Glisson's Capsule Research Articles

Left Hemi-Hepatectomy to Resect Metastatic Tumor of Round Ligament of Liver in Patients with Ovarian Cancer.

The objective of this study is to investigate the surgical, clinical and pathological outcomes of left hemi-hepatectomy during cytoreductive surgery (CRS) in patients with primary ovarian cancer. The electronic medical charts of patients with primary ovarian cancer who received CRS including left hemi-hepatectomy from 2000 to 2023 were reviewed and retrospectively analyzed. A total of 17 patients underwent left hemi-hepatectomy for resection of a deep peritoneal implant in the round ligament of the liver during primary CRS. Among these 17 patients, hepatic parenchymal invasion was confirmed in 10 patients (58.8%). Tumor distribution of others is as follows: Glisson's capsule, hilum, falciform ligament and gall bladder. Fourteen patients (82.4%) achieved CRS; the remaining three patients had residual tumors less than 1 cm. The median period to subsequent chemotherapy was 21 days (range, 12-35 days). No specific complications related to left hepatectomy were identified such as liver failure or bile leakage. Left hemi-hepatectomy for complete surgical resection of a deep peritoneal implant of the round ligament of the liver is surgically feasible and safe.

Prognosis and recurrence of spontaneously ruptured hepatocellular carcinoma treated after hepatectomy: A single institution experience.

Spontaneously ruptured hepatocellular carcinoma (srHCC) is a life-threatening disease. The prognosis of patients with srHCC after hepatectomy remains unclear. This study aimed to investigate the prognosis and recurrence after hepatectomy in patients with srHCC. From 2015 to 2020, a retrospective analysis of patients with srHCC who underwent hepatectomy was performed, and compared with patients with unruptured HCC. Among the 86 patients with HCC who underwent hepatectomy, 11 had srHCC. The median tumor size in the ruptured group was significantly larger than that in the unruptured group (P = .001). The incidence rate of vascular invasion and Glisson capsule invasion in the ruptured group was significantly higher than that in the unruptured group. (P = .012 and P < .001, respectively). The American Joint Committee on Cancer was significantly higher in the ruptured group than in the unruptured group (P < .001). In total, 8 (73%) patients in the ruptured group experienced recurrence, whereas the median recurrence-free survival (RFS) and overall survival (OS) periods in the ruptured group were 15 (11-32) and 23 (17-38) months, respectively. In the unruptured group, 34 (45%) patients experienced recurrence, and the median RFS and OS periods were 20 (8-37, P = .099) and 33 (12-51, P = .394) months, respectively. Patients who developed peritoneal metastases were included in the ruptured group (n = 3). Ruptured HCCs exhibit worse oncological outcomes have poorer survival and higher recurrence rates than unruptured HCCs.

Anatomical thermal ablation as an alternative to surgical resection for subcapsular hepatocellular carcinoma.

To simulate the advantages of anatomical resection, a new strategy of anatomical thermal ablation was proposed. The objective of this study was to evaluate the clinical value of anatomical thermal ablation (ATA) to treat subcapsular hepatocellular carcinoma by comparing it with anatomical resection (AR) and non-anatomical resection (NAR). This retrospective cohort study enrolled hepatocellular carcinoma patients with subcapsular tumor diameter ≤ 50mm treated by ATA or surgical resection at our center from October 2015 to December 2018. ATA features ablation of the Glisson capsule, ablation of the liver parenchyma between the tumor and hepatic veins or inferior vena cava and then puncture from the surrounding part to the central part of the tumor. Outcome parameters were compared. Seventy-six patients were grouped into ATA group, 95 patients into AR group and 41 patients into NAR group. The 1-, 2-, and 3-year local recurrence rates were 0.0%, 0.0%, 0.0% for ATA group, 0.0%, 1.4%, 1.4% for the AR group and 0.0%, 0.0%, and 0.0% for the NAR group, respectively (P = 0.449). The 1-, 2-, and 3-year progression-free survival rates were 90.6%, 80.9%, and 74.6% for ATA group, 91.5%, 80.2%, and 80.2% for the AR group and 82.9%, 73.8%, and 73.8% for the NAR group, respectively (P = 0.608). The 1-, 2-, and 3-year overall survival rates were 100.0%, 95.2%, and 95.2% for the ATA group, 96.8%, 95.6%, and 95.6% for the AR group and 97.6%, 95.0%, and 95.0% for the NAR group, respectively (P = 0.970). No difference was found in major complication rate among these groups (P = 0.091). For subcapsular hepatocellular carcinoma, ATA could be an alternative to surgical resection with its comparable treatment effect and safety.

