Metastatic melanoma of the gallbladder: A case report and systematic review.

We report a case of metastatic melanoma of the gallbladder diagnosed by contrast-enhanced ultrasound and systematically review the characteristics of transabdominal ultrasound, clinical manifestations, and treatment methods of gallbladder metastatic melanoma in order to provide reference ideas for the diagnosis and treatment of metastatic melanoma of gallbladder.

Rehmanniae Radix Preparata ameliorates behavioral deficits and hippocampal neurodevelopmental abnormalities in ADHD rat model.

Objectives: Abnormal hippocampal neurodevelopment, particularly in the dentate gyrus region, may be a key mechanism of attention-deficit/hyperactivity disorder (ADHD). In this study, we investigate the effect of the most commonly used Chinese herb for the treatment of ADHD, Rehmanniae Radix Preparata (RRP), on behavior and hippocampal neurodevelopment in spontaneously hypertensive rats (SHR). Methods: Behavior tests, including Morris water maze (MWM) test, open field test (OFT) and elevated plus maze (EPM) test were performed to assess the effect of RRP on hyperactive and impulsive behavior. Hippocampal neurodevelopment was characterized by transmission electron microscopy, immunofluorescence, Golgi staining and Nissl staining approaches. Regulatory proteins such as Trkb, CDK5, FGF2/FGFR1 were examined by Western blot analysis. Results: The results showed that RRP could effectively control the impulsive and spontaneous behavior and improve the spatial learning and memory ability. RRP significantly reduced neuronal loss and increased the number of hippocampal stem cells, and promoted synaptic plasticity. In addition, FGF/FGFR signaling was upregulated after RRP treatment. Conclusion: RRP can effectively reduce impulsive and spontaneous behavior and ameliorate hippocampal neurodevelopmental abnormalities in ADHD rat model.

No communication between the bile duct and intraductal papillary neoplasm of the bile duct on imaging: A case report.

As a rare biliary tract tumor, intraductal papillary neoplasm of the bile duct (IPNB) is most common in elderly men and can progress to cholangiocarcinoma- (CCa) if left untreated. It is reported that IPNB usually communicates with the bile duct. As a result, the downstream bile ducts are imaged asymmetrically dilated. However, a case of IPNB that we report here is different. Enhanced MRI revealed a lack of connectivity with the bile duct in this case. Based on this, the purpose of this case study is to suggest that the majority of imaging doctors should widely understand the various imaging manifestations of the disease to avoid misdiagnosis. In addition, although this feature was not indicated by ultrasound in this case, given previous studies and considering the convenience and non-ionizing radiation damage of CEUS, we recommend its use as a screening method for IPNB to improve diagnostic accuracy.

Risk stratification model for incidentally detected gallbladder polyps: A multicentre study.

PURPOSE: We aimed to develop a 4-level risk stratification model using a scoring system based on conventional ultrasound to improve the diagnosis of gallbladder polyp. METHOD: Patients with histopathologically confirmed gallbladder polyps were consecutively recruited from three medical centres. Conventional ultrasound findings and clinical characteristics were acquired prior to cholecystectomy. Risk factors for neoplastic and malignant polyps were used to build a risk stratification system via interobserver agreement and multivariate logistic regression analysis. The model was retrospectively trained using 264 pre-surgical samples and prospectively validated using 106 pre-surgical samples. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and malignant polyp rate. RESULTS: In total, 370 patients (mean age, 51.68 ± 14.41 years, 156 men) were enrolled in this study. Size (≥12 mm), shape (oblate or round), single, vascularity, gallbladder stone or sludge were considered risk factors for neoplastic polyps. Size (≥14 mm), shape (oblate), single, disrupted gallbladder wall, and gallbladder stone or sludge were risk factors for malignant polyps (all p < 0.05). In the scoring system, the sensitivity, specificity, and AUC of score ≥ 9 in diagnosing neoplastic polyps were 0.766, 0.788, and 0.876 respectively; and the sensitivity, specificity, and AUC of score ≥ 15 in diagnosing malignant polyps were 0.844, 0.926, and 0.949 respectively. In our model, the malignancy rates at the four levels were 0 % (0/24), 1.28 % (2/156), 9.26 % (5/54), and 70.37 % (38/54), respectively. CONCLUSIONS: The 4-level risk stratification model based on conventional ultrasound imaging showed excellent performance in classifying gallbladder polyps.

