A heterogeneous subtype of biliary epithelial senescence may be involved in the pathogenesis of primary biliary cholangitis.

Background & Aims: Biliary epithelial senescence is involved in the pathogenesis of primary biliary cholangitis (PBC). We hypothesized that a unique subtype of programmed death-ligand 1 (PD-L1)-positive senescent biliary epithelial cells (BECs) may be related to the pathogenesis of PBC in association with cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) pathway.

Approach & Results: The expression of PD-L1, STING and their association with senescent markers p16 and p21 were immunohistochemically determined in livers taken from the patients with PBC (n = 87) and 97 diseased and normal control livers.

Generation and Accumulation of Various Advanced Glycation End-Products in Cardiomyocytes May Induce Cardiovascular Disease.

Cardiomyocyte dysfunction and cardiovascular diseases (CVDs) can be classified as ischemic or non-ischemic. We consider the induction of cardiac tissue dysfunction by intracellular advanced glycation end-products (AGEs) in cardiomyocytes as a novel type of non-ischemic CVD. Various types of AGEs can be generated from saccharides (glucose and fructose) and their intermediate/non-enzymatic reaction byproducts.

Analysis of Crude, Diverse, and Multiple Advanced Glycation End-Product Patterns May Be Important and Beneficial.

Lifestyle-related diseases (LSRDs), such as diabetes mellitus, cardiovascular disease, and nonalcoholic steatohepatitis, are a global crisis. Advanced glycation end-products (AGEs) have been extensively researched because they trigger or promote LSRDs. Recently, techniques such as fluorimetry, immunostaining, Western blotting, slot blotting, enzyme-linked immunosorbent assay, gas chromatography-mass spectrometry, matrix-assisted laser desorption-mass spectrometry (MALDI-MS), and electrospray ionization-mass spectrometry (ESI-MS) have helped prove the existence of intra/extracellular AGEs and revealed novel AGE structures and their modifications against peptide sequences.

Nestin may be a candidate marker for differential diagnosis between small duct type and large duct type intrahepatic cholangiocarcinomas.

Backgrounds/aims: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small and large duct types. These two subtypes show distinct differences in various clinicopathological features and possible cell origin and pathways of carcinogenesis, however, a differential diagnosis may be sometimes difficult. Given the type IV intermediate filament, Nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and small duct type iCCAs, the significance of nestin as a differential diagnostic marker between small and large duct types of iCCAs was addressed in the present study.

Potential of the Novel Slot Blot Method with a PVDF Membrane for Protein Identification and Quantification in Kampo Medicines.

Kampo is a Japanese traditional medicine modified from traditional Chinese medicine. Kampo medicines contain various traditional crude drugs with unknown compositions due to the presence of low-molecular-weight compounds and proteins. However, the proteins are generally rare and extracted with high-polarity solvents such as water, making their identification and quantification difficult.

Bile duct adenoma and small-sized small duct type intrahepatic cholangiocarcinoma show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components.

Aims: Given that bile duct adenoma was significantly more prevalent in the liver with small duct type intrahepatic cholangiocarcinoma (small duct iCCA), compared to other primary liver carcinomas, we examined the possibility of bile duct adenoma as a precursor of small duct iCCA by analysing genetic alterations and other features in bile duct adenomas.

Methods And Results: Subjects included 33 bile duct adenomas and 17 small-sized (up to 2 cm in diameter) small duct iCCAs. Genetic alterations were examined by direct sequencing for hot-spot regions and immunohistochemical staining.

An involvement of Hippo-yes-associated protein pathway in biliary epithelial senescence in primary biliary cholangitis.

Background & Aims: Accumulating evidence suggest that Hippo-yes-associated protein (YAP) pathway plays important roles in development and repair after injuries in biliary system. We disclosed that senescent biliary epithelial cells (BECs) participate in the pathogenesis of primary biliary cholangitis (PBC). We hypothesized that dysregulation of Hippo-YAP pathway may be associated with biliary epithelial senescence in pathogenesis of PBC.

Is nestin a diagnostic marker for combined hepatocellular-cholangiocarcinoma?

Background And Aims: The type IV intermediate filament, nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Therefore, the significance of nestin as a diagnostic marker for cHCC-CCA categorized by the World Health Organization (WHO) 2019 classification and its relationship with clinicopathological features were examined in the present study.

Methods And Results: Nestin expression was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 22 with small duct-type intrahepatic cholangiocarcinoma (iCCA), 20 with large duct-type iCCA and 35 with hepatocellular carcinoma (HCC).

Prediction of post-radiotherapy survival for bone metastases: a comparison of the 3-variable number of risk factors model with the new Katagiri scoring system.

We investigated patient survival after palliative radiotherapy for bone metastases while comparing the prognostic accuracies of the 3-variable number of risk factors (NRF) model and the new Katagiri scoring system (Katagiri score). Overall, 485 patients who received radiotherapy for bone metastases were grouped as per the NRF model (groups I, II and III) and Katagiri score (low-, intermediate- and high-risk). Survival was compared using the log-rank or log-rank trend test.

[A case of metastatic melanoma in the gallbladder].

Malignant melanoma is an aggressive tumor with a high potential for distant metastases. Autopsy studies have shown that gallbladder metastases are found in 15% of patients. However, metastatic melanoma of the gallbladder is rarely discovered in living patients.

