Hyperactivation of mTOR/eIF4E Signaling Pathway Promotes the Production of Tryptophan-To-Phenylalanine Substitutants in EBV-Positive Gastric Cancer.

Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

Prognostic Significance of PD-L1 Expression in Gastric Cancer Patients with Peritoneal Metastasis.

BACKGROUND: Recently, many studies have explored the relationship between the expression of programmed death ligand 1 (PD-L1) and prognosis in gastric cancer, but there is still controversy. Additionally, few studies have specifically investigated the expression of PD-L1 in patients with peritoneal metastasis. METHODS: Immunohistochemistry was used to analyze the expression of PD-L1 in gastric cancer patients with peritoneal metastasis. The combined positive score (CPS) was calculated to evaluate the expression of PD-L1, and the clinicopathological data were analyzed to explore prognostic significance. RESULTS: In total, 147 gastric cancer patients with peritoneal metastasis were enrolled. The negative PD-L1 expression was defined as a CPS < 1, and high PD-L1 expression was defined as a CPS ≥ 10. PD-L1 expression with CPS ≥ 1 and CPS-negative was detected in 67 (45.58%) and 80 (54.42%) patients, respectively. High PD-L1 expression at PD-L1 CPS ≥ 10 was detected in 21(14.29%) patients. The median overall survival (OS) was 18.53 months in the CPS < 10 group and 27.00 months in the CPS ≥ 10 group; the OS difference between the two groups was significant (p = 0.015). Multivariate analysis demonstrated that a poor Eastern Cooperative Oncology Group performance score (ECOG PS) (p = 0.002) and severe peritoneal metastasis (p = 0.033) were significantly associated with poor survival, while palliative chemotherapy (p = 0.002) and high PD-L1 expression (p = 0.008) were independent and significantly favorable prognostic factors. CONCLUSIONS: Our study demonstrated that PD-L1 expression was widely presented in gastric cancer patients with peritoneal metastasis, while a CPS no less than 10 predicted better prognosis.

The genomic architecture of EBV and infected gastric tissue from precursor lesions to carcinoma.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood. METHODS: We applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments. RESULTS: Our analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function. CONCLUSIONS: We portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

Smoking status-based efficacy difference in anti-PD-1/PD-L1 immunotherapy: a systematic review and meta-analysis.

Aim: This study aimed to evaluate the relationship between smoking status and efficacy of PD-1/PD-L1 inhibitors compared with conventional agents. Materials & methods: We reviewed Phase II/III trials of PD-1/PD-L1 inhibitors that reported hazard ratio (HR) in current/former and never smoking patients. Results: 15 qualifying trials comprising 9073 patients were eligible in this study. Compared with conventional agents, PD-1/PD-L1 inhibitors correlated with prolonged progression-free survival (HR: 0.73; 0.58-0.92) and overall survival (HR: 0.75; 0.71-0.80) in current/former smoker patients but not in never-smoker patients (HR: 1.15 and 0.86 for progression-free survival and overall survival, respectively; both p > 0.05) irrespective of cancer type, target of experimental agents and treatment strategy. Conclusion: There exit smoking status-based efficacy difference in anti-PD-1/PD-L1 immunotherapy.

Disease-free survival as a surrogate endpoint for overall survival in adjuvant trials of pancreatic cancer: a meta-analysis of 20 randomized controlled trials.