Colorectal liver metastases: Correlations of contrast-enhanced ultrasound features with tumor clinicopathological factors and clinical outcomes following conversion therapy.

OBJECTIVE: To explore the prognostic impact of contrast-enhanced ultrasound (CEUS) features for initially unresectable colorectal liver metastases (CLMs) in a clinical setting of conversion therapy. METHODS: Between March 2015 and November 2020, consecutive patients with CLMs who received conversion treatment were prospectively enrolled. All participants underwent liver CEUS at baseline. The primary endpoint was conversion resection rate (R0 and overall resection). Secondary endpoints were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). RESULTS: 104 participants who completed conversion treatment were included. CEUS enhancement pattern was correlated with index lesion (size and echogenicity), primary (site, differentiation, perineural invasion, and RAS genotype) and serum (CA19-9 level) characteristics (P = <0.001-0.016). CEUS enhancement pattern was significantly associated with R0 resection rate, ORR, PFS, and OS (P = 0.001-0.049), whereas enhancement degree was associated with PFS and OS (P = 0.043 and 0.045). Multivariate analysis showed that heterogeneous enhancement independently predicted R0 and overall resection (P = 0.028 and 0.024) while rim-like enhancement independently predicted ORR and OS (P = 0.009 and 0.026). CONCLUSION: CEUS enhancement pattern was significantly associated with tumor characteristics and clinical outcomes following conversion therapy, and thus might be of prognosis impact for initially unresectable CLMs.

Integration of lipidomics and metabolomics reveals plasma and urinary profiles associated with pediatric Mycoplasma pneumoniae infections and its severity.

Mycoplasma pneumoniae is a significant contributor to lower respiratory infections in children. However, the lipidomics and metabolics bases of childhood M. pneumoniae infections remain unclear. In this study, lipidomics and metabolomics analyses were conducted using UHPLC-LTQ-Orbitrap XL mass spectrometry and gas chromatography-triple quadrupole mass spectrometry on plasma (n = 65) and urine (n = 65) samples. MS-DIAL software, in combination with LipidBlast and Fiehn BinBase DB, identified 163 lipids and 104 metabolites in plasma samples, as well as 208 metabolites in urine samples. Perturbed lipid species (adjusted p < 0.05) were observed, including lysophosphatidylethanolamines, phosphatidylinositols, phosphatidylcholines, phosphatidylethanol amines, and triglycerides. Additionally, differential metabolites (adjusted p < 0.05) exhibited associations with amino acid metabolism, nucleotide metabolism, and energy metabolism. Thirteen plasma metabolites, namely l-hydroxyproline, 3-phosphoglycerate, citric acid, creatine, inosine, ribitol, α tocopherol, cholesterol, cystine, serine, uric acid, tagatose, and glycine, showed significant associations with disease severity (p < 0.05) and exhibited distinct separation patterns in M. pneumoniae-infected bronchitis and pneumonia, with an area under the curve of 0.927. Nine of them exhibited either positive or negative correlations with neutrophil or lymphocyte percentages. These findings indicated significant systemic metabolic shifts in childhood M. pneumoniae infections, offering valuable insights into the associated metabolic alterations and their relationship with disease severity.

Contrast-enhanced ultrasound features of hepatic sarcomatoid carcinoma different from hepatocellular carcinoma.

