Liver Capsule Research Articles

Liver Ultrasound Histotripsy: Novel Analysis of the Histotripsy Site Cell Constituents with Implications for Histotripsy Application in Cell Transplantation and Cancer Therapy.

Introduction: Allogenic hepatocyte transplantation is an attractive alternative to whole-organ transplantation, particularly for the treatment of metabolic disorders and acute liver failure. However, the shortage of human donor organs for cell isolation, the low cell yield from decellularisation regimes, and low engraftment rates from portal administration of donor cells have restricted its clinical application. Using ultrasound histotripsy to provide a nidus in the liver for direct cell transplantation offers a new approach to overcoming key limitations in current cell therapy. We have analysed the liver cavity constituents to assess their potential as a site for cell delivery and implantation. Methods: Using human organ retrieval techniques, pig livers were collected from the abattoir and transported in ice-cold storage to the laboratory. Following 2 h of cold storage, the livers were flushed with organ preservation solution and placed on an organ perfusion circuit to maintain viability. Organs were perfused with Soltran™ organ preservation solution via the portal vein at a temperature of 24-30 °C. The perfusion circuit was oxygenated through equilibration with room air. Perfused livers (n=5) were subjected to ultrasound histotripsy, producing a total of 130 lesions. Lesions were generated by applying 50 pulses at 1 Hz pulse repetition frequency and 1% duty cycle using a single element 2 MHz bowl-shaped transducer (Sonic Concepts, H-148). Following histotripsy, a focal liver lesion was produced, which had a liquid centre. The fluid from each lesion was aspirated and cultured in medium (RPMI) at 37 °C in an incubator. Cell cultures were analysed at 1 and 7 days for cell viability and a live-dead assay was performed. The histotripsy sites were excised following aspiration and H&E staining was used to characterise the liver lesions. Cell morphology was determined by histology. Results: Histotripsy created a subcapsular lesion (~5 mm below the liver capsule; size ranging from 3 to 5 mm), which contained a suspension of cells. On average, 61×104 cells per mL were isolated. Hepatocytes were present in the aspirate, were viable at 24 h post isolation and remained viable in culture for up to 1 week, as determined by phalloidin/DAPI cell viability stains. Cultures up to 21 days revealed metabolically active live hepatocyte. Live-dead assays confirmed hepatocyte viability at 1 week (Day 1: 12% to Day 7: 45% live cells; p < 0.0001), which retained metabolic activity and morphology, confirmed on assay and microscopy. Cell Titre-GloTM showed a peak metabolic activity at 1 week (average luminescence 24.6 RLU; p < 0.0001) post-culture compared with the control (culture medium alone), reduced to 1/3 of peak level (7.85 RLU) by day 21. Conclusions: Histotripsy of the liver allows isolation and culture of hepatocytes with a high rate of viability after 1 week in culture. Reproducing these findings using human livers may lead to wide clinical applications in cell therapy.

Extraction of Liver Capsule from High-Frequency Ultrasound Images via Drift Iterative Search Algorithm

Extraction of Liver Capsule from High-Frequency Ultrasound Images via Drift Iterative Search Algorithm

A rare case of non-treated fetal–type hepatoblastoma for five years stayed without metastases in a young boy

Hepatoblastoma is the most common malignant neoplasm of the liver in infancy. In this paper, we present a rare case of non-treated hepatoblastoma in an 18-month-old baby male who presented with an asymptomatic abdominal mass associated with elevated Alpha-fetoprotein. Contrast-enhanced CT revealed a solid mass located in the left lobe of the liver, measuring about 6 × 6 cm, and not enhancing the contrast. US-guided Tru-cut biopsy was performed which showed pure epithelial fetal-type hepatoblastoma. The parents refused neoadjuvant chemotherapy and the connection was disconnected with them because of the ongoing crisis in Syria. After five years, the patient returned with the same clinical picture. CT scan was repeated which revealed the same tumor without metastases. The decision was made to do a left hepatectomy after another confirmation with a surgical biopsy. Histopathological examination showed a multifocal pure epithelial-fetal well-differentiated type of hepatoblastoma with a favorable grade. Moreover, surgical margins and liver capsule appeared free, and the tumor was considered in Stage 1 accordingly. To this date, the boy was followed up with serial US and Alpha-fetoprotein (AFP)levels without signs of recurrence. Hepatoblastoma with pure fetal-type histology can be treated with complete surgical excision without neoadjuvant or adjuvant chemotherapy if the tumor was resected completely because this type of neoplasm is slow growing and has a good prognosis.