BACKGROUND: We aimed to assess whether disease-free survival (DFS) could serve as a reliable surrogate endpoint for overall survival (OS) in adjuvant trials of pancreatic cancer. METHODS: We systematically reviewed adjuvant randomized trials for non-metastatic pancreatic cancer after curative resection that reported a hazard ratio (HR) for DFS and OS. We assessed the correlation between treatment effect (HR) on DFS and OS, weighted by sample size or precision of hazard ratio estimate, assuming fixed and random effects, and calculated the surrogate threshold effect (STE). We also performed sensitivity analyses and a leave-one-out cross validation approach to evaluate the robustness of our findings. RESULTS: After screening 450 relevant articles, we identified a total of 20 qualifying trails comprising 5170 patients for quantitative analysis. We noted a strong correlation between the treatment effects for DFS and OS, with coefficient of determination of 0.82 in the random effect model, 0.82 in the fixed effect model, and 0.80 in the sample size weighting; the robustness of this finding was further verified by the leave-one-out cross-validation approach. Sensitivity analyses with restriction to phase 3 trials, large trials, trials with mature follow-up periods, and trials with adjuvant therapy versus adjuvant therapy strengthened the correlation (0.75 to 0.88) between DFS and OS. The STE was 0.96 for DFS. CONCLUSIONS: Therefore, DFS could be regarded as a surrogate endpoint for OS in adjuvant trials of pancreatic cancer. In future similar adjuvant trials, a hazard ratio for DFS of 0.96 or less would predict a treatment impact on OS.

Downregulation of PSCA promotes gastric cancer proliferation and is related to poor prognosis.

Background: Dysregulation of prostate stem cell antigen (PSCA) has been implicated in human cancers. Studies have reported that PSCA expression is generally high in prostate cancer, which correlates with a worse survival. PSCA is also highly expressed in bladder, ovarian, and pancreatic cancers. However, PSCA is expressed at low levels in gastric, gallbladder and oesophageal cancers. At present, the clinical significance, expression pattern and biological function of PSCA in gastric cancer (GC) are still unclear. Methods: Previously, we used cDNA microarray as a screening tool to compare GC tissues with its matched normal gastric mucosa tissues (MNGT), and obtained the differentially expressed genes of the two tissue types. PSCA is one of the genes significantly down-regulated in GC tissues. In this study, we detected the expression of PSCA in GC tissues and MNGT by western-blot experiment and immunohistochemical staining (IHC). Then the relationship between the expression pattern of PSCA and the clinicopathological characteristics and survival in GC was analyzed. In order to further study the function of PSCA in GC, lentivirus was used to construct stable cell lines with knockdown and overexpression of PSCA gene. We used AGS and MKN45 cell lines for plasmid transfection. Colony formation assay, MTS and nude mice xenograft model were performed to investigate the effect of PSCA in GC. Results: Western-blot and IHC assays demonstrated that the expression of PSCA in GC tissues was significantly lower than that in the MNGT. PSCA expression in GC tissues was high in 252 (57.5%) and low in 186 (42.5%) of 438 patients. PSCA expression for MNGT was high in 273 (62.3%) and low in 165 (37.7%) of 438 patients. PSCA expression was significantly associated with T classification (P=0.024), N classification (P=0.018) and TNM stage (P=0.019) using χ2 test. The relationship between PSCA expression level and patient survival was analysed using Kaplan-Meier analysis and the log-rank test. Low levels of PSCA expression were significantly associated with a poorer OS than high expression levels of PSCA (P=0.011). In the COX regression analysis of OS, all 9 variables in the univariate analysis were significantly correlated with OS (P<0.05), while the variables found to be independently correlated with OS in the multivariate analysis were PSCA expression (P=0.036), age (P<0.001), gender (P=0.007), and TNM stage (P<0.001), respectively. Univariate and multivariate analyses showed that PSCA was an independent prognostic factor for OS in GC. In vitro MTS cell proliferation experiment and clonal formation experiment and in vivo nude mouse subcutaneous tumorigenesis experiment all proved that knockdown of PSCA gene can improve the proliferation ability of GC cells, while in vitro experiment proved that overexpression of PSCA can reduce the proliferation ability of GC cells.It was found that knockdown of PSCA gene can improve the proliferation ability of GC cells both in vitro and in vivo, while overexpression of PSCA can reduce the proliferation ability of GC cells in vitro. Conclusion: Our study showed that the expression of PSCA gene was decreased in GC, which was related to more advanced pathological stages. And the expression level of PSCA in GC was an independent good prognostic factor. PSCA gene had the function of inhibiting GC proliferation.

