Liver Capsule Research Articles

CK19 is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma

Objective: To study the role of CK19 in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of hepatocellular carcinoma (HCC). Methods: Patients with DPHCC (n=84) who had undergone surgical interventions at the 900th Hospital of Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between CK19 and patient survival. Results: (1)Tumor size, differentiation, peripheral hepatic fibrosis, liver capsule invasion, microvascular invasion (MVI) and serum CA-199 level showed a correlation with CK19, as per the outcomes of Chi-squared tests. (2)According to the univariate analysis, the expression of CK19, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, and serum levels of both alpha-fetoprotein (AFP) and CA-199 showed a strong correlation with overall survival. (3)Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Conclusions: The expression of CK19 may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Body Habitus vs. Hepatic Steatosis: Understanding the Drivers of Non-Diagnostic Shear Wave Elastography

PurposeShear Wave Elastography (SWE) is frequently non-diagnostic in obese patients, a key cohort at risk for liver disease. Subcutaneous fat and hepatic steatosis are suspected drivers, but their relative contribution is unknown. We compare ultrasound-guided attenuation parameter (UGAP), a marker of steatosis, body mass index (BMI), and skin-to-liver capsule distance (SCD) to predict non-diagnostic SWE. Materials and MethodsThis IRB approved, single center retrospective study included adults with SWE and diagnostic UGAP exams between June and December 2023. Fasting patients were imaged in supine position with right arm abducted, via an intercostal window during neutral breath hold. The median of 10 measurements in the right lobe was analyzed for SWE and UGAP. SWE measurements were ≥ 2 cm from the capsule while UGAP depth was fixed at 4 cm from the probe. Exams were considered non-diagnostic for SWE (measured in m/s) if the Interquartile Range/Median Ratio (IQR/M) was > 15% or if diagnostic measurements could not be obtained. UGAP IQR/M > 30% or complete measurement failure was considered non-diagnostic. Univariate Receiver Operating Characteristic (ROC) curves compared UGAP (dB/cm/MHz), BMI (kg/m2), and SCD (mm) prediction of non-diagnostic SWE by the DeLong test. Results87 participants (48 male) with mean age of 54.7 ± 15.7 years were analyzed. UGAP [OR: 1.63 per 0.1 dB/cm/MHz, p=0.02, AUC=0.66], BMI [OR: 1.23, p<0.001, AUC=0.77], and SCD [OR: 1.27, p<0.001, AUC=0.81) were predictors of non-diagnostic SWE. UGAP prediction of non-diagnostic SWE was similar in subgroups with the measurement region at least 1 cm (OR: 1.64, n = 68), and 2 cm (OR: 1.54, n = 16) from the liver capsule. UGAP was a worse predictor than SCD (p = 0.04), while not significantly different than BMI (p = 0.15). BMI and SCD did not differ in predicting non-diagnostic SWE (p = 0.44). ConclusionOur small preliminary study demonstrated that body habitus and hepatic attenuation, a marker of steatosis, both contribute to non-diagnostic SWE exams, however body wall thickness is the key driver. This informs patient selection for SWE exams and guides future research to mitigate these technical shortcomings. Clinical Relevance/ApplicationPatients with hepatic steatosis and large body habitus are at increased risk of non-diagnostic ultrasound shear wave elastography (SWE) exams. These patients, particularly those with increased body wall thickness, may benefit from liver fibrosis evaluation with alternative approaches following an initial non-diagnostic SWE exam. Researchers working to improve SWE technique should pay particular attention to mitigating attenuation and phase aberration from the body wall as this is the key driver of non-diagnostic exams.

Ultrasound normalized local variance to assess metabolic dysfunction-associated steatotic liver disease

PurposeIncreased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) highlights a desire for screening with liver ultrasound normalized local variance (NLV). We aimed to assess variations in NLV values measured at different sampling depths and discuss common technical considerations in measuring liver NLV. MethodsWe retrospectively measured liver NLVs at variable depths on ultrasound images pre-recorded in 116 participants who underwent liver magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and ultrasound to screen for MASLD. Liver NLVs were measured and differences at variable depths were tested using one-way analysis of variance (ANOVA) and multiple paired comparisons using post hoc Tukey honestly significant difference (HSD), Scheffé, Bonferroni, and Holm multiple comparisons. Diagnostic performance of NLV values were analyzed by area under the receiver operating characteristics (AUROC) curve. ResultsThe NLV measured at a depth of 10 cm significantly differed from those measured near the liver capsule and at depths of 6 cm and 8 cm (p < 0.001) from the skin. There was no significant difference in NLV value in other paired groups (p > 0.05). The difference in the area under AUROCs for NLVs measured at variable depths was not significant (p > 0.05). ConclusionsThe best diagnostic performance of liver NLV was measured at depth of 8 cm from the skin, although NLV measured at variable depth showed similar diagnostic performance for assessing ≥ mild hepatic steatosis. The study results provide a reference that can be used in the development of standardized scanning protocols and technical considerations in measuring liver NLV.

Hepatic compartment syndrome, a rare complication after any liver insult or liver transplantation: Three case reports and literature review.

