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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 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.

BackgroundThe optimal indications of staging laparoscopy in gastric cancer to detect peritoneal carcinomatosis are still controversial. We performed this systematic review and meta-analysis to quantify the relevance of the preoperative factors with peritoneal carcinomatosis to explore the indications of staging laparoscopy.Materials and methodsSystematic searches were conducted using Medline, Embase, and the Cochrane Library in December 2021. On the basis of calculating the odds ratio (OR) of each factor, we quantified the association between the risk factors and peritoneal carcinomatosis such as clinical T/N stage, Borrmann type, and tumor markers, using meta-analysis with a random-effects model.ResultsA total of 21 case-control studies and one cohort study were obtained. T stage, N stage, and differentiation degree were most widely studied, with OR values of 2.96 (95% CI: 1.87–4.69), 1.22 (95% CI: 0.86–1.73), and 1.91 (95% CI: 1.42–2.56), respectively. Among all the factors, elevated CA125 (OR = 19.45, 95% CI: 4.71–80.30), Borrmann type IV (OR = 7.68, 95% CI: 3.62–16.27), and large tumor diameter (OR = 5.12, 95% CI: 2.55–10.31) had the highest OR. In particular, CA125 had the best predictability for peritoneal carcinomatosis but was only mentioned by three articles.ConclusionsThere was a cognitive gap between the awareness and importance of risk factors for peritoneal carcinomatosis. In addition to T4 stage, patients with factors with high OR, such as Borrmann type IV, large tumor diameter, and elevated CA125, should undergo staging laparoscopy.

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 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.

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%, pI2=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%, pI2=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.

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.

BackgroundEpstein–Barr virus-associated gastric cancer(EBVaGC)has a unique tumor immune microenvironment. We performed a comprehensive analysis of the tumor-infiltrating immune cells in a cohort of EBVaGC in a Chinese population.MethodsEpstein–Barr encoding region (EBER) in situ hybridization was performed in 1,328 consecutive cases of surgically resected GC. Densities of immune cells, including T cells, B cells, natural killer cells, and macrophages from the patients were calculated after immunohistochemical staining with CD3, CD20, CD57, and CD68 antibodies in tissue microarrays, respectively.ResultsEBVaGC patients accounted for 4.1% (55 of 1,328) cases in the overall population. The average age of patients with EBVaGC was lower than that of non-EBVaGC patients. Histologically, EBVaGC patients exhibited poorly differentiated adenocarcinoma (P = 0.004) and lower frequency of vascular invasion (P = 0.034). The density of CD3+ T lymphocytes (CD3, 23.84 ± 14.49 vs. 12.76 ± 8.93, P < 0.001) and CD68+ macrophages (CD68, 9.73 ± 5.25 vs. 5.44 ± 4.18, P < 0.001) was significantly higher in EBVaGC patients. CD3+ T cell density predicted better 5-year overall survival of EBVaGC patients (P = 0.022).ConclusionsEBVaGC patients were younger with low-differentiated adenocarcinoma and less vascular invasion. Increased infiltration of multiple immune cells affected the prognosis of patients, especially EBVaGC patients with more CD3+ T lymphocytes, who survived longer.

Background Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. Patients and methods A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients’ PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. Results RS1, RS2, and Lauren type were significant predictors of occult PM (all P

Objective Diagnostic laparoscopy is recommended for the pretherapeutic staging of gastric cancer to detect any unexpected or unconfirmed intra-abdominal metastasis. The aim of this study was to evaluate the role and indications of diagnostic laparoscopy in the detection of intra-abdominal metastasis. Methods Standard diagnostic laparoscopy with peritoneal cytology examination was performed prospectively on patients who were clinically diagnosed with primary local advanced gastric cancer (cT≥2M0). We calculated the rate of intra-abdominal metastases identified by diagnostic laparoscopy, and examined the relationship between peritoneal dissemination (P) and cytology results (CY). Split-sample method was applied to find clinical risk factors for intra-abdominal metastasis. Multivariate logistic regression analysis and receiver-operator characteristic (ROC) analysis were performed in training set to find out risk factors of intra-abdominal metastasis, and then validate it in testing set. Results Out of 249 cM0 patients, 51 (20.5%) patients with intra-abdominal metastasis were identified by diagnostic laparoscopy, including 20 (8.0%) P1CY1, 17 (6.8%) P0CY1 and 14 (5.6%) P1CY0 patients. In the training set, multivariate logistic regression analysis and ROC analysis showed that the depth of tumor invasion on computer tomography (CT) scan ≥21 mm and tumor-occupied ≥2 portions of stomach are predictive factors of metastasis. In the testing set, when diagnostic laparoscopy was performed on patients who had one or two of these risk factors, the sensitivity and positive predictive value for detecting intra-abdominal metastasis were 90.0% and 32.1%, respectively. Conclusions According to our results, depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis.

