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Abstract Objectives To construct a combined model based on bi-regional quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), as well as clinical-radiological (CR) features for predicting microvascular invasion (MVI) in solitary Barcelona Clinic Liver Cancer (BCLC) stage A hepatocellular carcinoma (HCC), and to assess its ability for stratifying the risk of recurrence after hepatectomy. Methods Patients with solitary BCLC stage A HCC were prospective collected and randomly divided into training and validation sets. DCE perfusion parameters were obtained both in intra-tumoral region (ITR) and peritumoral region (PTR). Combined DCE perfusion parameters (C DCE) were constructed to predict MVI. The combined model incorporating C DCE and CR features was developed and evaluated. Kaplan–Meier method was used to investigate the prognostic significance of the model and the survival benefits of different hepatectomy approaches. Results A total of 133 patients were included. Total blood flow in ITR and arterial fraction in PTR exhibited the best predictive performance for MVI with areas under the curve (AUCs) of 0.790 and 0.792, respectively. C DCE achieved AUCs of 0.868 (training set) and 0.857 (validation set). A combined model integrated with the α-fetoprotein, corona enhancement, two-trait predictor of venous invasion, and C DCE could improve the discrimination ability to AUCs of 0.966 (training set) and 0.937 (validation set). The combined model could stratify the prognosis of HCC patients. Anatomical resection was associated with a better prognosis in the high-risk group (p

Abstract Background Tumor budding (TB) and tumor‐infiltrating lymphocyte (TIL) are significant predictive indicators of lymph node metastasis (LNM) and unfavorable prognosis in various tumors. Currently, there is no gold standard for TB and TIL evaluation in esophageal squamous cell carcinoma (ESCC). This study aimed to identify the standard of TB and TIL evaluations and build a predictive model for prognosis among patients with pT1b ESCC. Methods We retrospectively analyzed the prognostic values of TB and TIL in 150 pT1b ESCC cases. Hematoxylin and eosin (H&E) and immunohistochemistry (IHC) of anti‐pan cytokeratin (AE1/AE3) were used to analyze the threshold of TB, and intratumoral TIL and peritumoral TIL (pTIL) were evaluated using the receiver operating characteristic curves (ROC). Results We found that TB in a three‐tiered grading system (low‐TB: 0‐4; middle‐TB: 5–15; high‐TB: ≥16) displayed an excellent prognosis prediction for LNM and survival based on IHC staining using a 20× objective lens. Low pTIL level (≤20%) was a significant indicator of LNM and unfavorable prognosis (p

Abstract Objective To construct and validate a prediction model based on dual-layer detector spectral CT (DLCT) and clinico-radiologic features to predict the microsatellite instability (MSI) status of gastric cancer (GC) and to explore the relationship between the prediction results and patient prognosis. Methods A total of 264 GC patients who underwent preoperative DLCT examination were randomly allocated into the training set (n = 187) and validation set (n = 80). Clinico-radiologic features and DLCT parameters were used to build the clinical and DLCT model through multivariate logistic regression analysis. A combined DLCT parameter (CDLCT) was constructed to predict MSI. A combined prediction model was constructed using multivariate logistic regression analysis by integrating the significant clinico-radiologic features and CDLCT. The Kaplan–Meier survival analysis was used to explore the prognostic significant of the prediction results of the combined model. Results In this study, there were 70 (26.52%) MSI-high (MSI-H) GC patients. Tumor location and CT_N staging were independent risk factors for MSI-H. In the validation set, the area under the curve (AUC) of the clinical model and DLCT model for predicting MSI status was 0.721 and 0.837, respectively. The combined model achieved a high prediction efficacy in the validation set, with AUC, sensitivity, and specificity of 0.879, 78.95%, and 75.4%, respectively. Survival analysis demonstrated that the combined model could stratify GC patients according to recurrence-free survival (p = 0.010). Conclusion The combined model provides an efficient tool for predicting the MSI status of GC noninvasively and tumor recurrence risk stratification after surgery. Critical relevance statement MSI is an important molecular subtype in gastric cancer (GC). But MSI can only be evaluated using biopsy or postoperative tumor tissues. Our study developed a combined model based on DLCT which could effectively predict MSI preoperatively. Our result also showed that the combined model could stratify patients according to recurrence-free survival. It may be valuable for clinicians in choosing appropriate treatment strategies to avoid tumor recurrence and predicting clinical prognosis in GC. Key points • Tumor location and CT_N staging were independent predictors for MSI-H in GC. • Quantitative DLCT parameters showed potential in predicting MSI status in GC. • The combined model integrating clinico-radiologic features and CDLCT could improve the predictive performance. • The prediction results could stratify the risk of tumor recurrence after surgery. Graphical Abstract

