Pre- and Post-treatment Double-Sequential-Point Dynamic Radiomic Model in the Response Prediction of Gastric Cancer to Neoadjuvant Chemotherapy: 3-Year Survival Analysis.

BACKGROUND: Prognosis prediction of patients with gastric cancer after neoadjuvant chemotherapy is suboptimal. This study aims to develop and validate a dynamic radiomic model for prognosis prediction of patients with gastric cancer on the basis of baseline and posttreatment features. PATIENTS AND METHODS: This single-center cohort study included patients with gastric adenocarcinoma treated with neoadjuvant chemotherapy from June 2009 to July 2015 in the Gastrointestinal Cancer Center of Peking University Cancer Hospital. Their clinicopathological data, pre-treatment and post-treatment computed tomography (CT) images, and pathological reports were retrieved and analyzed. Four prediction models were developed and validated using tenfold cross-validation, with death within 3 years as the outcome. Model discrimination was compared by the area under the curve (AUC). The final radiomic model was evaluated for calibration and clinical utility using Hosmer-Lemeshow tests and decision curve analysis. RESULTS: The study included 205 patients with gastric adenocarcinoma [166 (81%) male; mean age 59.9 (SD 10.3) years], with 71 (34.6%) deaths occurring within 3 years. The radiomic model alone demonstrated better discrimination than the pathological T stage (ypT) stage model alone (cross-validated AUC 0.598 versus 0.516, P = 0.009). The final radiomic model, which incorporated both radiomic and clinicopathological characteristics, had a significantly higher cross-validated AUC (0.769) than the ypT stage model (0.516), the radiomics alone model (0.598), and the ypT plus other clinicopathological characteristics model (0.738; all P < 0.05). Decision curve analysis confirmed the clinical utility of the final radiomic model. CONCLUSIONS: The developed radiomic model had good accuracy and could be used as a decision aid tool in clinical practice to differentiate prognosis of patients with gastric cancer.

Long-term outcomes of laparoscopic versus open total gastrectomy in patients with advanced gastric cancer after neoadjuvant chemotherapy: a retrospective cohort study.

BACKGROUND: This study was conducted to investigate the long-term outcomes of laparoscopic total gastrectomy (LTG) versus open total gastrectomy (OTG) in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NACT). METHODS: Patients with AGC who received NACT before surgery were enrolled in either the LTG or OTG group. Propensity score matching (PSM) (1:2) was performed between the two groups based on the propensity score using a 0.15 calliper width. Three-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups before and after PSM. OS and DFS rates were calculated by the Kaplan‒Meier method, and any differences in survival were evaluated with a log-rank test. Univariate and multivariate Cox proportional hazards analyses were used to estimate the simultaneous effects of prognostic factors on survival and the hazard ratio (HR) between LTG and OTG patients. RESULTS: A total of 144 patients completed the follow-up, with 24 patients in the LTG group and 120 patients in the OTG group. After a mean follow-up of 64.40 months, there were no significant differences in the 3-year OS or DFS rates between the two groups before (P = 0.453 and P = 0.362, respectively) or after PSM (P = 0.972 and P = 0.884, respectively). Multivariate Cox proportional hazards analysis indicated that ypN stage was an independent risk factor for worse OS (P = 0.013). CONCLUSIONS: This study showed that LTG with D2 lymphadenectomy performed by an experienced surgical team resulted in comparable 3-year OS and DFS compared with OTG in patients with AGC after NACT. TRIAL REGISTRATION: This study is not registered.

Safety and short-term outcomes of a modified valvuloplastic esophagogastrostomy versus gastric tube anastomosis after laparoscopy-assisted proximal gastrectomy: a retrospective cohort study.

