Surgical Safety After Neoadjuvant Chemotherapy In Locally Advanced Gastric Cancer

Gastric cancer is a common malignant tumor of the digestive system,with morbidity and mortality in the forefront.China is a country with a high incidence of gastric cancer,and the diagnosis rate of early gastric cancer is low.Patients are mainly diagnosed with locally advanced gastric cancer,and the prognosis is poor.Surgery is still the only possible means for patients with locally advanced gastric cancer to obtain a radical cure.The NCCN guideline regard neoadjuvant chemotherapy as one of the standard treatments for advanced gastric cancer.With the wide application of neoadjuvant chemotherapy,surgical safety after chemotherapy has become an inevitable problem for surgeons.But there is currently no unified view.With the maturity of laparoscopic surgery,totally laparoscopic gastrectomy after neoadjuvant chemotherapy has also been applied in the treatment of gastric cancer.However,there are no studies on the surgical safety of totally laparoscopic gastrectomy after neoadjuvant chemotherapy.This paper will retrospectively study the safety of totally laparoscopic gastrectomy after neoadjuvant chemotherapy to provide evidence for clinical practice.On the other hand,we attempt to establish a simple and practical evaluation standard,to evaluate the gross tissue change reaction after neoadjuvant chemotherapy,and to explore the correlation between gross tissue change reaction and postoperative short-term clinical outcome,and to find the potential effect of neoadjuvant chemotherapy on subsequent surgery.Chapter 1 Literature reviewSurgical safety after neoadjuvant chemotherapy for locally advanced gastric cancer is a hot issue of concern to surgeons.This review discussed the surgical safety after neoadjuvant chemotherapy from three aspects.Firstly,we investigated the safety of open gastrectomy after neoadjuvant chemotherapy in locally advanced gastric cancer,and on this basis,the safety of laparoscopic gastrectomy after neoadjuvant chemotherapy was further discussed.Finally,we analyzed the histopathological changes after chemotherapy.We try to understand the impact of neoadjuvant chemotherapy on surgery for gastric cancer,compare the safety of different surgical approaches after neoadjuvant chemotherapy,and explore the potential impact of neoadjuvant chemotherapy on surgery,in order to provide help in clinical decision-making and follow-up studies.Chapter 2 Comparison of totally laparoscopic and laparoscopic assisted gastrectomy after neoadjuvant chemotherapy in Locally advanced gastric cancerBackground:Neoadjuvant chemotherapy(NACT)and laparoscopic surgery have been increasingly used in the treatment of gastric cancer,however,the feasibility and safety of totally laparoscopic gastrectomy after NACT still remain unknown.Materials and Methods:At the gastrointestinal cancer center of XX,clinical and pathological data of patients who has received NACT,followed by radical laparoscopic gastrectomy was retrospectively reviewed between March,2011 and November,2019.Patients were divided into 2 groups according to whether intracorporeal anastomosis or extracorporeal anastomosis had been performed,short-term outcomes(post-operative recovery index and complications)and economic cost were compared between 2 groups.Results:All of 139 patients underwent laparoscopic gastrectomy.87(62.6%)patients had totally laparoscopic gastrectomy(TLG)and 52(37.4%)patients had laparoscopic-assisted gastrectomy(LAG).Overall complication rate was 28.8%in all patients.TLG group was significantly associated with lower overall complication rate(21.8%VS 40.4%;p=0.019)and major complication rate(3.4%VS 13.5%;p=0.001)compared with LAG group.Overall cost was similar(p=0.077).In subgroup analysis,totally laparoscopic total gastrectomy(TLTG)group showed lower overall postoperative complication rate(19.0%VS 56.5%;p=0.011),as well as marginal significant differences in major complication(0%VS 21.7%;p=0.05)than laparoscopic-assisted total gastrectomy(LATG)group.Earlier first liquid diet(4(3.5-5)day VS 6(4-6.5)day;p=0.047),earlier first aerofluxus(3(3-4)day VS 4(3-4.5)day;p=0.02)and a shorter hospital stay(9(8-12)day VS 12(10-15)day;p=0.004)were observed in TLTG group.Overall and major complication rate were similar in totally laparoscopic distal gastrectomy(TLDG)and laparoscopic assisted distal gastrectomy(LADG)group(22.7%VS 27.6%;p=0.611,4.5%VS 6.9%;p=0.639;respectively).Significant differences were found between TLDG and LADG groups regarding time to first liquid diet(4(3-5)day VS 6(3.75-6)day;p=0.006),time to first aerofluxus(3(3-3)day VS 4(3-6)day;p<0.001),time to first defecation(4(4-5)day VS 5(4-6)day;p=0.045),time to remove all drainage(7(6-8)day VS 8(6-9)day;p=0.021),white blood cell count on postoperative Day 1(9.54±2.49 109/L VS 10.91 ±2.89 109/L;p=0.021)and postoperative hospital stay(9(8,10)day VS 10(9,13)day;p=0.009).Conclusions:For patients with Locally advanced gastric cancer who received NACT,totally laparoscopic gastrectomy,including TLTG and TLDG,doesn't increase complications and overall cost compared with LAG,and has advantages in gastrointestinal function recovery,incision length and postoperative