Randomized clinical trial on D2 lymphadenectomy versus D2 lymphadenectomy plus complete mesogastric excision in patients undergoing gastrectomy for cancer (DCGC01 study).

BACKGROUND: It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy. METHODS: Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1-3 M0 and pT2-4 N0-3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival. RESULTS: The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37-60) months and 51 (interquartile range 40-60) months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058). CONCLUSION: Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival. REGISTRATION NUMBER: NCT01978444 (http://www.clinicaltrials.gov).

Short-term outcomes of D2 lymphadenectomy plus complete mesogastric excision for gastric cancer: a propensity score matching analysis.

BACKGROUND: Our previous study has demonstrated the surgical advantages of D2 lymphadenectomy plus complete mesogastric excision (D2 + CME) in gastric cancer surgery. To further verify the safety of D2 + CME procedure, we conducted this large-scale, observational cohort study and applied propensity score matching (PSM) approach to compare D2 + CME with conventional D2 in terms of short-term outcomes in gastric cancer patients. METHODS: Data on 855 patients from Tongji Hospital who underwent laparoscopic-assisted distal gastrectomy (LADG) with R0 resection (496 in the conventional D2 cohort and 359 in the D2 + CME cohort) between Dec 12, 2013 and Dec 28, 2017 were retrieved from prospectively maintained clinical database. After PSM analysis at a 1:1 ratio, each cohort included 219-matched patients. Short-term outcomes, including surgical results, morbidity, and mortality within 30 days after the operation, were collected and analyzed. RESULTS: In this large-scale, observational cohort study based on PSM analysis, the D2 + CME procedure showed less intra-laparoscopic blood loss, more lymph node harvest, and faster postoperative flatus than the conventional D2 procedure. However, both the overall and severe postoperative adverse events (Clavien-Dindo classification grade ≥ III a) seemed comparable between two cohorts. CONCLUSION: The present study showed that D2 + CME was associated with better short-term outcomes than conventional D2 dissection for patients with resectable gastric cancer.

An Optimal Surgical Approach for Suprapancreatic Area Dissection in Laparoscopic D2 Gastrectomy with Complete Mesogastric Excision.

BACKGROUND: During the radical operation, the suprapancreatic area is featured by anatomical complexity, and the lymph node dissection for this area is technically difficult and demanding.1-4 Previously, we have demonstrated the presence of disseminated cancer cells in the mesogastrium5,6 and presented a mesogastrium model for gastrectomy.7 As a consequence, laparoscopic D2 lymphadenectomy plus complete mesogastric excision (D2+CME) was proposed as a new concept in the surgical treatment of advanced gastric cancer.8 D2+CME procedure has been shown to be associated to lower number of free intraperitoneal cancer cells and with a better disease-free survival than conventional D2 gastrectomy.9 Under the concept of mesogastrium model, the proposed D2+CME procedure could help surgeons better define the anatomical boundaries of suprapancreatic mesogastrium, thus using it to achieve a complete and standard excision of the suprapancreatic area dissection. Here, we briefly present perioperative results of our case series with the laparoscopic curative subtotal gastrectomy and D2+CME with a R0 resection and present a video to detail the technical aspects of a laparoscopic D2+CME approach for suprapancreatic area dissection. METHODS: All patients in this study underwent laparoscopic subtotal gastrectomy (D2+CME) with a curative R0 resection. This study was approved by the Tongji Hospital Ethics Committee (Unique Reference Number: TJ-IRB20180811). The procedures in the video are described as follows. Based on our previous mesogastrium model (also named "Table model", Supplemental Figure 1), the suprapancreatic mesogastrium is attached to the lesser curvature or the posterior gastric wall and extended to the suprapancreatic area, respectively.7 Surgeon stands on patient left side, and the assistant lifts the stomach upward and cephalic to expose the suprapancreatic mesogastrium including left gastric mesentery (LGM), right gastric mesentery (RGM) and posterior gastric mesentery (PGM). First of all, towards to the left side of the suprapancreatic area, the "tri-junction" point of LGM is exposed. Using an energy devise, surgeon opens serosa layer and identifies the retrogastric space. The LGM and PGM are mobilized bluntly, between which a fusion retrogastric space is revealed. Both the LGM and PGM are covered by smooth and shiny surfaces of fascial propria and regarded as the "meso-bed" mutually. Secondly, at the inner side of duodenum, surgeon bluntly separates the adjuvant tissues along gastro-duodenal artery (GDA) upward and exposes right gastric mesentery (RGM). Next, after mobilizing the left gastric mesentery, surgeon removes the adipose tissue adherent to the common hepatic artery (CHA) and exposes the root of the left gastric artery after dissecting the perivascular sheath with triple-clips. Then, surgeon dissects RGM along the CHA and portal vein (HPV) towards the right side of the suprapancreatic area; afterwards, the right gastric vessels and RGM are identified and ligated. Lastly, the superior border of splenic vessels is dissected. The anterior lobe of the PGM is raised up with ligated posterior gastric vessels. Remarkably, posterior gastric vessels may be absent in some cases. Reconstruction of the alimentary tract is Roux-en-Y method. Standard recovery protocols are followed in postoperative treatments. RESULTS: Between August 28th 2017 and December 27th 2018, 107 patients receiving laparoscopic curative subtotal gastrectomy (D2+CME) with a R0 resection were retrospective collected in this study. After exposing the suprapancreatic mesogastrium including RGM, PGM and LGM with D2+CME procedure, the LNs and fat tissues around 7, 9, 8a, 12a and 11p were removed en bloc in all patients. This study recruited 67 males and 40 females. The median age was 55 years, with body mass index (BMI) 23.0 kg/m2 (Supplemental Table 1). The median number of retrieved regional lymph nodes was 31 (range 25-41), including 22 (range 17-27.5) suprapancreatic lymph nodes. The median volume of blood loss was 14 ml (range 6-34). The median total operation time was 287 min (range 265.5-313.5) and laparoscopic surgery time was 132 min (range 116-142) (Supplemental Table 2). Postoperative morbidity occurred at a rate of 9.3 %, and the mortality rate was 0% (Supplemental Table 3). The median follow-up was 10 months (range 8-13). No patient was lost during follow-up (Supplemental Table 4). CONCLUSION: A laparoscopic subtotal gastrectomy with D2+CME procedure provides for a complete and standardized en bloc excision of the suprapancreatic area dissection.