BACKGROUND: There is no optimal reconstruction method after proximal gastrectomy. The valvuloplastic esophagogastrostomy can reduce postoperative reflux esophagitis, but it is technically complex with a long operation time. The gastric tube anastomosis is technically simple, but the incidences of reflux esophagitis and anastomotic stricture are higher. METHODS: We have devised a modified valvuloplastic esophagogastrostomy after laparoscopy-assisted proximal gastrectomy (LAPG), the arch-bridge anastomosis. After reviewing our prospectively maintained gastric cancer database, 43 patients who underwent LAPG from November 2021 to April 2023 were included in this cohort study, with 25 patients received the arch-bridge anastomosis and 18 patients received gastric tube anastomosis. The short-term outcomes were compared between the two groups to evaluate the efficacy of the arch-bridge anastomosis. Reporting was consistent with the STROCSS 2021 guideline. RESULTS: The median operation time was 180 min in the arch-bridge group, significantly shorter than the gastric tube group (p = 0.003). In the arch-bridge group, none of the 25 patients experienced anastomotic leakage, while one patient (4%) experienced anastomotic stricture requiring endoscopic balloon dilation. The postoperative length of stay was shorter in the arch-bridge group (9 vs. 11, p = 0.034). None of the patients in the arch-bridge group experienced gastroesophageal reflux and used proton pump inhibitor (PPI), while four (22.2%) patients in the gastric tube group used PPI (p = 0.025). The incidence of reflux esophagitis (Los Angeles grade B or more severe) by endoscopy was lower in the arch-bridge group (0% vs. 25.0%). CONCLUSION: The arch-bridge anastomosis is a safe, time-saving, and feasible reconstruction method. It can reduce postoperative reflux and anastomotic stricture incidences in a selected cohort of patients undergoing laparoscopy-assisted proximal gastrectomy.

Efficacy of chemotherapy versus surgery as initial treatment for gastric cancer with positive peritoneal cytology.

BACKGROUND: The prognosis of gastric cancer (GC) patients with positive peritoneal cytology (CY1) without other distant metastasis is poor, and there are no standard treatment strategies. Our study aimed to compare the survival outcomes of CY1 GC patients receiving chemotherapy or surgery as initial treatment. METHODS: From February 2017 to January 2020, clinical and pathological data of patients diagnosed with CY1 GC without other distant metastasis in the Peking University Cancer Hospital was reviewed. Patients were divided into two groups: chemotherapy-initial group and surgery-initial group. In chemotherapy-initial group, patients received preoperative chemotherapy initially. According to the treatment response, the patients were divided into three subgroups: conversion gastrectomy group, palliative gastrectomy group, and further systematic chemotherapy group. In surgery-initial group, patients underwent gastrectomy followed by postoperative chemotherapy. RESULTS: A total of 96 CY1 GC patients were included with 48 patients in each group. In chemotherapy-initial group, preoperative chemotherapy yielded an objective response rate of 20.8% and disease control rate of 87.5%. Conversion to CY0 after preoperative chemotherapy was obtained in 24 (50%) patients. The median overall survival was 36.1 months in chemotherapy-initial group and 29.7 months in surgery-initial group (p = 0.367). The median progression-free survival was 18.1 months in chemotherapy-initial group and 16.1 months in surgery-initial group (p = 0.861). The 3-year overall survival rates were 50.0% and 47.9%, respectively. In chemotherapy-initial group, twenty-four patients who converted to CY0 by preoperative chemotherapy and received surgery obtained a significantly better prognosis. The median overall survival was still not reached in these patients. CONCLUSION: There was no significant difference in survival outcomes between chemotherapy-initial group and surgery-initial group. CY1 GC patients who converted to CY0 by preoperative chemotherapy and received radical surgery could obtain a favorable long-term prognosis. Further investigation should focus on preoperative chemotherapy to eliminate peritoneal cancer cell. TRIAL REGISTRATION: This study is retrospectively registered.

Exploration and optimization of surgical techniques for laparoscopic transhiatal lower mediastinal lymph node dissection for adenocarcinoma of esophagogastric junction: A prospective IDEAL 2a study with qualitative design.

Objective: To explore the change and feasibility of surgical techniques of laparoscopic transhiatal (TH)-lower mediastinal lymph node dissection (LMLND) for adenocarcinoma of the esophagogastric junction (AEG) according to Idea, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) 2a standards. Methods: Patients diagnosed with AEG who underwent laparoscopic TH-LMLND were prospectively included from April 14, 2020, to March 26, 2021. Clinical and pathological information as well as surgical outcomes were quantitatively analyzed. Semistructured interviews with the surgeon after each operation were qualitatively analyzed. Results: Thirty-five patients were included. There were no cases of transition to open surgery, but three cases involved combination with transthoracic surgery. In qualitative analysis, 108 items under three main themes were detected: explosion, dissection, and reconstruction. Revised instruction was subsequently designed according to the change in surgical technique and the cognitive process behind it. Three patients had anastomotic leaks postoperatively, with one classified as Clavien-Dindo IIIa. Conclusions: The surgical technique of laparoscopic TH-LMLND is stable and feasible; further IDEAL 2b research is warranted.

Genomic landscape of microsatellite instability in Chinese tumors: A comparison of Chinese and TCGA cohorts.