Abstract Background Lymphovascular invasion (LVI) is a crucial predictor of lymph node metastasis (LNM). However, few studies have investigated the LVI positivity rate and its clinical significance in pT1b esophageal squamous cell carcinoma (ESCC) using immunohistochemistry and elastin staining. Methods We collected data from158 patients with pT1b ESCC who had undergone radical esophagectomy. All paraffin blocks of invasive carcinoma from each patient were subjected to HE staining, elastin staining + CK (AE1/AE3) immunohistochemistry (E&IHC), and CD31/D2-40 + CK (AE1/AE3) double immunohistochemistry (D-IHC). The LVI was classified into types, i.e., vascular invasion (VI) and lymphatic vessel invasion (LI), and its location, quantity, and clinical significance were explored. Results The positivity rates of VI by E&IHC (E-VI), VI by CD31D-IHC (CD31-VI), and LI by D2-40 D-IHC (D2-40-LI) were significantly higher than those obtained by HE staining (P

Abstract Siglec‐15, a novel immune suppressor, is upregulated in many human cancers. The aim of this study was to explore the expression of Siglec‐15 in colorectal cancer (CRC), and investigate whether Siglec‐15 could be a potential target for cancer immunotherapy in patients with CRC. We performed immunohistochemical analyses of Siglec‐15 on a cohort of 805 patients with CRC and made comparisons between clinicopathological characteristics, PD‐L1 expression, CD3, CD8, CD45RO tumor‐infiltrating lymphocytes (TILs), and prognosis. We found that Siglec‐15 expression was commonly detected in tumor cells (48.3%) and tumor‐associated stromal cells (33.4%), and was more frequently observed than PD‐L1 expression in tumor cells. In contrast, Siglec‐15 expression was weakly and scarcely found in normal mucosa (13%). Siglec‐15 overexpression in tumor cells was associated with advanced TNM stage (p = 0.020). Co‐expression of Siglec‐15 and PD‐L1 in tumor cells was found in 14.4% of patients, and Siglec‐15 expression was detected in almost half of PD‐L1 negative cases. Elevated Siglec‐15 expression in tumor and stromal cells was associated with sparser CD45RO and CD8 TILs (p = 0.035 and p = 0.004, respectively). The expression of Siglec‐15 did not have prognostic significance. In summary, compared to PD‐L1, Siglec‐15 protein expression is more prevalent in CRC and is associated with advanced disease stage and fewer TILs. These findings support Siglec‐15 as a potential cancer immunotherapy target, in addition to PD‐1/PD‐L1 inhibitors, in patients with CRC.

Objective: The postoperative survival rates of patients with gastric cancer at different stages treated at the National Cancer Center (NCC) of China have not been reported. Therefore, we evaluated the survival of patients with gastric cancer who underwent surgery at the NCC from 2011 to 2018 to provide baseline information for further studies. Methods: We identified 7,301 patients with primary gastric carcinoma who underwent surgery at the NCC between January 2011 and May 2018; among these, 5,008 patients were enrolled in this study. Follow up was completed on April 30, 2020. We analyzed the 5-year survival according to the stage, sex, age, and other clinicopathological features. Results: Five-year survival rates of patients with pTNM stages IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV treated at the NCC were 94.9%, 91.8%, 86.5%, 76.1%, 61.1%, 44.2%, 29.7%, and 8.1%, respectively, which were similar to those reported in Japan during the same period. Five-year survival rates of patients with ypTNM stages I, II, III, and IV were 93.1%, 63.2%, 27.2%, and 0.0%, respectively. In multivariable analysis, age, signet ring cell carcinoma, adjuvant chemotherapy, and degree of differentiation were revealed as important prognostic factors. Conclusion: The survival rates of patients with gastric cancer treated at the NCC have been significantly improved, reaching the levels of Japan in the same period.