Hepatic compartment syndrome (HCS) is a rare but life-threatening entity that consists of a decreased portal flow due to intraparenchymal hypertension secondary to subcapsular liver hematoma. Lethal liver failure can be observed. We report three cases, and review the literature. A 54-year-old male was admitted for extensive hepatic subcapsular hematoma after blunt abdominal trauma. Initially, he underwent embolization of the hepatic artery's right branch, after which he presented clinical deterioration, major cytolysis (310 times the upper limit of normal [ULN]), and liver failure with a prothrombin time (PT) at 31.0%. A 56-year-old male underwent liver transplantation for acute alcoholic hepatitis. On postoperative day 2, he presented a hemorrhagic shock associated with deterioration of liver function (cytolysis 21 ULN, PT 39.0%) due to extensive hepatic subcapsular hematoma. A 59-year-old male presented a hepatic subcapsular hematoma five days after a cholecystectomy, revealed by abdominal pain with liver dysfunction (cytolysis 10 ULN, PT 63.0%). All patients ultimately underwent urgent surgery for liver capsule excision, hematoma evacuation, and liver packing, if needed. The international literature was screened for this entity. These three patients' outcomes were favorable, and all were alive at postoperative day 90. The literature review found 15 reported cases. HCS can occur after any direct or indirect liver trauma. Surgical decompression is the main treatment, and there is probably no place for arterial embolization, which may increase the risk of liver necrosis. A 13.3% mortality rate is reported. HCS is a rare complication of subcapsular liver hematoma that compresses the liver parenchyma, and leads to liver failure. Urgent surgical decompression is needed.

Y90 Radiation Segmentectomy versus Microwave Ablation for Hepatocellular Carcinoma in Locations Suboptimal for Percutaneous Ablation

Abstract Purpose The purpose of our study was to evaluate outcomes following percutaneous microwave ablation (MWA) versus yttrium-90 (Y90) radiation segmentectomy (RS) for tumors in suboptimal locations for ablation. Materials and Methods Retrospective review (January 2014–July 2019) was performed on patients who underwent Y90-RS or MWA (with or without prior transarterial chemoembolization [TACE]) with curative intent for early-stage hepatocellular carcinoma (HCC) lesions in suboptimal locations for percutaneous ablation, defined as locations in which needle placement is within 5 mm of critical structures (liver dome, liver capsule, gallbladder, and hilum). The primary endpoints were treatment response as per the modified Response Evaluation Criteria in Solid Tumors criteria and complications. Statistical Analysis Fischer's exact test was performed for categorical variables, and Student's t-tests for nominal variables. Results Twenty-three lesions in 20 patients (13 male, 67 ± 8.8 years) and 30 lesions in 30 patients (18 male, 62.5 ± 10.6 years) were treated with Y90-RS and MWA (19 with prior TACE), respectively. There were no differences in demographics (p &gt; 0.05). Mean tumor diameter was 2.9 ± 1.0 in those treated with Y90-RS and 2.3 ± 0.9 for MWA (p &lt; 0.05). Lesions were located adjacent to the following structures: dome (n = 22), capsule (n = 16), hilum (n = 9), and gallbladder (n = 6). All patients were Eastern Cooperative Oncology Group performance status 0 to 1. Of the MWA cohort, 19 were Child-Pugh class A, 5 were B, and 6 were C and the mean pretreatment laboratory values were as follows: Model for End-stage Liver Disease sodium (MELD-Na) 12.7 ± 4.6, alpha-fetoprotein (AFP) 848 ± 3168.0, aspartate aminotransferase (AST) 71.9 ± 49.1, alanine aminotransferase (ALT) 48.0 ± 32.4, and total bilirubin 2.4 ± 2.7. Of the Y90-RS cohort, 15 were Child-Pugh class A, 4 were B, and 1 was C and pretreatment laboratory values were as follows: MELD-Na 10.5 ± 3.3 (Y90-RS), AFP 762.2 ± 1793.8 (Y90), AST 50.3 ± 30.5 (Y90), ALT 30.1 ± 16.9 (Y90), and total bilirubin 1.6 ± 1.1 (Y90). Complete response rate following Y90 was 96 versus 76% for MWA, with no disease progression after Y90-RS within the follow-up period. Three (13%) lesions demonstrated progression of disease (time to progression 6.3 months) after MWA. No grade &gt; 2 toxicities or procedure-related complications were noted following Y90-RS. There were 7 major (arterioportal fistula with hemoperitoneum, pneumothorax, liver infarction, and capsular burn) and 3 minor complications following MWA. Conclusion Y90-RS is a valuable alternative to percutaneous MWA as a first-line therapy for early-stage HCC for tumors in suboptimal locations for ablation, offering a favorable treatment response and safety profile.

Superimposed Electric Field Enhanced Electrospray for High-Throughput and Consistent Cell Encapsulation.

