The short peptide encoded by long non-coding RNA RNF217-AS1 inhibits stomach cancer tumorigenesis, macrophage recruitment, and pro-inflammatory responses.

Certain long non-coding RNAs (lncRNAs) have potential peptide-coding abilities. Here, the role and molecular basis of the RNF217-AS1-encoded peptide in stomach cancer (SC) tumorigenesis were explored. Here, lncRNAs associated with SC pathogenesis and macrophage infiltration and lncRNAs with peptide-coding potential were searched by bioinformatics analysis. The gene mRNA and protein levels were examined by RT-qPCR and western blot assays, respectively. Cell viability, migratory, and invasive abilities were measured by CCK-8, Transwell migration, and Transwell invasion assays, respectively. The potential biological processes related to lncRNA RNF217-AS1 were identified by single-gene GSEA analysis. The effect of RNF217-AS1-encoded peptide on SC tumorigenesis was examined by mouse xenograft experiments. The results showed that lncRNA NR2F1-AS1 and RNF217-AS1 were differentially expressed and associated with macrophage infiltration in SC, and they had the ability to translate into short peptides. The RNF217-AS1 ORF-encoded peptide could reduce SC cell viability, inhibit cell migration and invasion, as well as hinder the development of SC xenograft tumors. The RNF217-AS1 ORF-encoded peptide in human SC AGS cells suppressed THP-1 cell migration, triggered the differential expression of CXCL1/CXCL2/CXCL8/CXCL12, and inactivated the TLR4/NF-κB/STAT1 signaling pathways. As a conclusion, the RNF217-AS1 ORF-encoded peptide hindered SC progression in vitro and in vivo and suppressed macrophage recruitment and pro-inflammatory responses in SC.

PHF5A facilitates the development and progression of gastric cancer through SKP2-mediated stabilization of FOS.

BACKGROUND: Gastric cancer (GC) is the fifth most common cancer and the third most common cause of cancer death worldwide. Plant homeodomain (PHD)-finger domain protein PHF5A has been demonstrated to play a promoting role in a variety of cancers. This study aimed to clarify the role of PHF5A in the progression of GC and its potential mechanism of action. METHODS: Immunohistochemical staining experiments were performed based on tissues from clinical GC patients to reveal PHF5A expression. A series of functional experiments in vitro and in vivo were used to clarify the role of PHF5A in GC. RESULTS: Clinically, PHF5A was abundantly expressed in GC and existed clinical value indicating poor prognosis. In addition, GC cells with knockdown of PHF5A expression showed slowed proliferation, enhanced sensitivity to apoptosis and inhibition of migration. Mechanically, knockdown of PHF5A led to decreased protein stability of FOS, which was mediated ubiquitination of E3 ubiquitin ligase S-phase kinase-associated protein 2 (SKP2). Moreover, downregulation of FOS attenuated the promotion of PHF5A overexpression on GC cells. Consistently, Pladienolide B (PHF5A inhibitor) treatment reversed the induction of PHF5A overexpression on the malignant phenotypes and tumor formation of GC cells. CONCLUSION: Knockdown of PHF5A inhibited the progression of GC through SKP2-mediated ubiquitination of FOS, which may be a promising candidate target with potential therapeutic value.

Is single tract jejunal interposition better than double tract reconstruction after proximal gastrectomy?

Double tract reconstruction (DTR) is the main digestive tract reconstruction method after proximal gastrectomy (PG). Single tract jejunal interposition (STJI) derived from the double tract reconstruction is also increasingly used in clinical practice. However, there is still a great controversy as to which of the two reconstruction methods can achieve better results. In this study, we systematically reviewed studies on DTR and STJI after PG and performed a meta-analysis. We searched PubMed, Embase, and Cochrane Library databases for clinical studies comparing DTR and STJI after PG to December 2021 without language restriction. Review Manager (version5.4) software was used to perform meta-analysis on operative outcomes, postoperative complications and nutritional outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42022301455). Five randomized controlled trials involving 453 patients were included in the meta-analysis. There were no significant differences between DTR and STJI in terms of intraoperative blood loss, postoperative hospital stay, incidence of reflux esophagitis, anastomotic complications and total complications. The operation time of STJI group was longer than that of DTR group [WMD - 0.79; 95% CI (- 1.55, - 0.03)] [heterogeneity: χ2 = 4.94, df = 3 (P = 0.18); I2 = 39%, test for overall effect: Z = 2.04 (P = 0.04)]. The body weight of STJI group was significantly higher than that of DTR group at 6 months after surgery [WMD 3.90; 95% CI (0.56, 7.23)] [heterogeneity: τ2 = 7.67, χ2 = 19.76, df = 2 (P < 0.0001); I2 = 90%, test for overall effect: Z = 2.29 (P = 0.02)]. To the best of our knowledge, this is the first systematic review and meta-analysis to compare the outcomes of DTR and STJI after PG. There were no significant differences in operative outcomes and postoperative complications between DTR and STJI after PG. Although STJI prolonged the operation time compared to DTR, postoperative nutritional outcomes of patients in the STJI group was significantly better than that in the DTR group. Therefore, compared to DTR, STJI may be more suitable for the vast majority of patients undergoing PG due to its better postoperative nutritional status.