Abstract While recent technological developments contributed to breakthrough advances in single particle cryo-electron microscopy (cryo-EM), sample preparation remains a significant bottleneck for the structure determination of macromolecular complexes. A critical time factor is sample optimization that requires the use of an electron microscope to screen grids prepared under different conditions to achieve the ideal vitreous ice thickness containing the particles. Evaluating sample quality requires access to cryo-electron microscopes and a strong expertise in EM. To facilitate and accelerate the selection procedure of probes suitable for high-resolution cryo-EM, we devised a method to assess the vitreous ice layer thickness of sample coated grids. The experimental setup comprises an optical interferometric microscope equipped with a cryogenic stage and image analysis software based on artificial neural networks (ANN) for an unbiased sample selection. We present and validate this approach for different protein complexes and grid types, and demonstrate its performance for the assessment of ice quality. This technique is moderate in cost and can be easily performed on a laboratory bench. We expect that its throughput and its versatility will contribute to facilitate the sample optimization process for structural biologists.

Abstract Purpose About 15%—40% of gastric cancer patients have peritoneal metastasis, which leads to poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) is considered to be an effective treatment for these patients. This study evaluated the efficacy and safety of HIPEC in patients with gastric cancer diagnosed from laboratory tests. Methods The clinical and pathological data of 63 patients with gastric cancer who underwent HIPEC in 2017–2021 were prospectively recorded. Fifty-five patients underwent cytoreductive surgery + HIPEC, and eight patients received HIPEC alone. The factors associated with HIPEC safety and efficacy were analyzed. The primary endpoint was overall survival. Results The average patient age was 54.84 years and 68.3% of patients were male. Moreover, 79.4% of patients had a peritoneal carcinoma index (PCI) score of ≤ 7 and 61.9% had a completeness of cytoreduction score of 0. Because of peritoneal metastasis, 29 patients (46.03%) were classified as stage IV. Laboratory tests showed no differences in pre-HIPEC blood test results compared to post-HIPEC results after removing the effects of surgery. HIPEC treatment did not cause obvious liver or kidney damage. Serum calcium levels decreased significantly after HIPEC (P = 0.0018). The Karnofsky performance status (KPS) score correlated with the patient’s physical function and improved after HIPEC (P = 0.0045). In coagulation tests, FDP (P

ABSTRACT: Background: Gastric adenocarcinoma (GA) is a heterogeneous tumor, and the accurate classification of GA is important. Previous classifications are based on molecular analysis and have not focused on GA with the primitive enterocyte phenotype (GAPEP), a unique subtype with a poor prognosis and frequent liver metastases. New substituted molecular (SM) classifications based on immunohistochemistry (IHC) are needed. Methods: According to the IHC staining results, we divided 582 cases into six types: mismatch repair deficient (dMMR), Epstein-Barr virus associated (EBVa), the primitive enterocyte phenotype (PEP), the epithelial mesenchymal transition (EMT) phenotype, not otherwise specified/P53 mutated (NOS/P53m) and not otherwise specified/P53 wild-type (NOS/P53w). We analyzed the clinicopathological features, the immune microenvironment (PD-L1, CD8) and expression of HER2 and VEGFR2 of those types. Results: There were 31 (5.3%) cases of the dMMR type, 13 (2.2%) cases of the EBVa type, 44 (7.6%) cases of the PEP type, 122 (21.0%) cases of the EMT type, 127 (21.8%) cases of the NOS/P53m type and 245 (42.1%) cases of the NOS/P53w type. Patients with the dMMR type had the best survival (P < 0.001). Patients with the EBVa type were younger (P < 0.001) and had higher PD-L1 and CD8 expression (P < 0.001) than other patients. Patients with the EMT type exhibited poor differentiation and a higher rate of abdominal metastasis. Patients with the NOS/P53m and PEP types had the worst survival rates and the highest PD-L1/HER2/VEGFR2 expression levels among all patients (P < 0.001). Conclusion: Different SM classifications have different clinicopathological features and expression patterns, which indicate the probable clinical treatment strategies for these subtypes.

