Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study.

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.

A Bayesian network model to predict neoplastic risk for patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

BACKGROUND: Polyp size of 10 mm is insufficient to discriminate neoplastic and non-neoplastic risk in patients with gallbladder polyps (GPs). The aim of the study is to develop a Bayesian network (BN) prediction model to identify neoplastic polyps and create more precise criteria for surgical indications in patients with GPs lager than 10 mm based on preoperative ultrasound features. METHODS: A BN prediction model was established and validated based on the independent risk variables using data from 759 patients with GPs who underwent cholecystectomy from January 2015 to August 2022 at 11 tertiary hospitals in China. The area under receiver operating characteristic curves (AUCs) were used to evaluate the predictive ability of the BN model and current guidelines, and Delong test was used to compare the AUCs. RESULTS: The mean values of polyp cross-sectional area (CSA), long, and short diameter of neoplastic polyps were higher than those of non-neoplastic polyps (P < 0.0001). Independent neoplastic risk factors for GPs included single polyp, polyp CSA ≥ 85 mm 2, fundus with broad base, and medium echogenicity. The accuracy of the BN model established based on the above independent variables was 81.88% and 82.35% in the training and testing sets, respectively. Delong test also showed that the AUCs of the BN model was better than that of JSHBPS, ESGAR, US-reported, and CCBS in training and testing sets, respectively (P < 0.05). CONCLUSION: A Bayesian network model was accurate and practical for predicting neoplastic risk in patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

A Bayesian network prediction model for gallbladder polyps with malignant potential based on preoperative ultrasound.

BACKGROUND: It is important to identify gallbladder polyps (GPs) with malignant potential and avoid unnecessary cholecystectomy by constructing prediction model. The aim of the study is to develop a Bayesian network (BN) prediction model for GPs with malignant potential in a long diameter of 8-15 mm based on preoperative ultrasound. METHODS: The independent risk factors for GPs with malignant potential were screened by χ2 test and Logistic regression model. Prediction model was established and validated using data from 1296 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China. A BN model was established based on the independent risk variables. RESULTS: Independent risk factors for GPs with malignant potential included age, number of polyps, polyp size (long diameter), polyp size (short diameter), and fundus. The BN prediction model identified relationships between polyp size (long diameter) and three other variables [polyp size (short diameter), fundus and number of polyps]. Each variable was assigned scores under different status and the probabilities of GPs with malignant potential were classified as [0-0.2), [0.2-0.5), [0.5-0.8) and [0.8-1] according to the total points of [- 337, - 234], [- 197, - 145], [- 123, - 108], and [- 62,500], respectively. The AUC was 77.38% and 75.13%, and the model accuracy was 75.58% and 80.47% for the BN model in the training set and testing set, respectively. CONCLUSION: A BN prediction model was accurate and practical for predicting GPs with malignant potential patients in a long diameter of 8-15 mm undergoing cholecystectomy based on preoperative ultrasound.

Projected estimates of cancer in Canada in 2022.

BACKGROUND: Regular cancer surveillance is crucial for understanding where progress is being made and where more must be done. We sought to provide an overview of the expected burden of cancer in Canada in 2022. METHODS: We obtained data on new cancer incidence from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2018). Mortality data (1984-2019) were obtained from the Canadian Vital Statistics - Death Database. We projected cancer incidence and mortality counts and rates to 2022 for 22 cancer types by sex and province or territory. Rates were age standardized to the 2011 Canadian standard population. RESULTS: An estimated 233 900 new cancer cases and 85 100 cancer deaths are expected in Canada in 2022. We expect the most commonly diagnosed cancers to be lung overall (30 000), breast in females (28 600) and prostate in males (24 600). We also expect lung cancer to be the leading cause of cancer death, accounting for 24.3% of all cancer deaths, followed by colorectal (11.0%), pancreatic (6.7%) and breast cancers (6.5%). Incidence and mortality rates are generally expected to be higher in the eastern provinces of Canada than the western provinces. INTERPRETATION: Although overall cancer rates are declining, the number of cases and deaths continues to climb, owing to population growth and the aging population. The projected high burden of lung cancer indicates a need for increased tobacco control and improvements in early detection and treatment. Success in breast and colorectal cancer screening and treatment likely account for the continued decline in their burden. The limited progress in early detection and new treatments for pancreatic cancer explains why it is expected to be the third leading cause of cancer death in Canada.

Short-term cancer prevalence in Canada, 2018.