Increased Expression of POSTN Predicts Poor Prognosis: a Potential Therapeutic Target for Gastric Cancer.

BACKGROUND: Periostin (POSTN) is involved in many biological processes and is associated with the occurrence and development of several cancers, while its role in gastric cancer is not clear. We aimed to demonstrate the relationship between POSTN and gastric cancer based on publicly available data from The Cancer Genome Atlas (TCGA) database. METHODS: POSTN expression data and corresponding clinical information were downloaded from TCGA database. We compared the expression of POSTN in gastric cancer samples and normal samples. POSTN-related differentially expressed genes (DEGs) were identified for further functional enrichment analysis. In addition, the relationships between POSTN expression and clinicopathological features and survival in patients with gastric cancer were also investigated through univariate and multivariate Cox regression analyses. Furthermore, a nomogram was constructed to predict the survival probability of gastric cancer patients. RESULTS: POSTN expression in gastric cancer was significantly higher than that in normal gastric tissues (p < 0.001). High POSTN expression in gastric cancer was significantly related to poor prognostic features, including greater tumor extent (odds ratio [OR] = 1.638 for T3 and T4 vs. T1 and T2), worse histological type (OR = 0.329 for diffuse type vs. tubular type), and advanced histological grade (OR = 1.646 for grade 3 vs. grades 1 and 2) (all p < 0.05). The 118 identified DEGs were primarily enriched in pathways related to tumorigenesis and tumor progression, including the TGF-ß signaling pathway, the WNT signaling pathway, and the signaling by VEGF. POSTN expression was positively correlated with the enrichment of the macrophages (r = 0.599, p < 0.001), helper T2 cells (r = 0.146, p = 0.005), and CD8 + T cells (r = 0.190, p < 0.001), but negatively correlated with the enrichment of Th17 cells (r = - 0.130, p = 0.012) and NK CD56bright cells. Kaplan-Meier survival analysis showed that high POSTN expression is associated with a short overall survival (hazard ratio [HR] = 1.54; p = 0.011). In the multivariate cox regression analysis, high POSTN expression was confirmed to be an independent predictor of poor overall survival (HR = 1.681; p = 0.017). The constructed nomogram can well predict the 1 and 3 years overall survival probability of patients with GC (0.696 [95% CI, 0.671-0.721]). CONCLUSION: POSTN plays an important role in the progression and prognosis of gastric cancer, and it may serve as a useful biomarker to predict survival in gastric cancer patients.

Corrigendum: LncRNA MSC-AS1 Is a Diagnostic Biomarker and Predicts Poor Prognosis in Patients With Gastric Cancer by Integrated Bioinformatics Analysis.

[This corrects the article DOI: 10.3389/fmed.2021.795427.].

Integrated analysis of necroptosis-related genes for evaluating immune infiltration and colon cancer prognosis.