BackgroundDespite the recent progress of therapeutic strategies in treating prostate cancer (PCa), the majority of patients still eventually relapse, experiencing dismal outcomes. Therefore, it is of utmost importance to identify novel viable targets to increase the effectiveness of treatment. The present study aimed to investigate the potential relationship between N6-methyladenosine (m6A) RNA modification and PCa development and determine its clinical relevance.MethodsThrough systematic analysis of the TCGA database and other datasets, we analyzed the gene expression correlation and mutation profiles of m6A-related genes between PCa and normal tissues. Patient samples were divided into high- and low-risk groups based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis. Subsequently, differences in biological processes and genomic characteristics of the two risk groups were determined, followed by functional enrichment analysis and gene set enrichment (GSEA) analysis. Next, we constructed the protein-protein interaction (PPI) network of differentially expressed genes between patients in high- and low-risk groups, along with the mRNA-miRNA-lncRNA network. The correlation analysis of tumor-infiltrating immune cells was further conducted to reveal the differences in immune characteristics between the two groups.ResultsA variety of m6A-related genes were identified to be differentially expressed in PCa tissues as compared with normal tissues. In addition, the PPI network contained 278 interaction relationships and 34 m6A-related genes, and the mRNA-miRNA-lncRNA network contained 17 relationships, including 91 miRNAs. Finally, the immune characteristics analysis showed that compared with the low-risk group, the levels of M1 and M2 macrophages in the high-risk group significantly increased, while the levels of mast cells resting and T cells CD4 memory resting significantly decreased.ConclusionsThis study provides novel findings that can further the understanding of the role of m6A methylation during the progression of PCa, which may facilitate the invention of targeted therapeutic drugs.

Abstract Background Both gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (including hepatoid adenocarcinoma) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses. However, the value of the serum AFP test and AFP/glypican-3 (GPC3)/spalt-like transcription factor 4 (SALL4) immunohistochemistry is still not clear, and these two methods have not yet been thoroughly compared. Methods We collected 421 consecutive non-neoadjuvant surgically or endoscopically resected gastric adenocarcinoma patients with serum AFP results before surgery (group A). We divided these cases into serum AFP-high (sAFP-H) and serum AFP-normal (sAFP-N) by serum AFP levels, and into GAPEP (expressing AFP, GPC3, or SALL4) and non-GAPEP (nGAPEP) by AFP/GPC3/SALL4 immunohistochemistry results. We also collected 12 non-resected gastric adenocarcinoma patients with serum AFP ≥ 7 ng/mL before treatment (group B). We analyzed these patients’ clinicopathological characteristics and prognoses. Results Seventeen (4.04%) patients in group A were sAFP-H. These patients were younger and mainly had tubular adenocarcinoma with later pT (P = 0.014) and pN (P = 0.047) categories and more lymphovascular invasion (P 1000 ng/mL) had simultaneous metastases, mainly liver metastases. Both the serological method and immunohistochemical method were useful for predicting prognosis (AUC sAFP = 0.625, AUC A/G/S-IHC = 0.723, z statistic = 1.726, P = 0.084). The serum AFP level (especially > 1000 ng/mL) is more specific (100%), and immunohistochemistry is more sensitive (50%). Conclusion Both the serum AFP level and immunohistochemical expression of AFP/GPC3/SALL4 can be used to indicate a poor prognosis for gastric adenocarcinoma.

AimTo compare the long-term nutritional status, reflux esophagitis and anastomotic stenosis, between total gastrectomy (TG) and proximal gastrectomy (PG).MethodsPatients who underwent PG or TG in this single institution between January 2014 and December 2016 were included in this study. The inclusion and exclusion criteria were defined. One-to-one propensity score matching (PSM) by the demographic and pathological characteristics was performed to compare the long-term outcomes between the two groups. The primary endpoint was long-term nutritional status, and the second endpoints were reflux esophagitis and anastomotic stenosis. Long-term nutritional status was valued by percentage of body mass index (%BMI), body weight, and blood test including total protein, prealbumin, hemoglobin and total leukocytes.ResultsTotally 460 patients received PG or TG in our institution for the treatment between January 2014 and December 2016 and according to the inclusion and exclusion criteria 226 cases were included in this study finally. There was no significant difference as to nutritional status in the end of first 5 years after PG or TG. While reflux esophagitis and anastomotic stenosis were significantly higher in the PG group than in the TG group (54.4% versus 26.8%, p < 0.001; 14.9% versus 4.5%, p=0.015; respectively). Overall survival rates were similar between the two groups after PSM (5-year survival rates: 65.4% versus 61.5% in the PG and TG groups, respectively; p = 0.54). The rate of carcinoma of remnant stomach after PG was 3.5% in this group of patients.ConclusionsTG should be more aggressively recommended for the similar nutritional status, significantly lower reflux esophagitis and anastomotic stenosis, and free of carcinoma of remnant stomach compared with PG.

