In cancer treatment, adequate surgical resection, including lymph node dissection (LND), is essential to achieve a curative state. In advanced gastric cancer (AGC), total or subtotal gastrectomy with D2 LND is widely performed as the standard treatment [123]. Since proximal gastric cancer, which has a steadily rising incidence [4], metastasizes to the splenic hilar lymph nodes (LNs; station No. 10) in 9%–26% [5678], D2 LND, including splenic hilar LND, is recommended for proximal AGC as per previous treatment guidelines [9].

To remove splenic hilar LNs, surgeons should perform splenectomy or spleen-preserving hilar LND. The theoretical background for the removal of splenic hilar LNs in AGC has been explored using lymphangiography [10]. With evidence of lymphatic flow from the upper greater curvature through the splenic hilum to the celiac trunk, splenectomy has been considered as an effective method for performing en-bloc resection of gastric cancer and adjacent LNs [10]. However, because of compromised immunological functions along with high morbidity and mortality rates, splenectomy poses serious adverse effects [111213]. Meanwhile, because surgical techniques have improved, some experienced surgeons perform spleen-preserving hilar LND, which could be an ideal method [1415]. Nevertheless, although this procedure is theoretically rational, it is technically challenging, and the oncological validity of the procedure remains unclear [14]. Thus, splenectomy and spleen-preserving hilar dissection should be avoided, if possible, because of the difficulty in the procedure and other aspects.

In previous Japanese guidelines, the decision of performing hilar LND was based on clinical T classification of cancer (T2 or more advanced lesion). However, the recently revised guidelines do not include splenic hilar LND for all proximal advanced cancers unless it involves the greater curvature of the stomach. However, even among the indicated patients, there may be patients who would gain little benefit or even detrimental effects from hilar dissection. Identifying the characteristics of this group of patients could be useful to prevent unnecessary hilar dissection.

In the present study, we presumed that pT2-4aN0 patients would not gain any additional oncological benefits from hilar dissection. Accordingly, we aimed to determine the survival impact of splenectomy or splenic hilar dissection in the proximal AGC patients without LN metastasis who underwent curative total gastrectomy. We also sought to investigate whether D2 LND, including splenectomy and spleen-preserving hilar dissection, should be mandatory for LN negative proximal AGC.

In this study, we found that prior to propensity score matching, patients with splenectomy tended to have tumors of larger size and more advanced T classification than patients who did not undergo splenectomy. Thus, we performed a propensity score matching to correct the differences in clinicopathological characteristics due to selection bias that could skew oncological results. After propensity score matching, we noted no difference in the clinicopathological characteristics between patients who underwent splenectomy and those who did not. Similar results were obtained with patients who underwent D2 LND compared with those who underwent D1+ dissection. Survival curves after propensity score matching suggested that neither splenectomy nor D2 LND had a positive impact on long-term survival in patients with LN-negative T2-4a AGC.

The controversy surrounding the benefits of splenectomy to oncological outcomes in gastric cancer regardless of LN involvement has been longstanding. Previous reports have shown that splenectomy offers no survival benefit in the presence of metastatic LN [816]. Meanwhile, the recently published JCOG0110 trial, which compared splenectomy group with a non-splenectomy group for clinical AGC (cT2-4/N0-2) not invading the greater curvature, concluded that splenectomy was not superior to spleen preservation [1718]. However, a recent report from our institution demonstrated that splenic hilar LND during splenectomy or with spleen preservation had a positive impact on long-term survival similar to that with the removal of other extra-perigastric LN groups [19]. Watanabe et al. [20] also reported from a single institutional data that splenectomy offers a survival benefit when cancer involves the greater curvature. In this study, the LN positive ratio was 68.2% in cancers involving the greater curvature [20]. Additionally, Ji et al. [21] recently reported that spleen-preserving hilar dissection elicited better survival than splenectomy for upper and middle third AGC. Thus, dissecting hilar LNs and preserving the spleen could be desirable in certain patients with proximal AGC. In the current study, we focused on patients who could be exempted from splenectomy or splenic hilar dissection although they had advanced diseases. Thereby, we were able to analyze the impacts of splenectomy and D2 LND in patients with an advanced disease without LN metastasis. Our results suggest that the potential hazards posed by these procedures may outweigh their benefits in this specific group of patients.

