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Most of the patients with gastric cancer in China have been at the middle and advanced stages during diagnostic and treatment with poor prognosis overall. Perioperative radiotherapy, chemotherapy, immune therapy and other comprehensive treatment methods for gastric cancer patients preoperative and intraoperation may reduce tumor staging, increase the rate of surgical resection and prolong the time of patient survival. Perioperative comprehensive treatment has developed more than 30 years in China. Many results from relevant research were gotten combined with laying down the consensus and guidelines, and applied to clinic in recent years. With the emergence and development of new technologies and new strategies for comprehensive treatment, perioperative comprehensive treatment and conversion therapy will improve at much extent the rate of survival for gastric cancer patients in China.

Objective To analyze the port complications and risk factors associated with the port complications in gastric cancer patients with peritoneal metastasis. Methods The medical records of 323 patients with subcutaneous ports implantation for intraperitoneal chemotherapy were retrospectively analyzed and 261 gastric cancer patients with peritoneal metastasis were included. Port complications and risk factors associated with complications were analyzed. Results There were 59 (22.6%) cases with port complications associated with intraperitoneal chemotherapy in all included 261 cases. Subcutaneous effusion (25 cases, 42.4%) and port infection (16 cases, 27.1%) were the main complications, followed by port rotation (9 cases, 15.3%), partial port wound dehiscence (7 cases, 11.9%), catheter obstruction (1 case, 1.7%) and subcutaneous metastasis (1 case, 1.7%). The median period between port implantation and occurrence of complications was 3.0 months. Eastern Cooperative Oncology Group (ECOG) score, serum albumin, implantation management optimization and implantation specialized group were independent risk factors for port complications (P

Objective: The aim of this study was to develop and validate a radiomics model to predict treatment response in patients with advanced gastric cancer (AGC) sensitive to neoadjuvant therapies and verify its generalization among different regimens, including neoadjuvant chemotherapy (NAC) and molecular targeted therapy. Materials and Methods: A total of 373 patients with AGC receiving neoadjuvant therapies were enrolled from five cohorts. Four cohorts of patients received different regimens of NAC, including three retrospective cohorts (training cohort and internal and external validation cohorts) and a prospective Dragon III cohort (NCT03636893). Another prospective SOXA (apatinib in combination with S-1 and oxaliplatin) cohort received neoadjuvant molecular targeted therapy (ChiCTR-OPC-16010061). All patients underwent computed tomography before treatment, and thereafter, tumor regression grade (TRG) was assessed. The primary tumor was delineated, and 2,452 radiomics features were extracted for each patient. Mutual information and random forest were used for dimensionality reduction and modeling. The performance of the radiomics model to predict TRG under different neoadjuvant therapies was evaluated. Results: There were 28 radiomics features selected. The radiomics model showed generalization to predict TRG for AGC patients across different NAC regimens, with areas under the curve (AUCs) (95% interval confidence) of 0.82 (0.76~0.90), 0.77 (0.63~0.91), 0.78 (0.66~0.89), and 0.72 (0.66~0.89) in the four cohorts, with no statistical difference observed (all p > 0.05). However, the radiomics model showed poor predictive value on the SOXA cohort [AUC, 0.50 (0.27~0.73)], which was significantly worse than that in the training cohort (p = 0.010). Conclusion: Radiomics is generalizable to predict TRG for AGC patients receiving NAC treatments, which is beneficial to transform appropriate treatment, especially for those insensitive to NAC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastric cancer (GC) patients with peritoneal metastasis usually have extremely poor prognosis. Intraperitoneal infusion of paclitaxel (PTX) provides an effective treatment, but relapse and PTX-resistance are unavoidable disadvantages, and it is difficult to monitor the occurrence of PTX-resistance. OBJECTIVE: The aim of this study was to explore novel autoantibodies in the ascites of individuals with relapsed PTX-resistant GC with peritoneal metastasis. METHODS: Ascites samples were collected before PTX infusion and after the relapse in 3 GC patients. To determine the expression of significantly changed proteins, we performed autoantibody profiling with immunome protein microarrays and tandem mass tag (TMT) quantitative proteomics, and then, the overlapping proteins were selected. RESULTS: Thirty-eight autoantibodies that were differentially expressed between the ascites in the untreated group and relapsed PTX-resistant group were identified. For confirmation of the results, TMT quantitative proteomics was performed, and 842 dysregulated proteins were identified. Four proteins, TPM3, EFHD2, KRT19 and vimentin, overlapped between these two assays. CONCLUSIONS: Our results first revealed that TPM3, EFHD2, KRT19 and vimentin were novel autoantibodies in the ascites of relapsed PTX-resistant GC patients. These autoantibodies may be used as potential biomarkers to monitor the occurrence of PTX-resistance. [ABSTRACT FROM AUTHOR]