ObjectiveRobot-assisted radical prostatectomy (RARP) is a dynamically evolving technique with its new evolution of single-site RARP. Here we sought to describe our extraperitoneal technique, named the single-site multiport RARP (ssmpRARP) using the da Vinci Si® platform and compare it with the transperitoneal conventional multiport RARP (cmpRARP).Materials and MethodsData were retrospectively collected for patients who underwent RARP for localized prostate cancer from June 2020 to January 2022 in a single center. Propensity score matching was performed based on age, prostate size, body mass index, neoadjuvant hormonal therapy usage, prostate-specific antigen levels, and clinical T stage. The differences between the matched two groups were investigated.ResultsOf the patients, 20 underwent ssmpRARP and 42 underwent cmpRARP during the period. After matching, 18 patients from each group were selected. Median follow-up was 7.8 months (2–12 months) for the ssmpRARP group, and 15.0 months (3–26 months) for cmpRARP. The demographic features between the two groups were comparable. The median total operative time, estimated blood loss, pathologic data, early follow-up outcomes, and hospitalization stays and costs were similar between the two groups. The ssmpRARP group tended to return to their bowel activities earlier (44.78 ± 10.83 h vs. 54.89 ± 12.97 h, p = 0.016). There were no significant differences in complication rates.ConclusionsWe demonstrated the feasibility and safety of performing extraperitoneal ssmpRARP using the da Vinci Si® robotic platform. Our technique showed comparable short-term outcomes with the transperitoneal cmpRARP. Prospective trials and long-term follow-up are necessary to confirm these results.

We aimed to determine the pattern of delay and its effect on the short-term outcomes of total gastrectomy before and during the coronavirus disease 2019 (COVID-19) pandemic. Overlaid line graphs were used to visualize the dynamic changes in the severity of the pandemic, number of gastric cancer patients, and waiting time for a total gastrectomy. We observed a slightly longer waiting time during the pandemic (median: 28.00 days, interquartile range: 22.00–34.75) than before the pandemic (median: 25.00 days, interquartile range: 18.00–34.00; p = 0.0071). Moreover, we study the effect of delayed surgery (waiting time > 30 days) on short-term outcomes using postoperative complications, extreme value of laboratory results, and postoperative stay. In patients who had longer waiting times, we did not observe worse short-term complication rates (grade II–IV: 15% vs. 19%, p = 0.27; grade III–IV: 7.3% vs. 9.2%, p = 0.51, the short waiting group vs. the prolonged waiting group) or a higher risk of a longer POD (univariable: OR 1.09, 95% CI 0.80–1.49, p = 0.59; multivariable: OR 1.10, 95% CI 0.78–1.55, p = 0.59). Patients in the short waiting group, rather than in the delayed surgery group, had an increased risk of bleeding in analyses of laboratory results (plasma prothrombin activity, hemoglobin, and hematocrit). A slightly prolonged preoperative waiting time during COVID-19 pandemic might not influence the short-term outcomes of patients who underwent total gastrectomy.

Abstract Background Aging is a comorbidity of breast cancer suggesting that aging-associated transcriptome changes may promote breast cancer progression. However, the mechanism underlying the age effect on breast cancer remains poorly understood. Method We analyzed transcriptomics of the matched normal breast tissues from the 82 breast cancer patients in The Cancer Genome Atlas (TCGA) dataset with linear regression for genes with age-associated expression that are not associated with menopause. We also analyzed differentially expressed genes between the paired tumor and non-tumor breast tissues in TCGA for the identification of age and breast cancer (ABC)-associated genes. A few of these genes were selected for further investigation of their malignancy-regulating activities with in vitro and in vivo assays. Results We identified 148 upregulated and 189 downregulated genes during aging. Overlapping of tumor-associated genes between normal and tumor tissues with age-dependent genes resulted in 14 upregulated and 24 downregulated genes that were both age and breast cancer associated. These genes are predictive in relapse-free survival, indicative of their potential tumor promoting or suppressive functions, respectively. Knockdown of two upregulated genes (DYNLT3 and P4HA3) or overexpression of the downregulated ALX4 significantly reduced breast cancer cell proliferation, migration, and clonogenicity. Moreover, knockdown of P4HA3 reduced growth and metastasis whereas overexpression of ALX4 inhibited the growth of xenografted breast cancer cells in mice. Conclusion Our study suggests that transcriptome alterations during aging may contribute to breast tumorigenesis. DYNLT3, P4HA3, and ALX4 play significant roles in breast cancer progression.

