Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. METHODS: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. RESULTS: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. CONCLUSIONS: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.

Magnitude, Risk Factors, and Factors Associated With Adenoma Miss Rate of Tandem Colonoscopy: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: We performed a systematic review and meta-analysis to comprehensively estimate adenoma miss rate (AMR) and advanced AMR (AAMR) and explore associated factors. METHODS: We searched the PubMed, Web of Science, and Ovid EMBASE databases for studies published through April 2018 on tandem colonoscopies, with AMR and AAMR as the primary outcomes. We performed meta-regression analyses to identify risk factors and factors associated with outcome. Primary outcomes were AMR and AAMR and secondary outcomes were AMR and AAMR for different locations, sizes, pathologies, morphologies, and populations. RESULTS: In a meta-analysis of 43 publications and more than 15,000 tandem colonoscopies, we calculated miss rates of 26% for adenomas (95% confidence interval [CI] 23%-30%), 9% for advanced adenomas (95% CI 4%-16%), and 27% for serrated polyps (95% CI 16%-40%). Miss rates were high for proximal advanced adenomas (14%; 95% CI 5%-26%), serrated polyps (27%; 95% CI 16%-40%), flat adenomas (34%; 95% CI 24%-45%), and in patients at high risk for colorectal cancer (33%; 95% CI 26%-41%). Miss rates could be decreased by adequate bowel preparation and auxiliary techniques (P = .06; P = .04, and P = .01, respectively). The adenoma detection rate (ADR), adenomas per index colonoscopy, and adenomas per positive index colonoscopy (APPC) were independently associated with AMR (P = .02, P = .01, and P = .008, respectively), whereas APPC was the only factor independently associated with AAMR (P = .006). An APPC value greater than 1.8 was more effective in monitoring AMR (31% vs 15% for AMR P < .0001) than an ADR value of at least 34% (27% vs 17% for AMR; P = .008). The AAMR of colonoscopies with an APPC value below 1.7 was 35%, vs 2% for colonoscopies with an APPC value of at least 1.7 (P = .0005). CONCLUSIONS: In a systematic review and meta-analysis, we found that adenomas and advanced adenomas are missed (based on AMR and AAMR) more frequently than previously believed. In addition to ADR, APPC deserves consideration as a complementary indicator of colonoscopy quality, if it is validated in additional studies.

Comparison of smear cytology and liquid-based cytology in EUS-guided FNA of pancreatic lesions: experience from a large tertiary center.

BACKGROUND AND AIMS: Studies comparing the diagnostic efficacy of liquid-based cytology (LBC) and smear cytology (SC) of pancreatic tissue sampling obtained via EUS-guided FNA (EUS-FNA) are still insufficient, mainly because results were controversial. We compared the diagnostic efficiency of LBC and SC of EUS-FNA of pancreatic lesions in one of the largest tertiary hospitals in China. METHODS: A retrospective database search (January 2015 to January 2019) was performed for patients who underwent EUS-FNA with both LBC and SC. Demographic, cytologic, and endosonographic data were collected from 819 patients; 514 cases met the inclusion criteria. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were compared. Rapid on-site evaluation was not available in all cases. RESULTS: Three hundred eighty-five cases (74.90%) had confirmed malignancy, and 40 cases (7.78%) confirmed benign neoplasm. Adequate tissue sampling rates showed no significant difference between the 2 groups. The sensitivity, accuracy, and negative predictive value (NPV) of LBC were higher than those of SC with statistical significance (71.4% vs 55.1%, 76.1% vs 61.6%, and 40.6% vs 27.7%, respectively). The sensitivity, accuracy, and NPV of combined SC and LBC were higher than those of LBC alone with statistical significance (83.9% vs 71.4%, 86.5% vs 76.1%, and 56.8% vs 40.6%, respectively). Multivariate analysis revealed that pancreatic neck/body/tail lesions (P = .003), solid lesions (P < .001), 22-gauge needle size (P < .001), and number of needle passage >3 (P = .041) were associated with higher diagnostic sensitivity in all participants using LBC, whereas number of needle passage >3 (P = .017) was associated with higher diagnostic sensitivity using SC. CONCLUSIONS: LBC was more accurate and sensitive than SC in EUS-FNA of pancreatic lesions with higher NPV when rapid on-site evaluation is unavailable. Pancreatic neck/body/tail lesions, solid lesions, 22-gauge needle, and more than 3 passes were associated with higher sensitivity when using LBC. Performing more than 3 passes is associated with higher sensitivity when using SC.

Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer.

Background: The current tumor-node-metastasis (TNM) staging system is insufficient for predicting the efficacy of chemotherapy in patients with gastric cancer (GC). This study aimed to analyze the association between the focal adhesion pathway and therapeutic efficacy of chemotherapy in patients with GC. Methods: RNA sequencing was performed on 33 clinical samples from patients who responded or did not respond to treatment prior to neoadjuvant chemotherapy. The validation sets containing 696 GC patients with RNA data from three cohorts (PKUCH, TCGA, and GSE14210) were analyzed. A series of machine learning and bioinformatics approaches was combined to build a focal adhesion-related signature model to predict the treatment efficacy and prognosis of patients with GC. Results: Among the various signaling pathways associated with cancer, focal adhesion was identified as a risk factor related to the treatment efficacy of chemotherapy and prognosis in patients with GC. The focal adhesion-related gene model (FAscore) discriminated patients with a high FAscore who are insensitive to neoadjuvant chemotherapy in our training cohort, and the predicted value was further verified in the GSE14210 cohort. Survival analysis also demonstrated that patients with high FAscores had a relatively shorter survival compared to those with low FAscores. In addition, we found that the levels of tumor mutation burden (TMB) and microsatellite instability (MSI) increased with an increase in FAscore, and the tumor microenvironment (TME) also shifted to a pro-tumor immune microenvironment. Conclusion: The FAscore model can be used to predict the treatment efficacy of chemotherapy and select appropriate treatment strategies for patients with GC.

Clinical Significance and Immune Infiltration Analyses of the Cuproptosis-Related Human Copper Proteome in Gastric Cancer.

BACKGROUND: The human copper Cu proteome, also termed Cu-binding proteins (CBP), is responsible for transporting "free" Cu to the cell that is related to cuproptosis. However, their role in gastric cancer (GC) has not been reported. METHODS: RNA expression data of 946 GC patients were collected. A series of machine learning and bioinformatic approaches were combined to build a CBP signature to predict survival and immune microenvironment and guide the priority treatment. Immunohistochemistry and multicolor immunofluorescence (mIF) in 1076 resection slides were used to verify immune features. RESULTS: A CBP signature was constructed using the machine learning method from TCGA that classifies cases as CBP_low and CBP_high groups. Multivariable Cox analysis confirmed that the CBP signature was an independent prognostic factor in the training and validation cohorts. Additionally, GC patients with low CBPscores showed an increase in anti-tumor immune microenvironment, which was further verified by mIF in pathological resections following immunotherapy. Importantly, patients with low CBPscores had higher levels of TMB/MSI and responded well to immunotherapy. CONCLUSIONS: We conducted the first and comprehensive CBP analysis of GC patients and established a clinically feasible CBP signature for predicting survival and response to treatment, which will be helpful for guiding personalized medicine.

Neoadjuvant PD-1 blockade plus chemotherapy induces a high pathological complete response rate and anti-tumor immune subsets in clinical stage III gastric cancer.

