Radical gastrectomy still represents the treatment of choice for gastric cancer. In case of early gastric cancer, considering the reduced risk of node metastases and local recurrence , LG is deemed the gold standard approach, especially in most of Eastern countries [4, 21]. This recommendation comes from the results of some randomized trials which demonstrated a lower morbidity and a non-inferior OS than the open approach [22, 23].
More recently, some Eastern studies seem to confirm that LG can be also considered for the treatment of AGC [24,25,26]. The Chinese CLASS-01 trial investigated the short-term surgical outcomes of 1056 patients with T2-4aN0-3M0 cancer at 14 centers, reporting similar postoperative morbidity and mortality as well as severity of complications for laparoscopic and open D2 distal gastrectomy . Long-term results from this trial were reported in 2019, demonstrating as non-inferior the 3-year DFS of patients assigned to the laparoscopic group than those assigned to the open group . Other ongoing trials as JLSSG0901  and KLASS-02  reported similar or lower complication rates, less postoperative pain and faster recovery for laparoscopic vs. open distal gastrectomy, while the long-term oncologic outcomes are still awaited.
It is unclear whether these findings can be applied to Western patients, who tend to have more advanced disease at presentation and a higher incidence of proximally located as well as diffuse-type cancers than Eastern patients. Furthermore, surgeon and hospital volumes of laparoscopic gastrectomy are significantly higher in the East than in the West . Thus, high-quality evidence from large-scale studies on LG for AGC is lacking in Western countries, and most series include both early and advanced cancers, thus hampering a stage-based analysis [29,30,31,32,33,34,35,36].
In 2005 Huscher et al. published the only European randomized trial comparing laparoscopic and open subtotal gastrectomy for distal gastric cancer. In their analysis on 59 patients, LG was found to be a feasible and safe oncologic procedure with short- and long-term results similar or better than those of open surgery . The results from the LOGICA trial  and the STOMACH trial  are still expected.
Finally, staging, surgical training and use of adjuvant therapy are different in non-tertiary referral centers .
For all the above reasons, well-controlled clinical studies may not reflect the actual outcome of laparoscopy for AGC in the clinical practice , and results from our study do provide real-life data on the safety and oncologic efficacy of LG in a large series of patients from different Western institutions.
We recorded an overall postoperative morbidity of 27.3%, but the majority (66%) of complications were classified as grade II requiring only a pharmacological treatment. These results are consistent with those of most published Western series. Huscher et al. reported a morbidity rate of 26.7% following laparoscopic distal gastrectomy . Also, several other retrospective studies reported an incidence of postoperative complications ranging from 25 to about 32% [29,30,31,32,33,34,35,36]. It has been suggested that the laparoscopic approach may decrease the incidence of minor complications in the early and late postoperative periods compared with the open approach . In a recent study from Korea on 1483 laparoscopic gastrectomies for AGC, the overall morbidity rate was 9.1% with 54% of complications being classified as grade ≥ 3. At the multivariate analysis, age was found to be associated with postoperative morbidity, endorsing that extended surgery, although minimally invasive, may be risky for the elderly . Other predictive factors for complications have been suggested, including sex, comorbidity, type of resection and surgeon’s experience . Our study experience suggests that neoadjuvant therapy may lead to an increased risk of postoperative complications. Although this observation has not been confirmed by several other investigators [39,40,41], the analysis of the CRITICS gastric cancer trial revealed a morbidity rate as high as 47% in patients receiving neoadjuvant chemotherapy . On the other hand, it has been suggested that preoperative chemotherapy may abolish the poor prognosis induced by postoperative complications after curative resection .
We reported a 14.5% conversion rate. However, 40 conversions were recorded during the first ten years of the study period while, over the last five years, the rate decreased to 3.6% which favorably compares to that of some previous reports, ranging from 2.2 to 7% [11, 44,45,46]. Also, a conversion rate up to 17.4% has been reported following LTG in large series . Our finding is probably related to the improved technical skills and experience of the surgeons over the study period as well as to prompt consideration of conversion when concerned for adequate oncologic resection . The most common reason for conversion was a technical factor such as adhesions, bleeding during difficult lymphadenectomy, whereas tumor factors (bulky/T4) accounted for about 23% of conversions.
All procedures started with a DL in order to detect a possible carcinomatosis. DL represents the first step during LG. It plays an important role in avoiding unnecessary laparotomies, particularly in cases of AGC. Many studies showed that DL demonstrated moderate to substantial agreement with final pathology for T stage, but only fair agreement for N stage. For M staging, DL had an overall accuracy, sensitivity, and specificity ranging from 85–98.9%, 64.3–94%, and 80–100%, respectively .