Background: Colon cancer (CC) is the second most common gastrointestinal malignancy. About one in five patients have already developed distant metastases at the time of initial diagnosis, and up to half of patients develop distant metastases from initial local disease, which leads to a poor prognosis for CC patients. Necroptosis plays a key role in promoting tumor growth in different tumors. The purpose of this study was to construct a prognostic model composed of necroptosis-related genes (NRGs) in CC. Methods: The Cancer Genome Atlas was used to obtain information on clinical features and gene expression. Gene expression differential analysis, weighted gene co-expression network analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator regression algorithm were utilized to identify prognostic NRGs. Thereafter, a risk scoring model was established based on the NRGs. Biological processes and pathways were identified by gene ontology and gene set enrichment analysis (GSEA). Further, protein-protein interaction and ceRNA networks were constructed based on mRNA-miRNA-lncRNA. Finally, the effect of necroptosis related risk score on different degrees of immune cell infiltration was evaluated. Results: CALB1, CHST13, and SLC4A4 were identified as NRGs of prognostic significance and were used to establish a risk scoring model. The time-dependent receiver operating characteristic curve analysis revealed that the model could well predict the 1-, 3-, and 5-year overall survival (OS). Further, GSEA suggested that the NRGs may participate in biological processes, such as the WNT pathway and JAK-Stat pathway. Eight key hub genes were identified, and a ceRNA regulatory network, which comprised 1 lncRNA, 5 miRNAs and 3 mRNAs, was constructed. Immune infiltration analysis revealed that the low-risk group had significantly higher immune-related scores than the high-risk group. A nomogram of the model was constructed based on the risk score, necroptosis, and the clinicopathological features (age and TNM stage). The calibration curves implied that the model was effective at predicting the 1-, 3-, and 5-year OS of CC. Conclusion: Our NRG-based prognostic model can assist in the evaluation of CC prognosis and the identification of therapeutic targets for CC.

LncRNA MSC-AS1 Is a Diagnostic Biomarker and Predicts Poor Prognosis in Patients With Gastric Cancer by Integrated Bioinformatics Analysis.

Numerous studies have shown that long uncoded RNA (lncRNA) MSC-AS1 may play an important role in the occurrence and development of some types of cancer. However, its role in gastric cancer has rarely been discussed. This study aimed to clarify the association between lncRNA MSC-AS1 and gastric cancer using The Cancer Genome Atlas (TCGA) database. We determined the expression of MSC-AS1 using the Wilcoxon rank sum test; in addition, logistic regression was applied to evaluate the association between MSC-AS1 and clinicopathological characteristics. Also, Kaplan-Meier and Cox regression were used to evaluate the relationship between MSC-AS1 and survival. A nomogram was conducted to predict the impact of MSC-AS1 on prognosis. Moreover, Gene Set enrichment analysis (GSEA) was performed to annotate the biological function of MSC-AS1. Quantitative analysis of immune infiltration was carried out by single-set GSEA (ssGSEA). The MSC-AS1 level was elevated in gastric cancer tissues. An increased MSC-AS1 level was significantly correlated with T stage (odds ratio [OR] = 2.55 for T3 and T4 vs. T1 and T2), histological type (OR = 5.28 for diffuse type vs. tubular type), histological grade (OR = 3.09 for grade 3 vs. grades 1 and 2), TP53 status (OR = 0.55 for mutated vs. wild type), and PIK3CA status (OR = 0.55 for mutated vs. wild type) (all p < 0.05) by univariate logistic regression. Kaplan-Meier survival analysis showed high MSC-AS1 expression had a poor overall survival [hazard ratio (HR) = 1.75; 95% confidence interval (CI): 1.25-2.45; p = 0.001] and progression-free interval (HR = 1.47; 95% CI: 1.03-2.10; p = 0.034). Multivariate survival analysis revealed that MSC-AS1 expression (HR = 1.681; 95% CI: 1.057-2.673; p = 0.028) was independently correlated with overall survival. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway were differentially enriched in the high MSC-AS1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between MSC-AS1 and macrophages, NK cells, and Tems were the strongest. Coregulatory proteins were included in the PPI network. Upregulated lncRNA MSC-AS1 might be a potential biomarker for the diagnosis and prognosis of gastric cancer.

Various Kinds of Functional Digestive Tract Reconstruction Methods After Proximal Gastrectomy.

The incidence of proximal gastric cancer has shown a rising trend in recent years. Surgery is still the main way to cure proximal gastric cancer. Total gastrectomy with D2 lymph node dissection was considered to be the standard procedure for proximal gastric cancer in the past several decades. However, in recent years, many studies have confirmed that proximal gastrectomy can preserve part of the stomach function and can result in a better quality of life of the patient than total gastrectomy. Therefore, proximal gastrectomy is increasingly used in patients with proximal gastric cancer. Unfortunately, there are some concerns after proximal gastrectomy with traditional esophagogastrostomy. For example, the incidence of reflux esophagitis in patients who underwent proximal gastrectomy with traditional esophagogastrostomy is significantly higher than those patients who underwent total gastrectomy. To solve those problems, various functional digestive tract reconstruction methods after proximal gastrectomy have been proposed gradually. In order to provide some help for clinical treatment, in this article, we reviewed relevant literature and new clinical developments to compare various kinds of functional digestive tract reconstruction methods after proximal gastrectomy mainly from perioperative outcomes, postoperative quality of life and survival outcomes aspects. After comparison and discussion, we drew the conclusion that various functional reconstruction methods have their own advantages and disadvantages; large scale high-level clinical studies are needed to choose an ideal reconstruction method in the future. Besides, in clinical practice, surgeons should consider the condition of the patient for individualized selection of the most appropriate reconstruction method.