Microscopic changes in some organs of cats at the infectious peritonitis

The study's relevance is that pathomorphological changes in the infectious peritonitis of cats have been studied by a few authors and still need to be fully described. This paper describes the microscopic changes in the brain and spinal cord, liver, and somatic and visceral lymph nodes in cats with infectious peritonitis. The leading research method is a histological examination of sections obtained from the listed organs of cats of various ages that died from mixed (26 animals) and dry (7 animals) forms of infectious peritonitis. Sections were stained with hematoxylin and eosin according to the generally accepted method. It was found that microscopic changes in the brain and spinal cord do not depend on the form and duration of the disease. Gray and white matter are swollen, blood vessels are spasmodic, and nerve cells are in basophilia. A particularly significant swelling was found in the white matter of the spinal cord, which at the same time underwent lysis. In the liver, microscopic changes do not depend on the disease's form but are somewhat different depending on the duration of its course. In cats that were ill for less than three weeks before death, fibrinous-necrotic overlays are found on the surface of the capsule in places. Areas where mesotheliocytes of the capsule undergo metaplasia, are also seen – they acquire a cubic or columnar shape. In some places, the liver capsule is destroyed. The portal tracts are swollen and infiltrated with a small number of lymphocytes and monocytes, and the walls of the arteries of the hepatic triad are necrotized. Foci of tissue necrosis of the portal tract are also detected. Veins and bile ducts are not differentiated. Liver lobules are infiltrated with lymphocytes and monocytes. Cell swelling and destruction of hepatocytes were established. In animals that were ill for more than three weeks before death, in addition to the changes typical for infectious peritonitis, portal hepatitis, edema, and disorganization of liver lobules, hydropic dystrophy, destruction, and necrosis of hepatocytes were found. Changes in the lymph nodes are individual and do not depend on the form and duration of the course of the disease. However, in all cases of the registry, there were foci of necrosis in the central part of lymphoid nodules and the paracortical zone.

Ultrasensitive US Microvessel Imaging of Hepatic Microcirculation in the Cirrhotic Rat Liver.

Background Liver microcirculation dysfunction plays a vital role in the occurrence and development of liver diseases, and thus, there is a clinical need for in vivo, noninvasive, and quantitative evaluation of liver microcirculation. Purpose To evaluate the feasibility of ultrasensitive US microvessel imaging (UMI) in the visualization and quantification of hepatic microvessels in healthy and cirrhotic rats. Materials and Methods In vivo studies were performed to image hepatic microvasculature by means of laparotomy in Sprague-Dawley rats (five cirrhotic and five control rats). In vivo conventional power Doppler US and ex vivo micro-CT were performed for comparison. UMI-based quantifications of perfusion, tortuosity, and integrity of microvessels were compared between the control and cirrhotic groups by using the Wilcoxon test. Spearman correlations between quantification parameters and pathologic fibrosis, perfusion function, and hepatic hypoxia were evaluated. Results UMI helped detect minute vessels below the liver capsule, as compared with conventional power Doppler US and micro-CT. With use of UMI, lower perfusion indicated by vessel density (median, 22% [IQR, 20%-28%] vs 41% [IQR, 37%-46%]; P = .008) and fractional moving blood volume (FMBV) (median, 6.4% [IQR, 4.8%-8.6%] vs 13% [IQR, 12%-14%]; P = .008) and higher tortuosity indicated by the sum of angles metric (SOAM) (median, 3.0 [IQR, 2.9-3.0] vs 2.7 [IQR, 2.6-2.9]; P = .008) were demonstrated in the cirrhotic rat group compared with the control group. Vessel density (r = 0.85, P = .003), FMBV (r = 0.86, P = .002), and median SOAM (r = -0.83, P = .003) showed strong correlations with pathologically derived vessel density labeled with dextran. Vessel density (r = -0.81, P = .005) and median SOAM (r = 0.87, P = .001) also showed strong correlations with hepatic tissue hypoxia. Conclusion Contrast-free ultrasensitive US microvessel imaging provided noninvasive in vivo imaging and quantification of hepatic microvessels in cirrhotic rat liver. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Fetzer in this issue.