BACKGROUND: As the leading cause of death in Canada, cancer imposes an enormous burden on both the health of Canadians and the Canadian health care system. This study presents detailed tumour-based cancer prevalence estimates in Canada by sex, age group, cancer type and prevalence duration as of January 1, 2018. DATA AND METHODS: Estimates of two- and five-year cancer prevalence were calculated for an extensive list of cancers in the Canadian population (excluding Quebec) based on incidence data from the Canadian Cancer Registry linked to mortality data from the Canadian Vital Statistics - Death Database, and death-related information from tax data. RESULTS: The two- and five-year cancer prevalence counts were 236,785 (832.1 per 100,000 people) and 503,060 (1,767.8 per 100,000 people), respectively. Cancer prevalence estimates varied by cancer site, and the four most prevalent cancers (breast, prostate, colorectal, lung) accounted for 49.6% of total five-year cancer prevalence in Canada. Prevalence for all cancers combined increased dramatically with age: 74.3% of prevalent cases among males and 61.9% among females were encountered among the population aged 60 and older. Prevalence was higher among females than males before age 60, and higher among males thereafter, peaking in the 80-to-89 age group for both sexes. INTERPRETATION: Prevalence mirrors the effects of both cancer incidence and survival. Breaking down cancer prevalence by disease duration is useful to distinguish groups of patients in different phases of care. An increase in prevalence indicates a greater demand for health care services and translates into a significant economic burden for the jurisdictions that are responsible for providing such services.

Establishment of a nomogram prediction model for long diameter 10-15 mm gallbladder polyps with malignant tendency.

BACKGROUND: Surgical indications for the treatment of gallbladder polyps are controversial. Evaluation of gallbladder polyps with malignant tendency and indications for cholecystectomy in patients with long diameter polyps of 10 to 15 mm require further analysis and discussion. In this study, our objective was to re-evaluate indications for the surgical resection of gallbladder polyps and construct a nomogram model for the prediction of gallbladder polyps with malignant tendency. METHODS: Clinicopathologic data of 2,272 patients who had undergone cholecystectomy for gallbladder polyps were collected from 11 medical centers in China. Risk factor analyses and nomogram prediction model for gallbladder polyps with malignant tendency were conducted. RESULTS: Excluding 311 patients with cholelithiasis and 488 patients with long diameter polyps ≤5 and >15 mm, factors that differed significantly among patients with gallbladder polyps having a long diameter of 6 to 9 mm (885 cases) and 10 to 15 mm (588 cases) were polyp detection time, CEA and CA19-9 levels, number of polyps, fundus, echogenicity, gallbladder wall thickness and postoperative pathologic features (P < .05). Among 588 patients with gallbladder polyps with a long diameter of 10 of 15 mm, multivariate analysis indicated the following independent risk factors of gallbladder polyps with malignant tendency: single polyps (OR = 0.286/P < .001), polyps with broad base (OR = 2.644/P = .001), polyps with medium/low echogenicity (OR = 2.387/P = .003), and polyps with short diameter of 7 to 9 or 10 to 15 mm (OR = 3.820/P = .005; OR = 2.220/P = .048, respectively). The C-index of the nomogram model and internal validation were .778 and .768, respectively. In addition, a sample online calculator for the nomogram prediction model had been created (https://docliqi.shinyapps.io/dynnom/). CONCLUSION: Indications for cholecystectomy in patients with gallbladder polyps with a long diameter of 10 to 15 mm should be assessed by combining the information on short diameter, number of polyps, fundus, and echogenicity. The nomogram model can be used to predict the risk for the development of gallbladder polyps with malignant tendency.

Screening for DNA adducts in ovarian follicles exposed to benzo[a]pyrene and cigarette smoke condensate using liquid chromatography-tandem mass spectrometry.

A rapid mass spectrometric method was applied to non-targeted screening of DNA adducts in follicular cells (granulosa cells and theca cells) from isolated ovarian follicles that were exposed in-vitro to benzo[a]pyrene (B[a]P) and cigarette smoke condensate (CSC) for 13days of culture. The method employed a constant neutral loss (CNL) scan to identify chromatographic peaks associated to a neutral loss of deoxyribose moiety of DNA nucleosides. These peaks were subsequently analyzed by a product ion scan in tandem mass spectrometry to elucidate structures of DNA adducts. The identification was further confirmed through synthesis of proposed DNA adducts where possible. Three DNA adducts, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-dG (BPDE-dG), phenanthrene 1,2-quinone-dG (PheQ-dG) and B[a]P-7,8-quinone-dG (BPQ-dG) were identified in the follicular cells from isolated ovarian follicles exposed to B[a]P. Along with these three, an additional DNA adduct, 4-aminobiphenyl-dG, was identified in the follicular cells from isolated ovarian follicles exposed to CSC. The amounts of the identified DNA adducts in follicular cells increased in a dose-dependent manner for both B[a]P (0, 1.5, 5, 15 and 45ng/mL) and CSC (0, 30, 60, 90 and 130µg/mL). The results revealed that B[a]P-related DNA adducts were the major adducts in the ovarian follicular cells exposed to CSC. The results also revealed that two oxidative biomarkers, 8-hydroxy-2-deoxy guanosine (8-OH-dG) and 8-isoprostane (8-IsoP), in both B[a]P-exposed and CSC-exposed ovarian follicles had strong correlations with the three DNA adducts, BPDE-dG, BPQ-dG and PheQ-dG. A pathway to describe formation of DNA adducts was proposed based on the DNA adducts observed.