Microsatellite instability (MSI) is an important biomarker for predicting the response to immunotherapy and prognosis that mainly results from a defective DNA mismatch repair (MMR) system and strongly correlates with high tumor mutation burden (TMB). Herein, we developed a novel method that integrates MSI score, MMR mutation status and TMB level to identify MSI status from next-generation sequencing (NGS) data. The novel method displays a sensitivity of 96.80%, a specificity of 99.96% and an overall accuracy of 99.89%, compared to current standards. Using our novel method, we analyzed 11 395 Chinese patients across 30 cancer types. High microsatellite instability (MSI-H) was detected in 210 (1.84%) samples in 18 of 30 cancer types assessed. Mutations in ACVR2A (73%), KMT2D (68%), KMT2B (66%) and MMR-related genes (MLH1, MSH2, MSH6 and PMS2) were enriched in MSI-H samples. Furthermore, MSI-H samples were more likely to have high TMB (P < .01), high PD-L1 expression (P < .05) and more tumor-infiltrating immune cells than microsatellite-stable (MSS) samples. Compared to the TCGA patients, the prevalence of MSI-H in the Chinese cohort was significantly lower in colorectal, gastric and pancreatic cancer, while significantly higher in urinary and prostate cancer. Mutations in ACVR2A (73% vs 28%, P < .01) and MMR-related genes (51.4% vs 21.3%, P < .01) were significantly higher in the Chinese population. Thus, our study suggests the fraction of MSI-H attributable to MMR inactivation mutations were lower in European than in Chinese patients, while the proportion of MSI-H due to other events may be higher.

Safety and short-term outcomes of gastrectomy after preoperative chemotherapy plus immunotherapy versus preoperative chemotherapy: a retrospective cohort study.

BACKGROUND: The safety and short-term outcomes of gastrectomy after preoperative chemotherapy plus immunotherapy (PCIT) versus preoperative chemotherapy (PCT) in patients with advanced gastric cancer (AGC) remain unclear. This study was conducted to compare the safety and short-term efficacy of PCIT with those of PCT in patients with AGC. METHODS: We retrospectively reviewed the data of patients with AGC who received PCIT or PCT at Peking University Cancer Hospital and Institute Gastrointestinal Cancer Center I between January 2019 and June 2021. The clinical characteristics were recorded, and short-term oncological outcomes were compared. Independent t tests, Mann‒Whitney U tests, chi-square tests, and Fisher's exact tests were used to calculate differences. The correlation analyses were performed using Pearson correlation. All p values were two-sided, and a p value < 0.05 was considered statistically significant. All the above statistical analyses were conducted by the SPSS version 24.0 software package (IBM Corp., Armonk, NY, USA). RESULTS: A total of 162 AGC patients were included in this study, including 25 patients who received PCIT and 137 patients who received PCT. There were no significant differences in preoperative treatment-related adverse events (TRAEs) between the PCIT group and the PCT group (p = 0.088). Compared with the PCT group, the PCIT group had comparable postoperative functional recovery, with no significant differences in terms of time to first aerofluxus (p = 0.349), time to first defecation (p = 0.800), time to liquid diet (p = 0.233), or length of stay (p = 0.278). No significant differences were observed in terms of postoperative complications (p = 0.952), postoperative pain intensity at 24, 48, or 72 h (p = 0.375, p = 0.601, and p = 0.821, respectively), or postoperative supplementary analgesic use between the two groups (p = 0.881). In addition, the postoperative complication rate was 33.3% following laparoscopic approaches and 31.2% following open approaches in the PCIT group, with no significant difference (p = 1.000). CONCLUSION: In patients with AGC, gastrectomy with D2 or D2 + lymphadenectomy after PCIT had comparable short-term oncological outcomes to PCT.