First-line PD-1 blockade plus chemotherapy significantly improves the survival benefits in late-stage gastric cancer (GC) patients. However, the pathological response rate and effects on the immune microenvironment of neoadjuvant PD-1 blockade plus chemotherapy in patients with cTNM-stage III GC remain to be elucidated. Patients with cTNM-stage III GC who underwent neoadjuvant PD-1 blockade plus chemotherapy and surgery were enrolled. Four in vivo models bearing GC were jointly established to investigate the specific roles of chemotherapy and PD-1 blockade for GC treatment. The tumor immune microenvironment was analyzed by hematoxylin and eosin (H&E) and IHC staining, multicolor flow cytometry and immunofluorescence. A total of 75 patients with cTNM-stage III (cT2-4N1-3M0) gastric cancer who received neoadjuvant PD-1 blockade plus chemotherapy (SOX/XELOX) were included in this study. After treatment, 21 (28.0%) and 57 (76.0%) patients achieved pathological complete response (pCR) and post-therapy pathological downstaging. Subgroup analyses revealed that patients with CPS >1 (32.6% vs 8.3%) and dMMR (35.7% vs 25.4%) subtype had better efficacy. Additionally, the resected specimens showed more anti-tumor immune infiltration indicating a response to neoadjuvant PD-1 blockade plus chemotherapy. Multicolor immunofluorescence and in vivo experiments on mouse models revealed that elevated M1/M2 ratio of macrophages, CD8 + T cells and plasma cells indicated effective response to treatment. Furthermore, neoadjuvant PD-1 blockade plus chemotherapy neither delayed surgery nor increased postoperative complication rate. The analyses indicate neoadjuvant PD-1 blockade plus chemotherapy is a promising therapeutic strategy in patients with cTNM-stage III GC with an encouraging pCR rate.

A facile synthesis of Zn(x)Cd(1-x)S/CNTs nanocomposite photocatalyst for H2 production.

The sulfide solid solution has become a promising and important visible-light-responsive photocatalyst for hydrogen production nowadays. Zn(x)Cd(1-x)S/CNT nanocomposites were synthesized to improve the dispersion, adjust the energy band gap, and enhance the separation of the photogenerated electrons and holes. The as-prepared photocatalysts were characterized by scanning electron-microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and UV-visible diffuse reflectance spectra (UV-visible), respectively. And the effects of CNTs on structure, composition and optical absorption property of the sulfide solid solutions were investigated along with their inherent relationships. For Zn0.83Cd0.17S/CNTs, sulfide solid solution is assembled along the CNTs orderly, with a diameter of 100 nm or so. XPS analysis shows that there is bonding effect between the solid solutions and the CNTs due to the strong adsorption of Zn(2+) and Cd(2+) on the surface of CNTs. There are two obvious absorption edges for Zn0.83Cd0.17S/CNTs, corresponding to two kinds of sulfide solid solutions with different molar ratios of Zn/Cd. The hybridization of solid solutions with CNTs makes the absorption spectrum red shift. The photocatalytic property was evaluated by splitting Na2S + Na2SO3 solution into H2, and the highest rate of H2 evolution of 6.03 mmol h(-1) g(-1) was achieved over Zn0.83Cd0.17S/CNTs. The high activity of photocatalytic H2 production is attributed to the following factors: (1) the optimum band gap and a moderate position of the conduction band (which needs to match the irradiation spectrum of the Xe lamp best), (2) the efficient separation of photogenerated electrons and holes by hybridization, and (3) the improvement of the dispersion of nanocomposites by assembling along the CNTs as well.

Microporous Ni-doped TiO2 film photocatalyst by plasma electrolytic oxidation.

Ni-doped TiO2 film catalysts were prepared by a plasma electrolytic oxidation (PEO) method and were mainly characterized by means of SEM, EDS, XRD, XPS, and DRS, respectively. The effects of Ni doping on the structure, composition and optical absorption property of the film catalysts were investigated along with their inherent relationships. The results show that the film catalyst is composed of anatase and rutile TiO2 with microporous structure. Doping Ni changes the phase composition and the lattice parameters (interplanar crystal spacing and cell volume) of the films. The optical absorption range of TiO2 film gradually expands and shifts to the red with increasing dosages. Both direct and indirect transition band gaps of the TiO2 films are deduced consequently. Moreover, the photocatalytic activity of the film catalysts for splitting Na2S+Na2SO3 solution into H2 is enhanced by doping with an appropriate amount of Ni. The as-prepared TiO2 film catalyst doping with 10 g/L of Ni(Ac)2 presents the highest photocatalytic reducing activity.