// Ziyu Li 1, * , Xiaofang Xing 2, * , Fei Shan 1 , Shuangxi Li 1 , Zhongwu Li 3 , Aitang Xiao 1 , Zhaodong Xing 1 , Kan Xue 1 , Zhemin Li 1 , Ying Hu 4 , Yongning Jia 1 , Rulin Miao 1 , Lianhai Zhang 1 , Zhaode Bu 1 , Aiwen Wu 1 , Jiafu Ji 1, 2, 3 1 Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China 2 Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China 3 Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China 4 Tissue Bank, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China * These authors contributed equally to this work Correspondence to: Jiafu Ji, email: jiafuj@hotmail.com Keywords: ABCC2, rs717620, gastric cancer, neoadjuvant chemotherapy, overall survival Received: February 03, 2016 Accepted: June 29, 2016 Published: July 30, 2016 ABSTRACT 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 SNaPShot TM 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.

Background Preoperative diagnosis of peritoneal metastasis with gastric cancer remains challenging. This study explored the abnormal computed tomography (CT) signs of occult peritoneal metastasis (OPM) and evaluated it by region-to-region comparison using staging laparoscopy, from which a 4-point CT score system was developed. Methods Patients with advanced gastric cancer (stage cT ≥ 2M0) diagnosed by CT were enrolled in the study. Occult peritoneal metastasis detected during staging laparoscopy was compared with preoperative CT to investigate the presence of abnormal signs by a region-to-region comparison. A 4-point CT score system was developed to define the radiologic characteristics. Subsequently, the diagnostic efficacy of the CT score system was prospectively verified. Results In this study, 57 OPM regions were detected by staging laparoscopy in 33 of the 385 enrolled patients. The greater omentum was the most frequent site of OPM (38.60%, 22/57), which usually exhibited a smudge-like ground-glass opacity (S-GGO) (90.91%, 20/22) with a mean CT score of 2.14. The parietal and perihepatic peritoneum was the second most common site (22.81%, 13/57). A 4-point CT score system was developed based on the results. A cutoff CT score of 2 or higher was associated with a false-negative rate of 2% (2/99). This CT score system had a sensitivity of 87.5% and a specificity of 76.4% for an OPM-positive diagnosis (area under the curve, 0.848). The agreement between two radiologists on the assigned final score was 76.2% (kappa, 0.5). Conclusions Patients with OPM mostly exhibited S-GGO on CT, which should be interpreted cautiously. The 4-point CT score system may improve the pretreatment evaluation of occult peritoneal metastasis, and staging laparoscopy might not be necessary for patients with a score lower than 2.

Background Neoadjuvant chemotherapy before radical gastrectomy is preferred for locally advanced gastric cancer. To avoid the problematic use of pTNM for patients after neoadjuvant chemotherapy, the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer TNM staging system (8th edition) added ypTNM for the first time. But patients achieving pathological complete response were not covered by the new ypTNM staging system. To investigate whether pathological complete response is associated with better outcome in gastric cancer, as was reported in rectal, breast and bladder cancer. Methods We systematically searched the databases of PubMed, EMBASE, Web of Science and Cochrane Collaboration’s Central register of controlled trials from January 1988 to April 2015 for publications which reported outcomes of patients with and without pathological complete response (pCR) (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or gastroesophageal junction (GEJ) treated with radical surgery is associated with better survival. The primary outcome was overall survival (OS). The secondary outcome was disease-free survival (DFS). Both were measured with a relative risk (RR). A meta-analysis was performed using the fixed effects model. Forest plots and the Q test was used to evaluate overall heterogeneity for OS and DFS. Results A total of seven trials, 1143 patients were included and analyzed after neoadjuvant chemotherapy and radical surgery with no other preoperative treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence interval [CI], 0.25–0.98; p = 0.04), 0.34 (95% CI, 0.21–0.55; p