Recruitment of large peritoneal macrophages to capsular fibrosis developed on the liver surface.

Upon injury to Glisson's capsule, mesothelial cells covering the liver surface differentiate into myofibroblasts and participate in capsular fibrosis. In the fibrotic area, infiltrating macrophages are present, but their origin and role in capsular fibrosis remain elusive. In the present study, we examined whether macrophages in the peritoneal cavity migrate to the liver and participate in capsular fibrosis. Capsular fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. Chlorhexidine gluconate treatment induced disappearance of CD11bHigh F4/80High large peritoneal macrophages from the peritoneal cavity. Transplantation of TIMD4+ large peritoneal macrophages to the mouse peritoneal cavity resulted in their recruitment to the fibrotic area of the liver. Bone marrow-derived monocytes were also recruited to the chlorhexidine gluconate-induced fibrotic area upon their transplantation to the peritoneal cavity. However, bone marrow-derived macrophages, Kupffer cells, peritoneal B cells, and small peritoneal macrophages prepared from chlorhexidine gluconate-treated mice did not exhibit such potential. In the hepatic fibrotic area, peritoneal macrophages lost expression of unique markers (Gata6, Timd4) and increased expression of genes involved in inflammation (Il1b, Il6, Tnf) and extracellular matrix remodeling (Mmp13, Timp1). Depletion of peritoneal macrophages by clodronate liposomes reduced capsular fibrosis. Our data indicate that large peritoneal macrophages are recruited to the injured liver surface and promote capsular fibrosis by inducing inflammation and extracellular matrix remodeling. Modulating the function of peritoneal macrophages might be a new approach for suppressing capsular fibrosis.

An optimized visualization and quantitative protocol for in-depth evaluation of lymphatic vessel architecture in the liver.

The liver lymphatic system is essential for maintaining tissue fluid balance and immune function. The detailed structure of lymphatic vessels (LVs) in the liver remains to be fully demonstrated. The aim of this study is to reveal LV structures in normal and diseased livers by developing a tissue-clearing and coimmunolabeling protocol optimized for the tissue size and the processing time for three-dimensional (3-D) visualization and quantification of LVs in the liver. We showed that our optimized protocol enables in-depth exploration of lymphatic networks in the liver, consisting of LVs along the portal tract (deep lymphatic system) and within the collagenous Glisson's capsule (superficial lymphatic system) in different species. With this protocol, we have shown 3-D LVs configurations in relation to blood vessels and bile ducts in cholestatic mouse livers, in which LVs were highly dilated and predominantly found around highly proliferating bile ducts and peribiliary vascular plexuses in the portal tract. We also established a quantification method using a 3-D volume-rendering approach. We observed a 1.6-fold (P < 0.05) increase in the average diameter of LVs and a 2.4-fold increase (P < 0.05) in the average branch number of LVs in cholestatic/fibrotic livers compared with control livers. Furthermore, cholestatic/fibrotic livers showed a 4.3-fold increase (P < 0.05) in total volume of LVs compared with control livers. Our optimized protocol and quantification method demonstrate an efficient and simple liver tissue-clearing procedure that allows the comprehensive analysis of liver lymphatic system.NEW & NOTEWORTHY This article showed a comprehensive 3-D-structural analysis of liver lymphatic vessel (LV) in normal and diseased livers in relation to blood vessels and bile ducts. In addition to the LVs highly localized at the portal tract, we revealed capsular LVs in mouse, rat, and human livers. In cholestatic livers, LVs are significantly increased and dilated compared with normal livers. Our optimized protocol provides detailed spatial information for LVs remodeling in normal and pathological conditions.

