Integrated chromosomal instability and tumor microbiome redefined prognosis-related subtypes of pancreatic cancer.

BACKGROUND: Pancreatic cancer is a common malignancy with poor prognosis and limited treatment. Here we aimed to investigate the role of host chromosomal instability (CIN) and tumor microbiome in the prognosis of pancreatic cancer patients. METHODS: One hundred formalin-fixed paraffin-embedded (FFPE) pancreatic cancer samples were collected. DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing (WGS) via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector. RESULTS: Samples are tested according to the procedure of ultrasensitive chromosomal aneuploidy detector (UCAD). We excluded 2 samples with failed quality control, 1 patient lost to follow-up and 6 dead in the perioperative period. The final 91 patients were admitted for the following analyses. Thirteen (14.3%) patients with higher CIN score had worse overall survival (OS) than those with lower CIN score. The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses. Patients with high human herpesvirus (HHV)-7 and HHV-5 DNA reads exhibited worse OS. Furthermore, we classified 91 patients into 3 subtypes. Patients with higher CIN score (n =13) had the worst prognosis (median OS 6.9 mon); patients with lower CIN score but with HHV-7/5 DNA load (n = 24) had worse prognosis (median OS 10.6 mon); while patients with lower CIN score and HHV-7/5 DNA negative (n = 54) had the best prognosis (median OS 21.1 mon). CONCLUSIONS: High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer. The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.

[Characteristics of pulmonary function in infants and young children with pertussis-like coughing].

OBJECTIVE: To study the characteristics of pulmonary function in children with pertussis-like coughing caused by different pathogen infections. METHODS: The data on etiology and tidal breathing pulmonary function were collected from 95 hospitalized infants and young children with pertussis-like coughing. The tidal breathing pulmonary function was compared between these children and 67 healthy children. According to the type of pathogen, the children with pertussis-like coughing were classified to 6 groups: pertussis (n=17), viral infection (n=23), tuberculosis infection (n=6), Mycoplasma infection (n=9), other bacterial infection (n=8), and unknown pathogen (n=32). RESULTS: Among the 95 children with pertussis-like coughing, 15 (16%) had mild obstructive ventilatory dysfunction, 30 (32%) had moderate obstructive ventilatory dysfunction, and 22 (23%) had severe obstructive ventilatory dysfunction. Compared with the normal control group, the children with pertussis-like coughing had significant reductions in inspiratory-to-expiratory time ratio, ratio of time to peak tidal expiratory flow to total expiratory time (tPF%tE), and ratio of volume to peak tidal expiratory flow to total expiratory volume (vPF%vE) (P<0.05). The tuberculosis infection and Mycoplasma infection groups had a significantly lower tidal volume than the normal control group (P<0.05). All pathogen infection groups except the tuberculosis infection group had significantly lower tPF%tE and vPF%vE than the normal control group (P<0.05). The pertussis group had significantly lower tPF%tE and vPF%vE than the other infection groups (P<0.05). CONCLUSIONS: Most of children with pertussis-like coughing have abnormal pulmonary functions. The children with Bordetella pertussis infection have the most severe pulmonary function impairment. Tidal breathing pulmonary function test may provide a reference for pathogen analysis of children with pertussis-like coughing.

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma.

BACKGROUND: Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma. METHODS: Thirty-seven patients with 39 gallbladder adenomatoid lesions (maximal diameter ≥10 mm and without metastasis) were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individually among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. RESULTS: Adenoma lesions showed iso-echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and synchronous-out" contrast enhancement pattern and homogeneous at peak-time enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The characteristic of the eccentric enhancement pattern had the highest diagnostic ability in differentiating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively. CONCLUSIONS: CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps (≥10 mm in diameter). Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

Normal value of virtual touch imaging quantification elastography in measurements of pancreas.

