Introduction: intrahepatic cholangiocarcinoma (ICCA) are rare, aggressive cancers that develop in second order or smaller bile ducts. The aim of this review is to systematically review the most important prognostic factors affecting the long-term outcomes of these patients. Material and Methods: articles conducted on this issue, written in English, published between from January 2000 to December 2023 in Cochrane Library, PubMed, Embase, MedLine, Web of Science, Elsevier, Google Scholar were systematically researched and reviewed. Results: ICCA are usually late diagnosed cancers because of the asymptomatic character, and curative procedures are often not feasible, only 20 to 30% of patients being fit for surgery. With the prognostic of this aggressive malignancy being baleful, the most important risk factors but also prognosis factors seem to be represented by socioeconomic factors, morphological presentation, dimensions, number and extension of the tumor as well as resection margins. Conclusions: once these factors are widely recognized and identified in each case, the clinician will be able to find the best treatment for these patients in order to improve the long-term outcomes.

In fetal development, tissue interaction such as the interplay between blood vessel (BV) and epithelial tissue is crucial for organogenesis. Here we recapitulate the spatial arrangement between liver epithelial tissue and the portal vein to observe the formation of intrahepatic bile ducts (BDs) from human induced pluripotent stem cells (hiPSC). We co-culture hiPSC-liver progenitors on the artificial BV consisting of immature smooth muscle cells and endothelial cells, both derived from hiPSCs. After 3 weeks, liver progenitors within hiPSC-BV-incorporated liver organoids (BVLO) differentiate to cholangiocytes and acquire epithelial characteristics, including intercellular junctions, microvilli on the apical membrane, and secretory functions. Furthermore, liver surface transplanted-BVLO temporarily attenuates cholestatic injury symptoms. Single cell RNA sequence analysis suggests that BD interact with the BV in BVLO through TGFβ and Notch pathways. Knocking out JAG1 in hiPSC-BV significantly attenuates bile duct formation, highlighting BVLO potential as a model for Alagille syndrome, a congenital biliary disease. Overall, we develop a novel 3D co-culture method that successfully establishes functional human BDs by emulating liver epithelial-BV interaction.

BACKGROUND: Mass-forming intrahepatic cholangiocarcinoma (mICC) is the most frequent type of ICC. In contrast-enhanced computed tomography, mICC is visualized as a hypodense lesion with distal dilatation of intrahepatic bile ducts. The presented case illustrates the unusual manifestation of mICC in a 71-year-old male patient, where despite the extensive tumor mass and the hilar infiltration, the dilatation of intrahepatic bile ducts and cholestasis were not noted.
METHODS: A literature review on PubMed was performed. Primarily, 547 records were identified, and the titles and abstracts were systematically searched. Regarding the inclusion and exclusion criteria, 31 papers describing the non-cancerous liver lesions mimicking ICC were included in the further analysis.
RESULTS: In 41.9% of the analyzed non-cancerous lesions, the obstruction of the bile ducts was not noted, similar to our patient. A significant cholestasis has been found in 30.03% of analyzed patients. The invasion of the liver hilum was noted in one-third of the patients.
CONCLUSIONS: Atypical radiological features in lesions suspected of ICC, such as the absence of intrahepatic bile-duct dilation, are common in benign lesions. In the case of radiologically atypical lesions suspected of ICC, the diagnostic imaging needs to be correlated with clinical data, and the diagnosis should be confirmed with a pathological examination.

BACKGROUND: Complications after endoscopic retrograde cholangiopancreatography (ERCP) are diverse and usually treated with nonoperative management or percutaneous drainage; however, there are still some rare, life-threatening complications. This is an extremely rare case of biliary peritonitis caused by rupture of the intrahepatic bile duct after ERCP.
METHODS: A 63-year-old male underwent ERCP for common bile duct stones. On the second day after the procedure, the patient developed sepsis and abdominal distention. Contrast-enhanced computed tomography revealed a subcapsular hepatic fluid collection attached to the bile duct of segment VII.
METHODS: Sepsis resulted in liver parenchyma rupture and intrahepatic bile duct injury after ERCP. Intraoperative cholangiography revealed a connection between a hole in the liver parenchymal surface and the intrahepatic bile duct.
METHODS: Surgeons performed the cholecystectomy, inserted a T-tube into the common bile duct stones, sutured the defect, and put 2 drainage tubes around the lesion.
RESULTS: Postoperative recovery was uneventful, and the patient was discharged on the 17th postoperative day.
CONCLUSIONS: Intrahepatic bile duct perforation after ERCP can lead to rupture of the liver parenchyma, biloma, or abdominal peritonitis. Multidisciplinary management is necessary to achieve favorable outcomes.