MRI features of lymphoepithelioma-like intrahepatic cholangiocarcinoma

Objective: To investigate the MRI manifestations of lymphoepithelioma-like intrahep cholangiocarcinoma (LEL-ICC). Methods: MR images of 26 cases with LEL-ICC confirmed pathologically at Zhongshan Hospital Affiliated with Fudan University between March 2011 and March 2021 were retrospectively analyzed. The number, location, size, morphology, edges of lesions, non-scan signal intensity, cystic necrosis, enhancement mode, peak, and capsule, vascular invasion, lymph node metastasis, and other MR images were included for analysis. The apparent diffusion coefficient (ADC) value of the lesion and the surrounding normal liver parenchyma were measured. A paired-sample t-test was used to statistically analyze the measurement data. Results: All 26 cases of LEL-ICC had solitary lesions. Mass-type LEL-ICC was the most common [n=23, lesion size (4.02±2.32) cm] with distribution along the bile duct [n=3, lesion size (7.23±1.40 cm)]. Among the 23 lesions of mass type LEL-ICC, most of the lesions were close to the liver capsule (n=20), round (n=22), clearly bordered (n=13), and cystic necrosis (n=22). In the three lesions of LEL-ICC distributed along the bile duct, most of them were close to the liver capsule (n=2), irregular (n=3), blurred edges (n=3), and cystic necrosis (n=3). All 26 lesions showed a low/slightly low signal on T1WI, a high/slightly high signal on T2WI, and a slightly high or high signal on DWI. Three lesions showed fast-in and fast-out enhancement modes, and 23 lesions showed continuous enhancement. Twenty-five lesions showed peak enhancement in the arterial phase, and one lesion appeared in the delayed phase. The ADC value of 26 lesions and adjacent normal liver parenchyma was (1.112±0.274)×10-3 mm2/s and (1.482±0.346)×10-3 mm2/s, respectively, and the both had a statistically significant difference (P<0.05). Conclusion: Certain manifestations of LEL-ICC in magnetic resonance imaging are advantageous for diagnosis and differential diagnosis.

Prognostic analysis of hepatocellular carcinoma with macrovascular invasion after liver resection and a successful case of conversion therapy.

Macrovascular invasion (MVI) is an important factor leading to poor prognosis in hepatocellular carcinoma (HCC). Liver resection may offer favorable prognosis for selected patients with HCC. This study aimed to analyze the prognostic factors of HCC with MVI after liver resection as well as demonstrate a case of conversion therapy in an HCC patient with portal vein tumor thrombus (PVTT). A total of 168 HCC patients with MVI who underwent primary liver resection at the Affiliated Hospital of Qingdao University between January 2013 and October 2021 were enrolled in the study. Clinicopathological data were collected retrospectively. Univariate and multivariate regression analyses were used to investigate the risk factors influencing recurrence and overall survival. Additionally, conversion therapy with drug-eluting bead transarterial chemoembolization (D-TACE), and sorafenib plus sintilimab treatment was performed in an HCC patient with PVTT. Among the 168 patients with HCC, 11 were diagnosed with hepatic vein tumor thrombosis, and the rest were diagnosed with PVTT. The 1-year disease-free survival rate was 37.5%, and the 3-year overall survival rate was 52.7%. Univariate and multivariate regression analyses revealed that HBsAg positivity, alpha-fetoprotein (AFP) level ≥400 ng/ml, liver capsule invasion, and tumor number ≥2 were independent prognostic factors for tumor recurrence, whereas HBsAg positivity was an independent risk factor for overall survival. Postoperative prophylactic medication did not significantly prolong the recurrence time. The median survival time (MST) after tumor recurrence was 13.4 months. In the patient treated with conversion therapy, the tumor gradually shrank and was eventually surgically resected. This study identified the independent prognostic and risk factors associated with recurrence and overall survival in HCC patients with MVI. Additionally, we successfully performed conversion therapy in an HCC patient with PVTT. The findings would help identify patients at high risk of recurrence and indicate that combined therapy may prolong the survival of HCC patients with PVTT.

Effectiveness of ultrasound-guided percutaneous transhepatic biliary drainage to reduce radiation exposure: A single-center experience.

Percutaneous transhepatic biliary drainage (PTBD) has been an effective treatment to access the biliary tree, especially in case of endoscopically inaccessible biliary tree. In general, PTBD techniques are divided into two methods: fluoroscopy-guided PTBD and ultrasound (US)-guided PTBD. This study aimed to evaluate the effectiveness of US-guided PTBD, focusing on radiation exposure according to intrahepatic duct (IHD) dilatation degree, differences between right- and left-sided approaches and differences between benign and malignant biliary stenosis/obstruction. We evaluated technical success, clinical success, procedural data (the number of liver capsule punctures, procedural time, fluoroscopy time and radiation dose), and procedure-related complications. During the study period, a total of 123 patients with biliary stenosis/obstruction or bile leakage were initially eligible. We excluded 76 patients treated with only ERCP or initially treated with ERCP followed underwent PTBD insertion. Finally, a total of 50 procedures were performed in 47 patients. Of the 47 patients, 8 patients had anatomical alteration due to previous surgery, 6 patients refused ERCP, and 3 patients failed ERCP. For the remaining 30 patients, PTBD was performed on weekend or at night, 11 of whom had poor general condition, 10 patients underwent ERCP 3 to 4 days later after PTBD insertion, 6 patients improved after PTBD insertion without ERCP, 1 patient died, and 1 patient was referred to other hospital. Remaining 1 patient underwent surgery due to Mirizzi syndrome. All procedures were performed by two interventional radiologists. Technical success rate was 100%, clinical success was 94%, and the complication rate was 10%. Fluoroscopy time and the reported radiation dose were significantly lower in patients with dilated bile ducts than in those with non-dilated bile ducts, when biliary puncture under US guidance was performed initially. However, even in patients with non-dilated bile ducts undergoing initial trials of biliary puncture under US guidance, the fluoroscopy time and the reported radiation dose were low, based on current studies. No statistical significant differences were observed in terms of technical and dosimetry results according to right-sided and left-sided procedures and benign and malignant biliary stenosis/obstruction. Thus, US-guided PTBD was found to be a safe and effective technique that significantly reduced fluoroscopy time and radiation doses.