Laparoscopic-assisted versus open proximal gastrectomy with double-tract reconstruction for Siewert type II-III adenocarcinomas of esophago-gastric junction: a retrospective observational study of short-term outcomes.

BACKGROUND: Currently, the surgical approach to adenocarcinomas of esophago-gastric junction (AEG) remains controversial. Function-preserving gastric surgeries are becoming more popular, with proximal gastrectomy with double-tract anastomosis being one of the most important for AEG. Meanwhile, with the increasing use of laparoscopic techniques in the treatment of gastric cancer, the safety and effectiveness of laparoscopic-assisted proximal gastrectomy with double-tract anastomosis for Siewert type II-III AEG need to be further clarified. METHODS: Data of patients with Siewert type II/III AEG was collected at our center from October 2010 to December 2019 were retrospectively analyzed. 61 patients underwent open proximal gastrectomy with double-tract anastomosis (OPG-DT group) and 52 underwent laparoscopic-assisted proximal gastrectomy with double-tract anastomosis (LAPG-DT group). The clinical features, surgery, and short-term outcomes of patients in these 2 groups were collected to assess the safety and feasibility of LAPG-DT. RESULTS: A total of 113 patients were analyzed, there were 98 males and 15 females. No death during the operation. The differences in the number of lymph nodes, time to first flatus time to first eating, postoperative hospital stay, Additional analgesics were not statistically significant between two groups. Although the operative duration of LAPG-DT group was significantly longer than that of the OPG-DT group [(217±61) vs. (161±14) min, P=0.000), while less blood loss and less stress in LAPG-DT group. Early and late postoperative complications were similar between two groups. CONCLUSIONS: Although laparoscopic-assisted proximal gastrectomy with double-tract anastomosis requires long operative time, it is associated with less bleeding and milder stress. Therefore, it is a safe and feasible surgical method.

Short-term outcomes of laparoscopic versus open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction: a retrospective observational study of consecutive patients.

BACKGROUND: To investigate the safety and merits of laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DT) for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). METHODS: Retrospective analysis of the clinical data of 100 consecutive patients with Siewert II and III AEG treated at the Affiliated Tumor Hospital of Zhengzhou University from October 2010 to October 2019 was performed. Out of these patients, 69 underwent open proximal gastrectomy with double-tract reconstruction (OPG-DT), while 31 underwent LPG-DT. The clinicopathological characteristics, perioperative data, and short-term outcomes of the two groups were compared. A P value <0.05 was considered statistically significant. RESULTS: Males accounted for 87% of all patients. Lymph nodes (LNs) count, time to first meal, postoperative length of stay, and postoperative complications were similar between the OPG-DT and LPG-DT group. flatus time was significantly shorter in the LPG-DT group (P<0.05), while the duration of operation was significantly shorter in the the OPG-DT group (P<0.001). Furthermore, the LPG-DT group has less blood loss, shorter flatus time, and lower postoperative-day-5 white blood cell (WBC) count and C-reactive protein (CRP) levels (P<0.05). CONCLUSIONS: Although LPG-DT took longer to perform, its advantages of reduced blood loss and less surgical stress reflected on inflammatory markers supports an acceptable surgical option for Siewert II and III AEG.

Which is the optimal management for locally advanced gastric cancer patients with TRG 0 and 1 after R0 resection?