Apical Membrane Expression of Distinct Sulfated Glycans Is a Characteristic Feature of Ductules and Their Reactive and Neoplastic Counterparts.

Intrahepatic bile ducts transport bile between bile canaliculi and the extrahepatic bile duct. The luminal surface of this tract is lined by a layer of biliary epithelial cells, or cholangiocytes, which secrete mucins consisting of scaffold proteins and -glycosidically linked carbohydrate side chains. Although mucin core proteins have been extensively investigated, the structure and function of carbohydrate side chains have not.

Interferon-induced protein with tetratricopeptide repeats 3 may be a key factor in primary biliary cholangitis.

Accumulating studies suggest that senescent biliary epithelial cells (BECs) produce senescence-associated secretory phenotypes (SASPs) and play various roles in the pathogenesis of primary biliary cholangitis (PBC) and other cholangiopathies. We examined comprehensive profiles of senescent BECs and its contribution to the pathogenesis of PBC taking advantage of microarray analysis. cDNA microarray analysis revealed that 1841 genes including CCL2, IFIT3, CPQ were commonly up-regulated in senescent BECs cultured in serum depleted media or media with glycochenodeoxycholic acid.

Diversity in cell differentiation, histology, phenotype and vasculature of mass-forming intrahepatic cholangiocarcinomas.

Aims: 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.

Methods And 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.

Bile duct adenoma may be a precursor lesion of small duct type intrahepatic cholangiocarcinoma.

Background/aims: Precursor lesions of small duct type intrahepatic cholangiocarcinoma (small duct iCCA) have not been clarified so far. We hypothesised that precursor lesions may be frequently distributed in the background liver of small duct iCCA.

Methods And Results: We determined by histology the presence of bile duct adenomas and von Meyenburg complexes as candidate precursor lesions in the background liver of small duct iCCA, with other primary liver carcinomas as control.

Efficient Prophylactic Management of HBV Reactivation by an Information Technology Encoding System: Results of a 6-year Prospective Cohort Study.

Objective We started an information technology (IT) system that encodes the medical treatment status of hepatitis B virrus (HBV) with a 9-digit number, automatically checks for inappropriate situations occurring due to immunosuppression and chemotherapy that do not comply with the flowchart of the hepatitis B countermeasure guideline, and promotes correct HBV medical treatment in our hospital. We conducted a prospective study of HBV reactivation using this system. Methods Among 21,607 cases that were managed using this system, 1,206 patients who were HBs antigen-negative, HBc antibody- and/or HBs antibody-positive and in whom HBV DNA quantification was performed two times or more were examined for the occurrence of HBV reactivation.

Clinicopathological characteristics of intraductal papillary neoplasm of the bile duct: a Japan-Korea collaborative study.

Background: The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location.

Methods: IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated.

Canal of Hering loss is an initiating step for primary biliary cholangitis (PBC): A hypothesis.

The origin and initiating features of PBC remain obscure despite decades of study. However, recent papers have demonstrated loss of canals of Hering (CoH) to be the earliest histologic change in liver biopsy specimens from patients with primary biliary cholangitis (PBC). We posit that CoH loss prior to significant inflammation or evidence of bile duct injury might be a very early, perhaps even an initiating lesion of PBC.

Increased p16-expressing senescent bile ductular cells are associated with inadequate response to ursodeoxycholic acid in primary biliary cholangitis.

Background & Aims: Senescent biliary epithelial cells (BECs) may be involved in the pathophysiology of primary biliary cholangitis (PBC) by secreting senescence-associated secretory phenotypes. We examined an association of the extent of cellular senescence in BECs with clinicopathological features including response to ursodeoxycholic acid (UDCA) and a possibility of senolytic therapy in PBC.

Methods: The expression of senescent markers (p21, p16) and B-cell lymphoma-extra large (Bcl-xL), a key regulator of senescent cell anti-apoptotic pathway, was immunohistochemically examined in livers from patients with PBC (n = 145) and 103 control livers.

Peribiliary glands: development, dysfunction, related conditions and imaging findings.

Peribiliary glands are minute structures that are distributed along the intrahepatic large bile ducts, extrahepatic bile duct, and cystic duct. These glands regulate many physiological functions, such as enzyme secretion. Pancreatic exocrine tissues and enzymes are often observed in peribiliary glands; thus, peribiliary glands are involved in enzyme secretion.

The Pathologic and Genetic Characteristics of the Intestinal Subtype of Intraductal Papillary Neoplasms of the Bile Duct.

The present study aimed to identify the pathologic and genetic characteristics of intestinal subtype of intraductal papillary neoplasm of the bile duct (iIPNB) showing columnar cells with pseudostratified, cigar-shaped nuclei, and basophilic or amphophilic cytoplasm with the diffuse immunohistochemical expression of CK20 and/or CDX2. A total of 34 cases of iIPNB were pathologically examined according to their anatomic location (the bile duct) and were then compared with the intestinal subtype of intraductal papillary mucinous neoplasm (iIPMN) of the pancreas (n=22). Mutations of 26 somatic genes were examined in formalin-fixed paraffin-embedded tissue specimens from 21 cases of iIPNB using the TruSight Tumor 26 gene panel and next-generation sequencing.