The Value of PD-L1 Expression in Predicting the Efficacy of Anti-PD-1 or Anti-PD-L1 Therapy in Patients with Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Recent trials have shown an overall survival (OS) benefit in 10-40% advanced cancer patients treated with programmed cell death 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. Here, we aimed to evaluate the relationship between PD-L1 expression and the therapeutic efficacy of PD-1 or PD-L1 inhibitors in patients with cancer with recurrent or metastatic disease, compared with control treatments. METHODS: We systematically searched Medline (PubMed), Embase, and Cochrane Library databases up to Jan 2019 and pooled the treatment effects (hazard ratio or relative ratio) of PD-1/PD-L1 inhibitors in patients with different PD-L1 expression. RESULTS: Overall, twenty-four qualifying trials with over 14,860 subjects were eligible in this study. Compared with conventional agents, anti-PD/PD-L1 drugs significantly reduced the risk of death (hazard ratio 0.72, 95% CI 0.66 to 0.78), irrespective of the tumor type. Additionally, when PD-L1 expression ≥1% was defined as positive, anti-PD-1/PD-L1 monotherapy correlated with prolonged overall survival in patients with nonsmall cell lung cancer (NSCLC) (0.72, 0.61 to 0.86) and other cancer types (0.66, 0.57 to 0.76) patients with PD-L1 positive, rather than those with PD-L1 negative (hazard ratio for NSCLC and other cancer types: 0.84 and 0.87, respectively; all P > 0.05). The subgroup analyses to experimental agents, PD-1/PD-L1 inhibitors, PD-L1 antibody clone, and type of IHC scoring method validated the robustness of these findings. However, anti-PD-1/PD-L1 combination therapies can reduce the risk of death for patients with different cancer types, regardless of PD-L1 expression (P < 0.05 for all PD-L1 expression status). CONCLUSIONS: We recommend PD-L1 expression as a predictive biomarker in patient selection for anti-PD-1/PD-L1 monotherapy, but not for combination therapies.

Additional gastrectomy in early-stage gastric cancer after non-curative endoscopic resection: a meta-analysis.

BACKGROUND AND OBJECTIVE: The role of additional gastrectomy after non-curative endoscopic resection remains uncertain. The present meta-analysis aimed to explore the risk factors for early-stage gastric-cancer patients after non-curative endoscopic resection and evaluate the efficacy of additional gastrectomy. METHODS: Relevant studies that reported additional gastrectomy after non-curative endoscopic resection were comprehensively searched in MedLine, Web of Science and EMBASE. We first investigated the risk factors for residual tumor and lymph-node metastasis after non-curative endoscopic resection and then analysed the survival outcome, including 5-year overall survival (OS) and 5-year disease-free survival, of additional gastrectomy. RESULTS: Twenty-one studies comprising 4870 cases were included in the present study. We found that residual tumor was associated with larger tumor size (>3 cm) (odds ratio [OR] = 2.81, P < 0.001), undifferentiated tumor type (OR = 1.78, P = 0.011) and positive horizontal margin (OR = 9.78, P < 0.001). Lymph-node metastasis was associated with larger tumor size (>3 cm) (OR = 1.73, P < 0.001), elevated tumor type (OR = 1.60, P = 0.035), deeper tumor invasion (>SM1) (OR = 2.68, P < 0.001), lymphatic invasion (OR = 4.65, P < 0.001) and positive vertical margin (OR = 2.30, P < 0.001). Patients who underwent additional gastrectomy had longer 5-year OS (hazard ratio [HR] = 0.34, P < 0.001), 5-year disease-free survival (HR = 0.52, P = 0.001) and 5-year disease-specific survival (HR = 0.50, P < 0.001) than those who did not. Moreover, elderly patients also benefited from additional gastrectomy regarding 5-year OS (HR = 0.41, P = 0.001). CONCLUSIONS: Additional gastrectomy with lymph-node dissection might improve the survival of early-stage gastric-cancer patients after non-curative endoscopic resection. However, risk stratification should be performed to avoid excessive treatment.