Short-and long-term outcomes of laparoscopic versus open gastrectomy in patients with gastric cancer: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic gastrectomy (LG) for gastric cancer has rapidly developed and become more popular in recent decades. Additional high-quality randomized controlled trial (RCT) studies comparing LG versus open gastrectomy (OG) for gastric cancer (GC) have been published in recent years. An updated systematic review is warranted. The aim of our meta-analysis was to comprehensively evaluate the short- and long-term outcomes of LG versus OG for GC. MATERIALS AND METHODS: The PubMed, Embase, Web of Science, and Cochrane Center Register of Controlled Trials databases were comprehensively searched to identify RCTs comparing LG versus OG for GC published between January 1994 and December 7, 2021. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane Collaboration and the Quality of Reporting of Meta-analyses (QUORUM) guidelines. All RCTs comparing the short- and long-term outcomes of LG with those of OG were included. A random effects model was adopted with significant heterogeneity (I2 > 50%), while a fixed effects model was employed in all other cases (I2 ≤ 50%). RESULTS: A total of 26 RCTs with 8301 patients were included in this meta-analysis. The results indicated that the intraoperative complication rate was comparable between the LG group and the OG group (OR=1.14, 95% CI [0.76, 1.70], I2=0%, p=0.53). The LG group had fewer postoperative complications than the OG group (OR=0.65, 95% CI [0.57, 0.74], I2=26%, p<0.00001). However, the severe postoperative complication rate and perioperative mortality were comparable between the two groups (OR=0.83, 95% CI [0.67, 1.04], I2=10%, p=0.10; OR=1.11, 95% CI [0.59, 2.09], I2=0%, p=0.74, respectively). The number of lymph nodes retrieved by the LG group was less than that of the OG group (MD=-1.51, 95% CI [-2.29, -0.74], I2=0%, p<0.0001). The proximal resection margin distance in the LG group was shorter than that in the OG group (MD=-0.34, 95% CI [-0.57, -0.12], I2=23%, p=0.003), but the distal resection margin distance in the two groups was comparable (MD=-0.21, 95% CI [-0.47, 0.04], I2=0%, p=0.10). The time to first ambulation was shorter in the LG group than in the OG group (MD=-0.14, 95% CI [-.26, -0.01], I2=40%, p=0.03). The time to first flatus was also shorter in the LG group than in the OG group (MD=-0.15, 95% CI [-0.23, -0.07], I2=4%, p=0.0001). However, the first time on a liquid diet was comparable between the two groups (MD=-0.30, 95% CI [-0.64, 0.04], I2=88%, p=0.09). Furthermore, the postoperative length of stay was shorter in the LG group than in the OG group (MD=-1.26, 95% CI [-1.99, -0.53], I2=90%, p=0.0007). The 5-year overall survival (OS) was comparable between the two groups (HR=0.97, 95% CI [0.80, 1.17], I2=0%, p=0.73), and the 5-year disease-free survival (DFS) was also similar between the LG group and OG group (HR=1.08, 95% CI [0.77, 1.52], I2=0%, p=0.64). CONCLUSION: LG is a technically safe and feasible alternative to OG with the advantages of a fewer postoperative complication rate, faster recovery of gastrointestinal function, and greater cosmetic benefit for patients with GC. Meanwhile, LG has comparable long-term outcomes to OG for GC.

Laparoscopic vs. open lower mediastinal lymphadenectomy for Siewert type II/III adenocarcinoma of esophagogastric junction: An exploratory, observational, prospective, IDEAL stage 2b cohort study (CLASS-10 study).

Objective: This study aims to verify the feasibility and efficacy of laparoscopic lower mediastinal lymphadenectomy for Siewert type II/III adenocarcinoma of esophagogastric junction (AEG). Setting: An exploratory, observational, prospective, cohort study will be carried out under the Idea, Development, Exploration, Assessment and Long-term Follow-up (IDEAL) framework (stage 2b). Participants: The study will recruit 1,036 patients with cases of locally advanced AEG (Siewert type II/III, clinical stage cT2-4aN0-3M0), and 518 will be assigned to either the laparoscopy group or the open group. Interventions: Patients will receive lower mediastinal lymphadenectomy along with either total or proximal gastrectomy. Primary and secondary outcome measures: The primary endpoint is the number of lower mediastinal lymph nodes retrieved, and the secondary endpoints are the surgical safety and prognosis, including intraoperative and postoperative lower-mediastinal-lymphadenectomy-related morbidity and mortality, rate of rehospitalization, R0 resection rate, 3-year local recurrence rate, and 3-year overall survival. Conclusions: The study will provide data for the guidance and development of surgical treatment strategies for AEG. Trial registration number: The study has been registered in ClinicalTrials.gov (No. NCT04443478).

Treatment Switch in Poor Responders with Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy.