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery currently offers promise as a strategy for patients with locally advanced gastric cancer (GC). However, there is limited evidence to guide treatment for TRG 0 and 1 patients with locally advanced GC after R0 resection. This study set out to explore the optimal management for TRG 0 and 1 patients with locally advanced GC after R0 resection. METHODS: The retrospective data of 154 TRG 0 and 1 patients with locally advanced GC following R0 resection who were treated between January 2012 and December 2018 were collected and analyzed. The Kaplan-Meier method was used to estimate the survival rate. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: The median follow-up was 34.1 (range, 6.6-90.9) months. Six patients (3.9%) were lost during follow-up. Of the 27 patients who experienced relapse, 12 died, including 2 patients who died of non-neoplastic causes. The 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) were 71.6% (95% CI: 68.5-79.6) and 82.9% (95% CI: 76.9-86.1) for the whole cohort, respectively. Univariate analysis revealed that patients with carcinoembryonic antigen (CEA) <5.0 ng/ml after NAC (77.7% vs. 20.1%, P<0.001), distal gastrectomy (91.7% vs. 67.5%, P=0.046) had higher 5-year RFS. Meanwhile, combined resection (55.6% vs. 73.1%, P=0.042), major complications (42.7% vs. 80.50%, P<0.001), and lymph node metastasis (ypN+) (52.0% vs. 83.7%, P<0.001) had lower 5-year RFS. The multivariate analysis showed that CEA level after NAC (HR =2.876, 95% CI: 1.051-7.872, P=0.040), major complications (HR =2.432, 95% CI: 1.062-5.567, P=0.035), and lymph node metastasis (ypN+) (HR =3.183, 95% CI: 1.242-8.161, P=0.016) were independent prognostic factors. CONCLUSIONS: TRG 0 and 1 patients with local GC after R0 resection following NAC had a good prognosis, especially patients with CEA <5.0 ng/mL after NAC, and those without major complications or lymph node metastasis. Monotherapy or no chemotherapy may offer options for treating TRG 0 and 1 patients without adverse prognostic factors.

Short and long-term outcomes after proximal gastrectomy with double tract reconstruction for Siewert type III adenocarcinoma of the esophagogastric junction: a propensity score matching study from a 10-year experience in a high-volume hospital.

BACKGROUND: Total gastrectomy and proximal gastrectomy (PG) are both surgical options for the treatment of Siewert type III adenocarcinoma of the esophagogastric junction (AEG). Currently there is no consensus on selecting which procedure to perform; in particular, there are few reports of long-term outcomes for patients with local advanced AEG. The aim of this study was to validate the usefulness of PG with double-tract reconstruction in Siewert type III AEG. METHODS: The clinical data of patients with Siewert type III AEG underwent PG with double-tract reconstruction (PG-DT) or total gastrectomy with Roux-en-Y anastomosis (TG-RY) at our hospital between October 2010 and October 2018. According to the defined inclusion and exclusion criteria, 2,146 cases were enrolled in this study. A 1-to-1 propensity score matching (PSM) was performed to compare the short and long-term outcomes between the 2 groups. RESULTS: The operation time was longer in the PG-DT group, and the proportion rates of complications and recovery time was similar in the 2 groups. The rates of maintaining bodyweight and free-fat mass index were significantly higher in patients who underwent PG-DT compared to those who underwent TG-RY. While complications, recovery time and survival are similar between two groups. CONCLUSIONS: Regarding short-term outcomes, PG-DT seemed to be superior in terms of maintaining body weight and skeletal muscle compared to TG-RY, while both had similar complications. It was found that PG-DT enabled a potentially longer survival of pathological stage II and III Siewert type III AEG, although the finding was statistically insignificant. These results may help surgeons to determine the appropriate surgical approach and strategy for patients with early and locally advanced Siewert type III AEG.

Knockdown of lncRNA GHET1 inhibits osteosarcoma cells proliferation, invasion, migration and EMT in vitro and in vivo.