Pathomorphological characteristics of hemophilic polyserositis of pigs

It is difficult to differentiate the disease by clinical signs; therefore, the main criteria for diagnosing hemophilic polyserositis should be considered pathological changes characteristic of the disease. Piglets are aged 30–60 days are most often affected. On average, pigs can die five hours after the manifestation of clinical signs. The autopsy results have revealed severe polyserositis, fibrinous layering around the lungs and heart, swelling of the liver with fibrinous deposition, and intestinal epithelium overloaded with fibrin pellicle. The autopsy of the dead piglets has shown the changes, characterized by massive overlays of fibrin pellicles and threads on the surface of the costal and pulmonary pleura, diaphragm, peritoneum, omentum, the serous membrane of the intestine, as well as the liver capsule. In the thoracic and abdominal cavities and pericardium, a significant accumulation of straw-yellow exudate with abundant fibrin threads has been revealed. Rib and lung pleura were covered with fibrinous overlays of gray-white and gray-yellow color. When the overlays were removed, swelling, dullness, matting, and sometimes bluishness of the pleura with a grayish tint were found. In several cases, fibrinous layering was of considerable thickness, which caused the fusion of serous sheets. Macroscopically, the bronchial and mediastinal lymph nodes were enlarged, juicy, grayish, or grayish-red in color; sometimes, dotted hemorrhages were observed in them. A cloudy, reddish liquid was flowing from the surface of their cut. At the pathological examination, the lungs were enlarged in volume, dense in consistency, and dark red. Interstitial pneumonia was observed, and in some cases, fibrinous inflammation of the pleura and foci of atelectasis alternated with small emphysema areas. The liver was enlarged and flabby; the lobular structure was weakly expressed. The cut surface was dull, gray-red, and sometimes red-brown. The vessels of the small intestine were injected. That is, fibrinous polysterositis, arthritis, and meningoencephalitis are characteristic of the pathology. Therefore, from the pathomorphological changes, it can be assumed that the dissemination of the causative agent of hemophilic polyserositis occurs in a short time. In the acute stage of the disease and fatal cases, the pathogen is often found in the joints, serous membranes, spleen, liver, lungs, pericardium, and brain. The localization of the pathogen is specific – it is the serous membranes. The penetration of the causative agent into the brain can indirectly judge the relatively high invasive properties of the microorganism.

Feasibility of ultrasonographic hepatic parenchymal attenuation imaging in healthy Beagles.

To investigate the clinical feasibility of attenuation imaging of the hepatic parenchyma in healthy dogs, identify technical factors that influence measured attenuation coefficients, and determine intraobserver repeatability of measurements. 10 healthy Beagles. Attenuation coefficients were calculated for various measurement sites (left vs central division of the liver), scanning planes (transverse vs sagittal plane), scanning depths (10 to 20 mm vs 20 to 30 mm), scanning approaches (intercostal vs subcostal approach), and breathing conditions (free breathing vs breath holding at end expiration). Intraoperator intraday and interday reliability was assessed by computing intraclass correlation coefficients. Attenuation coefficients were not influenced significantly by scanning plane (P = .120 to 1.000), measurement site (P = .292 to .848), or breathing condition (P = .166). However, coefficients were significantly (P < .01) less with deeper scanning depths and significantly (P < .05) more for the subcostal approach than the intercostal approach. The intraday and interday intraclass correlation coefficients showed good repeatability (0.799 and 0.771, respectively), regardless of the scanning plane and measurement site. Scanning the central division of the liver with the right intercostal approach at a depth of 10 to 20 mm from the liver capsule yielded good reliability. Attenuation imaging was a feasible technique for evaluating the hepatic parenchyma in healthy dogs with good repeatability. Measured attenuation coefficients were not affected by the scanning plane, measurement site, or breathing condition.