Protective Effects of Omega-3 Supplementation against Doxorubicin-Induced Deleterious Effects on the Liver and Kidneys of Rats.

Anthracycline doxorubicin (DOX) is still widely used as a chemotherapeutic drug for some solid tumors. Although DOX is highly effective, its side effects are limiting factors, such as cardio, nephro and hepatotoxicity. As such, approaches used to mitigate these adverse effects are highly encouraged. Omega 3 (ω-3), which is a class of long-chain polyunsaturated fatty acids, has been shown to have anti-inflammatory and antioxidant effects in preclinical bioassays. Thus, we evaluated the protective effects of ω-3 supplementation on hepatotoxicity and nephrotoxicity induced by multiple DOX administrations in rodents. Male Wistar rats (10 rats/group) were treated daily with ω-3 (400 mg/kg/day) by gavage for six weeks. Two weeks after the first ω-3 administration, the rats received DOX (3.5 mg/kg, intraperitoneal, 1×/week) for four weeks. DOX treatment reduced body weight gain increased systemic genotoxicity and caused liver-related (increase in serum ALT levels, thickness of the Glisson's capsule, compensatory proliferation and p65 levels) and kidney-related (increase in serum urea and creatinine levels, and incidence of tubular dilatation) deleterious outcomes. In contrast, ω-3 supplementation was safe and abrogated the DOX-related enhancement of systemic genotoxicity, serum urea and creatinine levels. Furthermore, ω-3 intervention reduced by 50% the incidence of kidney histological lesions while reducing by 40-50% the p65 protein level, and the proliferative response in the liver induced by DOX. Our findings indicate that ω-3 intervention attenuated the DOX-induced deleterious effects in the liver and kidney. Therefore, our findings may inspire future mechanistical investigations and clinical interventions with ω-3 on the reported outcomes.

Isolation of Regenerating Hepatocytes after Partial Hepatectomy in Mice.

Partial hepatectomy has been widely used to investigate liver regeneration in mice, but the isolation of high yields of viable hepatocytes for downstream single-cell applications is challenging. A marked accumulation of lipids within regenerating hepatocytes is observed during the first 2 days of normal liver regeneration in mice. This so-called transient regeneration-associated steatosis (TRAS) is temporary but partially overlaps the major proliferative phase. Density-gradient purification is the backbone of most existing protocols for the isolation of primary hepatocytes. As gradient purification relies on the density and size of cells, it separates non-steatotic from steatotic hepatocyte populations. Therefore, fatty hepatocytes often are lost, yielding non-representative hepatocyte fractions. The presented protocol describes an easy and reliable method for the in vivo isolation of regenerating hepatocytes regardless of their lipid content. Hepatocytes from male C57BL/6 mice are isolated 24-48 h after hepatectomy by a classic two-step collagenase perfusion approach. A standard peristaltic pump drives the warmed solutions via the catheterized inferior vena cava into the remnant, using a retrograde perfusion technique with outflow through the portal vein. Hepatocytes are dissociated by collagenase for their release from the Glisson's capsule. After washing and careful centrifugation, the hepatocytes can be used for any downstream analyses. In conclusion, this paper describes a straightforward and reproducible technique for the isolation of a representative population of regenerating hepatocytes after partial hepatectomy in mice. The method may also aid the study of fatty liver disease.

Pathomorphological changes in the liver of broiler chickens caused by adeno-virus infection. Description of a spontaneous case in a private farm of the Lviv region