BACKGROUND: Hepatic sarcomatoid carcinoma (HSC) is a rare malignancy of the liver. The ultrasound and clinical features of HSC have not been determined. OBJECTIVE: To investigate and compare the ultrasound and clinical features of HSC and hepatocellular carcinoma (HCC), and to reveal the valuable features of HSC. METHODS: The ultrasound features and clinical data of pathologically proven HSC (n = 37) were compared with HCC (n = 92) in a matching ratio of 1:4 using the propensity score (age, gender and tumor size). RESULTS: The HSC patients were more likely to accompany with clinical symptoms and vascular invasion than HCC patients (40.5% vs 17.4%, 24.3% vs 6.5%, P < 0.05). The size of HSCs was significantly larger than that of HCCs (P < 0.05). The proportion of patients with elevated alpha-fetoprotein was significantly lower in HSC (35.1% vs 54.3%, P < 0.05). On gray-scale ultrasound images, the HSCs were more likely to demonstrate as indistinct margin and irregular shape lesions compared to HCCs (78.4% vs 48.8%; 70.3% vs 23.9%, P < 0.05). Under color Doppler flow imaging (CDFI), the blood flow signals were more frequently detected in HSC lesions (75.7% vs 56.5%, P < 0.05). Resistance index (RI) was higher in HSCs than in HCCs [0.78 (0.70,0.82) vs 0.70 (0.62,0.76), P < 0.05]. On contrast-enhanced ultrasound (CEUS), HSCs mainly showed entirety heterogeneous hyper-enhancement (48.6%), entirety homogeneous enhancement (18.9%), peripheral and internal septal enhancement (18.9%). The incidence of non-enhanced areas inside HSC lesions was higher than that inside HCC lesions (56.8% vs 31.5%, P < 0.05). During the portal venous and late phases, most of the lesions revealed hypo-enhancement in both groups, whereas earlier washout was observed in HSCs [43.0 s (30.5,58.0) vs 60.0 s (46.3,100.0), P < 0.05]. CONCLUSIONS: CEUS features are useful in preoperative and non-invasive differentiation of hepatic sarcomatoid carcinoma and hepatocellular carcinoma.

Clinical features and prognosis of acute-on-chronic liver failure in patients with recompensated cirrhosis.

BACKGROUND: There are few studies on acute-on-chronic liver failure (ACLF) in patients with recompensated cirrhosis. This study was aimed to investigate the clinical features of ACLF patients with recompensated cirrhosis. METHODS: A total of 461 ACLF patients were enrolled and divided into three groups: compensated, recompensated, and decompensated cirrhosis with ACLF. The baseline clinical data and 1-year survival rates were compared among the three groups. RESULTS: Compared with the decompensated group, in the recompensated group, the levels of hemoglobin, albumin, and serum sodium were significantly higher and the white blood cell count, international normalized ratio, and incidence of respiratory failure were significantly lower; there were no evident differences in other organ failures. The proportion of patients with ACLF grade 3 and 1-year survival rates significantly differed between the two groups. Conversely, compared with the compensated group, in the recompensated group, the platelet and total bilirubin levels were significantly lower and the proportion of patients with ACLF grade 1 was significantly higher. However, other clinical indicators or 1-year survival rates did not significantly differ between the two groups. CONCLUSIONS: Compared with patients who developed ACLF with decompensated cirrhosis, those who developed ACLF with recompensated cirrhosis had a less severe condition, lower incidence of respiratory failure, and better 1-year prognosis. However, the baseline clinical features and prognosis were similar between ACLF patients with recompensated and compensated cirrhosis. TRIAL REGISTRATION: Chinese clinical trials registry: ChiCTR1900021539.

Risk stratification of gallbladder masses by machine learning-based ultrasound radiomics models: a prospective and multi-institutional study.

