Surgical treatment is the only way to achieve radical cure for resectable GC32,and has been significantly improved through decades of development. The Japan Gastric Cancer Association was the first to define the three stations of GC in 1998, and defined the terminology of the operations as D1, D2, and D3 according to the range of lymph nodes in the operation33, and updated the lymph node dissection range of GC according to the extent of gastric resection in 201134, 35. Wu et al published a study comparing D1 and D2 in 2006, and the results showed that the 5-year survival rates of patients with advanced GC after D1 and D2 were 53.6% and 59.5%, respectively (P=0.041). Compared with D1 surgery, patients with advanced GC undergoing D2 surgery achieved better survival outcome36. Plenty of retrospective studies have shown that D2 resection can improve survival in patients with higher T &N-staged tumors, and in this regard, D2 surgery has been widely used to treat advanced GC in Asia37-43.
Controversy lies in whether to perform D2 or D2+ PALD surgery on patients with advanced GC44. According to relevant studies, once gastric tumors invade the subserosal (T3 phase), serosal (T4a phase) or adjacent structures (T4b phase), the metastatic risk of para-aortic lymph nodes (PANs) increases to 10% to 30%45-47. PALD may help to remove potential metastases, and in the meantime, surely help to collect more lymph nodes, which is critical to staging and prognosis prediction48-50. Maeta et al reported that a patient with pathological PAN metastases survived more than 80 months after systemic PALD46. Park et al found that the median overall survival of patients with isolated PAN metastases was significantly longer than that of patients with single organ metastases other than PAN or multiple organ metastases51. Tokunaga et al retrospectively analyzed 178 patients with pathologically positive PAN who underwent radical resection and observed a 5-year survival rate of 13.0%52. Fujiwara et al performed preoperative chemotherapy on 20 patients who had no other non-cure factors other than PALN metastasis and had a good clinical response to induction chemotherapy. After D2+PALD treatment, the 3-year and 5-year survival rates were increased to 72 % and 65%, respectively15. Fushida et al studied 24 patients with GC who were diagnosed with PAN metastasis, all patients underwent D2+PALD and the prognosis was good53. Tokunaga et al retrospectively studied the role of D3 lymphadenectomy in 173 patients, suggesting that D3 resection may be beneficial for selected PAN-positive patients without other incurable factors52. However, Hu et al showed that D2 plus PALD was not significantly superior, survival-wise, to D2 in patients with T3-4, N2 staging18. Besides, Sasako et al showed that D2 lymphadenectomy plus prophylactic PALD did not improve the survival rate of curable GC compared with D2 lymphadenectomy, even though D2+PALD did not increase the risk of anastomotic leakage, pancreatic fistula, and abdominal infection28. In line with the conclusion of the work by Sasako et al, the results of our comprehensive analysis on prophylactic and therapeutic D2+PALD showed that, compared with D2, D2+PALD did not improve the patients’ long-term survival, but nonetheless, did not increase the risk of postoperative complications.
It is well known that D2+PALD is more difficult to perform than D2, with longer operative time, more bleeding, and longer hospital stays, requiring experienced surgeons 18, 3. However, with the development of modern technology, the extensive use of advanced medical equipment has reduced the operation time, operative mortality and surgery-related morbidity. D2+PALD can also perform as safely as D2 in professional medical centers with well-trained surgeons 45.
Several limitations reside in our work. First, all the included studies are retrospective, which affects the level of evidence of this study to some extent. Second, we only focused on overall survival as efficacy outcome in this study, other outcomes like recurrence free survival and rate of recurrence were not covered due to lack of data. Third, we were unable to access the personalized data of included studies to perform any further analyses to adjust for confounding factors. Fourth, the surgical results are closely related to the surgeon's experience. The expertise and approach of surgeons differs and matters, in which resides heterogeneity54. Fifth, the postoperative intervention, such as postoperative radiotherapy and chemotherapy, on the patients also has a great impact on the outcome, however, due to the lack of relevant data, we did not account for this confounding factor. Sixth, the number of studies included is relatively small, especially for the studies concerning therapeutic D2+PALD, which might affect the credibility of the results of the analyses concerning long-term survival and perioperative complications. Besides, the lack of comparable studies on therapeutic D2+PALD makes it impossible to draw a conclusion, in this regard, more elaborately designed multi-center studies with larger sample size are needed in the future to illuminate the advantages and disadvantages of D2+PALD more comprehensively.