OBJECTIVE: To evaluate pancreatic tissue stiffness and provide a normal reference shear wave velocity (SWV) value of pancreas from healthy adults by Virtual Touch Imaging Quantification (VTIQ) measurements. METHODS: Healthy adult volunteers without known history of hepatobiliary or pancreatic diseases were included. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used. SWV values were measured at the cephalic, corpus and tail of pancreas and replicated different operators' obtained data. Subgroups were classified according to the volunteers' gender, age, body mass index (BMI), depth of measurements and the echogenicity of the pancreas. RESULTS: From February 2023 to July 2023, 33 healthy adult volunteers were included. The success rate of VTIQ measurements in cephalic, corpus and tail regions was 90.90 % (30/33), 96.97 % (32/33) and 90.90 % (30/33) respectively. The color elastograms of healthy adult pancreas showed uniform blue or simultaneously blue and green. The average SWV values were 0.97±0.26 m/s for cephalic, 0.91±0.24 m/s for corpus and 0.97±0.25 m/s for pancreatic tail respectively (P = 0.198). The mean SWV values of pancreas did not show significant difference with age, gender or depth (P >  0.05). BMI was an influence factor in the measurements of SWV values of cephalic and tail of pancreas (P <  0.05). Pancreas with hyperechoic parenchyma showed higher mean SWV values (P <  0.05). The intra-observer (ICC = 0.938 [95% CI: 0.869-0.971]) and the inter-observer (ICC = 0.887 [95% CI: 0.760-0.947]) agreements of VTIQ measurements were excellent. CONCLUSIONS: The mean SWV value of the pancreas in healthy adults was 0.96±0.20 m/s (range: 0.52-1.74 m/s). VTIQ technique can be used in pancreatic stiffness measurements with good reliability.

Contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features for characterizing serous microcystic adenomas (SMAs): In comparison to pancreatic neuroendocrine tumors (pNETs).

Objectives: Serous microcystic adenoma (SMA), a primary benign pancreatic tumor which can be clinically followed-up instead of undergoing surgery, are sometimes mis-distinguished as pancreatic neuroendocrine tumor (pNET) in regular preoperative imaging examinations. This study aimed to analyze preoperative contrast-enhanced ultrasound (CEUS) and shear wave elastography (SWE) features of SMAs in comparison to pNETs. Material and methods: In this retrospective study, patients with imaging-diagnosed pancreatic lesions were screened between October 2020 to October 2022 (ethical approval No. B2020-309R). Performing by a Siemens Sequoia (Siemens Medical Solutions, Mountain View, CA, USA) equipped with a 5C-1 curved array transducer (3.0-4.5 MHz), CEUS examination was conducted to observe the microvascular perfusion patterns of pancreatic lesions in arterial phase, venous/late phases (VLP) using SonoVue® (Bracco Imaging Spa, Milan, Italy) as the contrast agent. Virtual touch tissue imaging and quantification (VTIQ) - SWE was used to measure the shear wave velocity (SWV, m/s) value to represent the quantitative stiffness of pancreatic lesions. Multivariate logistic regression was performed to analyze potential ultrasound and clinical features in discriminating SMAs and pNETs. Results: Finally, 30 SMA and 40 pNET patients were included. All pancreatic lesions were pathologically proven via biopsy or surgery. During the arterial phase of CEUS, most SMAs and pNETs showed iso- or hyperenhancement (29/30, 97 % and 31/40, 78 %), with a specific early honeycomb enhancement pattern appeared in 14/30 (47 %) SMA lesions. During the VLP, while most of the SMA lesions remained iso- or hyperenhancement (25/30, 83 %), nearly half of the pNET lesions revealed an attenuated hypoenhancement (17/40, 43 %). The proportion of hypoenhancement pattern during the VLP of CEUS differed significantly between SMAs and pNETs (P = 0.021). The measured SWV value of SMAs was significantly higher than pNETs (2.04 ± 0.70 m/s versus 1.42 ± 0.44 m/s, P = 0.002). Taking a SWV value > 1.83 m/s as a cutoff in differentiating SMAs and pNETs, the area under the receiver operating characteristic curve (AUROC) was 0.825, with sensitivity, specificity and likelihood ratio (+) of 85.71 %, 72.73 % and 3.143, respectively. Multivariate logistic regression revealed that SWV value (m/s) of the pancreatic lesion was an independent variable in discriminating SMA and pNET. Conclusion: By comprehensively evaluating CEUS patterns and SWE features, SMA and pNET may be well differentiated before the operation. While SMA typically presents as harder lesion in VTIQ-SWE, exhibiting a specific honeycomb hyperenhancement pattern during the arterial phase of CEUS, pNET is characterized by relative softness, occasionally displaying a wash-out pattern during the VLP of CEUS.