Cell encapsulation technology, crucial for advanced biomedical applications, faces challenges in existing microfluidic and electrospray methods. Microfluidic techniques, while precise, can damage vulnerable cells, and conventional electrospray methods often encounter instability and capsule breakage during high-throughput encapsulation. Inspired by the transformation of the working state from unstable dripping to stable jetting triggered by local electric potential, this study introduces a superimposed electric field (SEF)-enhanced electrospray method for cell encapsulation, with improved stability and biocompatibility. Utilizing stiffness theory, the stability of the electrospray, whose stiffness is five times stronger under conical confinement, is quantitatively analyzed. The SEF technique enables rapid, continuous production of ≈300 core-shell capsules per second in an aqueous environment, significantly improving cell encapsulation efficiency. This method demonstrates remarkable potential as exemplified in two key applications: (1) a 92-fold increase in human-derived induced pluripotent stem cells (iPSCs) expansion over 10 d, outperforming traditional 2D cultures in both growth rate and pluripotency maintenance, and (2) the development of liver capsules for steatosis modeling, exhibiting normal function and biomimetic lipid accumulation. The SEF-enhanced electrospray method presents a significant advancement in cell encapsulation technology. It offers a more efficient, stable, and biocompatible approach for clinical transplantation, drug screening, and cell therapy.

Assessing Severity and Need for Delivery in Early Onset Preeclampsia Before 32 Weeks of Gestation: a Delphi Consensus Procedure.

Preeclampsia is a potentially life-threatening hypertensive pregnancy disorder that carries an acute risk of an unfavorable outcome of the pregnancy but also has consequences for the long-term health of the mother. Women who develop the early form of pre-eclampsia before the 32nd week of pregnancy have the highest risk and are also the most difficult to treat. The severity of pre-eclampsia is not characterized uniformly in Germany, so that the indication for delivery is rather individualized. The aim of this study was to reach a consensus on parameters that could serve as criteria for describing the severity of pre-eclampsia based on the urgency of delivery. To this end, a Delphi procedure was used to present a scenario in which a woman was admitted for preeclampsia before 32 gestational weeks and after completion of antenatal steroid therapy. Clinicians specialized in maternal-fetal medicine from German-speaking countries completed five rounds of a modified Delphi questionnaire. Presented parameters were selected by the section "Hypertensive Pregnancy Diseases and Fetal Growth Restriction" of the German Society of Gynecology and Obstetrics after reviewing the literature. These included objectifiable laboratory or clinical parameters as well as subjective symptoms of the patient. In addition, nine fetal parameters were taken into account. The clinicians were asked to rate presented parameters as an indication for delivery on a Likert scale from 0 to 4 (no indication to absolute indication without delay). For each item, the predefined cut-off for group consensus was ≥70% agreement. A total of 126 experts were approached. Sixty-nine experts (54.8%) took part in the first round; of those 50 completed the entire Delphi procedure. A consensus was reached on 14 parameters to be considered rapid preparation for delivery without delay (4 points on the Likert scale). These were among others hepatic hematoma or liver capsule rupture, acute liver failure with fulminant coagulation disorder or disseminated intravascular coagulation, eclampsia, pathologic findings in imaging (e.g. cMRI) or electrocardiogram arranged for new onset of headache or retrosternal pain, respectively. Twenty-six parameters were rated as factors that should be considered in the decision without being absolute (1 to 3 points), and 13 parameters should have no influence on the decision to deliver (0 points). No consensus on severe hypertension as an indication for delivery could be reached for blood pressure values below 220/140mmHg. A consensus was reached on whether to deliver in preeclampsia typic clinical findings and symptoms. The results can serve as guidance for current clinical practice and for the definition of clinical endpoints in intervention studies. Nevertheless, the isolated criteria are a theoretical construction since the combined deterioration or summation of several factors rather than a single factor most likely influences the decision to deliver and reflect the severity of preeclampsia. Moreover, the degree of hypertension as an indication for delivery remains controversial, unless the patient suffers additionally from complaints. Future research should be enforced to incorporate long-term risks for the mother into a decision aid.

An experimental model of liver echinococcosis in laboratory rats to study the effectiveness of anthelmintic drugs

BACKGROUND: The introduction into clinical practice of drug therapy with anthelmintic drugs from the carbamate-benzimidazole group has reduced the need for aggressive surgical interventions in the initial stages of parasitic cyst development. However, no consensus has been reached in which cases and for what size of cysts the use of monotherapy with carbamate benzimidazoles will be sufficient and in which cases a combination of surgical and therapeutic treatment methods is necessary. Experimental studies with human participants are impossible to solve this problem. AIM: To evaluate the proximity of the developed experimental model of liver echinococcosis to real clinical practice, including the response to the use of carbamate benzimidazoles. MATERIALS AND METHODS: Modeling of liver echinococcosis in laboratory animals was performed by suturing a part of an echinococcal bladder (Echinococcus granulosus) to the liver capsule. The model provides a high survival percentage of laboratory animals, in which after 60 days a typical hydatid cyst forms in the liver. The effects of albendazole and praziquantel were studied using this echinococcus model. One group of animals (n = 10) received albendazole through an intragastal tube for 28 days and the other (n = 10) received praziquantel for 15 days, after which the animals were autopsied. RESULTS: When using albendazole, destructive changes were microscopically determined in the structure of the walls of the echinococcal cyst on day 28 of therapy. Similar changes were observed when using praziquantel; however, they were characterized by more massive cellular infiltration of all cyst layers. CONCLUSIONS: The developed experimental model of liver echinococcosis in laboratory animals allowed us to experimentally examine the effect of various drugs on the larval stages of E. granulosus development and evaluate their effectiveness.