Evaluation of objective response, disease control and progression-free survival as surrogate end-points for overall survival in anti-programmed death-1 and anti-programmed death ligand 1 trials.

BACKGROUND: We aimed to assess whether the Response Evaluation Criteria in Solid Tumors (RECIST) criteria-based objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) could be valid surrogate end-points for overall survival (OS) in anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) trials. METHODS: We systematically reviewed phase 2 and phase 3 trials of anti-PD-1/PD-L1 drug trials of advanced or recurrent solid tumours that reported OS and at least one of the RECIST criteria-based end-points. We used Spearman rank correlation to evaluate the strength of the association between these end-points and OS and a linear regression model, weighted by the sample size, to assess the association between the treatment effect on these end-points and OS. We also performed sensitivity analyses and a leave-one-out cross-validation approach to evaluate the robustness of our findings. RESULTS: Forty-three qualifying trails comprising 15,088 patients were eligible. PFS showed good correlation with OS (squared Spearman rank correlation coefficient [rs2] = 0.54; P < 0.001), while ORR and DCR illustrated moderate association with OS (rs2 = 0.29 and 0.28, respectively; both P < 0.001). The correlation was moderate between the treatment effects on PFS and OS (coefficient of determination [R2] = 0.37, P < 0.001) and poor among ORR, DCR and OS (R2 = 0.10 and 0.08, respectively); these were confirmed by sensitivity analyses (all R2 < 0.75) and the leave-one-out cross-validation approach. CONCLUSIONS: No RECIST criteria-based end-points could be a valid surrogate for OS. At present, we proposed to set OS as the primary end-point in anti-PD-1/PD-L1 drug trials of advanced or recurrent solid tumours.

Persistence of Metarhizium (Hypocreales: Clavicipitaceae) and Beauveria bassiana (Hypocreales: Clavicipitaceae) in Tobacco Soils and Potential as Biocontrol Agents of Spodoptera litura (Lepidoptera: Noctuidae).

Entomopathogenic fungi (EPF), such as Metarhizium spp. and Beauveria bassiana, are widely used in the biocontrol of many species of insect pests. Tobacco is an economically important crop in Guangdong Province of China, but insect pests, such as Spodoptera litura Fabricius, are a major threat to production. Here, we tested the persistence of five Metarhizium species and B. bassiana in glasshouse pot and field experiments and assessed their long-term efficacy against S. litura. We found that the colony forming units of these EPF decreased by c. 93% by 180 d in the pot soils declines tended to be exponential. In contrast, declines of c. 99% in field soils were more gradual (linear), occurring throughout the 360 d experiment. Metarhizium anisopliae Ma09 had the longest estimated half-life of 41 d, while that of B. bassiana was the shortest (9 d). Fungal density in the upper soil layer (0-5 cm) decreased rapidly and was undetectable after 150 d, whereas density was consistently greatest in the mid-layer (10-15 cm). At 180 d after inoculation, strain Ma09 elicited highest rates of mortality in S. litura. We conclude that soils in Guangdong Province are all suitable for the use of Metarhizium as a biocontrol agent, where M. anisopliae Ma09 offers greatest residual activity.

Preoperative apolipoprotein B/apolipoprotein A1 ratio: a novel prognostic factor for gastric cancer.