Background: For gastric cancer (GC) with extensive lymph node metastasis (bulky N2 and/or para-aortic lymph node metastases), there is no standard therapy worldwide. In Japan, preoperative chemotherapy (PCT) followed by D2 gastrectomy plus para-aortic lymph node dissection (PAND) is considered the standard treatment for these patients. However, in China, the standard operation for GC patients with only bulky N2 metastases was D2 gastrectomy. Besides, after PCT, whether doing PAND improves survival or not is debatable for GC patients with para-aortic lymph node (PAN) metastases. Therefore, we conducted this study to investigate whether D2 lymphadenectomy alone is suitable for these patients after PCT. Methods: We retrospectively collected data on patients from our electronic medical record system. GC patients with bulky N2 and/or PAN metastases who underwent D2 lymphadenectomy alone after PCT were enrolled. The survival outcomes and chemotherapy responses were analyzed and compared with the results of the JCOG0405 study. Results: From May 2009 to December 2017, a total of 83 patients met all eligibility criteria and were enrolled. The median survival duration for all patients was 40.0 months. The 3-year and 5-year OS rates for all patients were 50.3% and 45.6%, respectively. For patients with only bulky N2 metastasis, the 3-year and 5-year OS rates were 77.1% and 71.6%, respectively, which were similar to the results of the JCOG0405 study (82.7% and 73.4%). For patients with only PAN metastases, the 3-year and 5-year OS rates were 50.0% and 50.0%, respectively, which seemed to be lower than those of the JCOG0405 study (64.3% and 57.1%). For patients with bulky N2 and PAN metastases, the 3-year and 5-year OS rates were 7.4% and 0.0%, respectively, which were lower than those of the JCOG0405 study (20.0% and 20.0%). Conclusion: The results of our study suggest that D2 lymphadenectomy alone is suitable for GC patients with only bulky N2 metastasis after PCT. However, D2 lymphadenectomy alone perhaps is not suitable for patients with bulky N2 and PAN metastases after PCT. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of the FLOT regimen in Chinese patients. Methods: Patients with adenocarcinoma of the stomach or esophagogastric junction received four cycles of neoadjuvant chemotherapy (NAC) and four cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities, and pathological tumor regression were analyzed. The 2-year overall survival (OS) and relapse-free survival are presented. Results: Altogether, 10 patients were enrolled, and all patients completed four cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and three patients had complete or subtotal pathological tumor regression. Nine patients completed four cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, eight patients achieved the overall survival endpoint, and seven patients had relapse-free survival for this period. Two patients died of disease progression. Conclusions: Our study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort. The trial is registered with ClinicalTrials.gov (number NCT03646591). [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most aggressive malignancies and has a poor prognosis. Identifying novel diagnostic and prognostic markers is of great importance for the management and treatment of GC. Long non-coding RNAs (lncRNAs), which are involved in multiple processes during the development and progression of cancer, may act as potential biomarkers of GC. Here, by performing data mining using four microarray data sets of GC downloaded from the Gene Expression Omnibus (GEO) database with different classifiers and risk score analyses, we identified a five-lncRNA signature (AK001094, AK024171, AK093735, BC003519 and NR_003573) displaying both diagnostic and prognostic values for GC. The results of the Kaplan-Meier survival analysis and log-rank test showed that the risk score based on this five-lncRNA signature was closely associated with overall survival time ( p = 0.0001). Further analysis revealed that the risk score is an independent predictor of prognosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of 30 pairs of GC tissue samples confirmed that the five lncRNAs were dysregulated in GC, and receiver operating characteristic (ROC) curves showed the high diagnostic ability of combining the five lncRNAs, with an area under the curve (AUC) of 0.95 ± 0.025. The five lncRNAs involved in several cancer-related pathways were identified using gene set enrichment analysis (GSEA). These findings indicate that the five-lncRNA signature may have a good clinical applicability for determining the diagnosis and predicting the prognosis of GC. [ABSTRACT FROM AUTHOR]