OBJECTIVE: This study aimed to evaluate the diagnostic performance of machine learning (ML)-based ultrasound (US) radiomics models for risk stratification of gallbladder (GB) masses. METHODS: We prospectively examined 640 pathologically confirmed GB masses obtained from 640 patients between August 2019 and October 2022 at four institutions. Radiomics features were extracted from grayscale US images and germane features were selected. Subsequently, 11 ML algorithms were separately used with the selected features to construct optimum US radiomics models for risk stratification of the GB masses. Furthermore, we compared the diagnostic performance of these models with the conventional US and contrast-enhanced US (CEUS) models. RESULTS: The optimal XGBoost-based US radiomics model for discriminating neoplastic from non-neoplastic GB lesions showed higher diagnostic performance in terms of areas under the curves (AUCs) than the conventional US model (0.822-0.853 vs. 0.642-0.706, p < 0.05) and potentially decreased unnecessary cholecystectomy rate in a speculative comparison with performing cholecystectomy for lesions sized over 10 mm (2.7-13.8% vs. 53.6-64.9%, p < 0.05) in the validation and test sets. The AUCs of the XGBoost-based US radiomics model for discriminating carcinomas from benign GB lesions were higher than the conventional US model (0.904-0.979 vs. 0.706-0.766, p < 0.05). The XGBoost-US radiomics model performed better than the CEUS model in discriminating GB carcinomas (AUC: 0.995 vs. 0.902, p = 0.011). CONCLUSIONS: The proposed ML-based US radiomics models possess the potential capacity for risk stratification of GB masses and may reduce the unnecessary cholecystectomy rate and use of CEUS. CLINICAL RELEVANCE STATEMENT: The machine learning-based ultrasound radiomics models have potential for risk stratification of gallbladder masses and may potentially reduce unnecessary cholecystectomies. KEY POINTS: • The XGBoost-based US radiomics models are useful for the risk stratification of GB masses. • The XGBoost-based US radiomics model is superior to the conventional US model for discriminating neoplastic from non-neoplastic GB lesions and may potentially decrease unnecessary cholecystectomy rate for lesions sized over 10 mm in comparison with the current consensus guideline. • The XGBoost-based US radiomics model could overmatch CEUS model in discriminating GB carcinomas from benign GB lesions.

The Development and Validation of a Nomogram for Predicting Cancer-Specific Survival and a Risk Stratification System for Patients with Primary Gastrointestinal Melanoma.

BACKGROUND/AIMS: The aim of our study was to develop and validate a nomogram to predict cancer-specific survival and make a risk stratification system for primary gastrointestinal melanoma. MATERIALS AND METHODS: Patients with primary gastrointestinal melanoma in the Surveillance, Epidemiology, and End Results database between 2000 and 2018 were included and randomly divided into the training and validation cohort (8:2). A prediction nomogram of cancer-specific survival was constructed based on the risk factors identified in the multivariate Cox regression. Calibration curve, time-dependent receiver operating characteristic, and decision curve analysis were performed. Further, a risk stratification system was developed based on the nomogram. RESULTS: A total of 433 patients were included. The nomogram was constructed based on age, site, and tumor size, Surveillance, Epidemiology, and End Results (SEER) stage, and therapy. The area under the curves of the nomogram predicting 6-, 12-, and 18-month cancer-specific survival were 0.789, 0.757, and 0.726 for the internal validation and 0.796, 0.763, and 0.795 for the external validation. Calibration curves and decision curve analysis were performed. Further, patients were divided into 2 risk subgroups. The Kaplan-Meier analysis and the log-rank test showed that the risk stratification made well differentiation of patients with different risks of cancerspecific survival. CONCLUSION: We developed and validated a practical prediction model of cancer-specific survival and a risk stratification system for patients with primary gastrointestinal melanoma, which might be available in clinical practices.

Differential diagnosis of gallbladder neoplastic polyps and cholesterol polyps with radiomics of dual modal ultrasound: a pilot study.

PURPOSE: To verify whether radiomics techniques based on dual-modality ultrasound consisting of B-mode and superb microvascular imaging (SMI) can improve the accuracy of the differentiation between gallbladder neoplastic polyps and cholesterol polyps. METHODS: A total of 100 patients with 100 pathologically proven gallbladder polypoid lesions were enrolled in this retrospective study. Radiomics features on B-mode ultrasound and SMI of each lesion were extracted. Support vector machine was used to classify adenomas and cholesterol polyps of gallbladder for B-mode, SMI and dual-modality ultrasound, respectively, and the classification results were compared among the three groups. RESULTS: Six, eight and nine features were extracted for each lesion at B-mode ultrasound, SMI and dual-modality ultrasound, respectively. In dual-modality ultrasound model, the area under the receiver operating characteristic curve (AUC), classification accuracy, sensitivity, specificity, and Youden's index were 0.850 ± 0.090, 0.828 ± 0.097, 0.892 ± 0.144, 0.803 ± 0.149 and 0.695 ± 0.157, respectively. The AUC and Youden's index of the dual-modality model were higher than those of the B-mode model (p < 0.05). The AUC, accuracy, specificity and Youden's index of the dual-modality model were higher than those of the SMI model (p < 0.05). CONCLUSIONS: Radiomics analysis of the dual-modality ultrasound composed of B-mode and SMI can improve the accuracy of classification between gallbladder neoplastic polyps and cholesterol polyps.