BackgroundThis study aimed to explore the predictive value of quantitative dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) quantitative parameters for the response to neoadjuvant chemotherapy (NCT) in locally advanced gastric cancer (LAGC) patients, and the relationship between the prediction results and patients’ prognosis, so as to provide a basis for clinical individualized precision treatment.MethodsOne hundred twenty-nine newly diagnosed LAGC patients who underwent IVIM-DWI and DCE-MRI pretreatment were enrolled in this study. Pathological tumor regression grade (TRG) served as the reference standard of NCT response evaluation. The differences in DCE-MRI and IVIM-DWI parameters between pathological responders (pR) and pathological non-responders (pNR) groups were analyzed. Univariate and multivariate logistic regressions were used to identify independent predictive parameters for NCT response. Prediction models were built with statistically significant quantitative parameters and their combinations. The performance of these quantitative parameters and models was evaluated using receiver operating characteristic (ROC) analysis. Clinicopathological variables, DCE-MRI and IVIM-DWI derived parameters, as well as the prediction model were analyzed in relation to 2-year recurrence-free survival (RFS) by using Cox proportional hazards model. RFS was compared using the Kaplan–Meier method and the log-rank test.ResultsSixty-nine patients were classified as pR and 60 were pNR. Ktrans, kep, and ve values in the pR group were significantly higher, while ADCstandard and D values were significantly lower than those in the pNR group. Multivariate logistic regression analysis demonstrated that Ktrans, kep, ve, and D values were independent predictors for NCT response. The combined predictive model, which consisted of DCE-MRI and IVIM-DWI, showed the best prediction performance with an area under the curve (AUC) of 0.922. Multivariate Cox regression analysis showed that ypStage III and NCT response predicted by the IVIM-DWI model were independent predictors of poor RFS. The IVIM-DWI model could significantly stratify median RFS (52 vs. 15 months) and 2-year RFS rate (72.3% vs. 21.8%) of LAGC.ConclusionPretreatment DCE-MRI quantitative parameters Ktrans, kep, ve, and IVIM-DWI parameter D value were independent predictors of NCT response for LAGC patients. The regression model based on baseline DCE-MRI, IVIM-DWI, and their combination could help RFS stratification of LAGC patients.

Abstract Background Despite great progress in surgery and other treatments, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) is still very poor. HER2 has strong therapeutic implications in certain cancers, such as breast cancer and gastric cancer. However, literature on the frequency of HER2 expression in ESCC is scarce. In the present study, HER2 protein expression, HER2 gene amplification and the relationship between HER2 status and clinicopathological characteristics were evaluated in a large cohort of Chinese ESCC patients. Methods A total of 857 consecutive ESCC patients who received radical esophagectomy without neoadjuvant therapy between January 2014 and October 2015 were included in this retrospective study. HER2 protein expression was analyzed by immunohistochemistry (IHC), and its correlation with clinicopathological parameters was assessed. In addition, 65 cases, including 13 HER2 overexpression (3+) cases and 52 HER2 equivocal (2+) cases from the 857-case cohort, and another 104 ESCC cases, including 1 HER2 overexpression (3+) case, 3 HER2 equivocal (2+) cases and 100 HER2 negative (1+/0) cases, were selected to construct tissue microarrays (TMAs). Dual-color in situ hybridization (DISH) was performed on the TMAs to assess HER2 gene amplification and the relationship with clinicopathological parameters. Results We found HER2 overexpression (3+) status in 1.5% (13/857) of cases and HER2 equivocal (2+) status in 6.1% (52/857) of cases. HER2 IHC expression was significantly associated with gender (P = 0.028). However, there were no significant correlations between HER2 IHC expression and age, tumor differentiation, pT stage, pN stage, pM stage and pTNM stage (P > 0.05). Regarding the 169 cases analyzed by DISH, 14 (of 14, 100%) HER2 overexpression (3+) cases, 10 (of 55, 18.2%) HER2 equivocal (2+) cases, and 0 (of 100, 0%) HER2 negative (1+/0) cases showed HER2 gene amplification. HER2 gene amplification was not significantly associated with clinicopathological characteristics such as age, gender, tumor differentiation, pT stage, pN stage, pM stage and pTNM stage (P > 0.05). Conclusions Approximately 1.5% of the Chinese ESCC patients had HER2 overexpression based on IHC. IHC and DISH had a high concordance rate. These results provide valuable insight for the future treatment of ESCC.

