Apparent diffusion coefficient in intrahepatic cholangiocarcinoma diffusion‐weighted magnetic resonance imaging noninvasively predicts Ki‐67 expression

Abstract

Aim

Tumor Ki-67 expression reflects prognosis and cancer grade, and biopsy-based preoperative assessment of Ki-67 expression is key to treatment. Apparent diffusion coefficient (ADC) values obtained with this imaging may noninvasively predict Ki-67 by reflecting tumor cell density and limited water molecule movement from irregular alignment. This study aimed to investigate the ability of ADC values to predict Ki-67 expression in intrahepatic cholangiocarcinoma (ICC).

Method

We retrospectively analyzed 39 cases of ICC confirmed by surgical pathology. All patients had undergone magnetic resonance imaging, and ADC values (mean, minimum, and maximum) were calculated. Ki-67 expression was assessed by immunohistochemistry, and patients were divided into groups of high (n = 18) and low (n = 21) Ki-67 expression. To assess the diagnostic performance of the ADC values for Ki-67 expression, we used the receiver operating characteristic curve and compared the areas under the curve (AUC).

Results

The mean and minimum ADC values were significantly lower in the group with high Ki-67 expression. For predicting high Ki-67 expression, the AUC values were 0.701 for mean ADC, 0.818 for minimum ADC, and 0.571 for maximum ADC. The diagnostic sensitivity and specificity of the minimum ADC values were 88.9% and 76.2%, respectively. In addition, with ADC values combined, the AUC increased to 0.831. Apparent diffusion coefficient is a useful predictor of Ki-67 expression level in ICC.

Conclusion

Apparent diffusion coefficient values, especially minimum ADC values, can noninvasively predict ICC associated with high Ki-67 expression.

Genome‐wide detection of structural variation in some sheep breeds using whole‐genome long‐read sequencing data

Abstract

Genomic structural variants (SVs) constitute a significant proportion of genetic variation in the genome. The rapid development of long-reads sequencing has facilitated the detection of long-fragment SVs. There is no published study to detect SVs using long-read data from sheep. We applied a long-read mapping approach to detect SVs and characterized a total of 30,771 insertions, deletions, inversions and translocations. We identified 716, 916, 842 and 303 specific SVs in Southdown sheep, Alpine merino sheep, Qilian White Tibetan sheep and Oula sheep, respectively. We annotated these SVs and found that these SV-related genes were primarily enriched in the well-established pathways involved in the regulation of the immune system, growth and development and environmental adaptability. We detected and annotated SVs based on NGS resequencing data to validate the accuracy based on third-generation detection. Moreover, five candidate SVs were verified using the PCR method in 50 sheep. Our study is the first to use a long-reads sequencing approach to construct a novel structural variation map in sheep. We have completed a preliminary exploration of the potential effects of SVs on sheep.

Impact of metabolic dysfunction‐associated fatty liver disease on the incidence of Helicobacter pylori‐negative gastric cancer

Impact of metabolic dysfunction-associated fatty liver disease on the incidence of Helicobacter pylori-negative gastric cancer

Metabolic dysfunction-associated fatty liver disease (MAFLD) was an independent risk factor for Helicobacter pylori-negative gastric cancer (HPNGC), along with age and smoking. Data mining analyses identified MAFLD as the most influential independent factor associated with HPNGC.


Abstract

Aim

The incidence of Helicobacter pylori-negative gastric cancer (HPNGC) is increasing worldwide. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been reported to be associated with various cancers, but its association with HPNGC has not been reported. We aimed to identify important independent factors associated with HPNGC, including MAFLD.

Methods

This multicenter observational cohort study enrolled patients with gastric cancer (n = 1078) and health checkup examinees (n = 17 408). We analyzed patients with HPNGC (n = 26) and healthy participants with no H. pylori infection or any abnormal findings on upper gastrointestinal endoscopy (n = 1130). A logistic regression model was used to identify independent factors associated with HPNGC. The priority of the factors associated with HPNGC was evaluated using a decision-tree algorithm and random forest analysis.