Exploring the impact of excluding intrahepatic segmental vessels on liver stiffness measurement and advanced fibrosis diagnosis using magnetic resonance elastography.

The impact of excluding intrahepatic segmental vessels from regions of interest (ROIs) on liver stiffness measurement (LSM) via magnetic resonance elastography (MRE) remains uncertain. To determine the effect of excluding intrahepatic segmental vessels from ROIs on LSM obtained from MRE. This retrospective analysis included 95 participants who underwent successful two-dimensional gradient recalled-echo MRE before hepatic tumor resection (n = 49) or living liver donation (n = 46). The conventional LSM was determined by manually drawing ROIs on the elastogram within the 95% confidence region, staying 1 cm within the liver capsule and excluding large hilar vessels, the gallbladder, hepatic lesions, and artifacts. In addition, the modified LSM was determined by excluding intrahepatic segmental vessels. LSMs obtained by the two methods were compared with paired sample signed-rank test. Diagnostic performance for advanced fibrosis was calculated and compared using McNemar's test and Delong's test. The stage of hepatic fibrosis was assessed using surgical specimens by the METAVIR system. The modified LSM was larger than the conventional LSM (2.4 kPa vs. 2.2 kPa in reader 1; 2.7 kPa vs. 2.4 kPa in reader 2; P < 0.001). The modified LSM showed superior sensitivity (0.841 vs. 0.659 in reader 1; 0.864 vs. 0.705 in reader 2; P < 0.05) and area under the curve (0.901 vs. 0.820 in reader 1; 0.912 vs. 0.843 in reader 2; P < 0.05) for detecting advanced fibrosis (≥F3) than conventional LSM. The exclusion of intrahepatic segmental vessels from ROIs in MRE affected the LSM and enhanced diagnostic performance for advanced fibrosis.

Establishing the Interrelations of the Laboratory Parameters in the Gut-Kidney Axis in Cats with Signs of Triple Phosphate Urolithiasis

Introduction. Efficient treatment of the feline urolithiasis much depends on the early diagnosis of the disease, however, the diagnostic algorithm of this type of pathology is extremely poor due to the various reasons, in particular, it does not take into account the interrelations in the gut-kidney axis. Analysis of the state of gastrointestinal tract functioning and the composition of the gut microbiota can improve the potential of diagnosing the urolithiasis, predict the risk, improve the prognosis and choose the correct treatment strategy. The aim of this publication is to establish the interrelations of the laboratory parameters in the gut-kidney axis in cats with struvite urolithiasis with the signs of cystolithiasis.Materials and Methods. The objects of the research were the outbred cats with the triple phosphate urolithiasis with the signs of cystolithiasis: 1st experimental group — females; 2nd experimental group — neutered males; the control group — clinically healthy animals of both sexes. The laboratory and clinical examinations of sick animals included: ultrasonography of abdominal organs; macroscopic and biochemical urine tests; microscopy of urine sediment and urine culture test without determination of antibiotic sensitivity; macroscopic, microscopic and simple chemical examinations of freshly excreted feces; bacteriological culture test of rectal flushes without determination of antibiotic sensitivity.Results. In the urine of cats of the experimental groups, under the activity of gram-negative microorganisms Escherichia coli (0.03±0.01×106 CFU (colony forming units) and 1.00±0.03×106 CFU) and gram-positive microorganisms Staphilococcus intermedius (1.05±0.07×106 CFU and 1.00±0.08×107 CFU) there were recorded within the microscope field of view: alkalization, development of hypersthenuria, proteinuria, hypercalciuria, hematuria, including microhematuria and leukocyturia, crystalluria. The results of coprological examinations in sick cats indicated the presence of stercobilin, well-digested muscle fibres, undigested and digested cellulose, extracellular and intracellular starch, as well as impurities of non-food origin (wool). The data of microbiological examinations of feces indicated the growth of Escherichia coli (1.00±0.05×105 CFU and 1.04±0.08×107 CFU). Along with the cystolytiasis, the acoustic shadowing of the gastrointestinal tract organs in the experimental animals revealed the hyperechogenicity of liver capsule and parenchyma and heterogeneity of the pattern.Discussion and Conclusion. The revealed character of the laboratory parameter changes in the experimental animals, such as the increase of protein and creatinine levels in urine and growth of Escherichia coli in feces, proved the existence of the pathogenetic relationship between the urogenital tract lesion caused by the gram-negative microorganisms and the gut microbiota in the gut-kidney axis. The results of our study of the sick animals’ urine indicated on the infection of the urogenital tract with the urease-producing microorganisms, which led to the alkalization of urine and formation of the infection struvite stones. Urolithiasis, in turn, had an impact on the gut microbiome due to the topographic proximity of the urogenital and gastrointestinal tracts: examination of feces in cats of the experimental group had confirmed the disorder of gastrointestinal tract functioning due to dysbiotic processes in the large intestine.

A Case Series and Literature Review of Alveolar Echinococcosis in Kashmir, India: An Emerging Endemic Zone for Echinococcus multilocularis.