The article covers the results of pathomorphological studies of broiler chickens' liver (Cobb 500 cross) spontaneously damaged by Group I fowl adenovirus. Clinical signs of the disease in broiler chickens appeared on the 15th day of life and were manifested by a sharp decrease in water and feed consumption. The fowl was lethargic for several days, breathing hard, mostly sitting with its head down and eyes closed. During the breeding period, the mortality rate reached 13.2 %, accompanied by significant growth retardation. A peak of mortality was observed within 20–24 days of life. Antibody titers monitored by immunoenzymatic method using BioChek ELISA tests for infectious bursal disease (IBD), infectious bronchitis (IBV), and Newcastle disease (ND) virus were within normal post-vaccination levels. Pathological autopsy of broiler chickens revealed hepatomegaly, diffuse punctate and petechial hemorrhages under the Glisson's capsule, and military necrosis in the liver parenchyma. Hydropericarditis, pulmonary edema, renal dystrophy, and catarrhal enteritis were also detected in some cases. Liver fragments were selected for histological examination, fixed in a 10 % aqueous solution of neutral formalin, washed in water, and dehydrated in an ascending series of alcohols, followed by sealing and embedding in paraffin. Deparaffinized sections were stained with Mayer's hematoxylin and eosin. Optical examination of hepatocytes revealed large, round basophilic intranuclear inclusion bodies, multifocal necrosis of hepatocytes, stasis, and fatty dystrophy. According to the molecular genetic test results of broiler chickens' liver fragments, the DNA of Group I fowl adenovirus, serotype FAdV-11, was isolated.

Construction of a predictive nomogram and bioinformatic investigation of the potential mechanism of postoperative early recurrence of hepatocellular carcinoma meeting the Milan criteria.

BackgroundHepatectomy is the most common treatment for hepatocellular carcinoma (HCC) meeting the Milan criteria; however, postoperative early recurrence (PER) compromises the survival time. This study aimed to construct a predictive nomogram for PER of HCC patients within the Milan criteria. And the underlying mechanism related to PER may associate with the independent risk factors used to construct the nomogram, therefore, we preliminarily investigated the potential mechanism of PER using The Cancer Genome Atlas (TCGA) database to provide an idea for preventing PER.MethodsPatients with HCC meeting the Milan criteria receiving hepatectomy in our center between 2009 and 2015 were enrolled. The clinical and histological data of all participants were collected. Follow-up was performed at outpatient and PER was defined as recurrence within 2 years after resection. All participants were randomly assigned to the training or validation cohort at a 4:1 ratio. A nomogram was constructed based on the independent risk factors in the training cohort. The accuracy and clinical utility of this nomogram were evaluated using the C-index, calibration plot, and decision curve analysis (DCA). The differentially-expressed genes (DEGs) between early-stage HCC patients with and without PER in TCGA database were identified. Enrichment analysis was performed to determine the potential relapse-related mechanism.ResultsThe independent risk factors were alpha-fetoprotein (AFP) ≥400 ng/mL, gamma-glutamyl transpeptidase (GGT) ≥60 U/L, Glisson’s capsule invasion, microvascular invasion (MVI), and satellite lesions. The C-index value of the nomogram was 0.693 [95% confidence interval (CI): 0.632–0.754; P<0.001] in the training cohort and 0.658 (95% CI: 0.529–0.787; P=0.016) in the validation cohort. The calibration and decision curves demonstrated good accuracy and clinical utility of this nomogram respectively. 133 DEGs were identified and enrichment analysis showed the bile secretion pathway related to PER and two bile secretion pathway-related genes {ATP1A2 [P=0.027; hazard ratio (HR) =2.086, 95% CI: 0.916–4.749] and SLC5A1 (P=0.0016; HR =0.361, 95% CI: 0.145–0.898)} were significantly associated with disease free survival (DFS).ConclusionsOur nomogram has satisfactory accuracy and clinical utility in predicting the PER of patients with HCC meeting the Milan criteria. Aberrant bile secretion may be an important mechanism of PER.