暂无摘要。

We report the case of a 49-year-old man who attended the emergency department for a two-month history of compromised general condition, weight loss, abdominal pain, fever, and elevated inflammatory parameters. An imaging study demonstrates a bulky liver tumor associated with dilation of the bile duct and retroperitoneal adenopathies (hepatic hilum, intermediate, and right lumbar groups). These findings raise intrahepatic cholangiocarcinoma within the differential diagnoses, reason why segmental hepatectomy and regional lymphadenectomy were performed. Histopathology and immunochemistry revealed a lymphoplasmacytic inflammatory process with IgG4-positive plasma cells compatible with IgG4-associated disease. After the resection, expectant management was decided, with the patient evolving favorably, asymptomatic, and without signs of recurrence. We present a case and a brief literature review of an hepatic inflammatory pseudotumor, a rare entity with a benign behavior.

OBJECTIVE: This study aimed to characterize intraductal papillary neoplasm of the bile duct (IPNB) in patients undergoing initial and recurrent surgical resection and to evaluate the appropriateness of surgical treatment strategies.
METHODS: This study included 14 patients who underwent liver resection for intrahepatic IPNB. We assessed intraoperative and postoperative clinicopathological factors in patients undergoing both initial and recurrent surgeries.
RESULTS: Four patients experienced recurrence after initial surgery; all underwent pancreaticoduodenectomy. Postoperative complications were classified as Clavien-Dindo Grade 1-2 in three patients and Grade IIIb in one patient. There were no in-hospital deaths.
CONCLUSIONS: Pancreaticoduodenectomy for recurrent cases following hepatectomy for IPNB is considered safe within an acceptable range and contributes to a favorable long-term prognosis.

暂无摘要。

The peribiliary capillary plexus (PCP) regularly and densely lines the basal side of the lining epithelia of normal bile ducts. To determine the pathology of the PCP in high-grade biliary intraepithelial neoplasms (BilINs) and intraductal papillary neoplasms of the bile duct (IPNBs), a precursor of cholangiocarcinoma (CCA), and CCA. Seventy-six cases of surgically resected high-grade BilIN and 83 cases of IPNB were histopathologically examined using endothelial immunostaining of PCP; all cases of high-grade BilIN and 40 cases of IPNB were associated with invasive CCA. Invasive and preinvasive neoplasms were pathologically examined referring to a two-layer pattern composed of biliary lining epithelia and underlying PCP unique to the bile duct. All high-grade BilIIN cases had an underlying single layer of capillaries, similar to PCP (PCP-like capillaries). In 43% of the 83 cases of IPNB, these capillaries were regularly distributed in almost all stalks and intervening stroma of intraluminal neoplastic components, while in the remaining 57% of IPNB, capillaries were sparsely or irregularly distributed in intraluminal components showing cribriform or solid growth patterns composed of striking atypical neoplastic epithelia. Invasive carcinomas associated with high-grade BilIN and IPNB were not lined with capillaries. The loss of PCP-like capillaries underlying high-grade BilIN and in stalks or stroma of IPNB may be involved in the malignant progression of these precursors. Immunostaining of PCP could be a new pathological tool for the evaluation of malignant progression and vascular supply in CCA and its precursors.