Interaction Potency of Single-Walled Carbon Nanotubes with DNAs: A Novel Assay for Assessment of Hazard Risk.

Increasing use of single-walled carbon nanotubes (SWCNTs) necessitates a novel method for hazard risk assessment. In this work, we investigated the interaction of several types of commercial SWCNTs with single-stranded (ss) and double-stranded (ds) DNA oligonucleotides (20-mer and 20 bp). Based on the results achieved, we proposed a novel assay that employed the DNA interaction potency to assess the hazard risk of SWCNTs. It was found that SWCNTs in different sizes or different batches of the same product number of SWCNTs showed dramatically different potency of interaction with DNAs. In addition, the same SWCNTs also exerted strikingly different interaction potency with ss- versus ds- DNAs. The interaction rates of SWCNTs with DNAs were investigated, which could be utilized as the indicator of potential hazard for acute exposure. Compared to solid SWCNTs, the SWCNTs dispersed in liquid medium (2% sodium cholate solution) exhibited dramatically different interaction potency with DNAs. This indicates that the exposure medium may greatly influence the subsequent toxicity and hazard risk produced by SWCNTs. Based on the findings of dose-dependences and time-dependences from the interactions between SWCNTs and DNAs, a new chemistry based assay for hazard risk assessment of nanomaterials including SWCNTs has been presented.

A nontargeted screening method for covalent DNA adducts and DNA modification selectivity using liquid chromatography-tandem mass spectrometry.

A method for nontargeted screening for covalent DNA adducts was developed using combination of neutral loss scan and product ion scan in a hybrid linear-ion-trap - triple quadrupole mass spectrometer system. DNA 2'-deoxynucleosides and adducts eluted from liquid chromatography were first analyzed in neutral loss mode to screen for the neutral loss of the deoxyribose moiety ([M+H-116](+)) from the protonated molecular ion ([M+H](+)). The product ion scan was subsequently used to elucidate the structures for the molecular ions observed from the peaks in the neutral loss scan chromatogram. The synthesized DNA adducts were used to evaluate the developed method by reaction of 20-mer DNA oligonucleotide with two direct agents respectively, specifically phenyl glycidyl ether and styrene-7,8-oxide. The modification selectivity of two compounds to the four nitrogenous bases on DNA sequence was also investigated in this study. The results showed that the two compounds had different modification selectivity to the four bases. Both compounds could modify all four nitrogenous bases (i.e. adenine, guanine, thymine, and cytosine) on DNA sequences to form various covalent DNA adducts. While phenyl glycidyl ether modified almost all of thymidine on DNA sequence, styrene-7,8-oxide, on the other hand, modified only a small portion of thymidine. The developed method proved possibly a potential tool for screening of unknown DNA adducts as exposure biomarkers of contaminants to human in the environment.

Recent developments in DNA adduct analysis by mass spectrometry: a tool for exposure biomonitoring and identification of hazard for environmental pollutants.

DNA adducts represent an important category of biomarkers for detection and exposure surveillance of potential carcinogenic and genotoxic chemicals in the environment. Sensitive and specific analytical methods are required to detect and differentiate low levels of adducts from native DNA from in vivo exposure. In addition to biomonitoring of environmental pollutants, analytical methods have been developed for structural identification of adducts which provides fundamental information for determining the toxic pathway of hazardous chemicals. In order to achieve the required sensitivity, mass spectrometry has been increasingly utilized to quantify adducts at low levels as well as to obtain structural information. Furthermore, separation techniques such as chromatography and capillary electrophoresis can be coupled to mass spectrometry to increase the selectivity. This review will provide an overview of advances in detection of adducted and modified DNA by mass spectrometry with a focus on the analysis of nucleosides since 2007. Instrument advances, sample and instrument considerations, and recent applications will be summarized in the context of hazard assessment. Finally, advances in biomonitoring applying mass spectrometry will be highlighted. Most importantly, the usefulness of DNA adducts measurement and detection will be comprehensively discussed as a tool for assessment of in vitro and in vivo exposure to environmental pollutants.

Hepatic perivascular epithelioid cell tumors-not otherwise specified: a case report.