BACKGROUND: Among locally advanced gastric cancer (LAGC) patients, poor response to initial neoadjuvant chemotherapy (NAC) is associated with unfavorable outcomes; however, changing the postoperative therapy regimen in this group of patients is unclear. We compared the poor responders who continued the original protocols with that of patients who switched treatment after NAC plus D2 gastrectomy. METHODS: Our study included LAGC patients who achieved tumor regression grade 3 according to the American Joint Committee on Cancer/College of American Pathologists system, after NAC, between December 2006 and December 2017 at our institution. Outcomes were overall survival (OS), progression-free survival (PFS), and adverse events during postoperative treatment. The propensity score matching method was used to match patients. RESULTS: Overall, 160 patients were enrolled in the final analysis set, including 21 switched cases and 139 non-switched cases. A 1:2 matched cohort (21 switching vs. 42 non-switching) was generated to eliminate all confounding factors. No statistical differences were observed in OS and PFS, either in the whole patients (OS: log-rank p = 0.804; PFS: log-rank p = 0.943) or in the matched cohort (OS: log-rank p = 0.907; PFS: log-rank p = 0.670) between the two groups. Patients with changed regimens had a significantly higher rate of peripheral neurotoxicity (p = 0.045). Contrarily, a lower rate of overall adverse events was observed in the non-switching group with marginal significance (p = 0.069). CONCLUSION: Adjusting to a non-cross-resistant regimen only by post-NAC pathological evaluation may not be sufficient for designing an effective treatment route for LAGC poor responders. Treatment change required a more scrutinized clinical track, which involved a multifaceted assessment.

Prognostic and predictive value of mismatch repair deficiency in gastric and gastroesophageal junction adenocarcinoma patients receiving neoadjuvant or adjuvant chemotherapy.

BACKGROUND AND OBJECTIVES: Evidence is inconclusive regarding the prognostic significance of deficient DNA mismatch repair (dMMR) in gastric and gastroesophageal junction (GEJ) adenocarcinoma patients receiving chemotherapy. We aim to explore such associations with a large cohort. METHODS: We retrospectively identified a consecutive cohort of patients who had histology proven gastric or GEJ adenocarcinoma and received neoadjuvant chemotherapy plus surgery or upfront surgery plus adjuvant chemotherapy. MMR status was assessed by immunohistochemistry staining on surgical specimen. The association of MMR status with tumor regression grade (TRG), overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: In total, 1568 patients received neoadjuvant or adjuvant chemotherapy, of which 128 (8.2%) had dMMR tumors. No significant difference was found in the frequencies of TRG categories between proficient MMR (pMMR) and dMMR tumors (p = .62). Among patients receiving neoadjuvant chemotherapy, dMMR status was associated with better OS (log-rank p = .044) and DFS (log-rank p = .022) in the univariate analysis; this association became nonsignificant after adjusting for pathologic stages and other prognostic factors. Similar results were found for patients receiving adjuvant chemotherapy. CONCLUSIONS: dMMR status was not significantly associated with OS and DFS among gastric and GEJ adenocarcinoma patients with neoadjuvant and adjuvant platinum and fluorouracil-based chemotherapy.

Short-term outcomes after totally laparoscopic total gastrectomy with esophagojejunostomy constructed by π-shaped method versus overlap method.

BACKGROUND: Regarding the overlap anastomosis and recently introduced π-shaped anastomosis, there is no consensus on which intracorporeal esophagojejunostomy (EJS) methods are preferred using linear stapler in totally laparoscopic total gastrectomy (TLTG). This study aims to evaluate the short-term outcomes using two methods. METHODS: Patients with upper gastric cancer underwent TLTG with either π-shaped (n = 48) or the modified overlap method using knotless barbed sutures (MOBS) (n = 37) were included in our study. Intraoperative and perioperative outcomes were compared. RESULTS: All patients achieved R0 resection margin. The overall esophagojejunal (E-J)-related complications rate was 7.06%. There was no significant difference between the two groups in terms of postoperative complications, margin distance, numbers of lymph nodes (LNs), length of stay. In the π-shaped group, anastomosis time (19.61 ± 7.17 min vs. 27.09 ± 3.59 min, p < 0.001) was significantly lower. The consumable costs for surgery were similar (44 507.74¥ [42 933.03-46 937.29] vs. 43 718.36¥ [42 743.25-47 256.06], p = 0.825). The first defection time was significantly longer in π-shaped group (131.00 h [93.75-171.25] vs. 100.00 h [85.00-120.00], p = 0.026), whereas the other postoperative recovery parameters were similar. No mortality was observed. CONCLUSIONS: Both methods showed similar short-term postoperative outcomes. The π-shaped technique was faster than the MOBS method without significantly increasing the supplies costs. Large prospective studies are warranted.

Combination of tumor markers predicts progression and pathological response in patients with locally advanced gastric cancer after neoadjuvant chemotherapy treatment.