A prospective study on 110 patients with echinococcosis at Dr. Khuroo's Medical Clinic, Srinagar, Kashmir, India, from March 2019 to April 2024 identified 12 cases (4 males, 8 females; mean age of 46.58 ± 11.97 years) of Alveolar echinococcosis (AE). Two patients were detected through ultrasound examinations carried out for unrelated causes; one presented with features of liver abscess, and nine had pain in the right upper quadrant for a mean period of 2.2 ± 1.79 years. All had the liver as the primary organ involved, with 15 tumor masses of a mean maximum diameter of 9.22 ± 3.21 cm and volume of 426 ± 374.61 cm3. Tumors placed centrally had invaded vessels and the biliary tract in eight patients, and those placed peripherally had invaded the liver capsule and adjacent organs in nine patients. Histologic examination of liver biopsies or resected organs revealed necrotic lesions, calcifications, and granulomatous inflammation with slender, thin-walled vesicles of bizarre configuration that stained strongly eosinophilic with periodic acid Schiff. Two patients had segmental liver resections; one was treated with liver aspiration, while the other nine with advanced disease received chemotherapy with albendazole along with praziquantel. Patients showed clinical improvement on a median follow-up of 12 months (range 1 to 60 months); however, MRI T2-weighted images and 18F-FDG-PET-CECT scans in two patients showed active disease on follow-up at one and five years, respectively. A systematic review detected 146 cases of AE in India from 1980 to April 2024. Twenty cases were from foreign countries, mostly from Central Asian republics, and 118 (93.65%) of the remaining 126 Indian patients were permanent residents of Kashmir Valley. The disease affected a population of 79,197 residing in 22 villages from 5 border districts of the valley. These villages were either high in or adjacent to the Himalayan mountain range. Disease prevalence in the affected population was 146.47/105 (males 131.53/105 and females 163.18/105) and the incidence was 12.41/105/year (males 11.16/105/year and females 13.81/105/year). Possible causes of the emergence of AE are discussed, and future directions for research to face this challenge arebeen identified.

Ultrasound backscatter coefficient for fat quantification is affected by the measurement depth.

It has been reported that the estimate of ultrasound attenuation coefficient (AC) is affected by depth of measurement, with linear decrease of values with depth. It is unknown whether backscatter coefficient (BSC) has similar behavior. This retrospective study was performed with Sequoia US system equipped with ultrasound derived fat fraction (UDFF) algorithm (Siemens Healthineers, Issaquah, WA, USA) that combines BSC with AC. UDFF was obtained positioning upper edge of the region of interest at 1.5,2,3,4,5cm below liver capsule. BSC data were extracted from UDFF offline. A fractional polynomial regression, which selects the best model considering the polynomial development of the variables of interest, was used. Covariates included were age, sex, skin-to-liver-capsule distance, stiffness. Distance was included as linear factor or with a power ranging from -2 to 3, and the best fitting model was chosen according to partial F test. Body mass index (BMI) was not included because of collinearity with skin-to-liver capsule distance. 104 individuals (56 females; age: 57.9 ± 13.0years; BMI: 29.0 ± 6.5kg/m2; skin-to-liver-capsule distance: 2.3 ± 0.7cm; liver stiffness: 7.5 ± 5.5 kiloPascal) were studied. Best fitting model for BSC included a combination of depth as linear factor and square root. BSC showed a decrease of -13.98dB/cm-steradian for each logarithmic increase of 1cm depth (coefficient: -13.98; 95% CI: -21.016; -5.379; p = .001). Skin-to-liver-capsule distance and stiffness also were independent predictors of BSC. The estimation of the BSC in the liver exhibits a depth dependence that significantly affects results. A standardized acquisition protocol is needed to compare results and reliably assess changes over time.

Methodology exploration and reproducibility evaluation of TAI and TSI for quantitative ultrasound assessment of hepatic steatosis

Background and aimNew quantitative ultrasound techniques can be used to quantify hepatic steatosis, including tissue attenuation imaging (TAI), tissue scatter -distribution imaging (TSI), and the hepatorenal index (HRI). However, the measurement norms and the effects of fasting on these measurements remain unclear. The present study performed a methodological exploration and investigated the reliability of these measurements. MethodsIn total, 103 participants were prospectively recruited for ultrasonography and magnetic resonance imaging (MRI) scans. For the TAI and TSI data, the upper (2 cm), middle (4 cm) and lower (6 cm) areas determined according to the depth of the region of interest from the liver capsule, were sampled three times. Correlation analyses were performed to compare the measurements of TAI, TSI, and HRI with the controlled attenuation parameter (CAP) or MRI-proton density fat fraction (MRI-PDFF). Intra- and inter-operator repeatability was assessed using intraclass correlation coefficients. The effects of fasting on these measurements were then compared. ResultsThe TAI and TSI measurements obtained from the upper and middle depths exhibited stronger correlations with the CAP measurements than those obtained from the lower depth. Specifically, the mean TAI had a significant positive correlation with MRI-PDFF (r = 0.753, P < 0.0001). TAI and TSI measurements exhibited excellent intra- (0.933 and 0.925, respectively) and inter- (0.896 and 0.766, respectively) examiner reliability. However, the correlation between HRI and CAP measurements was only 0.281, with no significant correlation with MRI-PDFF, and intra- and inter-examiner reproducibility of 0.458 and 0.343, respectively. Fasting did not affect these measurements. ConclusionsTAI and TSI measurements demonstrated good intra- and interobserver reliability and correlated well with CAP and MRI-PDFF measurements. However, in practice-based clinical applications, the sampling depth should be controlled within 2–4 cm of the hepatic capsule; no fasting is required before the examination.