Abstract Background Total gastrectomy (TG) is a widely accepted procedure for treating gastric stump cancer (GSC). However, subtotal gastrectomy (SG) would benefit elective patients with GSC. The aim of this study was to clarify the safety and long-term prognosis of SG in treating GSC after distal gastrectomy for benign lesions. Methods A total of 53 patients with GSC located at the anastomotic site or gastric body between May 1999 and December 2018 at our hospital were included. In total, 21 patients underwent SG, and the remaining 24 patients underwent TG. Clinicopathological data, operative data, and overall survival (OS) were compared. Results The operative duration, estimated blood loss volume, and length of hospital stay were similar between the SG and TG groups. The postoperative complications were similar between the two groups, but no cases of anastomotic leakage were noted in the SG group. TG was associated with significantly more retrieved lymph nodes than SG (18.5 ± 11.5 vs. 10.7 ± 9.2; p = 0.017), while the number of metastatic lymph nodes did not differ between the groups (2.9 ± 3.5 vs. 1.9 ± 3.6; p = 0.329). The median survival time in the SG group was 81.0 months (95% confidence interval (CI), 68.906 to 93.094 months), which was similar to the 45.0 months (95% CI, 15.920 to 74.080 months) observed in the TG group (p = 0.236). Both univariate and multivariate analyses showed that tumor location and histological type were prognostic factors, while surgery type was not a prognostic factor. Further stratified analyses according to tumor location revealed that OS was not significantly different between the two groups among patients with tumors located at the anastomotic site, while OS in the TG group was significantly better than that in the SG group among patients with tumors located in the gastric body (p = 0.046). Conclusions The results of the current study indicate that SG is a suitable alternative surgical procedure for GSC located at the anastomotic site after distal gastrectomy for benign lesions. The short-term outcomes and long-term prognoses of SG are comparable with those of TG.

Abstract Backgrounds The pulmonary ciliated muconodular papillary tumor (CMPT) is a very rare tumor with only several case reports in published literatures, and its clinicopathological features, standard treatment methods and prognosis has not been well defined. Methods Two cases of CMPT diagnosed and treated in our hospital and 39 cases reported in the published literature were analyzed retrospectively. Results The cohort of 41 CMPT patients comprised of 20 males and 21 females, aged 9–84 years. The diameter of the primary tumor was 0.3–4.5 cm. Most of these lesions were subsolid nodules, as observed on computed tomography and easily misdiagnosed as early lung adenocarcinoma. Tumors of 26 patients were stained by immunohistochemistry method, which revealed that CK7, CEA, and TTF-1 were positive and CK20 was negative in most patients. The results of gene alternation demonstrated mutations in EGFR, KRAS, and BRAF and ALK rearrangements in CMPT. All the patients underwent surgical treatment and did not receive postoperative adjuvant therapy. The follow-up duration was 0–120 months, and no case of tumor recurrence was found until the final follow-up. Conclusions The incidence of CMPT was low and rate of image misdiagnosis high. Immunohistochemistry is helpful for accurate diagnosis of CMPT. Sub-lobectomy may be proper and adjuvant treatment should be avoided since the disease is now prone to benign lesions. Furthermore, since the biological behavior of this tumor is not yet fully elucidated, additional case data are essential for accurate conclusions.

Abstract Background Intestinal metaplasia (IM) of the gastric mucosa is classified as complete (Type I) and incomplete IM (Type II and III) subtypes, which showed significantly different risk for developing to gastric adenocarcinoma (GAC). GCRG213, a variant of L1-endonuclease (L1-EN), first identified in our lab, was upregulated in GAC tissue. However, the relationship between GCRG213 and IM subtypes is not clear. Our study explored the association of GCRG213 protein (GCRG213p) with IM subtypes. Methods Gastric cancer and/or para-tumor tissue samples were collected from 123 patients who underwent gastrectomy for intestinal type gastric adenocarcinoma. The subtypes of IM were characterized with Alcian blue-periodic acid-Schiff and High Iron Diamine-Alcian blue staining methods. Immunohistochemistry of GCRG213p was performed, and its expression in gastric adenocarcinoma and para-tumor tissue including dysplasia, IM, and normal mucosa were analyzed. Results GCRG213p was expressed in 48.94% IM, 57.14% dysplasia and 55.32% GAC, respectively. GCRG213p expression was higher in well and moderately differentiated adenocarcinoma (P = 0.037). In IM glands, GCRG213p expressed mainly in the cytoplasm of absorptive enterocytes with defined brush borders, but not in goblet cells. The expression of GCRG213p in type I IM (90.00%) was significantly higher than that in type II (36.36%) and type III (25.00%) (P