Value of CEUS features in diagnosing thyroid nodules with halo sign on B-mode ultrasound.

BACKGROUND: The results of halo sign in the differential diagnosis of thyroid nodules were conflicting, and the value of contrast-enhanced ultrasound (CEUS) in characterization of thyroid nodules with halo has not been fully evaluated. This study was therefore designed to investigate the value of contrast-enhanced ultrasound features in the differential diagnosis of thyroid nodules with halo sign on B-mode ultrasound. MATERIAL AND METHODS: Seventy-four consecutive thyroid nodules with halo sign on B-mode ultrasound were pathologically confirmed by surgery or fine needle aspiration, including 43 benign and 31 malignant lesions. All these lesions underwent pre-operative CEUS examination. The CEUS features, including enhanced time, enhanced intensity and homogeneity, and presence of enhancing ring, were compared between benign and malignant ones. RESULTS: Enhanced intensity was significant different between benign and malignant lesions with halo. Hypo-enhancement was more frequently detected in malignant nodules than that in benign ones, compared with iso-enhancement and hyper-enhancement (p = 0.013, and = 0.014, respectively). Detection rate of high-enhancing ring was significantly higher in benign nodules than that in malignant group (p = 0.001). While in nodules > 10 mm, only high-enhancing ring was the distinguishing feature between benign and malignant nodules. CONCLUSIONS: Enhanced intensity and high-enhancing ring may be helpful in the differential diagnosis of thyroid nodules with halo sign on B-mode ultrasound.

Contrast-enhanced ultrasound combined with ultrasonic elastography to diagnose encapsulated papillary carcinoma: A case report.

Encapsulated papillary carcinoma is a rare malignant breast tumor with low malignancy, and is most commonly found in postmenopausal women. On ultrasound, encapsulated papillary carcinoma has an envelope, and anechoic areas inside the lesion. Contrast-enhanced ultrasound shows marked enhancement without size expand, and ultrasonic elastography suggests soft parenchyma in the lesion. However, it is often challenging to differentiate between encapsulated papillary carcinoma and other breast tumors, especially some benign lesions. Here, we reported a case of encapsulated papillary carcinoma in a 65-year-old female patient who discovered a breast mass three years ago and presented with nipple discharge and pain six months before. This case report demonstrated the ability of multimodal ultrasound to diagnose encapsulated papillary carcinoma.

Associations Between Endoscopic Primary Prophylaxis and Rebleeding in Liver Cirrhosis Patients with Esophagogastric Variceal Bleeding.

Aim: To identify the association between endoscopic primary prophylaxis and the risk of rebleeding in patients with liver cirrhosis receiving endoscopic therapy. Methods: This cohort study involved in 944 liver cirrhosis patients with esophagogastric variceal bleeding (EGVB) receiving endoscopic therapy. All participants were divided into two groups: rebleeding group (n = 425) and non-rebleeding group (n = 519) according to the occurrence of rebleeding in patients. Rebleeding indicated any bleeding after endoscopic therapy for the first bleeding of esophagogastric varices in liver cirrhosis patients. Univariate and multivariate logistic analyses were employed to identify the association between endoscopic primary prophylaxis and rebleeding in patients with liver cirrhosis after endoscopic therapy. Results: In total, 425 patients rebleeded at the end of the follow-up. The risk of rebleeding in patients with endoscopic primary prophylaxis decreased by 0.773 times (OR = 0.227, 95%CI: 0.139-0.372, P < 0.001) after adjusting covariables. Subgroups were divided according to the Child-Pugh (CP) score, and the results revealed that the risk of rebleeding in patients with endoscopic primary prophylaxis decreased by 0.858 times in Grade A patients (OR = 0.142, 95%CI: 0.066-0.304, P < 0.001) and 0.804 times in Grade B patients (OR = 0.196, 95%CI: 0.085-0.451, P < 0.001) compared with patients without endoscopic primary prophylaxis, but showed no difference in Grade C patients. Conclusion: Endoscopic primary prophylaxis was associated with a decreased risk of rebleeding in liver cirrhosis patients with EGVB after endoscopic therapy, which suggested that clinicians should pay more attention to endoscopic primary prophylaxis to prevent the occurrence of rebleeding in these patients.