BACKGROUND: The prognostic values of preoperative tumor markers (TMs) remain elusive in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy treatment (NACT). This study aimed to assess and establish a novel scoring system incorporating carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4) to enhance prognostic accuracy for progression-free survival (PFS) and pathological response (pCR). METHODS: Patients' data were retrospectively analyzed from December 2006 to December 2017 in our center. The cutoff value of TMs was determined using the time-dependent receiver operating test characteristics method. These three TMs were allocated 1 point each for the post neoadjuvant chemotherapy combination of tumor markers (post-NACT CTM) scores. The training group comprised 533 patients, responsible for full analysis, and the validation group comprised 137 patients based on the selection protocol. RESULTS: Of 533 enrolled patients, 138, 233, 117, and 45 patients scored 0, 1, 2, 3 respectively. The 3-year PFS rate Multivariate analysis revealed that post-NACT CTM score was an independent predictor of PFS (0 vs. 1, HR: 1.34, 95% CI: 0.92-1.96, P = 0.128; 0 vs. 2, HR: 2.03, 95% CI: 1.35-3.05, P = 0.001; 0 vs. 3, HR: 2.98, 95% CI: 1.83-4.86, P < 0.001). The time-dependent area under curve (AUC) revealed a consistent highest level for post-NACT CTM than other three single TMs. Lower post-NACT CTM score significantly correlated with higher pCR rate based on multivariate logistic regression (2/3 vs. 1, OR: 2.77, 95% CI: 0.90-8.53, P = 0.077; 2/3 vs. 0, OR: 4.33, 95% CI: 1.38-13.61, P = 0.012). A nomogram was formed with both internal and external validation. CONCLUSIONS: The post-NACT CTM score system served as a strong independent predictor for PFS and pCR in LAGC patients who received NACT. Further population-based studies are required to confirm our results.

Tumor mutation burden is correlated with response and prognosis in microsatellite-stable (MSS) gastric cancer patients undergoing neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NACT) before radical gastrectomy is preferred for locally advanced gastric cancer (GC). However, clinical practices demonstrate that a considerable proportion of GC patients do not benefit from NACT, largely due to the lack of biomarkers for patient selection and prognosis prediction. A recent study revealed that patients with microsatellite instability-high (MSI-H) may be resistant to NACT, however, most tumors in Chinese GC patients (~ 95%) are characterized by microsatellite stability (MSS). Here, we aimed to discover new molecular biomarkers for this larger population. METHODS: We performed whole-exome sequencing on 46 clinical samples (pre- and post-treatment) from 30 stage II/III MSS GC patients whose response to NACT was rigorously defined. Serum tumor markers (TMs), including AFP, CEA, CA199, CA724 and CA242 were measured during the course. RESULTS: High tumor mutation burden (TMB-H) and 19q12 amplification (19q12 +) were positively associated with the NACT response. When TMB and 19q12 amplification were jointly analyzed, those with TMB-H or 19q12 + showed favorable response to NACT (p = 0.035). Further, TMB-H was negatively correlated with ypN stage, lymph node metastasis, and macrophage infiltration. Patients with TMB-H showed better disease-free survival (DFS) than those with TMB-L (P = 0.025, HR = 0.1331), and this was further validated using two larger GC datasets: TCGA-STAD (p = 0.004) and ICGC-CN (p = 0.045). CONCLUSION: The combination of TMB-H and 19q12 + can serve as an early indicator of response to NACT. Superior to traditional clinical indicators, TMB-H is a robust and easily accessible candidate biomarker associated with better DFS, and can be evaluated at the time of diagnosis.

Comparison of the short-term outcomes of laparoscopic and open total or proximal gastrectomy using the transorally inserted anvil (OrVilTM) for the proximal reconstruction: a propensity score matching analysis.

PURPOSE: To compare the short-term surgical outcomes of laparoscopic and open total/proximal gastrectomy using transorally inserted anvil (OrVilTM). METHOD: Patients diagnosed with gastric cancer and underwent total or proximal gastrectomy using OrVilTM for reconstruction were included. Clinical and pathological characteristics, as well as postoperative outcomes, were analyzed. Propensity score matching was used to balance baseline factors. RESULTS: From April 2012 to April 2020, 199 patients at our center were included. A total of 166 underwent open total or proximal gastrectomy (OTG/OPG), and 33 underwent laparoscopic total or proximal gastrectomy (LTG/LPG). Twenty-seven patients from each group were paired with propensity score matching. The operation time was significantly shorter in the OTG/OPG group after matching. The overall complication rate and the incidence of each complication did not show significant differences between the two groups before and after matching. CONCLUSION: LTG/LPG and OTG/OPG using OrVilTM for the alimentary tract reconstruction are both feasible and can achieve similar short-term outcomes.