BACKGROUND: The correlations between lipid profile (lipid molecules and their derivative indexes) and clinical outcome have been widely testified in many carcinomas, but its prognostic value remains unknown in gastric cancer (GC). Our purpose in the study was to comprehensively evaluate the clinical significance of lipid profile in GC. METHODS: We retrospectively collected clinical information of 1,201 GC patients who received surgery at Sun Yat-sen University Cancer Center from 2005 to 2010. Kaplan-Meier analysis and Cox proportional hazards regression model were performed to determine its prognostic significance. RESULTS: Lipid profile including cholesterol, triglyceride, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), LDL-C/HDL-C ratio, and ApoB/ApoA1 ratio were analyzed. For the first time, we found ApoB/ApoA1 ratio showed the biggest prognostic potency among all lipid-related variables and could act as an independent prognostic factor in GC. Patients with a high ApoB/ApoA1 ratio (≥1) had a shorter overall survival (hazard ratio: 1.373, 95% confidence interval: 1.123-1.68; P=0.002). CONCLUSION: Preoperative serum ApoB/ApoA1 ratio might be used as a novel prognostic indicator of GC.

Glasgow Prognostic Score is superior to ECOG PS as a prognostic factor in patients with gastric cancer with peritoneal seeding.

The Glasgow Prognostic Score (GPS) has been shown to be associated with survival rates in patients with advanced cancer. The present study aimed to compare the GPS with the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in patients with gastric cancer with peritoneal seeding. For the investigation, a total of 384 gastric patients with peritoneal metastasis were retrospectively analyzed. Patients with elevated C-reactive protein (CRP; >10 mg/l) and hypoalbuminemia (<35 mg/l) were assigned a score of 2. Patients were assigned a score of 1 if presenting with only one of these abnormalities, and a score of 0 if neither of these abnormalities were present. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal seeding were analyzed. The results showed that the median overall survival (OS) of patients in the GPS 0 group was longer, compared with that in the GPS 1 and GPS 2 groups (15.50, vs. 10.07 and 7.97 months, respectively; P<0.001). No significant difference was found between the median OS of patients with a good performance status (ECOG <2) and those with a poor (ECOG ≥2) performance status (13.67, vs. 11.80 months; P=0.076). In the subgroup analysis, the median OS in the GPS 0 group was significantly longer, compared with that in the GPS 1 and GPS 2 groups, for the patients receiving palliative chemotherapy and patients without palliative chemotherapy. Multivariate survival analysis demonstrated that CA19-9, palliative gastrectomy, first-line chemotherapy and GPS were the prognostic factors predicting OS. In conclusion, the GPS was superior to the subjective assessment of ECOG PS as a prognostic factor in predicting the outcome of gastric cancer with peritoneal seeding.

Bursectomy for advanced gastric cancer: an update meta-analysis.

BACKGROUND: The present meta-analysis was to explore the surgical and oncological outcomes of bursectomy for advanced gastric cancer (AGC). METHODS: Relevant studies that evaluated the role of bursectomy for AGC were comprehensively examined to perform a meta-analysis. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were the number of harvested lymph nodes (LNs), operation time, operative bleeding, hospital stay, postoperative complication and mortality. RESULTS: A total of seven studies comprising 2633 cases (1176 cases in the bursectomy group and 1457 cases in the non-bursectomy group) were finally included. There was no significant difference in OS (HR 0.95, P = 0.647) and DFS (HR 0.99, P = 0.936) between the two groups. Even for patients with serosa-penetrating tumours, OS was comparable between the two groups (HR 0.87, P = 0.356). The operation time of the bursectomy group was longer (weighted mean difference, WMD 32.76 min, P = 0.002). No significant difference was found between the two groups in terms of the number of dissected LNs (WMD 5.86, P = 0.157), operative bleeding (WMD 66.99 ml, P = 0.192) and hospital stay (WMD - 0.15 days, P = 0.766). The overall postoperative complication (relative risk, RR 1.08, P = 0.421) and mortality (RR 0.44, P = 0.195) were similar between two groups. CONCLUSIONS: This meta-analysis indicated that bursectomy is time-consuming without increasing the number of harvested LNs. Although bursectomy can be safely performed without increasing complications and mortality, it does not prolong the OS and DFS of AGC patients, including patients with serosa-penetrating tumours. Therefore, bursectomy should not be recommended as a standard procedure for AGC.