OBJECTIVE: Osteosarcoma is the most common primary malignant skeleton tumor that derives from mesenchymal cells. Emerging evidences have identified the vital role of long non-coding RNAs (lncRNAs) in the development of osteosarcoma. In this study, we aimed to investigate the role of lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) in osteosarcoma progression. METHODS: The expression levels of relevant genes in clinical samples and cell lines were determined by quantitative real-time PCR. Cell proliferation was determined by CCK8 and cell colony formation assays. Transwell assay was used to detect the invasion and migration of osteosarcoma cells. Cell apoptosis and cell cycle were detected by flow cytometry. Protein levels were detected by western blot. In vivo tumor growth was investigated in the xenograft nude mice model. To determine whether growth inhibition and apoptosis are responsible for antitumor activity of silencing GHET1, immunohistochemistry for proliferation and TUNEL assay was performed in xenograft tissues. In vivo lung metastasis was performed to detect the effect of GHET1 on cell metastasis ability. RESULTS: Our results revealed that GHET1 was up-regulated in osteosarcoma tissues compared to normal tissues. GHET1 was also increased in osteosarcoma cell lines compared to normal osteoplastic cell line. The up-regulation of GHET1 was significantly associated with TNM stage, distant metastasis and lymph node metastasis in patients with osteosarcoma. In vitro studies showed that silencing GHET1 in MG-63 and U2OS cells inhibited cell proliferation, cell invasion and migration and epithelial-to-mesenchymal transition (EMT), promoted cell apoptotic rate, and also caused an increase in cell population at G0/G1 phase with a decrease in cell population at S phase. Overexpression of GHET1 promoted the proliferation, invasion and migration of osteosarcoma cells. Importantly, silencing GHET1 inhibited tumor growth and tumor metastasis in mice MG-63-xenograft model in association with changes of EMT-related genes, reduced expression of Ki-67 and promotion of apoptosis. CONCLUSION: GHET1 was up-regulated in osteosarcoma tissues and cell lines, inhibited cell apoptosis, promoted cell proliferation, invasion and migration by affecting EMT in vitro, and was correlated with the tumor growth and metastasis in vivo. GHET1 may be a potential therapeutic target of osteosarcoma treatment.

[Prognostic analysis of neoadjuvant chemotherapy for locally advanced gastric cancer with propensity score matching method].

OBJECTIVE: To compare the effects of neoadjuvant chemotherapy and adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer using propensity score matching method. METHODS: Clinical data of patients with locally advanced gastric cancer undergoing open D2 radical gastrectomy between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were analyzed retrospectively. Sixty-five patients receiving neoadjuvant chemotherapy (NAC) were allocated into the NAC group and 1243 patients receiving postoperative adjuvant chemotherapy (AC) were allocated into the AC group. INCLUSION CRITERIA: (1) age ranged from 18 to 75 years old, and biopsy specimen was confirmed as adenocarcinoma; (2) all the operative procedures were open D2 radical gastrectomy;(3)image examinations showed no distant metastasis or other unresectable factors. EXCLUSION CRITERIA: no open D2 radical gastrectomy, undergoing laparoscopic surgery, neoadjuvant chemotherapy course <2 cycles, without adjuvant chemotherapy, history of other malignancies, severe complications, incomplete data. SOX (tegafur-gimeracil-oteracil plus oxaliplatin) or XELOX (capecitabine plus oxaliplatin) was used as neoadjuvant and postoperative adjuvant chemotherapy regimen. One-to-two propensity score matching was performed to balance the covariance between two groups. Survival was analyzed using the Kaplan-Meier method. Differences between the curves were tested using log-rank test. RESULTS: After balancing the covariates including gender, age, tumor location, degree of differentiation, clinical stage, chemotherapy regimen, chemotherapy course and surgical approach, 195 patients were enrolled, including 65 patients of the NAC group and 130 patients of the AC group. The number of harvested lymph nodes in NAC and AC group was 22.3±4.6 and 22.6±5.1 respectively, without statistically significant difference(t=1.125, P=0.263). Pathological response assessment for NAC group showed TRG0 in 6 cases, TRG1 in 8 cases, TRG2 in 17 cases, TRG3 in 34 cases; sensitive (TRG 0 to 2) in 31 cases (47.7%), non-sensitive in 34 cases (52.3%). The 3-year progression-free survival rate of NAC and AC group was 73.6%(95%CI: 62.8-84.3) and 69.9%(95%CI:62.1-77.7) respectively, which was not significantly different(P=0.361). The 3-year overall survival rate of NAC and AC group was 80.0%(95%CI:70.2-89.8) and 74.6%(95%CI:67.2-82.0) respectively, which was not significantly different as well(P=0.387). Subgroup analysis revealed that the 3-year progression-free survival rate and 3-year overall survival rate of sensitive patients in NAC group were 83.3%(95%CI:70.0-96.6) and 87.1%(95%CI:75.3-98.9) respectively, which were significantly higher than 62.4%(95%CI:46.1-78.7, P=0.037) and 70.2%(95%CI:54.7-85.7, P=0.033) of non-sensitive patients in NAC group, and those in AC group(P=0.044 and P=0.040). CONCLUSIONS: Effects of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer are similar. Patients who are sensitive to neoadjuvant chemotherapy have better prognosis. It may be beneficial to improve prognosis that some appropriate patients with locally advanced gastric cancer are screened for neoadjuvant chemotherapy.