Ultrastructural investigation of iron oxide nanoparticles accumulation in the liver of common carp (Cyprinus carpio Linnaeus, 1758)

In recent years, the intensive production of nanoparticles with a wide application has led to their transfer to the environment, including the water ecosystem. The accumulation of nanoparticles in fish, causing various pathological changes in the host, raises certain concerns. In the current study, we investigated the penetration and bioaccumulation of Fe3O4 nanoparticles, in the liver of common carp (Cyprinus carpio Linnaeus, 1758). Common carp juveniles were exposed to Fe3O4 nanoparticles at concentrations of 10 and 100 mg. After 7 days, their livers were examined by light and transmission electron microscopes. Compared to normal fish's liver, after using a small concentration (10 mg) of nanoparticles, changes were observed in erythrocytes, hepatocytes, intracellular canaliculi, and bile ducts of the liver. At a high concentration (100 mg), the intensity of changes increased significantly. The liver's capsule was damaged, and a considerable number of hepatocytes were completely destroyed. Additionally, the walls of blood vessels and biliary ductule walls was notably disturbed. It was found that the intensity of pathologies occurring in the liver, increases proportionally with higher concentrations of nanoparticles. Confirmation via electron microscopic methods revealed that Fe3O4 nanoparticles, when administered with food to common carp, enter the fish's liver through erythrocytes localized in the lumen of blood vessels. From there, they traverse through the endothelium of vessels, proceed to hepatocytes, including cytoplasmic organelles, intracellular canaliculi, biliary ductules, and eventually reach the bile ducts. Fe3O4 nanoparticles in all structural elements of fish liver was up to 20 nm. Therefore, high concentrations of nanoparticles in the environment harms the bodies of aquatic organisms, including fish. The changes identified in the liver of common carp in the present study are valuable information in assessing possible risks to other components of the aquatic ecosystem and organisms.

Determining the ideal measurement site and respiratory condition for liver transient elastography: toward clinical practice standardization

ObjectivesLiver transient elastography (TE) has been endorsed by the WHO as the first-line diagnostic tool for liver diseases. Although unreliable and invalid results caused by intercostal space (ICS)-associated factors (including excessive subcutaneous fat and a narrow ICS relative to the transducer size) and operator inexperience are not uncommon, no standard guidelines for ideal probe placement are currently available. Herein, we conducted a prospective observational study to identify an ideal measurement site and respiratory condition for TE by characterizing anatomical and biomechanical properties of the ICSs using ultrasound B-mode and elasticity imaging.MethodsIntercostal ultrasound was performed pointwise at four specific sites in 59 patients to simultaneously measure the width, stiffness, and skin‒liver capsule distance (SCD) of the ICSs over the liver, under end-inspiratory and end-expiratory conditions. Intersections between the 8th ICS and anterior axillary line, the 7th ICS and anterior axillary line, the 8th ICS and mid-axillary line, and the 7th ICS and mid-axillary line were defined as Sites 1 to 4, respectively.ResultsResults indicated that Sites 2 and 3 presented greater intercostal width; Sites 3 and 4 displayed lower intercostal stiffness; Sites 2 and 3 exhibited a shorter SCD. The ICSs were significantly wider and stiffer at end-inspiration. Additionally, the liver was more easily visualized at Sites 1 and 3.ConclusionWe recommend Site 3 for TE probe placement owing to its greater width, lower stiffness, and smaller abdominal wall thickness. Performing TE at end-inspiration is preferred to minimize transducer-rib interferences. This study paves the way toward a standardized TE examination procedure.Critical relevance statementA standardized measurement protocol for WHO-recommended liver TE was first established to improve the success and efficiency of the examination procedure.Key PointsWHO-recommended TE is unreliable or fails due to intercostal space-related factors.The 8th intercostal space on the mid-axillary line and end-inspiration are recommended.This standardized protocol aids in handling challenging cases and simplifies operational procedures.Graphical

Multicolor Two-Photon Microscopy Imaging of Lipid Droplets and Liver Capsule Macrophages In Vivo.

Lipid droplets (LDs) store energy and supply fatty acids and cholesterol. LDs are a hallmark of chronic nonalcoholic fatty liver disease (NAFLD). Recently, studies have focused on the role of hepatic macrophages in NAFLD. Green fluorescent protein (GFP) is used for labeling the characteristic targets in bioimaging analysis. Cx3cr1-GFP mice are widely used in studying the liver macrophages such as the NAFLD model. Here, we have developed a tool for two-photon microscopic observation to study the interactions between LDs labeled with LD2 and liver capsule macrophages labeled with GFP in vivo. LD2, a small-molecule two-photon excitation fluorescent probe for LDs, exhibits deep-red (700 nm) fluorescence upon excitation at 880 nm, high cell staining ability and photostability, and low cytotoxicity. This probe can clearly observe LDs through two-photon microscopy (TPM) and enables the simultaneous imaging of GFP+ liver capsule macrophages (LCMs) in vivo in the liver capsule of Cx3cr1-GFP mice. In the NAFLD mouse model, Cx3cr1+ LCMs and LDs increased with the progress of fatty liver disease, and spatiotemporal changes in LCMs were observed through intravital 3D TPM images. LD2 will aid in studying the interactions and immunological roles of hepatic macrophages and LDs to better understand NAFLD.