Review on Pediatric Malignant Focal Liver Lesions with Imaging Evaluation: Part I.

Malignant focal liver lesions (FLLs) are commonly reported in adults but rarely seen in the pediatric population. Due to the rarity, the understanding of these diseases is still very limited. In children, most malignant FLLs are congenital. It is very important to choose appropriate imaging examination concerning various factors. This paper will outline common pediatric malignant FLLs, including hepatoblastoma, hepatocellular carcinoma, and cholangiocarcinoma and discuss them against the background of the latest knowledge on comparable/similar tumors in adults. Medical imaging features are of vital importance for the non-invasive diagnosis and follow-up of treatment of FLLs in pediatric patients. The use of CEUS in pediatric patients for characterizing those FLLs that remain indeterminate on conventional B mode ultrasounds may be an effective option in the future and has great potential to be integrated into imaging algorithms without the risk of exposure to ionizing radiation.

Review on Pediatric Malignant Focal Liver Lesions with Imaging Evaluation: Part II.

Malignant focal liver lesions (FLLs) represent various kinds of epithelial and mesenchymal tumors. In pediatric patients, the understanding of pediatric liver diseases and associated imaging manifestations is essential for making accurate diagnosis and differential diagnosis. This paper will discuss the latest knowledge of the common pediatric malignant FLLs, including undifferentiated embryonal sarcoma, rhabdomyosarcoma, epithelioid hemangioendothelioma, angiosarcoma, and malignant rhabdoid tumor. Medical imaging features are not only helpful for clinical diagnosis, but can also be useful in the evaluation and follow-up of pre- and post-treatment. The future perspectives of contrast-enhanced ultrasound (CEUS) enhancement patterns of FLLs in pediatric patients are also mentioned.

Baseline and contrast-enhanced ultrasound features of hepatic epithelioid angiomyolipoma.

BACKGROUND: Recurrence or metastasis after surgery had been reported in hepatic epithelioid angiomylipoma (epi-AML). Most hepatic epi-AMLs were misdiagnosed with hepatocellular carcinoma or other hepatic tumors before surgery. OBJECTIVE: To describe the baseline and contrast-enhanced ultrasound (CEUS) features of hepatic epi-AMLs and to explore the potential ultrasonic features for prognosis. METHODS: The retrospective study enrolled 67 patients (56 females, 11 males) with 67 pathologically confirmed hepatic epi-AML lesions. All the lesions were examined by baseline ultrasound and 42 lesions were examined using CEUS with SonoVue (Bracco, Milan, Italy) before surgery. RESULTS: Baseline ultrasound features of hepatic epi-AMLs included heterogeneous echo (86.6%), well-defined border (68.7%), hypoecho (64.2%), regular morphology (62.7%), peripheral-tumor arc-shaped or ring-like vessels (53.7%), and low value of resistive index (0.51±0.08). CEUS features of hepatic epi-AMLs included arterial phase hyper-enhancement with smooth and well-defined margin (100%), peripheral-tumor ring-like vessels (57.1%), and intra-tumor vessels (52.4%). Some CEUS features, including arterial phase heterogeneously tortuous filling, intra-tumor vessels and peripheral-tumor ring-like vessels were more commonly found in hepatic epi-AMLs of uncertain malignant potential/malignant than in benign hepatic epi-AMLs (p < 0.05). CONCLUSIONS: Baseline ultrasound and CEUS features may be useful in diagnosis of hepatic epi-AML, and some CEUS features may be indicative of its malignant potential.