D2 lymph node dissection is of paramount importance for curative gastrectomy, but due to the technical difficulties it has limited enthusiasm for laparoscopic approach to AGC . Concern about achieving adequate lymph node retrieval has been raised in some earlier series, where up to 38% of patients had less than the AJCC minimum number of lymph node harvest needed for proper staging . In our experience, the mean number of 25 harvested nodes allowed us to meet the criteria for adequate laparoscopic lymphadenectomy in AGC . Since early 2000s, there have been many controversies on the performance of splenectomy, and the prognostic value of lymphadenectomy of the n.10 station is debated . In accordance with the SIC-GIRCG 2013 Consensus Conference on Gastric Cancer, radical excision of the splenic hilum lymph nodes or splenectomy was reserved for AGC cases of the upper greater curvature, in which the malignancy was suspected to be T4 or there were suspected nodes at splenic hilum . Similarly, according to the most recent Japanese guidelines, dissection of n. 10 nodes/splenectomy is excluded from standard D2 dissection, unless a tumor of the upper stomach invades the greater curvature or there are metastases to no. 4sb lymph nodes . In those cases, we believe that the open approach should be preferred .
In our series, the OS probability was 0.94 at 1 year and 0.63 at 5 years, while the DFS probability was 0.85 at 1 year and 0.62 at 5 years. These figures favorably compare to those of the few Western studies which analyzed survival data. In their series of 30 laparoscopic cases with 57% of stage ≥ II cancers, Huscher et al. found 5-year OS and DFS rates of 58.9% and 57.3%, respectively . Similar results have been reported in a series of 70 AGC (stage IB-IV) patients undergoing laparoscopic gastrectomy . Kelly et al. reported higher rates of 81% and 85% in their cohort of 87 patients; however, only 37% of tumors were stage II and III . Three-year survival data have been analyzed in a series of 21 AGC patients, with an OS of 69.5% and a relapse-free survival of 44.5% . At 5 years, we found an OS probability of 0.73 for stage II and 0.56 for stage III. Survival data for cancer stage are mainly available Eastern studies. In their retrospective analysis of a 15-year experience, Min et al. reported a 5-year OS of 88.7% for stage IIA, 84.2 for stage IIB and 60.3% for stage III, with a significant difference between stages IIIA, IIIB and IIIC .
We reported an overall recurrence rate of 28.6%, which is in the range of 13.3% to 50% reported by other authors [29,30,31,32,33,34,35,36, 48, 49]. Peritoneal involvement has been reported as the most common type of recurrence after LG in several Eastern series , while recurrence patterns in Western patients have not been well established . In our study, the most common sites of recurrence were peritoneum (7.1%), liver (5.7%) and regional lymph nodes (4%). Similarly, in a series of 21 patients, the recurrence rate was 38.1% (8/21); peritoneal recurrence was recorded in 19% (4/21), distant recurrence in 14.3% (3/21) and a mixed pattern (both locoregional and distant) in 4.8% (1/21) . Strong et al.  found an equal distribution of local (n = 2, 6.6%) and distant (n = 2, 6.6%) recurrence in a cohort of 30 patients. Sica et al.  reported 11 cases (11/22, 50%) of recurrence after a median follow-up of 39 months, with hepatic metastases being the most common (6/22, 27.3%), followed by other distant recurrences (3/22, 13.7%) and locoregional recurrence (2/22, 9%). Some authors argue that while distant metastases after LG can be explained by invisible micro-metastasis during or before surgery, local recurrence may be associated with the adequacy of surgery .
Many doubts still concern the role of neoadjuvant chemotherapy for gastric cancer [50,51,52].
In the present study, neoadjuvant chemotherapy is not associated with recurrence or death. This finding is consistent with the EORTC trial  that failed to demonstrate prognostic benefits regarding OS after neoadjuvant chemotherapy, despite a significantly increased R0 resection rate. Furthermore, only 26% of patients in our series received neoadjuvant treatment. Finally we argue that a quality of surgery with adeguate lymphadenectomy performed by experienced surgeons could minimize the risk of metastatic nodes.
Our study has some limitations mainly related to the retrospective design. Data have been collected from different institutions over a 15-year period. Thus, treatment protocols and perioperative management were not standardized. No patients received neoadjuvant therapy until 2010, which can influence postoperative outcomes. Moreover, there has been much development of procedures and technologies over time, and this does influence the data. Also, although proficiency of participating surgeons has been established, their experience and technical skill increased as time passed. However, these limitations are inherent in that the study provides a true representation of outcomes in a general practice setting.
In conclusion, our study has led us to conclude that laparoscopic gastrectomy for advanced gastric cancer is feasible and safe in the general practice of Western institutions when performed by trained surgeons. Similarly, some caution must be exercised when translating the current evidence also on Robotic Assisted Gastrectomy (RAG) to a European population. Benefits of RAG include the use of ICG to assess vascularity and (sentinel) lymph nodes. Inclusion of artificial intelligence and machine learning to aid the surgeon in these complex procedures are coming on the horizon .
Randomized controlled trials carried out in this setting are needed to corroborate our results.