Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

A Ni-free ZrCuFeAlAg bulk metallic glass with potential for biomedical applications.

The mechanical properties and biocompatibility of an Ni-free Zr-based bulk metallic glass (BMG) Zr60.14Cu22.31Fe4.85Al9.7Ag3 were investigated in detail to evaluate its potential as a biomaterial. The BMG was found to have a low Young's modulus of 82±1.9GPa, a high strength of 1720±28MPa and a high fracture toughness of 94±19MPam(1/2), as well as good fatigue strength over 400MPa. The corrosion behavior of the alloy was investigated in simulated body fluid (SBF) by electrochemical measurements, which indicates that the Zr-based BMG has a better corrosion resistance than pure Zr and Ti6Al4V. X-ray photoelectron spectroscopy analysis revealed that the passive film formed on the BMG surface is enriched in Al- and Zr-oxides, which could account for the good corrosion resistance of the BMG. On the other hand, metal ion release of the BMG in SBF was determined by inductively coupled plasma mass spectrometry after the BMG was immersed in SBF at 37°C for 30days, showing a ppb (ngml(-1)) level of metal ion release. The in vitro test via cell culture indicates that the BMG exhibits a cytotoxicity of Grade 0-1, which is as good as Ti6Al4V alloy. Cell adhesion morphological analysis shows that the cells were flattened and well spread out on the surfaces of the BMG, showing that the BMG had good biocompatibility. The combination of good mechanical properties and biocompatibility demonstrates that the Ni-free Zr-based BMG studied in this work is a good candidate for a new type of load-bearing biomedical material.

Evaluation of a new method for placing nasojejunal feeding tubes.

AIM: To compare fluoroscopic, endoscopic and guide wire assistance with ultraslim gastroscopy for placement of nasojejunal feeding tubes. METHODS: The information regarding nasojejunal tube placement procedures was retrieved using the gastrointestinal tract database at Tongji Hospital affiliated to Tongji Medical College. Records from 81 patients who underwent nasojejunal tubes placement by different techniques between 2004 and 2011 were reviewed for procedure success and tube-related outcomes. RESULTS: Nasojejunal feeding tubes were successfully placed in 78 (96.3%) of 81 patients. The success rate by fluoroscopy was 92% (23 of 25), by endoscopic technique 96.3% (26 of 27), and by guide wire assistance (whether via transnasal or transoral insertion) 100% (23/23, 6/6). The average time for successful placement was 14.9 ± 2.9 min for fluoroscopic placement, 14.8 ± 4.9 min for endoscopic placement, 11.1 ± 2.2 min for guide wire assistance with transnasal gastroscopic placement, and 14.7 ± 1.2 min for transoral gastroscopic placement. Statistically, the duration for the third method was significantly different (P < 0.05) compared with the other three methods. Transnasal placement over a guidewire was significantly faster (P < 0.05) than any of the other approaches. CONCLUSION: Guide wire assistance with transnasal insertion of nasojejunal feeding tubes represents a safe, quick and effective method for providing enteral nutrition.

Response gene to complement-32 enhances metastatic phenotype by mediating transforming growth factor beta-induced epithelial-mesenchymal transition in human pancreatic cancer cell line BxPC-3.

BACKGROUND: Response gene to complement-32 (RGC-32) is comprehensively expressed in many kinds of tissues and has been reported to be expressed abnormally in different kinds of human tumors. However, the role of RGC-32 in cancer remains controversial and no reports have described the effect of RGC-32 in pancreatic cancer. The present study investigated the expression of RGC-32 in pancreatic cancer tissues and explored the role of RGC-32 in transforming growth factor-beta (TGF-ß)-induced epithelial-mesenchymal transition (EMT) in human pancreatic cancer cell line BxPC-3. METHODS: Immunohistochemical staining of RGC-32 and E-cadherin was performed on specimens from 42 patients with pancreatic cancer, 12 with chronic pancreatitis and 8 with normal pancreas. To evaluate the role of RGC-32 in TGF-ß-induced EMT in pancreatic cancer cells, BxPC-3 cells were treated with TGF-ß1, and RGC-32 siRNA silencing and gene overexpression were performed as well. The mRNA expression and protein expression of RGC-32 and EMT markers such E-cadherin and vimentin were determined by quantitative reverse transcription-PCR (qRT-PCR) and western blot respectively. Finally, migration ability of BxPC-3 cells treated with TGF-ß and RGC-32 siRNA transfection was examined by transwell cell migration assay. RESULTS: We found stronger expression of RGC-32 and higher abnormal expression rate of E-cadherin in pancreatic cancer tissues than those in chronic pancreatitis tissues and normal pancreatic tissues. Immunohistochemical analysis revealed that both RGC-32 positive expression and E-cadherin abnormal expression in pancreatic cancer were correlated with lymph node metastasis and TNM staging. In addition, a significant and positive correlation was found between positive expression of RGC-32 and abnormal expression of E-cadherin. Furthermore, in vitro, we found sustained TGF-ß stimuli induced EMT and up-regulated RGC-32 expression in BxPC-3 cells. By means of siRNA silencing and gene overexpression, we further demonstrated that RGC-32 mediated TGF-ß-induced EMT and migration in BxPC-3 cells. CONCLUSIONS: The results above indicated that RGC-32 might be a novel metastasis promoting gene in pancreatic cancer and it enhances metastatic phenotype by mediating TGF-ß-induced EMT in human pancreatic cancer cell line BxPC-3.