Peri-Kasai portoenterostomy sutures anchoring the jejunal loop to Glisson capsule: A novel modification to reduce the incidence of cholangitis

BackgroundKasai portoenterostomy (KPE) is the standard surgical management for biliary atresia (BA). To improve the outcome these infants were operated on within the first two months of life. The success of the procedure is reflected by clearance of jaundice and either absence or occurrence of fewer attacks of cholangitis. The failure of the procedure indicates liver transplantation (LT). Objectiveto reduce the incidence of the recurrent attacks of cholangitis by peri-KPE sutures anchoring the jejunal loop to the Glisson capsule. MethodsIt is a retrospective study that included 45 infants diagnosed with BA and who were operated on at an age younger than 60 days. They were categorized into two groups, Group A (n = 23) included infants treated with the classic KPE, and Group B (n = 22) included infants treated in the same way plus peri KPE sutures anchoring the jejunal loop to the Glisson capsule. ResultsThe mean operative time in Group A was 149.3 min versus 164.8 min in Group B (p-value 0.039). The mean level of bilirubin was 2.2 versus 2.1 in Group A and Group B respectively at two years follow up. The total attacks of cholangitis per patient were significantly lower in Group B than in Group A (cutoff value = 3), which was reflected by the significant reduction of the incidence of LT in Group B. Conclusionperi KPE sutures anchoring the jejunal loop to the Glisson capsule significantly reduced the incidence of recurrent attacks of cholangitis and subsequently decreased the requirement of LT on the short-term follow-up.

Effect of cultured white soft cheese on the histopathological changes in the kidneys and liver of albino rats

Three different types of lactic acid bacteria (Lactobacillus helveticus, Lactobacillus rhamnosus and Streptococcus thermophilus S3855) were used to manufacture white soft cheese. The resultant white soft cheeses were pickled for 28 days at refrigerator temperatures and were fed to the experimental rats. The chemical and microbiological analyses of white soft cheese were conducted at different storage periods (fresh, 7 days, 14 days, 21 days, and 28 days). The pH values and protein content of white soft cheese gradually decreased during the storage peroid. Conversely, the moisture content, titratable acidity, and fat/DM % of white soft cheese were found to increase with of the increase in pickling periods of up to 28 days. Microbiologically, the total viable count of bacteria in the control samples was lower than that in the other treatments. Furthermore, the treatments containing the L. helveticus and L. rhamnosus strains had the highest lactoacilli counts whereas the treatment containing the S. thermophilus strain had the highest streptococci counts. Twenty-five male Albino rats were used for experiemntal technique. Rats were fed with 70% basal diet with addition of 30% white soft cheese. Several pathological findings were present in all experimental groups apart from the control rats, and the kidney samples exhibited renal vascular congestion especially in the cortical area. The changes of the glomeruli comprise atrophy, distortion, hypocellularity of the glomerular tuft, and focal lymphoid cell reactions. The renal tubular epithelium showed a series of degenerative changes ranging up to necrosis. The liver samples showed variable hepatic injury in the form of thickening in the Glisson capsule, as well as dissociation and disorganization of hepatic cords. Hepatocellular vacuolar degeneration, presence of focal areas of nodular hyperplasia, the hyperplastic cells mixed with lymphocytic infiltration, congestion in the portal vein, periportal fibrosis and edema with the presence of newly formed nonfunctional bile ductulus. Based on the histopathology scores, the severity of renal and hepatic changes was significantly increased (P ≤ 0.05) in all of the experimental groups compared with the control group. Generally, the chemical composition, microbiological analysis and vital organs were significantly affected by using cultured white soft cheese.

Sub-Capsular Hematoma of the Liver Complicating Preeclampsia

Subcapsular hematoma of the liver Subcapsular hematoma of the liver (SCLH) is defined as an anatomical-clinical entity corresponding to the appearance of a hematic collection located between the intact GLISSON capsule and the hepatic parenchyma. It is a rare complication of pregnancy with a high maternal-fetal mortality, occurring most often in the context of pre-eclampsia or HELLP syndrome (Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome). We report the case of a 25-year-old parturient, primiparous woman, with no previous history, admitted to the emergency room for shock in a 29-week amenorrhea pregnancy. Ultrasound examination revealed a ruptured sub capsular hematoma of the liver. An urgent surgical exploration was required, during which a rupture of the subcapsular hematoma of the liver was revealed, accompanied by a state of hemorrhagic shock. The management consisted in a polytransfusion with suture of the hepatic lesion without paking. The evolution was favorable with clinico-biological normalization and the patient was declared discharged at D10 of her hospitalization.