Identification of CDCA2 as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis, and limited therapy options, resulting in a poor prognosis. Cell division cycle associated 2 (CDCA2), also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear. METHODS: The differentially expressed genes that were significantly upregulated in multiple RNA sequencing datasets of HCC were screened. Receiver operating characteristic (ROC) curve analysis was performed to identify diagnostic markers for HCC. Least absolute shrinkage and selection operator Cox regression analysis was performed to screen the prognosis-related genes. The screening and analyses identified CDCA2 as the target gene in this study. The expression of CDCA2 was analyzed in public databases and clinical specimens, and CDCA2 involvement in HCC was explored by both bioinformatic analysis and in vitro experiments. RESULTS: The level of CDCA2 was enhanced in HCC compared with healthy livers. Overexpression of CDCA2 positively correlated with the pathological grade and TNM stage of the diseases. Furthermore, CDCA2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with CDCA2 in combination with TNM stage. Bioinformatic analysis revealed that CDCA2 was closely associated with the cell cycle, apoptosis, and p53 signaling pathway. Silencing CDCA2 in Huh7 cells resulted in significant upregulation of p53 and the downstream PUMA and NOXA and a subsequently increased apoptosis. Inhibition of p53 signaling and apoptosis was found after overexpression of CDCA2 in L02 cells. Strikingly, the proliferation of cells was not affected by CDCA2. CONCLUSIONS: CDCA2 was a novel diagnostic marker for HCC, and overexpression of this gene reflected poor pathological grade, stage, and clinical prognosis. CDCA2 promoted the pathogenesis of HCC by suppressing the p53-PUMA/NOXA signaling and the subsequent apoptosis.

Liver injury in COVID-19: Known and unknown.

Since the first report of the coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, the outbreak of the disease is currently continuously evolving. Previous studies have shown varying degrees of liver damage in patients with COVID-19. However, the exact causes of liver injury and the relationship between COVID-19 and liver injury is unclear. This article describes liver injury induced by COVID-19, analyzes its causes, and discusses the treatment and prognosis of liver damage in patients with COVID-19.

Efficacy and safety of anticoagulants in liver cirrhosis patients with portal vein thrombosis: A meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of anticoagulants in liver cirrhosis patients with portal vein thrombosis (PVT). METHODS: PubMed, BioMed Central, Cochrane Library and Web of Science were retrieved to identify relevant literature. Forest plots were applied to display the results of the meta-analysis. The odds ratios (ORs) were used as the effect index for the enumeration data, and the effect size was expressed as 95% confidence intervals (CIs). Publication bias was evaluated by funnel plots and Egger's test. RESULTS: Eight articles included 225 patients with liver cirrhosis and PVT receiving anticoagulants and 232 not receiving anticoagulants. The data demonstrated that the recanalization rate of PVT was significantly higher in patients with anticoagulant treatment than in patients without anticoagulant treatment (OR=5.60; 95% CI: 3.40-9.22; P<0.001). The exacerbation risk of PVT was significantly lower in patients with anticoagulant treatment than in patients without anticoagulant treatment (OR=0.15; 95% CI: 0.04-0.54; P<0.001). A significantly lower portal hypertension bleeding effect was observed in patients with anticoagulant treatment than in patients without anticoagulant treatment (OR=0.21; 95% CI: 0.10-0.45; P<0.001). Low molecular weight heparins (LMWH) were more effective in preventing the PVT exacerbation in liver cirrhosis patients with PVT than warfarin (OR=0.16; 95% CI: 0.08-0.35). CONCLUSIONS: Anticoagulants were effective and safe in treating patients with liver cirrhosis and PVT as they could increase the PVT recanalization rate and decrease the risks of PVT exacerbation and portal hypertension bleeding.