Prediction of Histological Grades and Ki-67 Expression of Hepatocellular Carcinoma Based on Sonazoid Contrast Enhanced Ultrasound Radiomics Signatures.

Objectives: Histopathological tumor grade and Ki-67 expression level are key aspects concerning the prognosis of patients with hepatocellular carcinoma (HCC) lesions. The aim of this study was to investigate whether the radiomics model derived from Sonazoid contrast-enhanced (S-CEUS) images could predict histological grades and Ki-67 expression of HCC lesions. Methods: This prospective study included 101 (training cohort: n = 71; validation cohort: n = 30) patients with surgical resection and histopathologically confirmed HCC lesions. Radiomics features were extracted from the B mode and Kupffer phase of S-CEUS images. Maximum relevance minimum redundancy (MRMR) and least absolute shrinkage and selection operator (LASSO) were used for feature selection, and a stepwise multivariate logit regression model was trained for prediction. Model accuracy, sensitivity, and specificity in both training and testing datasets were used to evaluate performance. Results: The prediction model derived from Kupffer phase images (CE-model) displayed a significantly better performance in the prediction of stage III HCC patients, with an area under the receiver operating characteristic curve (AUROC) of 0.908 in the training dataset and 0.792 in the testing set. The CE-model demonstrated generalizability in identifying HCC patients with elevated Ki-67 expression (>10%) with a training AUROC of 0.873 and testing AUROC of 0.768, with noticeably higher specificity of 92.3% and 80.0% in training and testing datasets, respectively. Conclusions: The radiomics model constructed from the Kupffer phase of S-CEUS images has the potential for predicting Ki-67 expression and histological stages in patients with HCC.

Preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma based on kupffer phase radiomics features of sonazoid contrast-enhanced ultrasound (SCEUS): A prospective study.

OBJECTIVES: To establish and to evaluate a machine learning radiomics model based on grayscale and Sonazoid contrast enhanced ultrasound images for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. METHODS: 100 cases of histopathological confirmed HCC lesions were prospectively included. Regions of interest were segmented on both grayscale and Kupffer phase of Sonazoid contrast enhanced (CEUS) images. Radiomic features were extracted from tumor region and region containing 5 mm of peritumoral liver tissues. Maximum relevance minimum redundancy (MRMR) and Least Absolute Shrinkage and Selection Operator (LASSO) were used for feature selection and Support Vector Machine (SVM) classifier was trained for radiomic signature calculation. Radiomic signatures were incorporated with clinical variables using univariate-multivariate logistic regression for the final prediction of MVI. Receiver operating characteristic curves, calibration curves and decision curve analysis were used to evaluate model's predictive performance of MVI. RESULTS: Age were the only clinical variable significantly associated with MVI. Radiomic signature derived from Kupffer phase images of peritumoral liver tissues (kupfferPT) displayed a significantly better performance with an area under the receiver operating characteristic curve (AUROC) of 0.800 (95% confidence interval: 0.667, 0.834), the final prediction model using age and kupfferPT achieved an AUROC of 0.804 (95% CI: 0.723, 0.878), accuracy of 75.0%, sensitivity of 87.5% and specificity of 69.1%. CONCLUSIONS: Radiomic model based on Kupffer phase ultrasound images of tissue adjacent to HCC lesions showed an observable better predictive value compared to grayscale images and has potential value to facilitate preoperative identification of HCC patients at higher risk of MVI.

[Quantitative evaluation of contrast-enhanced ultrasound in the early diagnosis of acute renal failure of rabbits].