Identification of Glisson's Capsule Invasion During Hepatectomy for Colorectal Liver Metastasis by Contrast-Enhanced Ultrasonography Using Perflubutane.

Glisson invasion by CLM is associated with a risk of margin-positive resection, leading to poor long-term outcomes after hepatectomy. This study was performed to evaluate the efficacy of intraoperative ultrasonography (IOUS) for the diagnosis of Glisson's capsule invasion by colorectal liver metastasis (CLM). This prospective study involved 50 consecutive patients undergoing hepatectomy for CLM. Preoperatively, all patients had undergone gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). During hepatectomy, a contrast agent (perflubutane) was intravenously injected and Glisson invasion was estimated based on three characteristic findings: a tumor thrombus, peripheral dilatation, and border irregularity/caliber change. The diagnostic abilities of the preoperative and intraoperative imaging studies were evaluated based on pathological examinations of resected specimens. Among 187 CLMs resected, pathological examinations proved Glisson invasion in 24 tumors (13%). IOUS revealed a tumor thrombus in 3 tumors (1.6%), peripheral dilatation in 4 (2.1%), and border irregularity and/or caliber change in 24 (12.8%). The sensitivity and specificity of IOUS with any of the above three findings for diagnosis of Glisson invasion was 79% and 96%, respectively, while preoperative EOB-MRI detected Glisson invasion in only four tumors (sensitivity/specificity, 17%/100%). The cutoff value of caliber change for diagnosis of Glisson invasion was set at 140% by receiver operating characteristic analysis. The R0 resection rates were not significantly different between patients with (82%) and without (85%) Glisson invasion. Identification of characteristic findings (tumor thrombus, peripheral dilatation, and border irregularity/caliber change) by contrast-enhanced IOUS is useful for the prediction of Glisson invasion by CLM.

Immobilization of amikacin on dextran: biocomposite materials that release an antibiotic in the presence of bacterial dextranase

AbstractThe immobilization of a broad‐spectrum antibiotic amikacin on macromolecules of dextran previously modified with epichlorohydrin is described. It is shown that the release of amikacin is observed only in the presence of dextranase, which is produced by bacteria. For the first time, biocomposite materials based on the Glisson capsule of the liver and the pericardium, containing a layer of grafted dextran acting as a carrier of amikacin and capable of releasing amikacin derivatives that have antibacterial activity in the case of infection, have been developed. It was found that the release rate of amikacin derivatives formed in the presence of dextranase is determined by diffusion and is inversely proportional to the squared thickness of the dextran‐containing layer on the surface of biocomposite materials. © 2020 Society of Chemical Industry

Identification of Glisson's Capsule Invasion during Hepatectomy for Colorectal Liver Metastasis by Contrast-Enhanced Ultrasonography Using Perflubutane

Background: The aim of this study was to evaluate efficacy of contrast-enhanced intraoperative ultrasonography (IOUS) in diagnosis of Glisson invasion in hepatectomy for colorectal liver metastasis (CLM). Methods: Subject consisted of 50 consecutive patients undergoing hepatectomy for CLM. Intraoperatively, presence or absence of Glisson invasion was estimated by IOUS with Perflubutane, based on the following four key findings on Glisson's capsule adjacent to the tumor: [Pattern-1] tumor thrombus, [2] border irregularity, [3] caliber change, and [4] peripheral dilatation. These findings were compared with results of pathological examinations. Results: Among 187 CLMs resected, Glisson invasion was proved in 24 tumors (13%; 7 tumors with macroscopically-obvious Glisson invasion and 17 tumors with microscopic Glisson invasion). Sensitivity/specificity of contrast-enhanced IOUS for diagnosis of macroscopic Glisson invasion was 43%/98% for the [Pattern-1], 14%/97% for [2], 86%/97% for [3], and 43%/98% for [4]. If presence of one or more key findings by IOUS were determined as a predictor of Glisson invasion, its sensitivity and specificity reached up to 100% and 90%, respectively. In contrast, sensitivity and specificity of preoperative contrast-enhanced MRI for Glisson invasion were respectively 29% and 97%. The proportion of R1 resection was not significantly different between CLM patients with Glisson invasion (82%) and those without Glisson invasion (85%). Conclusions: Evaluation of Glisson capsule adjacent to CLM by contrast-enhanced IOUS may be effective for estimation of Glisson invasion, which enables surgeons to divide Glisson capsule at the site free from the invasion, leading to avoid unexpected R1/R2 resection.

