Nomogram to Predict Recurrence and Guide a Pragmatic Surveillance Strategy After Resection of Hepatoid Adenocarcinoma of the Stomach: A Retrospective Multicenter Study.

BACKGROUND: An accurate recurrence risk assessment system and surveillance strategy for hepatoid adenocarcinoma of the stomach (HAS) remain poorly defined. This study aimed to develop a nomogram to predict postoperative recurrence of HAS and guide individually tailored surveillance strategies. METHODS: The study enrolled all patients with primary HAS who had undergone curative-intent resection at 14 institutions from 2004 to 2019. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram to build a recurrence predictive model. RESULTS: The nomogram of recurrence-free survival (RFS) based on independent prognostic factors, including age, preoperative carcinoembryonic antigen, number of examined lymph nodes, perineural invasion, and lymph node ratio, achieved a C-index of 0.723 (95% confidence interval [CI], 0.674-0.772) in the whole cohort, which was significantly higher than those of the eighth American Joint Committed on Cancer (AJCC) staging system (C-index, 0.629; 95% CI, 0.573-0.685; P < 0.001). The nomogram accurately stratified patients into low-, middle-, and high-risk groups of postoperative recurrence. The postoperative recurrence risk rates for patients in the middle- and high-risk groups were respectively 3 and 10 times higher than for the low-risk group. The patients in the middle- and high-risk groups showed more recurrence and metastasis, particularly multiple site metastasis, within 36 months after the operation than those in the low-risk group (low, 2.2%; middle, 8.6%; high, 24.0%; P = 0.003). CONCLUSIONS: The nomogram achieved good prediction of postoperative recurrence for the patients with HAS after radical resection. For the middle- and high-risk patients, more active surveillance and targeted examination methods should be adopted within 36 months after the operation, particularly for liver and multiple metastases.

A Novel ypTLM Staging System Based on LODDS for Gastric Cancer After Neoadjuvant Therapy: Multicenter and Large-Sample Retrospective Study.

BACKGROUND: The accuracy of the eighth AJCC ypTNM staging system on the prognosis of gastric cancer (GC) patients after neoadjuvant therapy (NAT) is controversial. This study aimed to develop and validate a novel staging system using the log odds of positive lymph nodes scheme (LODDS). METHODS: A retrospective analysis of 606 GC patients who underwent radical gastrectomy after neoadjuvant therapy was conducted as the development cohort. (Fujian Medical University Affiliated Union Hospital (n = 183), Qinghai University Affiliated Hospital (n = 169), Mayo Clinic (n = 236), Lanzhou University First Hospital (n = 18)). The validation cohort came from the SEER database (n = 1701). A novel ypTLoddsS (ypTLM) staging system was established using the 3-year overall survival. The predictive performance of two systems was compared. RESULTS: Two-step multivariate Cox regression analysis in both cohorts showed that ypTLM was an independent predictor of overall survival of GC patients after neoadjuvant therapy (HR: 1.57, 95% CI: 1.30-1.88, p < 0.001). In the development cohort, ypTLM had better discrimination ability than ypTNM (C-index: 0.663 vs 0.633, p < 0.001), better prediction homogeneity (LR: 97.7 vs. 70.9), and better prediction accuracy (BIC: 3067.01 vs 3093.82; NRI: 0.36). In the validation cohort, ypTLM had a better prognostic predictive ability (C-index: 0.614 vs 0.588, p < 0.001; LR: 11,909.05 vs. 11,975.75; BIC: 13,263.71 vs 13,328.24; NRI: 0.22). The time-dependent ROC curve shows that the predictive performance of ypTLM is better than ypTNM, and the analysis of the decision curve shows that ypTLM achieved better net benefits. CONCLUSION: A LODDS-based ypTLM staging system based on multicenter data was established and validated. The predictive performance was superior to the eighth AJCC ypTNM staging system.

Delta computed tomography radiomics features-based nomogram predicts long-term efficacy after neoadjuvant chemotherapy in advanced gastric cancer.