OBJECTIVE: To evaluate the early diagnostic value of contrast-enhanced ultrasound (CEUS) in acute renal failure (ARF) of rabbit. METHODS: The rabbit model of ARF was established by intramuscular injection of 50% glycerin (12 ml/kg) into the hind legs of 18 New Zealand rabbits. CEUS was performed for both kidneys before injection and 6 hours after the injection. The slope rate of ascending curve (A), the slope rate of descending curve (alpha), area under curve (AUC), derived peak intensity (DPI), and time to peak (TTP) were measured in renal cortex of rabbits using Q-lab software package. Blood serum urea nitrogen (BUN) and serum creatinine (SCr) were measured. RESULTS: The values of A and alpha before the injection of glycerin were (3.07 +/- 1.83) dB/s and (0.19 +/- 0.15)/s, respectively, which were significantly higher than the values after injection [ (2.76 +/- 1.31) dB/s and (0.09 +/- 0.02)/s, respectively] (P < 0.05). The values of AUC and TTP before the injection of glycerin were (137.4 +/- 68.4) dB s and (6.33 +/- 3.71) s, which were significantly lower than the values after injection [(309.5 +/- 88.9) dB s and (8.61 +/- 3.97) s, respectively] (P < 0.01). No significant change of DPI, BUN or SCr was found. CONCLUSIONS: CEUS can precisely display the hemodynamic change of ARF model of rabbit in the early stage, with superior sensitivity than BUN and SCr. It may be a promising imaging method for the early diagnosis of ARF.

Quantitative evaluation of acute renal failure in rabbits with contrast-enhanced ultrasound.

BACKGROUND: Assessment of perfusion in the early period of acute renal failure (ARF) is important, and can not be made by conventional ultrasound. The aim of this study was to prospectively test in a rabbit ARF model whether real-time contrast-enhanced ultrasound (CEUS) can quantitatively evaluate the hemodynamic changes of renal cortex in the early period. METHODS: The model of ARF was induced in 30 healthy New Zealand white rabbits (2.5 - 3.0 kg), by intramuscular injection of 50% glycerin solution (12 ml/kg). CEUS were performed on right kidneys before, 6 and 24 hours after glycerin injection. CEUS quantitative indexes were measured in renal cortex using QLAB software. Comparisons between different stages were performed using paired t test. The sensitivity of CEUS in diagnosing ARF was compared with blood serum urea nitrogen (BUN), serum creatinine (SCr) level and color Doppler flow imaging (CDFI). RESULTS: Among quantitative indexes, time to peak (TTP) and area under curve (AUC) increased significantly from (5.86 ± 2.57) seconds and (124.4 ± 46.7) dB·s before glycerin injection to (7.66 ± 2.05) seconds and (288.1 ± 64.9) dB·s 6 hours after injection (P < 0.05). Slope rate of ascending curve (A) and descending curve (a) decreased slightly from (3.00 ± 1.22) dB/s and (0.19 ± 0.15) 1/s to (2.80 ± 1.45) dB·s and (0.09 ± 0.02) 1/s (P < 0.05). Twenty-four hours later, only AUC increased significantly from (124.4 ± 46.7) dB·s to (466.2 ± 52.2) dB·s (P < 0.05). CONCLUSION: Quantitative indexes of CEUS might be useful in predicting the hemodynamic changes of renal cortex in the early six hours of ARF model.

Ultrasonography of sclerosing angiomatoid nodular transformation in the spleen.

We report three rare cases of sclerosing angiomatoid nodular transformation (SANT) in the spleen. We compared the conventional and contrast-enhanced ultrasonographic appearance. The conventional sonographic examinations exhibited solitary lesions without common respects, while contrast-enhanced ultrasonography (CEUS) revealed nodular appearance mimicking its pathologic characteristics. It suggests that CEUS can provide morphologic information for diagnosing SANT.