暂无摘要。

UNASSIGNED: Liver biopsy is still the standard method for the diagnosis of ductal plate malformations (DPM). However, it is an invasive tool. Magnetic resonance imaging (MRI) has shown its accuracy in the diagnosis of this pathology. Herein, a study was conducted to elucidate the role of diffusion MRI parameters in predicting the degree of hepatic fibrosis.
UNASSIGNED: This prospective study included 29 patients with DPM and 20 healthy controls. Both groups underwent diffusion tensor magnetic resonance imaging (DT-MRI), and its parameters were compared between patients and controls, and then they were correlated with the degree of liver fibrosis in the patient group.
UNASSIGNED: All patients with DPM, whatever its type, expressed a significantly lower hepatic apparent diffusion coefficient (ADC) compared to controls. However, fractional anisotropy (FA) showed no significant difference between them. The ADC value of 1.65 × 10-3 mm2/s had sensitivity and specificity of 82.1% and 90%, respectively, in differentiating DPM patients from healthy controls. It was evident that patients with higher fibrosis grades had significantly lower hepatic ADC, indicating a negative correlation between ADC and the grade of hepatic fibrosis; rs = -0.901, p < 0.001.
UNASSIGNED: DT-MRI showed good efficacy in the diagnosis of congenital DPM. Moreover, ADC could be applied to monitor the degree of liver fibrosis rather than the invasive liver biopsy. No significant correlation was noted between the FA and the grades of liver fibrosis.

Ductal plate malformations (DPM) arise from abnormal remodeling of the embryologic ductal plate of the liver. Malignant transformation of DPMs to intrahepatic cholangiocarcinoma (iCCA) has been reported in very rare instances but is viewed with some skepticism. We report the clinicopathological findings in five cases of iCCA, occurring in liver with DPM-like features. All tumors were less than 5 cm, often presented as stage T1a tumors. Histologically, a typical tumor showed a vague multinodular architecture with larger, irregular, tortuous glandular structures with microcystic dilation, intraluminal fibroepithelial projection, and bridge/island formation. The tumor cells were relatively small, bland, and without obvious pleomorphism. Interestingly, DPM presented as a histopathological transition sequence of definitively benign to biliary intraepithelial neoplasia (bilIN), then finally to iCCA. A complete pushing border, with entrapped portal tracts at the edge of the main tumor, suggested a replacing growth pattern. There was gradually increased expression of Ki-67 and p53 in these transition phases from benign to bilIN then to iCCA with DPM-like features. The neoplastic epithelium exhibited immunoreactivity in EpCAM, MUC1, NCAM, and CK19. KRAS mutation was found in 2 of the 5 iCCA cases with DPM-like features. Multifocal DPMs or VMCs with bilIN were dispersed in the non-tumor liver parenchyma in 3 of the 5 cases. The neoplasm was interpreted as iCCA arising in DPM, which may have originated from small bile duct or hepatic precursor cells. More studies are needed to verify this scarce entity and its premalignant properties.

OBJECTIVE: Mass-forming intrahepatic cholangiocarcinomas (MF-iCCAs), involving small bile ducts, bile ductules or canals of Hering, remain treated as a single entity. We aimed to examine the diversity in histology, phenotype and tumour vasculature of MF-iCCAs.
RESULTS: Based on morphology and immunophenotype, we classified MF-iCCAs into small bile duct (SBD), cholangiolocarcinoma (CLC), ductal plate malformation (DPM) and hepatocellular carcinoma (HCC)-like subtypes. Genetic correlations among the histological subtypes were examined by multi-region tumour sequencing. Vasculatures and other clinicopathological features were compared among tumour groups with various proportions of the histological subtypes in 62 MF-iCCAs. Cases of pure SBD, CLC, DPM and HCC-like subtypes numbered 18 (29%), seven (11.3%), none (0%) and two (3%), respectively; the remaining 35 (56.4%) cases comprised several components. Genetic alterations, isocitrate dehydrogenase (IDH)1/2, KRAS, TP53, polybromo-1 (PBRM1) and BRCA1-associated protein 1 (BAP1), were shared among SBD, CLC, DPM and hepatoid components within a tumour. We uncovered distinct vascularisation mechanisms among SBD, CLC and DPM subtypes with a prominent vessel co-option in CLC tumours. iCCA with a DPM pattern had the highest vascular densities (mean microvascular density,140/mm2 ; arterial vessel density, 18.3/mm2 ). Increased CLC component was correlated with longer overall survival time (r = 0.44, P = 0.006). Pure SBD tumours had a lower 5-year overall survival rate compared with MF-iCCA with CLC pattern (30.5 versus 72.4%, P = 0.011).
CONCLUSIONS: MF-iCCAs comprise four histological subtypes. Given their sharing some driver gene alterations, indicating they can have a common cell origin, SBD, CLC and DPM subtypes, however, differ in cell differentiation, histology, phenotype or tumour vasculature.