Abstract: According to the World Health Organization, 800,000 cancer-related deaths are caused by gastric cancer each year globally, hence making it the second leading cause of cancer-related deaths in the world. Gastric cancer is often either asymptomatic or causing only nonspecific symptoms in its early stages. By the time the symptoms occur, the cancer has usually reached an advanced stage, which is one of the main reasons for its relatively poor prognosis. Therefore, early diagnosis and early treatment are very crucial. The differential analysis of serum protein between cancer patients and healthy controls can be performed using proteomics techniques and can hence be adopted as tumor biomarkers for the early diagnosis of cancer. So far, several serum tumor biomarkers have been identified for gastric cancer. However due to their poor specificity and sensitivity, they have proven to be insufficient for the reliable diagnosis of gastric cancer. Thus, using modern advanced proteomics techniques to find some new and reliable serum tumor biomarkers for earlier and reliable diagnosis of gastric cancer is a must. Nowadays, proteomic-based techniques, such as SELDI and HCLP, are available to discover biomarkers in gastric cancer. Numerous novel serum tumor biomarkers such as SAA, plasminogen and C9c, have been discovered through serological proteomics strategies. This review mainly focuses on the serum proteomics techniques and their application in the research of gastric cancer. [Copyright &y& Elsevier]

Abstract: Background: Early diagnosis and treatment of gastric cancer patients is essential for improving prognosis. However, no available serum-based test provides sufficient sensitivity or specificity for widespread use. Therefore, in this study we aimed to identify cancer biomarkers in human sera using 2-dimensional difference gel electrophoresis (2D-DIGE), and to characterize protein biomarkers with tandem mass spectrometry. Methods: We compared the serum proteomic profiles of 20 gastric cancer patients and 10 healthy volunteers. Serum samples were first chromatographed using an immunoaffinity high-performance liquid chromatography (HPLC) column to selectively remove albumin, immunoglobulins, transferrin, haptoglobin, and antitrypsin. Differential protein analysis was then performed using DIGE. Significantly increased and decreased protein spot features were excised, trypsin digested, and analyzed by tandem matrix-assisted laser desorption/ionization (MALDI) time of flight (TOF)/TOF and a linear trap quadrupole (LTQ) mass spectrometer. Results: Seventeen protein spot features were significantly increased and 7 were significantly decreased in cancer serum samples compared to healthy controls. We identified 7 unique proteins that were upregulated, including plasminogen, apolipoprotein A-IV, Kininogen-1, complex-forming glycoprotein HC, complement component C4A, apolipoprotein J, and clusterin, and 5 that were decreased. Conclusions: These results suggest that the combination of multi-dimensional HPLC and 2D-DIGE provides a valuable tool for serum proteomics in gastric cancer. [Copyright &y& Elsevier]

Abstract: Background: Screening tests are needed for gastric cancer. In order to find serologic biomarkers for gastric cancer screening, we used proteomics to search for protein biomarkers that may be detected in serum of gastric cancer patients. Methods: Four groups of serum samples (from 20 gastric cancer patients) included pTNM stages I to IV were compared with two control groups of serum samples. The serum samples were first chromatographed using an immunoaffinity column to selectively remove albumin and IgG. Then serum proteins separated by 2-DE and identified by MALDI–TOF/TOF–MS. Results: There were 3 proteins including complement C4-B precursor, complement factor I (CFI) precursor and haptoglobin precursor were found significantly different between the healthy and gastric cancer patients. Further validation study by Western blot showed that the detection of CFI precursor was under-expressed in gastric cancer sera compared to normal sera (p <0.05), in addition to a declining expression with the advanced pTNM stage from stage I to IV of gastric cancer patients. Area under the receiver operating characteristic (ROC) curve was 0.78 for the expression of CFI precursor (p <0.01). Conclusions: 2-DE-based serum proteome analysis may be useful in the screening of serum biomarkers for gastric cancer. CFI precursor could aid in the diagnosis and indicate the advancement of gastric cancer. [Copyright &y& Elsevier]