Prognostic factors for olfactory groove meningioma with nasal cavity extension.

OBJECTIVES: Meningioma recurrence remains a significant issue. No study has described the relationship between the clinical features and prognosis of communicating meningioma that primarily originates from the olfactory groove. The aim of the study was to identify prognostic factors of communicating olfactory groove meningiomas that could be stratified according to their risk of recurrence. RESULTS: A Simpson grade one or two resection was achieved. Complications with cerebrospinal rhinorrhoea occurred in two patients: one required reoperation, and the other was managed successfully with external drainage of lumbar cistern. There were 5 known clinical recurrences within the median follow-up of more than 5 years. The median 5-year recurrence-free survival for patients was 88.4%. Factors such as gender, tumour size, T2 signal and the hyperostotic bone had no significant effect on recurrence-free survival. However, recurrence was activated by oedema range, hyperostosis, dural tail sign and tumor texture (p < 0.05). Interestingly, female patients with the disease were younger than males at diagnosis, and the difference was statistically significant ( p = 0.013). CONCLUSIONS: Based on these features of communicating olfactory groove meningiomas, different strategies may be adopted for the follow-up and subsequent treatment. Due to the relatively uncommon incidence, more investigations into the clinical behaviour of this entity are crucial. PATIENTS AND METHODS: A retrospective study of 43 patients harbouring olfactory groove meningiomas invading the ethmoid or nasal cavity was conducted at three medical centers from 2000 to 2010. The records were reviewed for clinical presentations, imaging studies, surgical observation, histological features and follow-up.

Clinicopathological Characteristics and Prognostic Value of Signet Ring Cells in Gastric Carcinoma: A Meta-Analysis.

Background and Objectives: Previous studies of the prognostic value of the signet ring cell (SRC) type have yielded inconsistent results. Therefore, the aim of the present meta-analysis is to explore the clinicopathological characteristics and prognostic value of SRCs. Methods: Relevant articles that compared SRC and non-SRC type in PubMed and Web of Science were comprehensively searched. Then, a meta-analysis was performed. Results: A total of 19 studies including 35947 cases were analyzed. Compared with non-SRC patients, SRC patients tended to be younger (WMD: -3.88, P=0.001) and predominantly female (OR: 1.60, P<0.001). Additionally, SRC patients exhibited less upper third tumor location (OR: 0.62, P<0.001) and less frequent hematogenous metastasis (OR: 0.41, P<0.001). There was no difference in overall survival (OS) between SRC and non-SRC patients in the total population (HR: 1.02, P=0.830). Early gastric cancer with SRCs was associated with better OS (HR: 0.57, P=0.002), while advanced gastric cancer with non-SRCs was associated with a worse prognosis (HR: 1.17, P<0.001). Conclusions: This meta-analysis revealed that SRC tends to affect young females and tends to be located in the middle and lower third of the stomach. Early SRCs are associated with better prognoses, while advanced SRCs are associated with worse prognoses.

Selective Gastric Cancer Patients with Peritoneal Seeding Benefit from Gastrectomy after Palliative Chemotherapy: A Propensity Score Matching Analysis.

Background: The present study aimed to explore whether gastric cancer patients with peritoneal seeding after receiving palliative chemotherapy could benefit from gastrectomy and to identify patients with peritoneal seeding who should be selected to receive gastrectomy. Methods: A total of 201 gastric cancer patients were diagnosed with peritoneal seeding and received palliative chemotherapy. Propensity score matching (PSM) was performed to balance the selection bias. Results: After PSM, compared with non-gastrectomy group, gastrectomy group had a longer median overall survival (OS) (23.60 vs. 13.80 moths; P=0.034). Patients with R0 resection had a median OS of 43.60 months compared with 11.27 months in patients who underwent R1/2 resection (P<0.001). The median OS times between the R1/2 resection and non-gastrectomy groups were not different (P=0.139). Subgroup analysis revealed that only patients receiving more than 4 periods of first-line chemotherapy benefited from gastrectomy (P=0.018), whereas patients receiving 1-4 periods of first-line chemotherapy did not (P=0.275). Multivariate analysis showed that gastrectomy (P=0.012) and the period of first-line chemotherapy (P<0.001) were independent prognostic factors. The overall postoperative morbidity was 3.03% (1/33) in the gastrectomy group, and no treatment-related death was observed. Conclusions: The present study indicated that gastrectomy after palliative chemotherapy is a safe procedure and showed a survival benefit for gastric cancer patients with peritoneal seeding. Moreover, clinically curative R0 gastrectomy and more than 4 periods of palliative chemotherapy resulted in better clinical outcomes.