BACKGROUND AND OBJECTIVE: No effective preoperative tool is available for predicting the prognosis of advanced gastric cancer (AGC) treated by neoadjuvant chemotherapy (NAC). We aimed to explore the association between change values ("delta") in the radiomic signatures of computed tomography (CT) (delCT-RS) before and after NAC for AGC and overall survival(OS). METHODS AND DESIGN: A total of 132 AGC patients with AGC were studied as a training cohort in our center, and 45 patients from another center were used as an external validation set. A radiomic signatures-clinical-nomogram(RS-CN) was established using delCT-RS and preoperative clinical variables. The prediction performance of RS-CN was evaluated using the area under the receiver operating characteristic (ROC)curve (AUC values), time-dependent ROC, decision curve analysis(DCA) and C-index. RESULTS: Multivariable Cox regression analyses showed that delCT-RS, cT-stage, cN-stage, Lauren-type and the value of variation of carcinoma embryonic antigen (CEA) between NAC were independent risk factors for 3-year OS of AGC. In the training cohort, RS-CN had a good prediction performance for OS (C-Index 0.73) and AUC values were significantly better than those of delCT-RS, ypTNM-stage and tumor regression grade(TRG) (0.827 vs 0.704 vs 0.749 vs 0.571, p < 0.001). DCA and time-dependent ROC of RS-CN were better than those of ypTNM stage, TRG grade and delCT-RS. The prediction performance of the validation set was equivalent to that of the training set. The cut-off (177.2) of RS-CN score was obtained from X-Tile software, a score of > 177.2 was defined as high-risk group(HRG), and scores of ≤ 177.2 were defined as the low-risk group(LRG). The 3-year OS and disease free survival(DFS) of patients in the LRG were significantly better than those in the HRG. Adjuvant chemotherapy(AC) can only significantly improve the 3-year OS and DFS of the LRG. (p < 0.05). CONCLUSIONS: Our nomogram based on delCT-RS has good prediction of prognosis before surgery and helps identify patients that are most likely to benefit from AC. It works well in precise and individualised NAC in AGC.

Effect of Helicobacter Pylori on Plasma Metabolic Phenotype in Patients With Gastric Cancer.

BACKGROUND: Although Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. PURPOSE: Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. RESULTS: Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. CONCLUSION: This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

Development of a staging system for hepatoid adenocarcinoma of the stomach based on multicenter data: A retrospective cohort study: A Staging System for Hepatoid Adenocarcinoma of the Stomach.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC). METHODS: The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at 2 centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival. RESULTS: After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the 8th American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the 8th AJCC staging system (0.667, 95% CI: 0.610-0.723, P<0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the 8th AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively the mpTNM staging system outperformed the 8th AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P<0.05). Time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the 8th AJCC staging system with increasing observation time. CONCLUSION: The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the 8th AJCC staging system.

Long-term prognostic benefit of adjuvant chemotherapy for patients with hepatoid adenocarcinoma of the stomach after radical resection: A national multicenter study.

BACKGROUND: There is no consensus on whether adjuvant chemotherapy (AC) is effective for hepatoid adenocarcinoma of the stomach (HAS). The aim of this study was to investigate the relationship between AC and the long-term prognosis of patients with HAS. METHODS: The clinicopathological data of 239 patients with primary HAS who underwent radical surgery from April 1, 2004 to December 31, 2019 in 14 centers in China were retrospectively analyzed. Patients were divided into the AC group (127 patients) and the nonadjuvant chemotherapy (NAC) group (112 patients). RESULTS: Kaplan‒Meier (KM) analysis showed that there were no significant differences in the 1-year3-year overall survival rate (OS) and 1-year, 3-year recurrence-free survival rate (RFS) between the AC group and the NAC group (1-year OS: 85.6% vs. 79.8%, 3-year OS: 59.8% vs. 62.4%, 1-year RFS: 69.8% vs. 74.4%, 3-year RFS: 57.2% vs. 55.9%, all P > 0.05). The subpopulation treatment effect pattern plots (STEPP) did not show treatment heterogeneity of AC in patients with HAS. The proportions of local recurrence and metastasis sites in the two groups were similar. Although the smoothed hazard curves of the NAC and AC groups crossed, the peak hazard time was later in the AC group (5.9 and 4.7 months), and the peak hazard rate was lower (0.032 and 0.038, P = 0.987). CONCLUSION: The current AC regimen may not significantly improve the survival of patients with HAS after radical surgery.

Analysis of genetic diversity among Chinese Cyclocybe chaxingu strains using ISSR and SRAP markers.