Effectuality study of a 3D motion correction algorithm in C-arm CTs of severely impaired image quality during transarterial chemoembolization

BackgroundTo evaluate effectivity of a 3D-motion correction algorithm in C-Arm CTs (CACT) with limited image quality (IQ) during transarterial chemoembolization (TACE).MethodsFrom 1/2015–5/2021, 644 CACTs were performed in patients during TACE. Of these, 27 CACTs in 26 patients (18 m, 8f; 69.7 years ± 10.7 SD) of limited IQ were included. Post-processing of the original raw-data sets (CACTOrg) included application of a 3D-motion correction algorithm and bone segmentation (CACTMC_no_bone). Four radiologists (R1-4) compared the images by choosing their preferred dataset and recommending repeat acquisition in case of severe IQ-impairment. R1,2 performed additional grading of intrahepatic vessel visualization, presence/extent of movement artifacts, and overall IQ.ResultsR1,2 demonstrated excellent interobserver agreement for overall IQ (ICC 0.79,p < 0.01) and the five-point vessel visualization scale before and after post-processing of the datasets (ICC 0.78,p < 0.01). Post-processing caused significant improvement, with overall IQ improving from 2.63 (CACTOrg) to 1.39 (CACTMC_no_bone;p < 0.01) and a decrease in the mean distance of identifiable, subcapsular vessels to the liver capsule by 4 mm (p < 0.01). This proved especially true for datasets with low parenchymal and high hepatic artery contrast. A good interobserver agreement (ICC = 0.73) was recorded concerning the presence of motion artifacts, with significantly less discernible motion after post-processing (CACTOrg:1.31 ± 1.67, CACTMC_no_bone:1.00 ± 1.34, p < 0.01). Of the 27 datasets, ≥ 23 CACTMC_no_bone were preferred, with identical datasets chosen by the readers to show benefit from the algorithm.ConclusionApplication of a 3D-motion correction algorithm significantly improved IQ in diagnostically limited CACTs during TACE, with the potential to decrease repeat acquisitions.

Probiotic Supplementation Suppresses Tumor Growth in an Experimental Colorectal Cancer Liver Metastasis Model.

Colorectal cancer (CRC) ranks third in incidence and second in mortality of all cancers worldwide. At the time of primary diagnosis, around 20% of patients already have metastatic CRC and only around 20% are candidates for radical resection. Thus, most of the patients have to undergo chemotherapy (CTx). Due to chemoresistance and side effects, novel treatment additives are crucial for controlling the disease and prolonging patient survival. The aim of this study was to evaluate probiotic supplementation and its antitumorigenic effects in an experimental CRC liver metastasis model. Six-week-old male Wistar rats received either a multispecies probiotic (1.2 × 109 CFU/daily) or placebo mixture. On day 14 of the experiment, rat CRC cells (CC531) were implanted under the liver capsule later treated by FOLFOX CTx. Change in tumor volume was measured by performing micro computed tomography (micro-CT) scanning on experimental days 28 and 34. Additionally, immunohistochemical staining with anti-MPO, anti-Ki67, and anti-CD31 were performed. Tumor apoptosis was evaluated using TUNEL staining. Micro-CT image analysis indicates that probiotic supplementation significantly inhibits tumor growth. No synergistic effects between probiotic supplementation and FOLFOX CTx was observed. Reduced tumor volume was achieved by inhibiting angiogenesis, as tumor microvascular density was significantly lower in rats receiving probiotic supplementation. This study shows that a multispecies probiotic mixture significantly reduces angiogenesis and inhibits CRC liver metastasis growth in an experimental rat model.

Development of a prognostic score for recommended transarterial chemoembolization candidates with spontaneous rupture of hepatocellular carcinoma.

Although transarterial chemoembolization (TACE) has been widely used for treating the spontaneous rupture of hepatocellular carcinoma (HCC), no existing model exists for predicting survival. The aim of this study was thus to develop and validate a nomogram for estimating the prognosis in patients with ruptured HCC upon undergoing TACE treatment. This study included 55 patients with spontaneously ruptured HCC who underwent TACE treatment between January 2015 and April 2019. The diagnosis of spontaneous HCC rupture was based on the disruption of the peritumoral liver capsule with surrounding fluid in the perihepatic region. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. The median overall survival (OS) was 6.4 months, with 6-month and 1-year survival rates of 52.7% and 41.8%, respectively. In the univariate analysis, the size of the largest tumor, total bilirubin (TBIL) levels, and aspartate aminotransferase (AST) levels were associated with the OS of patients. Multivariate analysis suggested that TBIL levels (HR =0.358, P=0.036) and diameter of the largest tumor (HR =1.012, P=0.044) were independent prognostic factors for predicting the OS. Based on these variables, we developed and validated a nomogram for the risk stratification of HCC rupture after TACE treatment for individual patients. According to the nomogram risk assessment, we were able to evaluate the approximate 1- and 2-year survival rates based on patients' tumor diameter and TBIL level after TACE treatment of ruptured HCC. The concordance index for the OS prediction was 0.748 (95% CI: 0.691-0.805). This newly developed nomogram represents an intuitive tool for predicting the OS of patients with ruptured HCC. This study indicated that TBIL levels and diameter of the largest tumor were independent prognostic factors for predicting the OS of ruptured HCC. This study may help maximize favorable TACE treatment outcomes.