The encoding product of Chordin-like 2 (CHRDL2) is a member of the chordin family of proteins, which has been shown to be aberrantly expressed in several types of solid tumors. The regulatory underlying mechanisms of CHRDL2, however, remain poorly understood in gastric cancer (GC). In the present study, we determined that CHRDL2 was abnormally upregulated in human gastric cancer tissues compared with adjacent normal tissues. We also showed that CHRDL2 was positively associated with T stage, the pathological stage, distant metastasis, and poor patient prognosis. Furthermore, the serum level of CHRDL2 was obviously higher in GC patients than normal people, and is positively correlated with later TNM stage, deeper T stage, later N stage and poorer differentiation. Moreover, we verified that overexpressing CHRDL2 promoted the proliferation and cell cycle transition of GC cells both in vitro and in vivo , whereas the opposite results were observed in CHRDL2-depleted cells. In addition, the phosphorylation levels of Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ) and the total levels MST2 were decreased in CHRDL2 overexpressing cells. Consistent with previous findings, we observed the converse results in CHRDL2-silenced GC cells. Additionally, knockdown of YAP and overexpression of STK3 (MST2) could reverse the effects of CHRDL2 overexpression-induced proliferation of GC cells in vitro. Taken together, CHRDL2 plays a key role by activating the YAP/TAZ pathway in gastric cancer. Therefore, CHRDL2 could serve as a potential therapeutic tool for the treatment of gastric cancer. • The level of CHRDL2 was not only remarkably upregulated in gastric cancers' tumor tissues, but also obviously elevated in GC patients' serum. • CHRDL2 silencing and overexpression influenced GC cell growth and cell cycle in vitro , and alter tumor growth in vivo. • CHRDL2 promotes GC cells proliferation through influencing the total level of YAP/TAZ and also affecting the phosphorylation level of YAP/TAZ. [ABSTRACT FROM AUTHOR]

The evidence of combining neoadjuvant chemotherapy with targeted therapy for patients with locally advanced gastric cancer is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of S-1, oxaliplatin and apatinib (SOXA) in patients with locally advanced gastric adenocarcinoma. Treatment-naïve patients received three preoperative cycles of S-1 (80–120 mg/day on days 1–14) and oxaliplatin (130 mg/m2 on day 1) and two cycles of apatinib (500 mg/day for 21 days) at 3-week intervals, followed by surgery. The primary end-point was pathologic response rate (pRR). This trial is registered at ChiCTR.gov.cn: ChiCTR-OPC-16010061. Of 29 patients included, median age was 60 (range, 43–73) years; 20 (69.0%) were male. The pRR was 89.7% (95% confidence interval [CI], 72.7%–97.8%; 26 of 29 patients; P < 0.001) with 28 patients treated with surgery. All 29 patients were available for preoperative response evaluation, achieving an objective response rate of 79.3% (95% CI, 60.3%–92.0%) and a disease control rate of 96.6% (95% CI, 82.2%–99.9%). The margin-free resection rate was 96.6% (95% CI, 82.2%–99.9%). The pathologic complete response rate was 13.8% (95%CI, 1.2%–26.3%). Downstaging of overall TNM stage was observed in 16 (55.2%) patients. During neoadjuvant therapy, 10 (34.5%) patients had grade ≥III adverse events. No treatment-related death occurred. Surgery-related complications were observed in 12 of 28 (42.9%) patients. SOXA followed by surgery in patients with locally advanced gastric adenocarcinoma showed favourable activity and manageable safety. A randomised controlled trial in locally advanced gastric or oesophagogastric junction adenocarcinoma is ongoing (ClinicalTrials.gov: NCT04208347). • Treatment-naïve patients received S-1, oxaliplatin and apatinib before surgery. • Pathologic response rate was used as a primary end-point. • The pathologic response rate was 89.7%, with acceptable safety. • The pathologic complete response rate was 13.8%. • Neoadjuvant chemotherapy + apatinib was feasible for locally advanced gastric cancer. [ABSTRACT FROM AUTHOR]