Fotosensibilización hepatógena en bovinos provocada por fasciolasis crónica

Hepatogenic photosensitization in cattle is a pathology that can be caused by several diseases, such as chronic fasciolasis, as a consequence of the damage provoked, causing an inability of the liver to excrete photodynamic agents. Fasciolasis is a disease of high prevalence in Uruguay. Photosensitization is one of the clinical signs that can be observed in chronic fasciolasis, based on its ability to produce liver fibrosis, cholangitis with biliary stasis. In this work, two outbreaks of hepatogenic photosensitization in cattle are described in the counties of Tacuarembo and Soriano (Uruguay). The disease affected a herd of Hereford and crossbreed cows, and a herd crossbreed heifers. In both outbreaks animals were grazing in humid woodlands. The main clinical signs observed were weight loss, crusting and peeling of the nose, photophobia, sialorrhea and eye shifts. Main macroscopic findings at necropsy were bilateral necrotic dermatitis of the eyelids, ulcers on the ventral side of the tongue. Thickening of the liver`s Glisson capsule, diffuse hepatic fibrosis and chronic cholangitis with canalicular calcification. Histopathology showed liver fibrosis and canalicular obstruction with the presence of Fasciola hepatica as main lesions. The clinical signs of hepatogenic photosensitization observed in animals are related to the described liver disorders caused by F. hepatica

Axolotl liver regeneration is accomplished via compensatory congestion mechanisms regulated by ERK signaling after partial hepatectomy.

Axolotls have remarkable organ-level regeneration capability. They can regenerate their limbs, tail, brain, gills, and heart. The liver had been considered to be a regenerative organ in these highly regeneration-competent animals. Therefore, no research had been performed on liver regeneration in urodele amphibians. In the present study, we focused on axolotl liver regeneration and found a unique regeneration mechanism compared with other vertebrates. Partial hepatectomy (PH) was performed to assess axolotl liver regeneration. Regeneration was assessed using block-face imaging (CoMBi), histology, cell proliferation, weight gain, and Albumin (Alb) + area. Axolotl liver histology was compared with other vertebrates. Axolotl liver consists of Glisson's capsule, sinusoids, and hepatic cord with no apparent lobule structures. Hepatocytes were mononucleated or multinucleated. PH increased the multinucleated hepatocytes and the Alb+ area, but there was no apparent liver shape recovery even 40 days after PH. Gene expression pattern suggests that no epimorphic regeneration takes place. We also found that the increase in the number of proliferating hepatocytes was regulated by ERK-signaling. Our findings suggest that axolotls, which have epimorphic regeneration ability, regenerate their liver via unique mechanisms, compensatory congestion.

Differential Localization and Invasion of Tumor Cells in Mouse Models of Human and Murine Leukemias.

Leukemias are refractory hematopoietic malignancies, for which the development of new therapeutic agents requires in vivo studies using tumor-bearing mouse models. Although several organs are commonly examined in such studies to evaluate the disease course, the effectiveness of interventions and the localization of tumor cells in the affected organs are still unclear. In this study, we histologically examined the distribution of leukemia cells in several organs using two leukemic mouse models produced by the administration of two cell lines (THP-1, a human myelomonocytic leukemia, and A20, a mouse B cell leukemia/lymphoma) to severe immunodeficient mice. Survival of the mice depended on the tumor burden. Although A20 and THP-1 tumor cells massively infiltrated the parenchyma of the liver and spleen at 21 days after transplantation, A20 cells were hardly found in connective tissues in Glisson’s capsule in the liver as compared with THP-1 cells. In the bone marrow, there was more severe infiltration of A20 cells than THP-1 cells. THP-1 and A20 cells were widely spread in the lungs, but were rarely observed in the small intestine. These findings suggest that each leukemia model has a unique localization of tumor cells in several affected organs, which could critically affect the disease course and the efficacy of therapeutic agents, including cellular immunotherapies.