The effect of the skin-liver capsule distance on the accuracy of ultrasound diagnosis for liver steatosis and fibrosis.

Transient elastography (TE) and the controlled attenuation parameter (CAP) have been used for diagnosis of liver fibrosis and steatosis. Obesity is a limiting factor to the accuracy of elastography; however, an XL probe was validated for use in obese patients. Two-dimensional shear wave elastography (2D-SWE) and attenuation imaging (ATI) have also been developed. It is unknown if obesity affects 2D-SWE/ATI values for evaluation of liver fibrosis and steatosis. We assessed the reliability of the measurement rate and the diagnostic performance of TE/CAP versus SWE/ATI. The patients (n = 85) underwent TE/CAP, 2D-SWE/ATI, and liver biopsy on the same day. They were diagnosed with chronic hepatitis based on liver biopsy. The patients were divided into three groups by skin-liver capsule distance (SCD). The reliability of the measurement rate for the M probe was lower than that for the XL probe in the group with SCD over 22.5mm. The rate achieved with 2D-SWE was high in all groups regardless of the SCD. In the assessment of the diagnostic performance, there was no difference between the area under the receiver-operating curve (AUROC) of TE compared to 2D-SWE to stratify the fibrosis stage. There was no difference in the AUROC for the stratification of the steatosis grades between CAP and ATI. The diagnostic accuracy of TE for F ≥ 3 fibrosis evaluated with the M probe and 2D-SWE was lower than that of TE evaluated with the XL probe in the group with SCD over 22.5mm. The ability of 2D-SWE to stratify fibrosis stage and steatosis grade was as good as FibroScan. However, 2D-SWE had a high reliability in the measurement rate regardless of the SCD with one probe. And the XL probe showed high diagnostic accuracy for severe fibrosis in the group with SCD over 22.5mm.

Toxic form of steatosis in dairy cows (clinical, hematological and histological data)

Steatosis is a common disease in dairy cattle, especially during the transit period. Usually, the subclinical form of hepatosis is evenly distributed in the population throughout the year: 30‐70% of cows can be affected. However, severe (toxic) steatosis is rare. The study was carried out on 505 dairy cows in the North‐West of Russia in July‐August. In the blood serum, the concentrations of the main substances were investigated, and the morphological examination of the blood was carried out. Liver samples for histological examination were collected posthumously. 47% of cows had subclinical hepatopathy, 1.78% (9 cows) ‐ a toxic form of steatosis. Clinical signs of severe hepatopathy were observed from 1 to 10 days after calving: anorexia, icterus, ventroflexia, excitability, convulsions, exophthalmos. In the blood: total protein 59.8±0.9 g/l, albumin ‐ 35.1±2.5%, total bilirubin ‐ 23.8±0.8 μmol/l, triglycerides ‐ 0.329±0.01 mmol/l, cholesterol ‐ 8.7±1.0 mmol/l, RBC 3.9±0.1*1012/l, PLT ‐ 190.1±39.8*109/l, WBC ‐ 8.36±0.75*109/l, HCT – 29.1±0.5%. Autopsy: icterus of the mucous membranes, petechiae in the kidneys, intestines, brain membrane, injection of blood vessels, enlargement of the liver and kidneys, the liver capsule breaks easily, the parenchyma is loose. Liver’s parenchyma imprint smears: staining with Saathof solution ‐ much neutral fat. Rumen: detachment of the mucous membrane. Liver: large and small vacuole diffuse fatty infiltration of hepatocytes, thickening of the portal tracts with expressed mononuclear infiltration. The liver has an ordered lobular structure, is moderately full‐blooded, the sinusoids of the liver and the Disse spaces are moderately dilated, staining with Schiff‐iodic acid according to McManus ‐ the absence of glycogen in hepatocytes. Kidneys: hyaline‐drop dystrophy of the epithelium of the renal tubules, fibrosing interstitial glomerulonephritis. Rumen: the mucous membrane forms convex structures of the main plate of various sizes and shapes, covered with multilayer squamous epithelium; there are areas of degeneration. The muscle plate was formed by separate bundles of smooth myocytes lying at the base of the papillae; individual muscle cells were found in the main plate of the papilla. The plate consisted of an inner annular and an outer longitudinal layer of smooth muscle cells, among which there were individual fibers of striated muscle tissue. The serous membrane of the rumen had a typical structure; it was represented by loose connective tissue covered with mesothelium. According to the results of this study, it was revealed that the toxic form of hepatosis is accompanied by multiple organ failure: an expressed violation of the nervous system, hypoprotein‐, dysprotein‐, hyperbilirubin‐ and anemia, large and small‐drop fatty infiltration of hepatocytes, glomerulonephritis, lesions of the rumen and intestinal wall.