Abstract 2393: Development of a novel implantable drug-eluting product for the local treatment of pancreatic adenocarcinoma

Abstract Background Local control of non-metastatic pancreatic ductal adenocarcinoma (PDAC) remains a major challenge. Therapies with reduced systemic toxicity are needed as intravenous (IV) infusions are limited by patient tolerance with only small amounts reaching the tumor. PanTher created PTM-101, a novel absorbable drug formulation containing paclitaxel, designed to be locally applied via minimally invasive surgery to provide chemotherapy precisely to the peritumoral area in PDAC. Methods A study was conducted using 3 cadaveric abdomens to evaluate surgical feasibility of delivering PTM-101 via laparoscopy. Prior to insertion of PTM-101 into the peritoneum, the surgeons prepared each product by suturing a 3-0 Vicryl SH (Ethicon) at four evenly spaced locations around the edge of the flat circular product. A periumbilical 10mm Hasson port was placed to insufflate the abdomen, followed by placement of 3 additional working ports (5mm). The liver capsule was carefully surveyed to exclude metastatic disease. The surgeons opened a window into the lesser sac through the greater omentum, lifting the stomach up from the transverse colon to expose the pancreas. PTM-101 (a 1mm thick and 6cm diameter film) was rolled into a tubular shape, inserted through the cannula, and affixed to the peri-pancreatic fat with existing vicryl stitches. Results The estimated total operative time from placement of the first trocar to removal of all equipment was 45 minutes, for the 3 procedures. The operations included 25 minutes for entry, port placement, exposure of the simulated pancreatic tumor location and 20 minutes to place and suture PTM-101. PTM-101 was easy to fit through the cannula and was sutured without difficulty to the peri-pancreatic fat that surrounds the capsule of the pancreas. To simulate a tumor with hepatic artery involvement, the implant was sutured towards the hepatoduodenal ligament in one specimen, near the area of the gastroduodenal artery takeoff, proper hepatic artery, and proximal portal vein. PTM-101 covered the entire head/neck area of the simulated tumor locations without requiring disruption of the tumor area or dissection of the tunnel under the pancreatic neck. Conclusion PTM-101 is flexible and conforms easily to the underlying topography, both in a concave (i.e., with the tumor intact) and convex (i.e., after resection) scenario. Although human anatomy does not allow for PTM-101 to completely wrap around the pancreas, the size and flexibility of the product enables it to “drape” over the edges covering areas near the superior mesenteric vein and artery (SMV/SMA). This placement could hypothetically increase the amount of drug reaching the area behind the pancreas to target tumors which abut or encase the mesoportal vasculature. A decrease in the tumor-vessel interface could downsize pancreatic tumors, with the goal of increasing resection rates and post-resection local control. Citation Format: Margaret Lashof-Sullivan, Leslie S. Sloan, Michael P. Kim, Laura Indolfi, Ching-Wei D. Tzeng. Development of a novel implantable drug-eluting product for the local treatment of pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2393.

A299 ACUTE TUMOUR RUPTURE POST-TRANSARTERIAL CHEMOEMBOLIZATION IN A PATIENT WITH HEPATOCELLULAR CARCINOMA

Abstract Background Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with increasing worldwide incidence. Transarterial chemoembolization (TACE) is an interventional radiological (IR) therapy used largely in intermediate stage HCC, which can provide successful bridge or downstaging to liver transplantation and increased survival rates. Tumour rupture is a very rare complication of TACE, with an estimated incidence of 0.68%. Potential risk factors include tumour size ampersand:003E 10 cm, and location of lesions in the right lobe or near the liver capsule. However, the pathophysiology of post-TACE tumour rupture is still not fully understood. Aims We aim to describe a case of HCC tumour rupture that occurred in the first 30 hours post-TACE. We also aim to highlight the extent of multiorgan ischemia associated with this tumour-related arterial bleed. Methods A PubMed literature review was done to ensure that post-TACE tumour rupture was a rare and sparsely reported event. Subsequently, inpatient notes, laboratory and imaging data were obtained from the patient's medical record in an anonymized manner. Results A 66-year-old male with alcohol-related liver cirrhosis (MELDNa 7; Child-Pugh Class A) was diagnosed with a 3.3 cm HCC, spanning segments 5 and 8. Six months later, after multidisciplinary discussion, he underwent successful elective TACE of a segment 8 artery that was supplying the HCC, as a bridge to liver transplantation. The next day, he developed diffuse abdominal pain, emesis, tachycardia, and abdominal firmness and tenderness. Labs showed a 45 g/L drop in hemoglobin (121 g/L to 76 g/L), leukocytosis (27.0 x109/L), and an elevated lactate (4.4 mmol/L). Computed tomography (CT) scan confirmed tumour rupture, with moderate-to-large hemoperitoneum with active bleeding from the embolized region of the HCC, and associated gas. Emergent IR-guided embolization was performed to the bleeding segment 8 artery. CT scan two days later revealed interval ischemic infarction of the spleen, pancreatic tail, and stomach. This widespread ischemia was suspected to be due to hypovolemic hypoperfusion vs. post-TACE embolic phenomena. Aggressive supportive measures, antibiotics, and anticoagulation were implemented. Due to tumour rupture, the patient was deemed no longer a suitable candidate for liver transplantation. Futility of definitive management was discussed, and the patient opted for medical care without resuscitation. After optimization of nutritional and physical functioning parameters, he was discharged home with medical management for pain and ascites. Conclusions Post-TACE tumour rupture is a rare occurrence for which the pathophysiology is not fully understood. This case provides an important reminder of this potential adverse event. Early detection and management are imperative to facilitating a favourable outcome in this life-threatening condition. Funding Agencies None