Purpose Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of anti-angiogenic agents in gastric cancer. Design A systematic search of PubMed, Embase and conference databases is performed to identify clinical trials with specific anti-angiogenic agents in gastric cancer treatment Results The risk of disease progression (37–52%) and death (19–22%) with ramucirumab as second-line treatment decreases in phase III trials in advanced gastric cancer. No significant improvement in overall survival (OS) with the addition of bevacizumab to chemotherapy is shown. Bevacizumab or ramucirumab combined with traditional chemotherapy is associated with higher adverse event rate compared to chemotherapy alone. Except for apatinib, phase II trials of other tyrosine kinase inhibitors (TKIs) may improve overall response rate, but there are no significant improvements in OS and progression-free survival (PFS) when combined with chemotherapy. Conclusion Phase III trials in advanced gastric cancer have demonstrated improved outcome with ramucirumab as second-line treatment. Most of the other studies on anti-angiogenic agents in gastric cancer have reported improvement in response rate but not in OS compared to chemotherapy alone. Future research is expected in optimizing the anti-angiogenic therapy combined with traditional treatment.

Aim: Gastric cancer accounts for >325,000 deaths in China annually. MET and its ligand hepatocyte growth factor are promising targets in G/GEJ cancer. This study evaluated overall survival (OS) by tumor MET expression and by treatment disposition in Chinese pts with advanced G/GEJ cancer. Methods: Baseline formalin-fixed, paraffin-embedded tumor samples from pts with stage IV unresectable G/GEJ cancer enrolled in clinical trials during 2008–2010 were assessed for MET protein levels and MET gene copy numbers by immunohistochemistry (IHC; Dako) and fluorescence in situ hybridization (FISH; Dako), respectively. MET-positive: membrane protein staining in ≥25% tumor cells. MET-amplified: MET:centromere ratio ≥2.0. We tested the association between Kaplan-Meier OS and MET status (log-rank test) and clinical parameters (Fisher's exact), and the association between MET expression and amplification (Fisher's exact). Results: 168 pts were eligible; 137 had evaluable IHC samples. OS by MET status is shown (Table). Of 113 pts with evaluable FISH samples, 8 were MET-amplified. MET expression and amplification were not associated with sex, primary tumor site, prior surgery, lung or liver metastases, or number of metastases. Lauren classification was associated with MET amplification (P=0.038) but not MET expression (P=0.446). In 95 pts with evaluable IHC and FISH samples, MET expression was associated with MET amplification (P Patients Evaluable for IHC MET-positive MET-negative P-valued Overall, n 53 84 – OS analysis, n 51 82 – Median OS, mo 12.3 10.9 0.799 First-line platinum-based,a n 35 47 – OS analysis, n 33 47 – Median OS, mo 11.3 11.8 0.367 First-line platinum-based only,b n 30 34 – OS analysis, n 28 34 – Median OS, mo 10.6 11.9 0.119 First-line taxane-based,a,c n 23 50 – OS analysis, n 23 48 – Median OS, mo 12.6 10.8 0.259 aIncludes platinum- and taxane-based triplet (n=18). bExcludes platinum- and taxane-based triplet (n=18). cIncludes paclitaxel alone (n=1). dLog-rank test. Conclusions: Tumor MET expression was not significantly associated with OS in this population of Chinese pts with advanced G/GEJ cancer. The study was limited by the small sample size and unbalanced treatment disposition between MET-positive and MET-negative pts. Prospective analysis of potential prognostic markers in Chinese pts with advanced G/GEJ cancer is needed. Disclosure: K.S. Oliner: employment by and stock ownership in Amgen Inc.; Y. Hei: employment by and stock ownership in Amgen Inc.; H. Zhou: employment by and stock ownership in Amgen Inc. All other authors have declared no conflicts of interest.