THE ANATOMICAL GROUNDING OF ISOLATED LOBAR PORTOCAVAL PERFUSION OF THE LIVER

With the development of perfusion technologies in oncology, the problem of finding the optimal ways to perfusates injections has become fundamental, and in this regard, the study of the features of liver angioarchitectonics in normal and pathological conditions does not lose its relevance. The aim of our study was to study the features of the portal architectonics of the liver in relation to the possibility of its isolated lobar perfusion. Using the methods of color perfusion (n=50), separate injections of a hardening mass and the preparation of corrosive preparations (n=3), microfocus angiography (n=8), transparenchymal sections and light microscopy (n=5), 53 liver preparations explanted from non-embalmed corpses of people who died from diseases not directly related to the liver pathology. As a result of the study, it was found that the border of the zones of blood supply by the lobar branches of the portal vein after the introduction of dyes passes along the lateral border of the fourth segment of the liver in the projection of the main trunk of the middle hepatic vein, and not along the falciform ligament. According to the distribution criterion of the portal vein branches, the anatomical and surgical concepts of the interlobar boundaries of the liver do not coincide. Macro- and microscopically visible interlobar intraorgan portal anastomoses are normally absent, which indicates the relative isolation of the lobar portal blood flow of the liver. The intrahepatic bed of the proper hepatic artery has a rich architectonics in the surface layers of the parenchyma and abundantly supplies the liver capsule with blood. When performing transparenchymal sections, the boundaries of the blood supply zones of the lobar branches of the portal vein coincided with the interlobar boundaries in all cases of observation. It was also noted that the topography of the border of the blood supply zones with the lobar branches of the portal vein to match the diaphragmatic surface of the liver and in its parenchyma. Thus, it seems possible to reliably determine the indicated boundary by the pattern on the surface of the liver preparation. The relative autonomy of the channels of the lobar portal vein branches can be used to develop techniques for vascular isolation of the lobar portal blood flow in the liver to assess its selective isolated perfusion.

Conventional Ultrasound and Contrast-Enhanced Ultrasound in Hepatic Epithelioid Hemangioendothelioma: Retrospective Evaluation in 20 Cases.

ObjectivesThis study aimed to analyze the patterns of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) in 20 patients with diagnosis of hepatic epithelioid hemangioendothelioma (HEHE).MethodsTwenty patients (12 females and 8 males) with mean age of 43.6 ± 13.6 years were included in this study from January 2012 to May 2020. CUS, CEUS, computed tomography (CT) and magnetic resonance imaging (MRI) features of the twenty patients with histologically proven HEHE were retrospectively reviewed by two radiologists. The clinical manifestations and the pathological findings of all patients with HEHE are described.ResultsThere were 3 types of HEHE in imaging, including single nodular (8/20, 40%), multifocal nodular (10/20, 50%), and diffuse type (2/20, 10%). The mean size of lesions was 4.2 ± 2.6 cm. B-mode ultrasound of HEHE showed hypoechoic (15/20, 75%), heterogeneous echogenicity (4/20, 20%), or hyperechoic (1/20, 5%) lesions with regular shape (18/20, 90%) near the liver capsule (17/20, 85%), and occasionally with a halo (4/20, 20%) and calcifications (3/20, 15%). Eight out of the 20 patients also had CEUS. On CEUS, HEHE demonstrated peripheral rim-like (5/8, 62.5%), heterogeneous (2/8, 25%), or homogeneous (1/8, 12.5%) hyperenhancement in the arterial phase. All patients (8/8, 100%) showed hypoenhancement in the portal and late phase. CEUS detected more lesions than CUS in 3 patients (3/8, 37.5%). In addition, central irregular unenhanced zones were observed in 6 patients (6/8, 75%). On contrast-enhanced CT or MRI, most cases presented with capsule retraction sign and lollipop sign.ConclusionsHEHE demonstrated specific findings on ultrasound, which includes multifocal hypoechoic lesions in a subcapsular distribution with typical enhancement characteristics of malignant hepatic tumors.