Endoscopic ultrasonography compared with multidetector computed tomography for the preoperative staging of gastric cancer: a meta-analysis.

BACKGROUND: The current study sought to perform a meta-analysis to compare the preoperative staging of endoscopic ultrasonography (EUS) and multidetector computed tomography (MDCT) in gastric carcinoma. METHODS: Articles published between January 1, 2000, and April 1, 2016, that compared EUS with MDCT were included, and data were presented as 2 × 2 tables. The sensitivities, specificities and summary receiver operating characteristic (ROC) curves for T and N staging were calculated using a bivariate mixed effects model. Data were weighted by generic variance and then pooled by random-effects modeling. RESULTS: Eight studies comprising 1736 patients were included in this meta-analysis. For T1 staging, the sensitivity value for EUS (82%) was significantly higher than that for MDCT (41%) (relative risk (RR): 2.06, 95% confidence interval (CI) 1.07-3.94; P = 0.030). For lymph node involvement, the sensitivity value for EUS (91%) was also significantly higher than that for MDCT (77%) (RR 1.14, 95% CI 1.05-1.23; P = 0.001). However, the specificity values of both EUS and MDCT were quite low, at 49 and 63%, respectively. No significant differences in T2-4 staging between EUS and MDCT were noted. CONCLUSION: This meta-analysis indicates that EUS may be superior to MDCT in preoperative T1 and N staging. Additionally, the low specificity values of EUS and MDCT for N staging merits attention.

Significant Role of Palliative Gastrectomy in Selective Gastric Cancer Patients with Peritoneal Dissemination: A Propensity Score Matching Analysis.

OBJECTIVE: The aim of this study was to explore whether palliative gastrectomy is suitable for gastric cancer patients with peritoneal metastasis, and for patients in whom the type of peritoneal metastasis should be selected to receive palliative gastrectomy. METHODS: A total of 747 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis at our centers between January 2000 and April 2014 were retrospectively analyzed. After propensity score matching, the clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. RESULTS: After propensity score matching, the median overall survival (OS) of patients in the gastrectomy group was longer than that for patients in the non-gastrectomy group (11.87 vs. 9.27 months; p = 0.020). Patients who received first-line chemotherapy had a significantly longer median OS than those who did not (11.97 vs. 7.03 months; p < 0.001); among these patients, those undergoing more than eight periods of first-line chemotherapy benefited the most (p < 0.001). Subgroup analyses revealed that patients classified as P1 who were undergoing chemotherapy benefited from gastrectomy (p = 0.024), and patients without multisite metastasis also benefited from gastrectomy with regard to OS (p = 0.007). In the multivariate survival analysis, multisite distant metastasis was the independent poor prognostic factor (p < 0.001), while palliative gastrectomy (p = 0.006) and a period of first-line chemotherapy (p < 0.001) were good prognostic factors. Morbidity rates in the gastrectomy and non-gastrectomy groups were 10.4 and 1.0 %, respectively (p = 0.003); however, no difference in mortality was noted between the two groups (p = 0.590). CONCLUSIONS: Palliative gastrectomy can prolong the survival of P1 patients without multisite distant metastasis when combined with more than five periods, and particularly more than eight periods, of first-line chemotherapy.