lymph node stations [11], including the lymph node station no. 10.

The effectiveness of splenectomy during the treatment of remnant gastric cancer is uncertain. Therefore, we conducted a retrospective study how splenectomy affects survival in patients who underwent complete total gastrectomy for remnant gastric cancer using propensity score matching analysis.

We retrospectively reviewed the medical records of 390 patients diagnosed with remnant gastric cancer who had surgery in Samsung Medical Center, between September 1996 and December 2017. Remnant gastric cancer was defined as any cancer that develops in the remnant stomach that remains after partial gastrectomy irrelevantly of the initial diagnosis or surgery. Among them, we excluded the patients who were diagnosed with stage IV (n=37), other solid tumors (n=9), and those who had non-curative resection (n=11). The patients diagnosed with other histologic types of gastric cancer (neuroendocrine carcinoma G3, n=1) was also excluded in the analysis. We set the minimum follow-up period to be 3 years so that surgery after December 2017 was excluded (n=47). All included patients (n=285) had completion total gastrectomy with or without splenectomy. After surgery, the patients were followed through scheduled outpatient visits. During their follow-up period, esophagogastroduodenoscopy and abdominopelvic computed tomography were performed to evaluate the recurrence. The median follow-up for all patients was 44.5 months (range, 0–271 months). We performed 1:1 propensity score matching using three covariates (age, sex, and pathologic stage) to match 77 patients who had splenectomy and 77 patients who did not.

The clinicopathologic characteristics of age, sex, primary disease at 1st operation (benign or malignant), 1st operation reconstruction method (Billroth I, Billroth II, or others), the site of recurrence (anastomosis or remnant), remnant gastric cancer histology (differentiated or undifferentiated), remnant gastric cancer Lauren type, Bormann classification, remnant gastric cancer size, remnant gastric cancer pathologic stage (including depth of invasion, lymph node metastasis), number of dissected lymph nodes, lymphatic invasion, venous invasion, perineural invasion were reviewed in patient medical records. Tumor histology was dichotomized as differentiated, which included papillary adenocarcinoma, and well or moderately differentiated adenocarcinoma, or undifferentiated, which included poorly or undifferentiated adenocarcinoma, signet ring cell carcinoma, mucinous carcinoma and other types. The pathologic stage was classified according to the eighth edition of the American Joint Committee on Cancer classification. We obtained the survival data of included patients from their updated medical records and the National Statistical Office in South Korea. This study was approved by the Institutional Review Board of Samsung Medical Center, Seoul, Korea (IRB No. SMC 2020-07-033-001). Informed consent was waived.

To control for confounders, we matched two study groups (no splenectomy vs. splenectomy, 1:1) by using the propensity scores. The matching factors were age, sex, and pathologic stage. Before matching, we used chi-square for categorical variables and Wilcoxon rank-sum test for continuous variables. We used generalized estimating equations for analyzing all variables of the matched patients. The 5-year overall survival (OS) and disease-free survival (DFS) were calculated by the Kaplan-Meier method. The variables with P<0.05 on univariate analysis using Cox regression were included for multivariate analysis to identify independent prognostic factors. Before the multivariate analysis, we also excluded the variables with variance inflation factor >10 to avoid multicollinearity. P values <0.05 were considered significant in statistical assessment. Statistical analysis was carried out using SAS version 9.4 (SAS Institute, Cary, NC, USA) and SPSS version 25.0 for Windows (IBM Corp., Armonk, NY, USA).

In this study, 5-year OS and 5-year DFS were compared between the group with and without splenectomy during completion total gastrectomy in patients with remnant gastric cancer. In propensity matched patients, there were no significant differences both in the 5-year OS and 5-year DFS.

The effectiveness of splenectomy has remained uncertain [12]. Routine splenectomy during gastric resection is not recommended because it is known that splenectomy do not improve survival rather increases morbidity and mortality [13]. Spleen has many functions, and among that functions, the major contribution of spleen is immune response, and splenectomy could leads to negative effect for host defense [14]. Previous research reported that complications such as abdominal infection and effusion were significantly increased in patients who had splenectomy. Regardless of TNM stage, there was no difference in survival rate between patients who underwent splenectomy and those who did not [15]. There have been many studies on the effectiveness of splenectomy in gastric cancer patients. Yang et al. [16] reported that splenectomy could not increase the OS rate in gastric cancer. And there was no significant difference on postoperative mortality and morbidity. Yu et al. [17] reported that splenectomy did not improve survival rate in proximal gastric cancer.

On the other hand, Li et al. [18] reported that the spleen preserving lymphadenectomy demonstrated better survival rate in patients with advanced middle third gastric cancer. Kosuga et al. [19] reported that lymph node dissection at the splenic hilum by splenectomy might improve a survival in patients with primary gastric cancer localized on the greater curvature and Borrmann type IV.

Role of splenectomy for remnant gastric cancer is controvertible issue. Komatsu et al. [20] reported that the lymphatic flow in the remnant stomach has changed since the initial distal gastrectomy. For this reason, the need for lymphadenectomy including jejunal mesentery and splenic hilar lymph node was suggested for treatment of remnant gastric cancer. In previous studies, high rate of splenic hilar metastasis was reported in remnant gastric cancer [11]. However, few studies have been conducted to evaluate the benefits of splenectomy in remnant gastric cancer. Sugita et al. [6] performed the retrospective study on the significance of lymphadenectomy with splenectomy in the surgical treatment of advanced remnant gastric cancer. Patients with pT3/pT4 remnant gastric cancer who underwent lymphadenectomy with splenectomy reported better survival rates compared with patients who did not. However, this was not observed in the patients with pT1/pT2 remnant gastric cancer. However, Sugita’s study did not stratify stages. They only classified the patient’s stages into two groups. This might be the reason why splenectomy was meaningful in the advanced stage in their research.

Son et al. [21] reported that in patients with remnant gastric cancer, prophylactic splenectomy did not affect OS, regardless of stage. Also, they found that metastasis to the mesojejunal lymph node was relatively high (31.8%), but metastasis to the splenic hilum (6.3%) and distal splenic artery (12.5%) was not.

In our study, we found that splenectomy was not affected survival after propensity score matching which is control the confounding factors. Although splenectomy is required for complete lymph node dissection in remnant gastric cancer, lymph node metastasis to splenic hilum may not frequently occur. Depending on the initial surgical technique of distal gastrectomy, lymphatic flow may have changed differently. Indeed, in Son’s study, metastasis toward splenic hilum was observed only in the group with Billroth II/Roux-en-Y gastrojejunostomy. Similar results were reported in our study, where metastasis of lymph node 10 (splenic hilum) was found in only one case in 2019.

The limitation of this study is that it is a retrospective study. So, there may be an information bias. After matching, our study included only 77 patients in each group. As we reviewed the medical records of 390 patients between September 1996 and December 2017, we could not consider the development of medical technology such as surgical technique and adjuvant chemotherapy and these would certainly have affected the patient’s prognosis.

In conclusion, splenectomy has no effect on the OS and DFS in patients with remnant gastric cancer. Therefore, splenectomy during completion total gastrectomy may not be necessary.