Results

Among all patients with gastric cancer, 2.4% (26/1078) were diagnosed with HPNGC (mean age, 64 years; male/female, 13/13). In the logistic regression analysis, age, smoking, and MAFLD (odds ratio, 6.5359; 95% confidence interval, 2.5451–16.7841; p < 0.0001) were identified as independent factors associated with HPNGC. Metabolic dysfunction-associated fatty liver disease was also identified as the most important classifier for the presence of HPNGC in decision-tree analyses. Helicobacter pylori-negative gastric cancer was observed in 5.2% of patients with MAFLD and 0.8% of patients without MAFLD. In the random forest analysis of the HPNGC, MAFLD was identified as the distinguishing factor with the highest variable importance (0.32).

Conclusions

Metabolic dysfunction-associated fatty liver disease was the most influential independent factor associated with HPNGC. These findings suggest that fatty liver and metabolic dysfunction could be involved in the pathogenesis of HPNGC.

Development and validation of a prognostic model for 90‐day survival in patients with alcohol‐associated cirrhosis and acute decompensation

Development and validation of a prognostic model for 90-day survival in patients with alcohol-associated cirrhosis and acute decompensation

We established a nomogram to identify the 90-day mortality risk of alcoholic cirrhosis and acute decompensation and validated the model's high reliability and better diagnostic performance in both cohorts.


Abstract

Background/purpose

Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression.

Methods

We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90-day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C-index, area under the receiver operating curve, calibration curve, and decision curve analysis.

Results

Total bilirubin >10 upper limit of normal, high-density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90-day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C-index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high- and low-risk groups. Mortality was significantly higher in the high-risk group than in the low-risk group (p < 0.0001).

Conclusion

The nomogram could accurately predict the 90-day mortality risk in patients with alcohol-associated cirrhosis and acute decompensation, helping to identify high-risk patients and personalize treatment at their first admission.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real‐world study

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study

Hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) showed considerable antitumor effects and low systemic toxicity in hepatocellular carcinoma (HCC) patients after systemic treatment failure. HAIC-FOLFOX treatment potentially could serve as second-line therapy for treating HCC patients who failed systemic treatments, even in patients with Child–Pugh B liver function.


Abstract

Aim

The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents.

Methods

Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed.

Results

The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1–12.9) and 6.0 months (95% CI, 5.1–6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin–bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05–2.34; p = 0.028), tumor number (>3 vs. 1–3, HR 2.18; 95% CI, 1.10–4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06–2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37–0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17–0.53; p < 0.001). Grade 3–4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed.

Conclusions

Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Defining desired genetic gains for Pacific white shrimp (Litopenaeus vannamei) breeding objective using participatory approaches

Abstract

The objective of this study was to define desired genetic gains from economically important traits of Pacific white shrimp (Litopenaeus vannamei) using participatory approaches. Two questionnaires were sent out to 100 Pacific white shrimp farmers in all five Iranian shrimp farming provinces. Questionnaire A (Q-A) includes management factors and farming environments. Moreover, in this questionnaire, farmers were asked to rank the fourth most important traits in shrimp among 10 economic traits in the list for genetic improvement. In questionnaire B (Q-B), priorities of the four traits with the highest value were obtained using pairwise comparison. The results showed that the four most important traits were white spot syndrome virus resistance (WSSV), growth rate before 4 months (GR), acute hepatopancreatic necrosis disease resistance (AHPND), and female total weight at ablation (FTW). Medians of the best individual preference values were WSSV (0.222), GR (0.173), AHPND (0.157), and FTW (0.053). Most disagreements were found between the social group preference values in the commercial products and water salinity categories. Desired genetic gains were 1.71%, 1.57%, 0.53% and 0.31% for GR, AHPND, WSSV and FTW, respectively. This study highlighted that despite environmental and management differences, participatory approaches can achieve desired genetic results for Pacific white shrimp breeding programme.