Weighted correlation network analysis (WGCNA) is a statistical method that has been widely used in recent years to explore gene co-expression modules. Competing endogenous RNA (ceRNA) is commonly involved in the cancer gene expression regulation mechanism. Some ceRNA networks are recognized in gastric cancer; however, the prognosis-associated ceRNA network has not been fully identified using WGCNA. We performed WGCNA using datasets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) to identify cancer-associated modules. The criteria of differentially expressed RNAs between normal stomach samples and gastric cancer samples were set at the false discovery rate (FDR) < 0.01 and |fold change (FC)| > 1.3. The ceRNA relationships obtained from the RNAinter database were examined by both the Pearson correlation test and hypergeometric test to confirm the mRNA–lncRNA regulation. Overlapped genes were recognized at the intersections of genes predicted by ceRNA relationships, differentially expressed genes, and genes in cancer-specific modules. These were then used for univariate and multivariate Cox analyses to construct a risk score model. The ceRNA network was constructed based on the genes in this model. WGCNA-uncovered genes in the green and turquoise modules are those most associated with gastric cancer. Eighty differentially expressed genes were observed to have potential prognostic value, which led to the identification of 12 prognosis-related mRNAs (KIF15, FEN1, ZFP69B, SP6, SPARC, TTF2, MSI2, KYNU, ACLY, KIF21B, SLC12A7, and ZNF823) to construct a risk score model. The risk genes were validated using the GSE62254 and GSE84433 datasets, with 0.82 as the universal cutoff value. 12 genes, 12 lncRNAs, and 35 miRNAs were used to build a ceRNA network with 86 dysregulated lncRNA–mRNA ceRNA pairs. Finally, we developed a 12-gene signature from both prognosis-related and tumor-specific genes, and then constructed a ceRNA network in gastric cancer. Our findings may provide novel insights into the treatment of gastric cancer.

Abstract Background Programmed death ligand 1 (PD-L1) is a ligand for the inhibitory programmed cell death protein 1 (PD-1), which are targeted by several anti-PD-1 and PD-L1 drugs for a variety of human cancers. However, only a few studies have evaluated PD-L1 expression in esophageal squamous cell carcinoma (ESCC) with a large Chinese cohort. Our present study is to evaluate the association of PD-L1 expression with clinicopathological features on ESCC. Methods Using tissue microarray and immunohistochemistry, PD-L1 expression on tumor cells and tumor-infiltrating immune cells was studied in 378 advanced ESCC patients without neoadjuvant chemoradiotherapy. Its correlation with clinicopathological parameters was analyzed. Results PD-L1 was expressed on 29.9% (113/378) ESCC tumor cells and 40.2% (152/378) tumor-infiltrating immune cells. PD-L1 expression in tumor cells was significantly correlated with age, degree of differentiation, T stage, N stage and metachronous hematogenous metastasis, and PD-L1 expression in tumor-infiltrating immune cells was significantly associated with N stage (P

Background: Despite the recent progress of therapeutic strategies in treating prostate cancer (PCa), the majority of patients still eventually relapse, experiencing dismal outcomes. Therefore, it is of utmost importance to identify novel viable targets to increase the effectiveness of treatment. The present study aimed to investigate the potential relationship between N6- methyladenosine (m6A) RNA modification and PCa development and determine its clinical relevance. Methods: Through systematic analysis of the TCGA database and other datasets, we analyzed the gene expression correlation and mutation profiles of m6Arelated genes between PCa and normal tissues. Patient samples were divided into high- and low-risk groups based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis. Subsequently, differences in biological processes and genomic characteristics of the two risk groups were determined, followed by functional enrichment analysis and gene set enrichment (GSEA) analysis. Next, we constructed the protein-protein interaction (PPI) network of differentially expressed genes between patients in high- and low-risk groups, along with the mRNA-miRNA-lncRNA network. The correlation analysis of tumor-infiltrating immune cells was further conducted to reveal the differences in immune characteristics between the two groups. Results: A variety of m6A-related genes were identified to be differentially expressed in PCa tissues as compared with normal tissues. In addition, the PPI network contained 278 interaction relationships and 34 m6A-related genes, and the mRNA-miRNA-lncRNA network contained 17 relationships, including 91 miRNAs. Finally, the immune characteristics analysis showed that compared with the low-risk group, the levels of M1 and M2 macrophages in the high-risk group significantly increased, while the levels of mast cells resting and T cells CD4 memory resting significantly decreased. Conclusions: This study provides novel findings that can further the understanding of the role of m6A methylation during the progression of PCa, which may facilitate the invention of targeted therapeutic drugs. [ABSTRACT FROM AUTHOR]