Background: Cyclocybe chaxingu is an edible and medicinal fungal species commonly cultivated in China. The major problems currently facing by growers of C. chaxingu is the random labeling of strains and strains aging and degeneration. Therefore, an evaluation of genetic diversity is essential for the conservation and reproducing programs of this species. Methods: In the present study, 24 widely cultivated strains were collected from the main producing areas of China, and the genetic diversity analysis was performed. DNA polymorphism among these Chinese C. chaxingu strains was analyzed using inter-simple sequence repeat (ISSR) and sequence-related amplified polymorphism (SRAP) markers. Results: Eight ISSR primers amplified a total of 75 DNA fragments of which 61 (81.33%) were polymorphic. Fifteen SRAP primer combinations amplified 166 fragments of which 132 (79.52%) were polymorphic. Cluster analysis showed that the C. chaxnigu strains fall into five groups with a genetic distance values ranging from 0.06 to 0.60 by ISSR analysis, while the SRAP analysis divided the test strains into four groups within the range of genetic distance from 0.03 to 0.57. The results of the present study reveal a high level of genetic diversity among the widely cultivated C. chaxingu strains.

hUCB-MSC derived exosomal miR-124 promotes rat liver regeneration after partial hepatectomy via downregulating Foxg1.

Liver regeneration after partial hepatectomy (PH) is a complex and well-orchestrated process involving multiple factors such as cytokines, growth factors, and signaling pathways. MicroRNAs (miRNAs) participate in various biological processes including liver regeneration after PH. In the current study, we investigated the expression and function of human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived exosomal miRNAs on liver regeneration using a rat PH model. We found that hUCB-MSC derived exosomes promoted rat liver regeneration and ameliorated liver injury after PH. MicroRNA microarray was performed to identify the differentially expressed miRNAs in hUCB-MSC derived exosomes involving in liver regeneration after PH. We demonstrated that hUCB-MSC derived exosomal miR-124 could promote liver regeneration and prevent against liver injury after PH in rats. Inhibition of miR-124 abrogated the protective role of hUCB-MSC derived exosome in rat liver regeneration after PH. In addition, we identified that transcription factor Foxg1 was a direct target of miR-124 and miR-124 promoted rat liver cell proliferation via suppressing Foxg1 expression. Furthermore, we demonstrated that hUCB-MSC derived exosomal miR-124 enhanced liver regeneration via inhibiting Foxg1 in rats after PH. In summary, our findings suggest that hUCB-MSC-derived exosomal miR-124 could promote rat liver regeneration after PH via downregulating Foxg1.

Transcatheter closure of multiple paravalvular leaks by a transapical approach under echocardiographic guidance: A case report.

CASE SUMMARY: A patient who underwent mechanical aortic and mitral valve replacement developed three paravalvular leaks 10 months later. We located the tracks by puncturing the apex cordis under transoesophageal echocardiography guidance alone and puncturing the femoral artery guided by fluoroscopy. Three paravalvular leaks were occluded with a hybridization method simultaneously. The patient was followed up for 24 months and maintained a good condition. CONCLUSION: Multiple paravalvular leaks after double valve replacement can be occluded in patients by the use of different approaches under echocardiographic guidance alone.

Assessment of Clinicopathological Characteristics and Development of an Individualized Prognostic Model for Patients With Hepatoid Adenocarcinoma of the Stomach.

Importance: Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). Objective: To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). Design, Setting, and Participants: This prognostic study involved a retrospective analysis of data from 315 patients who received a diagnosis of primary HAS between April 1, 2004, and December 31, 2019, at 14 centers in China. Main Outcomes and Measures: OS and prognostic factors. Patients were randomly assigned to a derivation cohort (n = 220) and a validation cohort (n = 95). A nomogram was developed based on independent prognostic factors identified through a multivariable Cox mixed-effects model. Results: Among 315 patients with HAS (mean [SD] age, 61.9 [10.2] years; 240 men [76.2%]), 137 patients had simple HAS (defined as the presence of histologically contained hepatoid differentiation areas only), and 178 patients had mixed HAS (defined as the presence of hepatoid differentiation areas plus common adenocarcinoma areas). Patients with simple HAS had a higher median preoperative α-fetoprotein level than those with mixed HAS (195.9 ng/mL vs 48.9 ng/mL, respectively; P < .001) and a higher rate of preoperative liver metastasis (23 of 137 patients [16.8%] vs 11 of 178 patients [6.2%]; P = .003). The 3-year OS rates of patients with simple vs mixed HAS were comparable (56.0% vs 60.0%; log-rank P = .98). A multivariable Cox analysis of the derivation cohort found that the presence of perineural invasion (hazard ratio [HR], 2.13; 95% CI, 1.27-3.55; P = .009), preoperative carcinoembryonic antigen levels of 5 ng/mL or greater (HR, 1.72; 95% CI, 1.08-2.74; P = .03), and pathological node category 3b (HR, 3.72; 95% CI, 1.34-10.32; P = .01) were independent risk factors for worse OS. Based on these factors, a nomogram to predict postoperative OS was developed. The concordance indices of the nomogram (derivation cohort: 0.72 [95% CI, 0.66-0.78]; validation cohort: 0.72 [95% CI, 0.63-0.81]; whole cohort: 0.71 [95% CI, 0.66-0.76]) were higher than those derived using the American Joint Committee on Cancer's AJCC Cancer Staging Manual (8th edition) pathological tumor-node-metastasis (pTNM) staging system (derivation cohort: 0.63 [95% CI, 0.57-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]) and those derived using a clinical model that included pTNM stage and receipt of adjuvant chemotherapy (derivation cohort: 0.64 [95% CI, 0.58-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]). Based on the nomogram cutoff of 10 points, the whole cohort was divided into high-risk and low-risk groups. The 3-year OS rate of patients in the high-risk group was significantly lower than that of patients in the low-risk group (29.7% vs 75.9%, respectively; log-rank P < .001), and the 3-year prognosis of high-risk and low-risk groups could be further distinguished into pTNM stage I to II (33.3% vs 80.2%; exact log-rank P = .15), stage III (34.3% vs 71.3%; log-rank P < .001), and stage IV (15.5% vs 70.3%; log-rank P = .009). Conclusions and Relevance: This study found that perineural invasion, preoperative carcinoembryonic antigen levels of 5 ng/mL or greater, and pathological node category 3b were independent risk factors associated with worse OS. An individualized nomogram was developed to predict OS among patients with HAS. This nomogram had good prognostic value and may be useful as a supplement to the current American Joint Committee on Cancer TNM staging system.

Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer.

BACKGROUND: Early gastric cancer (EGC), compared with advanced gastric cancer (AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method. AIM: To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs (miRNAs) in EGC and AGC and compared them with those in benign gastritis (BG). METHODS: We examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori (H. pylori)-negative gastritis (Control-1), and H. pylori-positive atrophic gastritis (Control-2). To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups. RESULTS: Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori-negative gastritis (Control-1) and H. pylori-positive atrophic gastritis (Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs, miR-7641, miR-425-5p, miR-1180-3p and miR-122-5p, were used to effectively distinguish the Cancer group (EGC + AGC) from the Control group [area under the curve (AUC) = 0.799, 95% confidence interval (CI): 0.691-0.908, P < 0.001]. Additionally, miR-425-5p, miR-24-3p, miR-1180-3p and miR-122-5p were utilized to distinguish EGC from the Control group (AUC = 0.829, 95%CI: 0.657-1.000, P = 0.001). Moreover, the miR-24-3p expression level in EGC was lower than that in the AGC (AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5p expression level in EGC was significantly higher than that in AGC (AUC = 0.791, 95%CI: 0.574-1.000, P = 0.024). CONCLUSION: The differentially expressed circulatory plasma miR-425-5p, miR-1180-3p, miR-122-5p, miR-24-3p and miR-4632-5p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings.

Efficacy of antiviral therapy with nucleotide/nucleoside analogs after curative treatment for patients with hepatitis B virus-related hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: A systematic review was conducted to evaluate whether or not antiviral therapy with nucleotide/nucleoside analogs (NA) have survival benefit for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative treatment. METHODS: An electronic search of PubMed, EMBASE, and the Cochrane Library was performed to identify comparative studies in which the adjuvant effects of NA for patients with HBV-related HCC after curative treatment were evaluated. Primary outcome included survival rate, and secondary outcomes included tumor recurrence rate and side effects. Review Manager 5.1.6 software was used for meta-analysis. RESULTS: Twelve studies involving 6682 patients were included in our review. Meta-analysis results demonstrated that significant differences favoring the antiviral treatment groups were observed in 1-year survival rate (RR: 0.65, 95% CI: 0.53-0.79, P<0.0001), 3-year survival rate (RR: 0.58, 95% CI: 0.46-0.74, P<0.0001), and 5-year survival rate (RR: 0.56, 95% CI: 0.43-0.74, P<0.0001) compared with the control group. After NA was administered, recurrence was significantly reduced after one year (RR: 0.77, 95% CI: 0.64-0.93, P=0.006) and three years (RR: 0.81, 95% CI: 0.71-0.93, P=0.002) but not after five years (RR: 0.94, 95% CI: 0.76-1.16, P=0.55) compared with non-NA therapy. CONCLUSION: Current evidence showed that antiviral therapy with NA could improve survival and reduce early recurrence for patients with HBV-related HCC after curative treatment. More high-quality prospective trials are expected.