Genotypic characterization of Escherichia coli isolated from infected chicken in Basrah, Iraq

This study aimed to detect the presence of Escherichia coli in broiler and layer hens in the Basrah province, Iraq using macroscopic and microscopic diagnosis and bacterial isolation that causes infection insome internal organs (liver and heart), and by polymerase chain reaction. Randomly chosen samples were taken from different places within Basrah province for further investigation (poultry fields in Al-Qurnah and Al-Hartha). The bacteriological analysis revealed that the presence of Escherichia coli is responsible for causing fibrinous pericarditis and perihepatitis in birds. The macroscopic examination revealed hemorrhagic lesions and a significant buildup consisting of a white fibrous accumulation in the pericardial sac of the infected birds' hearts. The livers of infected birds exhibited significant deposition of white fibrous exudate on the liver surface, along with hepatomegaly. The afflicted heart displays a microscopic appearance marked by a notable aggregation of inflammatory cells in the pericardial sac and the release of fibrinous exudate. Additionally, there is an accumulation of edematous exudate in the cardiac muscle fibers, accompanied with congestion of blood vessels in the myocardium. The microscopic examination of the infected liver revealed the existence of a significant infiltration of inflammatory cells in the liver capsule, as well as the presence of a thick fibrinous exudate encapsulated on the liver surface and congestion of the central vein. The histological analysis of the affected heart and liver revealed a significant buildup of collagen and fibrin fibers, which exhibit a prominent dark bluish staining. This buildup is widely distinguished in the pericardial and hepatic capsules. The study indicated that fibrinous pericarditis and perihepatitis affected birds, as indicated by the examination of bacterial results. Escherichia coli emits endotoxins that induce vascular damage in the heart and liver, resulting in an elevated presence of fibrin exudate around the affected tissue. The histological analysis supported this conclusion. Keywords: Fibrinous, Pericarditis, Perihepatitis, Pathology, Biological.

Efficacy analysis of hepatic arterial infusion chemotherapy combined with targeted and immune therapy followed by 125I seeds implantation in the treatment of hepatocellular carcinoma with portal vain tumor thrombus

Objective: To investigate the safety and efficacy of Hepatic Arterial Infusion Chemotherapy(HAIC) combined with targeted and immune therapy followed by 125I seeds implantation in portal vain tumor thrombus (PVTT) in the treatment of hepatocellular carcinoma(HCC) with PVTT. Methods: A retrospective study was performed on the clinical data of 21 patients [ (11 men, 10 women) aged 34-73 (52.6±13.7) years] with HCC with PVTT in The First Affiliated Hospital of Zhengzhou University from October 2020 to October 2022, all of them were treated with HAIC plus targeted and immune therapy,and 125I seeds implanted into PVTT. The patients were followed up to January 2023, the efficacy was evaluated according to the modified version of the solid tumor efficacy evaluation criteria (mRECIST). The progression-free survival (PFS) rate, overall survival(OS) rate and portal tumor thrombus control rate at 3, 6, 12 and 18 months after treatment were recorded, and PFS and OS time were followed up. The changes of liver function, AFP, coagulation function and adverse events were observed. Results: Each patient received 2 to 7 (mean: 3.3±1.2) cycles of HAIC. 10-37 seeds (mean:16.6±6.7) were implanted per patients. The median follow-up time was 15 (range from 5 to 25) months.During the follow-up time, 15 patients showed progression and 6 patients died, and the PFS rates at 3, 6, 12, and 18 months after treatment were 90.5%, 71.4%, 42.9%, and 23.8%, respectively, and at 3, 6, 12, and 18-month OS rates were 100%, 100%, 81.0%, and 61.9%, respectively.The PVTT control rates at 3, 6, and 12 months were 90.5%, 90.5%, and 62.5%, respectively. Overall efficacy evaluation of CR rate 0, PR rate 47.6% (10/21), SD rate 38.1% (8/21), and PD rate 14.3% (3/21). The total incidence of treatment-related adverse events was 100%.Grade 3 treatment related adverse events were observed for 4 cases, the rest wereⅠtoⅡadverse events. Right upper abdominal pain, fever and hemorrhage in liver capsule related to the procedures were observed in 11(52.4%), 5(23.8%) and 3(14.3) patients, respectively. Conclusion: HAIC combined with targeted and immune therapy followed by 125I seeds implantation in PVTT is a safe and efficacy therapy for HCC with PVTT.