Early brain metastasis of advanced gastric cancer with a pathological complete response to neoadjuvant chemotherapy followed by surgery: A case report and literature review.

Advanced gastric cancer with a pathological complete response to neoadjuvant chemotherapy and surgery followed by early brain metastasis is rare. A 52-y-old male patient who was diagnosed with advanced gastric cancer (cT4N2M0, stage ШB). Radiological examinations after three cycles of preoperative chemotherapy with a modified FOLFOX6 (mFOLFOX6) regimen showed a partial response (PR) had been achieved. The patient underwent curative surgery consisting of proximal gastrectomy, and D2 lymph node dissection. The lack of abnormal gastric cancer cells in the primary lesion or lymph nodes confirmed a pathological complete response (pCR). Postoperative chemotherapy with oral S-1 was administrated. However, during the second cycles of postoperative chemotherapy, the patient experienced headaches, projectile vomiting and convulsion. Upon further examination, a tumor representing metastasis to the brain was recognized by cranial enhanced magnetic resonance imaging (MRI) examination and cytopathology of cerebrospinal fluid. In addition to documenting the case report, we reviewed the literature associated to features of metastatic brain malignancies that form from gastric cancer. In short, advanced gastric cancer patents achieved pCR after preoperative chemotherapy typically have good prognosis; however, great attention should be paid on detecting metastatic events.

[Clinical features and prognosis analysis of 21 gastric cancer patients with pathological complete response after neoadjuvant chemotherapy].

OBJECTIVE: To evaluate the clinical features and prognosis of gastric cancer patients with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). METHODS: Clinical data of 159 gastric cancer patients who received NAC followed by surgical resection between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were collected and clinical features of those with pCR were analyzed retrospectively. Kaplan-Meier method was used to estimate 3-year overall survival (OS) rate and recurrence-free survival (RFS) rate. Recurrence factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model. RESULTS: A total of 21 patients(13.2%) achieved pCR, including 13 male and 8 female cases, with the median age at diagnosis of 56 (40 to 70) years. Eleven cases were differentiated tumor and 10 were undifferentiated. Six cases were in clinical baseline stage II(, and 15 were in III(. Five cases received the mFOLFOX6 (oxaliplatin + leucovorin +5-FU), 6 received the SOX (oxaliplatin +S-1), 4 received the XELOX (oxaliplatin + capecitabine), 2 received the EOX (epirubicin + oxaliplatin +capecitabine) and 4 received the DOX (docetaxel + oxaliplatin +capecitabine) chemotherapy regimens. Two cases achieved CR, 18 achieved PR, and 1 was SD after NAC. The median (range) course of preoperative and postoperative chemotherapy were 4(2 to 5) and 2(0 to 5) . All the patients underwent R0 resection plus D2 lymphadenectomy, and 4 cases were performed with proximal gastrectomy, 3 cases were performed with distal gastrectomy, 13 cases were performed with total gastrectomy, and one case was performed with total gastrectomy plus pancreatic splenectomy. Pneumonia, abdominal bleeding and infection, anastomotic leakage, and gastroplegia occurred respectively in one case, who all were cured by conservative treatment. The median follow-up of the survivors was 39.3 (range 22.7 to 56.9) months. Three cases died of recurrence: 1 case in the liver, 1 in the lung, and 1 in the brain. Two cases developed recurrence and survived: 1 in the liver and 1 in celiac lymph nodes. The overall survival and 3-year recurrence-free survival rates were 90.2%(95%CI: 100 to 77.3) and 90.5%(95%CI: 100 to 78.0). Fourteen cases did not complete scheduled chemotherapy course, and the overall 3-year survival rate was 85.1%. Older age(>50 years old)(P=0.028, RR=0.063, 95%CI: 0.005 to 0.743) and no postoperative complication (P=0.023, RR=0.065, 95%CI: 0.006 to 0.689) were identified as independent prognostic factors with Cox multivariate analysis. CONCLUSION: Patients diagnosed as gastric cancer with pCR after NAC have good prognosis, but the pCR ratio is low, and those with younger age and more postoperative complications may have higher risk for recurrence and metastasis.