Ductal plate malformations are abnormalities in the liver that arise from inappropriate or incomplete remodeling of the embryologic ductal plate. Various types of ductal plate malformations are reported in the human and veterinary literature, most commonly affecting domestic mammalian species but also fish. We investigated the occurrence and described the histopathologic features of ductal plate malformations in captive snakes. Malformations were identified in 18 snakes: 10 colubrids, 6 vipers, and 2 boids. There was no sex predilection, and the mean age was 17 years. The majority of lesions were incidental with most snakes having one or more comorbidities, most commonly neoplasia or systemic inflammation, that resulted in natural death or euthanasia. Ductal plate malformations in all livers were broadly characterized by a well-demarcated nodule of irregular bile ducts embedded within a varying amount of fibrous stroma. Malformations were further categorized based on the amount of fibrous stroma and dilation of the bile ducts as von Meyenburg complexes, cystic liver disease, and/or an intermediate hybrid subtype representative of cysts arising within von Meyenburg complexes. Histochemical and immunohistochemical staining, including Gomori\'s trichome and pan-cytokeratin, respectively, were applied on select cases to confirm histologic features. Malignant transformation was not identified within this population.

BACKGROUND: A retrospective chart review of liver histologies in Kasai biliary atresia BA patients operated 1/2017- 7/2019 at our institution was conducted to identify histologic prognostic factors for biliary outcome.
METHODS: Patients with wedge liver biopsies and portal plate biopsies (n = 85) were categorized into unfavorable and favorable outcome, based on a 3-month serum total bilirubin level of <34 μM or mortality. Hepatocellular histologies, presence of ductal plate malformation (DPM) and of large bile duct of ≥ 150 μm diameter size at the portal plate were evaluated.
RESULTS: Total Bilirubin levels> 34 μM correlates with worse 1-year survival. Age at surgery, histologic fibrosis or inflammation does not predict outcome. Potential adverse predictors are severe hepatocellular swelling, severe cholestasis, presence of DPM (n = 24), and portal plate bile duct size < 150 µm (n = 28). In multivariate analyses adjusting for age at Kasai and postop cholangitis, bile duct size and severe hepatocellular swelling remain independent histologic prognosticators (OR 3.25, p = 0.039 and OR 3.26, p = 0.006 respectively), but not DPM.
CONCLUSIONS: Advanced histologic findings of portal plate bile duct size of <150 µm and severe hepatocellular damage predict poor post-Kasai jaundice clearance and short-term survival outcome, irrespective of Kasai timing.
METHODS: Level III.

Hepatic cysts are found in heterogeneous disorders with different pathogeneses, of which simple hepatic cysts and polycystic liver diseases are two major types. The process of hepatic cytogenesis for these two diseases is caused by defects in remodelling of the ductal plate during biliary tract development, which is called ductal plate malformation. SOX9 is a transcription factor participating in the process of bile duct development, and thus, its dysregulation may play important roles in hepatic cystogenesis. SEC63 encodes an endoplasmic reticulum membrane protein that is mutated in human autosomal dominant polycystic liver disease. However, the transcriptional regulation of SEC63 is largely unknown. In the present study, a liver-specific Sox9 knockout (Sox9LKO ) mouse was generated to investigate the roles and underlying mechanism of SOX9 in hepatic cystogenesis. We found that hepatic cysts began to be observed in Sox9LKO mice at 6 months of age. The number and size of cysts increased with age in Sox9LKO mice. In addition, the characteristics of hepatic cytogenesis, including the activation of proliferation, absence of primary cilium, and disorder of polarity in biliary epithelial cells, were detected in the livers of Sox9LKO mice. RNAi silencing of SOX9 in human intrahepatic biliary epithelial cells (HIBEpic) resulted in increased proliferation and reduced formation of the primary cilium. Moreover, Sec63 was downregulated in primary biliary epithelial cells from Sox9LKO mice and SEC63 in HIBEpic transfected with siSOX9. Chromatin immunoprecipitation assays and luciferase reporter assays further demonstrated that SOX9 transcriptionally regulated the expression of SEC63 in biliary epithelial cells. Importantly, the overexpression of SEC63 in HIBEpic partially reversed the effects of SOX9 depletion on the formation of primary cilia and cell proliferation. These findings highlight the biological significance of SOX9 in hepatic cytogenesis and elucidate a novel molecular mechanism underlying hepatic cytogenesis. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