OBJECTIVE: To explore whether sivelestat sodium could reduce the expression of mucin 5AC (MUC5AC) in intrahepatic bile duct epithelial cells by inhibiting neutrophil elastase (NE) and thus provide new potential therapeutic ideas for the treatment of intrahepatic bile duct stone (IBDS).
METHODS: (1) Bioinformatics analysis: differential gene analysis was performed on gallbladder stone cholecystitis sequencing data based on the gene expression omnibus (GEO) to screen for significantly different genes related to neutrophils and mucins. The search tool for the retrieval of interacting genes database (STRING) was used for protein interaction analysis to predict whether there was an interaction between NE and MUC5AC genes. (2) Animal experiment: a total of 18 male SD rats were divided into the sham-operated group, cholangitis model group and sivelestat sodium treatment group according to the random number table method, with 6 rats in each group. The cholangitis rat model was established by a one-time injection of 1.25 mg/kg lipopolysaccharide (LPS) into the right anterior lobe of the liver of rats in combination with the pre-experiment; the liver of the sham-operated group was injected with an equal volume of saline. After the modelling, 100 mg/kg of sivelestat sodium was injected into the tail vein of the cevalexin treatment group once a day for 5 days, and an equal volume of saline was injected into the tail vein of the sham-operated group and the cholangitis model group. Two weeks later, the rats were euthanized and their liver and bile duct tissues were taken. The pathological changes in the liver and bile duct tissues were observed under the light microscope. Immunohistochemical staining was used to detect the expressions of NE and MUC5AC in liver and bile duct tissues. The protein expressions of NE, MUC5AC and Toll-like receptor 4 (TLR4) were detected by Western blotting. (3) Cell experiment: primary human intrahepatic biliary epithelial cell line (HiBEpiC) was divided into blank control group, NE group (10 nmol/L NE), NE+sivelestat sodium low dose group (10 nmol/L NE+1×10-8 g/L sivelestat sodium 1 mL), NE+sivelestat sodium medium dose group (10 nmol/L NE+1×10-7 g/L sivelestat sodium 1 mL), NE+sivelestat sodium high dose group (10 nmol/L NE+1×10-6 g/L sivelestat sodium 1 mL). Cells were collected after 48 hours of culture, and EdU was performed to detect the proliferative activity of cells; enzyme linked immunosorbent assay (ELISA) and Western blotting were performed to detect the expression of MUC5AC in cells.
RESULTS: (1) Bioinformatics analysis: the NE gene (ELANE) had a reciprocal relationship with MUC5AC. (2) Animal experiment: light microscopy showed that hepatocyte edema, hepatocyte diffuse point and focal necrosis, confluent area fibrous tissue and intrahepatic bile ducts hyperplasia and inflammatory cell infiltration in the cholangitis model group; hepatic lobule structure of sivelestat sodium treatment group was clear, and the degree of peripheral inflammatory cell infiltration was reduced compared with the cholangitis model group. Immunohistochemical staining showed that the expressions of NE and MUC5AC were increased in the cholangitis model group compared with the sham-operated group, and the expressions of NE and MUC5AC were decreased in the sivelestat sodium group compared with the cholangitis model group [NE (A value): 5.23±2.02 vs. 116.67±23.06, MUC5AC (A value): 5.40±3.09 vs. 23.81±7.09, both P < 0.05]. Western blotting showed that the protein expressions of NE, MUC5AC, and TLR4 in the hepatic biliary tissues of the cholangitis model group were significantly higher than those of the sham-operated group; and the protein expressions of NE, MUC5AC, and TLR4 in the liver biliary tissues of the sivelestat sodium treatment group were significantly higher than those of the sham-operated group (NE/β-actin: 0.38±0.04 vs. 0.70±0.10, MUC5AC/β-actin: 0.37±0.03 vs. 0.61±0.05, TLR4/β-actin: 0.39±0.10 vs. 0.93±0.15, all P < 0.05). (3) Cell experiment: fluorescence microscopy showed that the proliferation of HiBEpiC cells in each group was good, and there was no significant difference in the proportion of positive cells. ELISA and Western blotting showed that the expressions of MUC5AC in cells of the NE group were significantly higher than those of the blank control group. The expressions of MUC5AC in the NE+different dose of sivelestat sodium group were significantly lower than those in the NE group, and showed a decreasing trend with the increase of sevastatin sodium concentration, especially in the highest dose group [MUC5AC (μg/L): 3.46±0.20 vs. 6.33±0.52, MUC5AC/β-actin: 0.45±0.07 vs. 1.75±0.10, both P < 0.05].
CONCLUSIONS: LPS can upregulate the expression of NE and MUC5AC in rats with cholangitis, while sodium sivelestat can reduce the expression of MUC5AC in in intrahepatic biliary epithelial cells by inhibiting NE, providing a new direction for the treatment of IBDS.