Prospective randomized controlled trial to compare laparoscopic distal gastrectomy (D2 lymphadenectomy plus complete mesogastrium excision, D2 + CME) with conventional D2 lymphadenectomy for locally advanced gastric adenocarcinoma: study protocol for a randomized controlled trial.

BACKGROUND: Although radical gastrectomy with D2 lymph node dissection has become the standard surgical approach for locally advanced gastric cancer, patients still have a poor prognosis after operation. Previously, we proposed laparoscopic distal gastrectomy (D2 lymphadenectomy plus complete mesogastrium excision [D2 + CME]) as an optimized surgical procedure for locally advanced gastric cancer. By dissection along the boundary of the mesogastrium, D2 + CME resected proximal segments of the dorsal mesogastrium completely with less blood loss, and it improved the short-term surgical outcome. However, the oncologic therapeutic effect of D2 + CME has not yet been confirmed. METHODS/DESIGN: A single-center, prospective, parallel-group, randomized controlled trial of laparoscopic distal gastrectomy with D2 + CME versus conventional D2 was conducted for patients with locally advanced gastric cancer at Tongji Hospital, Wuhan, China. In total, 336 patients who met the following eligibly criteria were included and were randomized to receive either the D2 + CME or D2 procedure: (1) pathologically proven adenocarcinoma; (2) 18 to 75 years old; cT2-4, N0-3, M0 at preoperative evaluation; (3) expected curative resection via laparoscopic distal gastrectomy; (4) no history of other cancer, chemotherapy, or radiotherapy; (5) no history of upper abdominal operation; and (6) perioperative American Society of Anesthesiologists class I, II, or III. The primary endpoint is 3 years of disease-free survival. The secondary endpoints are overall survival, recurrence pattern, mortality, morbidity, postoperative recovery course, and other parameters. DISCUSSION: Previous studies have demonstrated the safety and feasibility of D2 + CME for locally advanced gastric cancer; however, there is still a lack of evidence to support its therapeutic effect. Thus, we performed this randomized trial to investigate whether D2 + CME can improve oncologic outcomes of patients with locally advanced gastric cancer. The findings from this trial may potentially optimize the surgical procedure and may improve the prognosis of patients with locally advanced gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01978444 . Registered on October 31, 2013.

ABCC2-24C > T polymorphism is associated with the response to platinum/5-Fu-based neoadjuvant chemotherapy and better clinical outcomes in advanced gastric cancer patients.

Several studies have evaluated the efficacy of neoadjuvant treatment using oxaliplatin and fluoropyrimidines in advanced gastric cancer (GC). However, preoperative biomarkers predictive of clinical outcome remain lacking. We examined polymorphisms in the MTHFR, DPYD, UMPS, ABCB1, ABCC2, GSTP1, ERCC1, and XRCC1 genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 103 GC patients treated with preoperative chemotherapy. DNA was extracted from peripheral blood cells, and the genotypes were analyzed using a SNaPShotTM assay, polymerase chain reaction amplification, and sequencing. The ABCC2-24C > T (rs717620) genotype was associated with pathologic response to neoadjuvant chemotherapy. Patients with the TT and TC genotypes responded to neoadjuvant chemotherapy 3.80 times more often than those with the CC genotype (95% CI: 1.27-11.32). Patients with the CC genotype also had poorer outcomes than those with other genotypes. Thus, ABCC2-24C > T polymorphism may help to predict the response to preoperative chemotherapy in GC patients.