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Jia Zhao,1,* Wenbin Ding,1,* Benfang Fan,2 Chunxia Chen,1 Lihua Wang2 1Department of Interventional Radiology, Nantong First People’s Hospital, Nantong, 226001, People’s Republic of China; 2Nursing Department, Nantong First People’s Hospital, Nantong, 226001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lihua Wang, Nursing Department, Nantong First People’s Hospital, No. 666 of Shengli Road, Chongchuan District, Nantong, 226001, People’s Republic of China, Tel +86 513 81111039, Email wanglihuawlh6@126.comObjective: We develop the Readiness for Hospital Discharge Scale (RHDS) for patients with bile duct carcinoma catheterized after percutaneous transhepatic cholangial drainage (PTCD) and test the reliability and validity of the scale, so as to provide a quantitative tool for evaluating the discharge readiness of patients catheterized after PTCD.Methods: The initial scale was developed following literature review, qualitative interviews, expert consultation, and other methods based on Meleis’ Theory of Transition. We selected a total of 286 patients with bile duct carcinoma catheterized after PTCD from four tertiary A-grade hospitals in Nantong City. We conducted a cross-sectional survey using the initial scale to test the validity and reliability of the scale.Results: RHDS for patients catheterized post-PTCD consisted of five dimensions, with a cumulative variance contribution rate of 74.6%. The Cronbach’s α coefficient of the scale was 0.856, and that of each dimension was between 0.740 and 0.891; the scale-content validity index (S-CVI) was 0.875.Conclusion: RHDS for patients with bile duct carcinoma catheterized after PTCD developed in this study, has good reliability and validity, and can be a useful tool for evaluating the discharge readiness of patients with bile duct carcinoma catheterized after PTCD.Keywords: bile duct carcinoma, discharge readiness, percutaneous transhepatic cholangial drainage, scale

There is scant literature on primary nonhematopoietic malignant liver tumours (PMLT) in cats. In this retrospective study, medical data of 40 cats diagnosed with PMLT were reviewed over a period of 22 years (2000–2021). The most frequent epithelial tumours were hepatocellular (42.5%) and bile duct carcinomas (32.5%), only six (15%) cats had mesenchymal tumours. The median age was 13 years and clinical signs commonly included ano‐/hyporexia (62.5%), apathy/lethargy (52.5%), weight loss (42.5%) and vomiting (35%). At initial diagnosis, metastases were confirmed in 1 (2.5%) and suspected in three (7.5%) cats. Massive was the most frequent morphology (75%). Most intrahepatic tumours were left‐sided (54.2%) with the left medial lobe being primarily affected (25%). Extrahepatic tumours were rare (5%). In 34 (85%) cats, liver lobectomy was performed (surgery group), four (10%) were treated palliatively (non‐surgery group), and two (5%) received no treatment. Intraoperative complications occurred in 11.8% with four (15.4%) postoperative deaths. Recurrence was detected in 28.6% at a median of 151 days (range, 79–684 days), while postoperative metastases were suspected in 21.4% at a median of 186 days (range, 79–479 days). The median survival time (MST) was significantly longer in cats of the surgery group (375 days) than in the non‐surgery group (16 days) (p =.002). MST was 868 days for hepatocellular compared to 270 days for bile duct carcinomas (p =.06). In summary, liver lobectomy is associated with prolonged survival times and good prognosis in cats with hepatocellular, and an acceptable prognosis in cats with bile duct carcinoma. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is a cancer that emerges from the biliary epithelium neoplastic transformation and has a steadily increasing incidence and prevalence. It is the 2ndmost prevalent primary hepatic cancer, accounting for around 15% of cases and 3% of GITcancers. Objectives: are to determine risk factors and prevalence for various forms of Cholangiocarcinoma (CCA). Patients and methods: A prospective study was conducted at Qena university hospital on 62 patients with cholangiocarcinoma proved by imaging, cytological or pathological evidence. Complete full history was taken, then full clinical examination and laboratory study were done. Result: Prevalence of distal cholangiocarcinoma was 56.5%, but hilar cholangiocarcinoma was 43.5% (n=27). A significant relation between gender and type of cholangiocarcinoma, where hilar type was more common among females P value= 0.02. Also, a significant relation between smoking and obesity and type of cholangiocarcinoma where distal type was more common among smokers and obese patients (P = 0.05 and P=0.03 respectively). Conclusion:Gender variation, smoking and obesity are the most important risk factors of cholangiocarcinoma, with hilar type more common among females, distal type more common among smokers and obese patients. Distal cholangiocarcinoma is more prevalent than hilar cholangiocarcinoma (56.5% and 43.5% respectively).