After the results of JCOG 0110 trial were published, there was a drive to alter the extent of LND in proximal AGC. Because this trial did not include tumors located in the greater curvature, it was considered that tumors on the other side of the proximal stomach could be indicated for limited LND. In this regard, Kinoshita [22] recently suggested 3 different procedures as follows: D2-No. 10, spleen-preserving D2, and splenectomy D2. In addition, according to the latest guidelines revised in 2018, splenic hilar LND is not necessary unless cancer involves the greater curvature of the stomach. However, in the JCOG 0110 trial, N0 cancer accounted for 42.2% (213/505) of all cancers. Thus, there was a possibility of decreased survival in the splenectomy group because of the potential adverse oncological impact of splenectomy on N0 cancer, although in the subgroup analysis of the study, contrary to our expectations, splenectomy in patients with N0 cancer tended to have a positive impact on the survival (HR, 1.23; 95% CI, 0.68–2.25) [17]. In this study, we tried to investigate whether it is possible to identify patients who do not require splenic hilar LND based on tumor factors, including the location. Accordingly, we suggested that patients with T2-4aN0M0 tumors, which are classified as stage IB–IIB based on the 7th Union for International Cancer Control/American Joint Committee on Cancer TNM staging system, could be the ideal candidates for limited LND regardless of tumor location. These patients in our database comprised 28.7% of the patients for whom D2 LND was indicated with a curative aim.

Herein, we showed the survival impact of splenectomy or D2 LND in patients with pT2-4aN0M0 cancer involving a large amount of data using propensity score matching. However, there are some limitations to this study. The critical limitation of our study is that we compared pathological findings. Thus, it would be difficult to apply these results to clinical practice, because the current preoperative diagnosis is limited to predicting pN0 cancer. While computed tomography (CT), endoscopic ultrasound, and positron emission tomography-CT are used for gastric cancer staging before surgery, their sensitivity and specificity are not high enough to confirm nodal involvement [23]. Although Tokunaga et al. [24] showed that clinical findings have an effect on the survival outcomes even among patients with the same pathological findings, we attempted to identify the specific patient group which does not require splenectomy or splenic hilar LND by analyzing the pathological data. Nevertheless, with ongoing research, we expect that the accuracy of the preoperative diagnosis of N classification will improve with time, and our results could be more applicable for the accurate preoperative prediction of N classification. Secondly, our study was performed as a retrospective analysis using data from a single institution. Although the reasons for splenectomy were sometimes unclear, we tried to reduce selection bias by excluding T4b cancer and using propensity score matching. In addition, our data could be considered robust because these were derived from the results of a standardized treatment administered by experienced surgeons from a center with a high volume of patients with gastric cancer. For instance, although the extent of LND did not adhere to the standard treatment guidelines in the D1+ group, more than 40 LNs were retrieved, which was much greater than the 16 LNs required for proper staging (50.7, 46.6, and 42.9 in splenectomy, SPHLD, and D1+ groups, respectively). Furthermore, there was no accurate information on postoperative adjuvant chemotherapy which might have an impact on the survival. However, in general, gastric cancer patients in stage II or higher received our institution's standard 5-fluorouracil-based adjuvant chemotherapy since early 2000. Finally, even after propensity score matching, there were still differences in the clinicopathological characteristics and unseen bias due to latent variables, although we tried to reduce the bias by matching the patients for seven clinically important characteristics known to affect survival after treatment.

In conclusion, we found that splenectomy does not have an oncological benefit in patients with LN-negative AGC. In addition, we deemed D2 LND to be unnecessary for these patients. Although the accuracy of current preoperative nodal classification is not high enough, our results could play an important role in determining and revising the extent of LND for the treatment of proximal AGC.