Significance of glisson's capsule invasion in patients with colorectal liver metastases undergoing resection

Background: To determine the clinical significance of Glisson's capsule invasion in patients with colorectal liver metastases (CLM) undergoing resection, which has not been fully investigated. Methods: We identified 244 consecutive CLM patients who underwent resection with curative intent between 2011-2016. The cohort was divided into two groups: patients with (Group 1; n=49 [20%]) and without (Group 2; n=195 [80%]) histologically-proven Glisson invasion. Among Group 1, eight (16%) patients with macroscopic Glisson invasion were identified by pre- or intra-operative findings. We then compared patient characteristics and survival between Group 1 and 2, and determined independent prognostic factors for long-term postsurgical outcomes. Results: Group 1 was more commonly associated with right-sided primary disease, larger CLM, and underwent R1 resection significantly more often. The 3-year recurrence-free survival (RFS; 28%) and 5-year overall survival (OS; 64%) of Group 1 were similar to those of Group 2 (3-year RFS, 24% [P=0.825]; 5-year OS, 56% [P=0.494]). Independent factors associated with reduced OS in the entire cohort were chemotherapy pre-hepatic resection [hazard ratio (HR): 2.68, P=0.001], larger sized CLM (>5 cm) (HR: 4.39, P=0.002), moderately or poorly differentiated CLM (HR: 2.38, P=0.004), and R1 resection (HR: 1.92, P=0.035). Conclusions: Glisson invasion by CLM, most cases of which were identified histologically, was significantly associated with R1 resection. Further advancements in accurately determining Glisson invasion pre- or intra-operatively might produce clinical benefit for CLM patients undergoing resection by reducing their rates of R1 resection.

2296 Hepatic Rupture Due to Subcapsular Liver Hematoma in HELLP Syndrome

INTRODUCTION: Subcapsular liver hematoma (SLH) is a rare complication that occurs in about 1 in 45,000 pregnancies almost exclusively in the setting of preeclampsia or HELLP syndrome. Subcapsular and intraparenchymal hemorrhage can lead to hepatic capsular rupture which is associated with significant maternal and fetal mortality. We present a rare case of a pregnant woman who developed HELLP syndrome complicated by ruptured subcapsular liver hematoma. CASE DESCRIPTION/METHODS: A 33-year-old woman at 31 weeks of pregnancy presented with generalized abdominal pain. She was hypertensive and urinalysis showed proteinuria thus the clinical scenario was concerning for preeclampsia. Development of non-reassuring fetal heart tones led to an emergent C-section with delivery of a healthy infant. Within hours she became hypotensive and somnolent requiring vasopressors and intubation. The patient developed significantly elevated liver enzymes (peak ALT 15,463 U/L and AST 36,653 U/L), hyperbilirubinemia, oliguric renal failure, and hemolysis. A CT abdomen was obtained which demonstrated hepatomegaly with an extensive subcapsular and intraparenchymal hematoma and large volume hemoperitoneum, consistent with hepatic capsular rupture. Angiography showed extravasation of contrast from a branch of the right hepatic artery, which was embolized. The hospital course was complicated by disseminated intravascular coagulation, liver and bowel necrosis due to microthrombi requiring multiple laparotomies and resections, and persistent respiratory and renal failure. Ultimately the patient expired as a result of these complications. DISCUSSION: SLH can lead to rupture of the Glisson capsule and subsequent intraperitoneal bleeding and hemorrhagic shock. Hemodynamically stable patients can be managed conservatively. Unstable patients require hepatic artery embolization or surgical ligation, hepatic resection, or in severe cases liver transplantation. This case demonstrates a severe episode of hepatic rupture complicated by disseminated intravascular coagulation and thrombosis leading to patient mortality.