BACKGROUND: Biliary adenofibroma is an exceptionally rare benign liver tumor with the potential for malignant transformation. In literature, only 21 cases have been described.
METHODS: In a healthy 63-year-old woman, a partly solid, partly cystic mass in the left lobe of the liver during a routine ultrasound examination was found. The computed tomography (CT) scan of the abdomen showed a 6.3 × 5.0-cm multilobulated cystic, partly hypervascularized mass in the liver segment IVa, with extension into segments II and IVb. There was no evidence of lymph node or distant metastases. Extirpation of the tumor was indicated by the multidisciplinary tumorboard. Microscopic examination showed a biphasic composed tumor with tubules embedded in fibrous stroma. In addition, there were also areas with pseudopapillary projections, as well as parts with focal cribriform-like growth pattern, which have been indicated as a possible sign of malignant transformation. Additionally, we found two different polymorphisms in the encoded TP53 und KIT in both distinct morphology tumor areas by molecular analysis, which ensured a tumor in malignant transformation. The patient has been alive for 24 months after R0 resection without tumor recurrence. Further investigation of more cases of this rare entity is necessary to proof molecular genesis.
CONCLUSIONS: We report a rare case of a biliary adenofibroma with transition to an intrahepatic cholangiocellular carcinoma and present a brief literature review.

Congenital hepatic fibrosis (CHF) is a genetic liver disease resulting in abnormal proliferation of cholangiocytes and progressive hepatic fibrosis. CHF is caused by mutations in the PKHD1 gene and the subsequent dysfunction of the protein it encodes, fibrocystin. However, the underlying molecular mechanism of CHF, which is quite different from liver cirrhosis, remains unclear. This study investigated the molecular mechanism of CHF pathophysiology using a genetically engineered human induced pluripotent stem (iPS) cell model to aid the discovery of novel therapeutic agents for CHF.
PKHD1-knockout (PKHD1-KO) and heterozygously mutated PKHD1 iPS clones were established by RNA-guided genome editing using the CRISPR/Cas9 system. The iPS clones were differentiated into cholangiocyte-like cells in cysts (cholangiocytic cysts [CCs]) in a 3D-culture system.
The CCs were composed of a monolayer of cholangiocyte-like cells. The proliferation of PKHD1-KO CCs was significantly increased by interleukin-8 (IL-8) secreted in an autocrine manner. IL-8 production was significantly elevated in PKHD1-KO CCs due to mitogen-activated protein kinase pathway activation caused by fibrocystin deficiency. The production of connective tissue growth factor (CTGF) was also increased in PKHD1-KO CCs in an IL-8-dependent manner. Furthermore, validation analysis demonstrated that both the serum IL-8 level and the expression of IL-8 and CTGF in the liver samples were significantly increased in patients with CHF, consistent with our in vitro human iPS-disease model of CHF.
Loss of fibrocystin function promotes IL-8-dependent proliferation of, and CTGF production by, human cholangiocytes, suggesting that IL-8 and CTGF are essential for the pathogenesis of CHF. IL-8 and CTGF are candidate molecular targets for the treatment of CHF.
Congenital hepatic fibrosis (CHF) is a genetic liver disease caused by mutations of the PKHD1 gene. Dysfunction of the protein it encodes, fibrocystin, is closely associated with CHF pathogenesis. Using an in vitro human induced pluripotent stem cell model and patient samples, we showed that the loss of fibrocystin function promotes proliferation of cholangiocytes and the production of connective tissue growth factor (CTGF) in an interleukin 8 (IL-8)-dependent manner. These results suggest that IL-8 and CTGF are essential for the pathogenesis of CHF.

A 6-year-old entire female rottweiler dog with a recent history of ascites and respiratory disease was submitted for necropsy examination. The dog had been diagnosed ultrasonographically with biliary cysts as a puppy. Grossly, the liver was smaller than expected with an irregular surface. Islands of hepatocytes were separated by bands of fibrosis and many bile ducts were markedly dilated. Histologically, extensive fibrosis extended beyond the limiting plate and into the surrounding hepatic parenchyma and was associated with abundant small bile ducts throughout. In conjunction with the detection of biliary cysts early in life, the gross and histological findings were consistent with a diagnosis of Caroli syndrome. In man, Caroli syndrome is frequently associated with renal and pancreatic cysts; a single renal cyst was identified in this case.