The clinical value and usage of inflammatory and nutritional markers in survival prediction for gastric cancer patients with neoadjuvant chemotherapy and D2 lymphadenectomy.

BACKGROUND: The clinical values of inflammatory and nutritional markers remained unclear for gastric cancer with neoadjuvant chemotherapy (NACT). METHODS: The inflammatory, nutritional markers and their changes were analyzed for locally advanced gastric cancer with NACT. The predictive value was evaluated by the Cox proportional hazards regressions under three hypothesized scenarios. The nomograms including independent prognostic factors were plotted for survival prediction. RESULTS: A total of 225 patients were included in the study. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index, and hemoglobin (Hgb) were significantly reduced, and the body mass index was significantly increased after NACT (all P < 0.05). The pre-NACT NLR [hazard ratio (HR) = 1.176, P = 0.059] showed a trend to correlate with the overall survival (OS) when only pre-NACT markers available; The post-NACT Hgb (HR = 0.982, P = 0.015) was the independent prognostic factor when only post-NACT markers available; The post-NACT Hgb (HR = 0.984, P = 0.025) and the change value of LMR (HR = 1.183, P = 0.036) were the independent prognostic factors when both pre- and post-NACT markers available. The nomogram had a similar Harrell's C-statistic compared to ypTNM stage (0.719 vs. 0.706). CONCLUSION: For locally advanced gastric cancer, the NACT could significantly decrease some inflammatory markers. The pre-NACT NLR, the post-NACT Hgb and the change value of LMR had some values in survival prediction combined with age, sex, tumor location and the clinical stages under different clinical scenarios. The elevated initial NLR, the preoperative anemia and the greater change value of LMR implied a poor prognosis.

Different prognostic implication of ypTNM stage and pTNM stage for gastric cancer: a propensity score-matched analysis.

BACKGROUND: Pathological stage is considered as the best prognosis indicator for gastric cancer. With the increasing use of neoadjuvant chemotherapy (NACT), the latest TNM staging included a new pathological stage of ypTNM for patients with NACT. However, no study has investigated if ypTNM stage has the same prognostic implication as pTNM stage for gastric cancer. METHODS: We retrospectively selected eligible patients within a prospectively maintained database containing all patients treated with gastric cancer in Peking University Cancer Hospital from 2007 to 2015 using overall survival as the outcome. Patients using ypTNM and pTNM were 1:1 matched by propensity scores (PS) calculated from a model containing variables associated with ypTNM use or survival. Overall survival was compared by unconditional Cox regression. Conventional multivariate analysis was conducted to corroborate PS matching results. RESULTS: 1441 patients were included in the analysis with a median follow-up of 37 months (range = 2-106). The matched sample contained 756 patients. After PS matching, patients with specific ypTNM stage were 1.34 (95%CI = 1.05-1.72, P = 0.019) times more likely to die than patients with the same pTNM stage. Similar to the results of PS matching, multivariate Cox regression yielded a hazard ratio (HR) of 1.35 (95%CI = 1.09-1.67, P = 0.006). Subgroup analysis indicated this survival difference between ypTNM and pTNM stage varied by the specific TNM stage of patients. The HR was 3.44 (95%CI = 1.06-11.18, P = 0.040) and 1.28 (95%CI = 1.00-1.62, P = 0.048) for patients in stage I and III, respectively; whereas for stage II patients, no significant difference was observed (HR = 1.37, 95%CI = 0.78-2.38, P = 0.27). CONCLUSION: Gastric cancer patients with specific ypTNM stage had worse prognosis compared to those at the same stage defined by pTNM.

The effect of preoperative treatments on lymph node counts after total gastrectomy in esophagogastric adenocarcinoma.

OBJECTIVES: This study aims to explore the effects of preoperative treatments on lymph nodes (LNs) counts after total gastrectomy with D2 lymphadenectomy in esophagogastric adenocarcinoma. METHODS: A retrospective analysis was performed for 446 patients with locally advanced esophagogastric adenocarcinoma. The patients were divided into three groups: surgery first (SF), preoperative chemotherapy (PCT), and preoperative chemoradiotherapy (PCRT). Clinical-pathological data were analyzed. RESULTS: The case number in SF, PCT, and PCRT groups was 281, 109, and 56, respectively, and the median total LNs count was 32.0 (10.0-102.0), 31.0 (12.0-62.0), and 25.5 (10.0-50.0), respectively, (P < 0.001). Univariate and multivariate analyses demonstrated the total LNs count was lower in PCRT than SF/PCT (P < 0.001), and had no correlation with tumor regression grades (TRGs). Subgroup comparison showed radiation target LNs count was lower in PCRT than SF/PCT (P < 0.001), and peritarget LNs count was lower in PCRT than SF (P = 0.002). CONCLUSION: For esophagogastric adenocarcinoma, PCRT reduced total LNs count after total gastrectomy with D2 lymphadenectomy, whereas PCT did not. In the PCRT group, LNs count was lower in both radiation target and peritarget areas than in the SF group but only in radiation target area than in the PCT group. The correlation between TRGs and total LNs count remained unclear.

Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing.

Gastro-oesophageal junction (GEJ) carcinoma and distal gastric cancer (GC) have distinct epidemiology and clinical features and their relationship is uncertain. Synchronous multiple gastric cancers located mostly at proximal and distal sites provide rare specimens for investigating the comprehensive genomic relationships among these cancers in the context of identical genetic circumstances. Formalin-fixed, paraffin-embedded (FFPE) samples from 12 patients with synchronous GEJ carcinoma and distal GC were collected in this study. Whole-exome sequencing (WES) was performed using normal tissues as a control. Mutational profiling, clonality analysis, a detailed clinico-pathological review, determination of MSI status, EBER in situ hybridization (ISH), and programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunohistochemical staining were performed. Twenty-three of the 24 samples were microsatellite-stable (MSS). Subclonal analysis revealed that nine pairs of GEJ and distal GC tumours in neoadjuvant chemotherapy naïve patients developed independently from different origins. Two patients who received neoadjuvant chemotherapy shared clonal origins with highly similar somatic alterations. The remaining one patient who shared a rare mutation died within 6.2 months at the N3 stage. However, the enriched pathway identified from the overall mutation spectra in distal GC and GEJ carcinoma showed the close relationship of these cancers. Thus, although these cancers may have similar characteristics, histopathological and genetic profiling from single tumour specimens may still underestimate the mutational burden and somatic heterogeneity of multiple GCs. In addition, this series of cases also showed a PD-L1 expression rate of 58.3% and 66.7% in distal GC and GEJ carcinoma, respectively, with all the cases expressing PD-1. This result suggests the potential benefit of immunotherapeutic treatments. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[Effect of MicroRNA-199 on Proliferation and Migration of Gastric Carcinoma Cells].

Objective To detect the expression of microRNA(miR)-199 in gastric carcinoma tissues and cell lines, and further explore the effect and molecular mechanism of miR-199 on the proliferation and migration of gastric carcinoma cell lines. Methods Reverse transcriptase-polymerse chain reaction was used to detect the expression of miR-199 in gastric carcinoma and adjacent normal tissue obtained from 51 patients and in gastric carcinoma cell lines and human gastric epithelial cell line GES-1. The gastric carcinoma cell lines over-expressing and low-expressing miR-199 were established to detect their proliferation and migration abilities. Dual-luciferase reporter assay was performed to detect the regulatory effect of miR-199 on the 3'untranslated region of TBL1XR1. Western blot was used to explore the miR-199-related mechanism. Results The relative expression of miR-199 in gastric carcinoma tissues was significantly lower than that in the adjacent normal tissue (0.2635±0.0303 vs. 1.6700±0.9613, t=13.95, P<0.001). The relative expressions of miR-199 in gastric carcinoma cell lines AGS (0.81, t=9.13, P<0.001), SGC-7901 (0.83, t=8.88, P<0.001), MKN28 (0.58, t=10.80, P<0.001), KATO-3 (0.60, t=10.31, P<0.001), MKN-45 (0.27, t=13.10, P<0.001) were significantly lower than that in the normal gastric cell line GES-1 (2.1). In miR-199 over-expressed cell lines, the cell proliferation and migration significantly decreased as compared with the control group of gastric carcinoma cells (731±13 vs. 345±18, t=24.90, P<0.001), and in miR-199 low-expressed group, the cell proliferation and migration increased compared with the control group of gastric carcinoma cells (257±16 vs. 657±8, t=32.59, P<0.001). Dual-luciferase reporter assay proved that miR-199 directly targeted on the 3' untranslated region of TBL1XR1. Western blot analysis showed that miR-199 inhibited the expression of TBL1XR1. Conclusion The over-expression of miR-199 in gastric carcinoma is associated with the decreased ability of proliferation and migration of gastric carcinoma cells by targeting TBL1XR1.