OBJECTIVE: Neoplasms of perivascular epithelioid cells (PEComas) are characterized by epithelioid to spindle cells with eosinophilic to clear cytoplasm, an intimate relationship with blood vessels, and coexpression of myoid and melanocytic immunohistochemical markers. While most reported hepatic PEComas, such as angiomyolipoma (AML), behave in a benign fashion, emerging PEComas cases without typical characteristics require further clarification. We report a case of primary hepatic perivascular epithelioid cell tumors-not otherwise specified (HPEComas-NOS) with untypical pathological and immunohistochemical features compared to those of the benign hepatic AML cases. HPEComas-NOS may represent a special type of PEComas classified as having "malignant potential" or at "high risk of aggressive behavior", suggesting the need for further clarification of hepatic PEComas and long-term follow-up of patients with HPEComas-NOS.

Immobilization of trypsin on sub-micron skeletal polymer monolith.

A new kind of immobilized trypsin reactor based on sub-micron skeletal polymer monolith has been developed. Covalent immobilization of trypsin on this support was performed using the epoxide functional groups in either a one- or a multi-step reaction. The proteolytic activity of the immobilized trypsin was measured by monitoring the formation of N-α-benzoyl-L-arginine (BA) which is the digestion product of a substrate N-α-benzoyl-L-arginine ethyl ester (BAEE). Results showed that the digestion speed was about 300 times faster than that performed in free solution. The performance of such an enzyme reactor was further demonstrated by digesting protein myoglobin. It has been found that the protein digestion could be achieved in 88 s at 30°C, which is comparable to 24 h digestion in solution at 37°C. Furthermore, the immobilized trypsin exhibits increased stability even after continuous use compared to that in free solution. The present monolithic enzyme-reactor provides a promising platform for the proteomic research.

High-performance affinity monolith chromatography for chiral separation and determination of enzyme kinetic constants.

A new kind of immobilized human serum albumin (HSA) column was developed by using the sub-micron skeletal polymer monolith based on poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) [poly(GMA-EDMA)] as the support of high-performance affinity chromatography. Using the epoxide functional groups presented in GMA, the HSA immobilization procedure was performed by two different means. The affinity columns were successfully adopted for the chiral separation of D,L-amino acids (AAs). Then this method was shown to be applicable to the quantitative analysis of D-tryptophan, with a linear range between 12.0 microM and 979.0 microM, and a correlation coefficient above 0.99. Furthermore, it was used for the analysis of urine sample. This assay is demonstrated to be facile and relatively rapid. So it allows us to measure the enzyme catalytic activity in the incubation of D,L-AAs with D-AA oxidase and to study the kinetics of the enzyme reaction. It implied that the affinity monolithic columns can be a useful tool for studying DAAO enzyme reaction and investigating the potential enzyme mechanism requirement among chiral conversion.

Preparation of sub-micron skeletal monoliths with high capacity for liquid chromatography.

A novel kind of poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate)-based monolithic column was developed for LC by directing supramolecular self-assembly of high internal phase emulsion. Mercury intrusion porosimetry characterization and scanning electron microscope pictures showed that these monoliths presented micrometer-sized throughpores, unique sub-micron skeletons and relatively large specific surface area. Additionally, porosity of monoliths could be adjusted while skeletons remained in the size range of 100.0-1000.0 nm. The new monoliths demonstrated not only better column efficiency, but also larger binding capacity. Dynamic binding capacity for protein (BSA) was evaluated to be 42.5 mg/mL, above two times higher than that of the general monoliths (19.1 mg/mL) and higher than that of commercial "Convective Interaction Media" monolithic columns (30.0 mg/mL). Moreover, their chromatographic behaviors were also evaluated in detail by chemical stability and swelling characterization of the monolithic column. Separation of proteins mixture (cytochrome c, myoglobin, ribonuclease A, lysozyme and BSA) on the monolith was achieved within 4 min at velocity of 1440.0 cm/h. Those unique properties made the novel monolithic column a promising alternative to commercially available monolithic supports in LC applications.

Assay of vitamin B in urine by capillary electrochromatography with methacrylate-based monolithic column.

A novel and simple method for the separation of major vitamin B analytes, such as thiamine, riboflavin, nicotinamide, vitamin B4, pyridoxine, has been developed by CEC using the monolithic column. It has been found that the baseline separation of the five analytes could be achieved with 5.0 mM phosphate buffer at pH 4.0. Compared with the open-tubular capillary and the bared capillary columns, the poly(butylmethacrylate-co-ethylene glycol dimethacrylate) monolithic capillary could exhibit the best resolution in the analysis. Then the method was validated and the linear calibration ranges were obtained with correlation coefficients more than 0.997. The precision and the recovery were also investigated and showed a good result. Furthermore, the proposed method was successfully applied to assay the concentration of vitamin B analytes and the metabolic situation in human urine samples.