First experience of transjugular intrahepatic portosystemic shunting at multidisciplinary hospital with a liver transplantation program

Aim: Analysis of the first experience of transjugular intrahepatic portosystemic shunting (TIPS) in patients with liver cirrhosis at a multidisciplinary hospital with a liver transplantation program.Materials and methods: The authors examined 206 patients with liver cirrhosis from July 2019 to June 2021, with 20 of them undergoing TIPS. The mean age of the patients was 47.59 ± 9.55 years (35–65 years). Dynamic follow-up was performed at 3, 6, 9, 12, and 18 months. As a part of the dynamic follow-up, the patients underwent laboratory tests, abdomen ultrasound examination, and computed tomography imaging enhanced by the intravenous use of contrasting agent, endoscopy, esophagogastroduodenoscopy, and encephalopathy assessment.Results: No in-hospital TIPS-associated mortality has been reported. Two patients died in the hospital at the 19th and 26th day following the surgery because of the progression of liver failure, the 6-week mortality rate was 10%. In one patient (5%), an intraoperative complication was reported, i.e., intra-abdominal hemorrhage secondary to the migration of the stent under the liver capsule. The length of hospital stay after surgery was 7.34 ± 1.89 days (5–26 days). Long-term outcomes were available for 17 patients. The duration of the dynamic follow-up was 13.23 ± 2.47 months (3–24 months) and 2 (11,7%) deaths were reported. One patient (5.8%) was diagnosed with a shunt thrombosis at 12 months after the surgery. Three patients underwent liver transplantation after TIPS. The current one-year survival rate is 90%.Conclusion: TIPS is a safe and effective procedure decreasing mortality and improving quality of life of patients awaiting cadaveric liver transplantation. TIPS should be widely implemented in multidisciplinary hospitals having liver transplant program.

CtBP1 Mediates Hypoxia-Induced Sarcomatoid Transformation in Hepatocellular Carcinoma.

BackgroundSarcomatoid hepatocellular carcinoma (sHCC), a highly aggressive subtype of hepatocellular carcinoma (HCC), mostly transforms from classical hepatocellular carcinoma (cHCC). The study intended to explore the role of C-terminal binding protein 1 (CtBP1) in sarcomatoid transformation of hepatocellular carcinoma.MethodsWestern blotting and/or immunohistochemistry were used to confirm the expression of CtBP1 and other proteins in HCC cells, xenografts and clinical tissue samples. CtBP1 shRNA-expressing lentivirus was used to infect HepG2 cells to construct CtBP1 knockdown cells. Cell migration was determined by scratch wound assays and Transwell assays. Immunofluorescence was used to label the a-tubulin cytoskeleton to evaluate cell morphology. HepG2 cells were inoculated subcutaneously in nude mice to construct xenografts and beneath the liver capsule to evaluate in vivo metastasis.ResultsCompared to that in the cHCC area, CtBP1 expression was significantly upregulated in the sHCC area, as shown by immunohistochemistry. HE staining showed that cells in the sHCC area were spindle-shaped, while those in the cHCC area were polygonal. Immunohistochemically, the epithelial markers pancytokeratin (CK) and E-cadherin were partially or completely lost, while the expression of the mesenchymal marker vimentin was upregulated in the sHCC area. Moreover, HepG2, an HCC cell line with high expression of CtBP1, autonomously underwent sarcomatoid transformation, showing a sarcomatoid morphology and phenotype. HIF1a expression was upregulated in epithelial cells adjacent to the sHCC area. Hypoxia upregulated CtBP1 protein expression and induced an EMT phenotype with increased migration and a spindle-shaped morphology in HepG2 cells. Knockdown of CtBP1 partially reversed the EMT phenotype induced by hypoxia. Silencing CtBP1 completely blocked the sarcomatoid transformation of subcutaneous xenografts and decreased lung metastasis in subcapsular xenografts of the liver in nude mice.ConclusionCtBP1 plays a key role in hypoxia-induced EMT and sarcomatoid transformation in HCC and could be a candidate target for the management of sHCC.

The first identification of Tembusu virus in a Pekin duck farm in Taiwan

ABSTRACT In this study, Tembusu virus (TMUV) 1080905 isolate was isolated from 29-week-old breeder Pekin ducks in Taiwan in 2019. Clinical history showed that the clinical features were a temporary decrease in egg production, decline of feed uptake, watery diarrhea, nervous signs and sporadic mortality. Necropsy findings were congestion, hyperemia and hemorrhage of the ovary follicles, swollen spleen and deposits of fibrinous exudate on the pericardium and the liver capsule. The polyprotein gene of TMUV 1080905 was 10,278 nucleotides long, encoded 3425 amino acids and exhibited 99.3% nucleotide similarity and 99.7% amino acid similarity with Taiwanese mosquito-derived isolate TMUV TP1906. Our phylogenetic analysis revealed that the Taiwanese TMUVs were grouped together with Malaysian TMUV (chicken-derived Sitiawan virus and the TMUV prototype strain MM1775). To our knowledge, this is the first report of duck-derived TMUV in Taiwan. Further studies of the pathogenicity and host range of the TMUV 1080905 are required. Research Highlights First identification of Tembusu virus in Pekin ducks in Taiwan. Investigation of the phylogeny of TMUV 1080905 isolate from Pekin ducks in Taiwan.