hospital stay.Chapter 3 Establishment of evaluation standard for gross tissue changes grading after neoadjuvant chemotherapy in gastric cancerObjective:To establish an operation video based and practical evaluation criteria for gross tissue changes grading after neoadjuvant chemotherapy in gastric cancer,and to explore the correlation between gross tissue change reaction and postoperative short-term clinical outcome in order to improve the safety of radical gastrectomy after neoadjuvant chemotherapy.Materials and Methods:At the Gastrointestinal cancer center of XX,clinical and pathological data of patients who has received laparoscopic gastrectomy was retrospectively reviewed between March,2011 and November,2019.The inclusion criteria of neoadjuvant chemotherapy group includes:?gastric adenocarcinoma diagnosed by pathology,clinical staging cT2-4NanyM0;?receiving laparoscopic radical distal subtotal gastrectomy or radical total gastrectomy;?receiving neoadjuvant chemotherapy preoperatively;?age between 18-80 years old;?Karnofsky performance scale(KPS)score higher than 70;?available complete surgical video.Exclusion criteria includes:?history of upper abdomen surgery(except for laparoscopic cholecystectomy);?history of upper abdomen radiation therapy;?emergency or palliative surgery;?transfer to open surgery;?history of other malignant tumors.A total of 35 patients with upfront operation during the same period were randomly selected as the control group,and the inclusion and exclusion criteria were the same as the neoadjuvant chemotherapy group except for preoperative chemotherapy.The first GTCG criteria was proposed through the expert investigation and literature review.Ten surgeons with different years of experience were invited to conduct an anonymous,back-toback evaluation of tissue changes during the dissection of the suprapancreatic area in the manner of surgical video clip evaluation,and to mark the significant locations of tissue changes.Referring to the Delphi method,three rounds of evaluation were conducted to modify and determine the final GTCG criteria.The correlation between GTCG criteria and tumor regression grading(TRG),surgical related indexes,as well as postoperative complications and recovery was analyzed.Results:A total of 115 patients were included,including 80 in the neoadjuvant group and 35 in the direct surgery group.Ten surgeons were invited to participate in the evaluation.Of the 115 patients,5 patients underwent 3 rounds of surgical video evaluation,and 20 patients underwent 2 rounds,all of which were from the neoadjuvant chemotherapy group.Totally 1450 times of evaluations were completed in 3 rounds of evaluation.After three rounds of adjustment,the GTCG criteria was finally determined.Based on the results,92 patients received a consistent GTCG evaluation.There were 11 GTCG grade 0 patients(12%)and 81 GTCG grade 1 patients(88%).The proportion of GTCG grade 1 in the neoadjuvant group was significantly higher than that in the direct surgery group(94.1%VS 70.8%;p=0.006).Among all patients,there were no statistically significant differences between patients with GTCG grade 0 and GTCG grade 1 regarding overall(45%VS 27.2%;p=0.289)and major complications(9.1%VS 4.9%;p=0.479).There were no perioperative deaths and no patient required reoperation.Patients with GTCG grade 0 showed shorter operation time(200.09±36.90 min VS 229.62±42.48 min;p=0.031)and less intraoperative blood loss(64.55±29.90 ml VS 123.26±85.68 ml;p=0.027)compared with GTCG grade 1,number of retrieved lymph nodes were similar.Among neoadjuvant chemotherapy group,there were no statistically significant differences between patients with GTCG grade 0 and GTCG grade 1 regarding overall(25%VS 29.7%;p>0.99)and major complications(0.0%VS 4.7%;p>0.99).GTCG grade 0 had shorter operation time and less intraoperative blood loss compared with GTCG grade 1,although without statistically significance.Number of retrieved lymph nodes were similar.A total of 900 markers of obvious tissue change were carried out.The anatomical sites with significant histological changes were NO.8a(339(38%)),NO.11p(210(23%)),NO.7(164(18%)),NO.9(115(13%),NO.12a(72(8%)).There was no significant correlation between GTCG grade and TRG(Kendall tau-b=0.007;p=0.555).Univariate analysis showed sex(p=0.039),history of abdomen surgery(p=0.009),neoadjuvant chemotherapy(p=0.006)were related to GTCG grade 1.Multivariate analysis showed that only neoadjuvant chemotherapy(OR=5.895,95%CI:1.378-25.220;p=0.017)was independent predictor of GTCG grade 1.Conclusions:1.This study established the GTCG criteria for gross tissue change after neoadjuvant chemotherapy based on surgical video.According to this,the neoadjuvant treatment group had a higher proportion of tissue changes(GTCG grade 1)than the upfront surgery group.2.There is no significant difference in the complication rate of patients with GTCG grade 1 and GTCG grade 0 patients,but the difficulty of operation may increase.It is safe to perform radical surgery in GTCG 1 patients by experienced surgeon.3.There is no significant correlation between GTCG criteria and TRG criteria,and neoadjuvant chemotherapy is an independent predictive factor for GTCG grade 1.