Purpose: We used a novel diagnostic Fourier transform (FT) algorithm of the entire extrahepatic bile duct (EHBD) measured by magnetic resonance cholangiography (MRC) to evaluate subtle deformation of bile duct lumen, indicating the malignant potential of EHBD, in patients with pancreaticobiliary maljunction (PBMJ) and in a comparative group of controls without PBMJ. Methods: From the workstation, the EHBD lumen was traced automatically and a 2D diagram cross section was measured at 0.5 mm-longitudinal intervals. The FT-based integrated power spectral density function value (FTPSDI) of the diameter or area (mm2 or mm4/Hz) and the phase value distribution entropy (PVDE) were also measured. Results: There were 16 patients with undilated PBMJ and 7 with dilated PBMJ. The control group comprised 10 patients with a normal bile duct, 20 with bile duct carcinoma (BDC), and 1 with primary sclerosing cholangitis. Both the diameter and area of the dilated bile ducts and the ducts with early- or advanced-stage BDC were significantly greater than those of the normal duct (p < 0.05). The undilated type of PBMJ tended to have a larger FTPSDI diameter than a normal bile duct, which had a smaller diameter than the dilated type of PBMJ or BDC. BDC had a significantly larger FTPSDI diameter (p < 0.05) and the cutoff value for accuracy was 168 mm2 Hz−1. Conclusion: The novel mathematical FTPSDI is a promising indicator of whether preventive EHBD resection is necessary for patients with PBMJ, which can be widely applied in the early diagnosis of other biliary diseases. [ABSTRACT FROM AUTHOR]

A 17-year-old captive male puma (Puma concolor) died after presenting anorexia, vomiting, weight loss and lethargy. At necropsy, the right middle lobe of the liver was severely affected by a tumor, and small tumor nodules were disseminated throughout the other lobes. The numerous tumor nodules were also found in the lung, stomach, kidney, heart and diaphragm, which were growing together, suspiciously metastatic, projecting, 5 to 40 mm in diameter and tawny to white in color. Histopathologically, the tumor was composed of prominent papillary-acinar structures and the cells had a resemblance to the biliary epithelium. Immunohistochemically, the tumor cells were strongly reactive for cytokeratin and CD10 and were negative for carcinoembryonic antigen, fetoprotein and hepatocyte paraffin-1. Taken together, the tumor was diagnosed as cholangiocarcinoma. This is the first case report of a cholangiocarcinoma in the puma. [ABSTRACT FROM AUTHOR]

Objective: Prognosis of patients with irresectable cholangiocarcinoma is still poor. The ABC-02 trial established the current first line (1L) standard systemic chemotherapy (CT) with gemcitabine/platinum derivate for advanced cholangiocarcinoma. However, the majority of patients needed therapy adaptions. Thus, the aim of this study was to evaluate 1L and second line (2L) therapy regimens and the impact of therapy adaptions in an unselected real-life cohort of patients with advanced cholangiocarcinoma. Materials and Methods: This is a single institution retrospective analysis of patients with irresectable cholangiocarcinoma who were treated with gemcitabine/platinum derivate from 2010 to 2018. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially with regard to CT de-escalation. Results: Fifty-eight patients receiving gemcitabine/platinum derivate were included in the analysis. Median OS and PFS were 12.2 and 6.9 months. Interestingly, 41 patients (71%) needed therapy de-escalation. However, despite reduced CT exposition, there was no-significant difference in OS (10.8 months vs. 15.6 months, p = 0.127), and patients suffered from less adverse events during CT. 21 (36%) patients reached 2L CT, most often with FOLFIRI (57%). Survival beyond the end of 1L CT was 7.1 months with 2L CT vs. 2.9 months with BSC. Conclusion: In our study, the combination of gemcitabine/platinum derivate showed similar OS and PFS as randomized prospective phase II/III trials. Therapy regimen adaptions were needed in the majority of patients. However, individualized modifications of the therapy regimen allowed better tolerance as well as continuation of therapy and did not significantly influence median OS. Furthermore, our study revealed a potential survival benefit with 2L CT for selected patients. [ABSTRACT FROM AUTHOR]

ObjectivePrognosis of patients with irresectable cholangiocarcinoma is still poor. The ABC-02 trial established the current first line (1L) standard systemic chemotherapy (CT) with gemcitabine/platinum derivate for advanced cholangiocarcinoma. However, the majority of patients needed therapy adaptions. Thus, the aim of this study was to evaluate 1L and second line (2L) therapy regimens and the impact of therapy adaptions in an unselected real-life cohort of patients with advanced cholangiocarcinoma.Materials and MethodsThis is a single institution retrospective analysis of patients with irresectable cholangiocarcinoma who were treated with gemcitabine/platinum derivate from 2010 to 2018. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially with regard to CT de-escalation.ResultsFifty-eight patients receiving gemcitabine/platinum derivate were included in the analysis. Median OS and PFS were 12.2 and 6.9 months. Interestingly, 41 patients (71%) needed therapy de-escalation. However, despite reduced CT exposition, there was no-significant difference in OS (10.8 months vs. 15.6 months, p = 0.127), and patients suffered from less adverse events during CT. 21 (36%) patients reached 2L CT, most often with FOLFIRI (57%). Survival beyond the end of 1L CT was 7.1 months with 2L CT vs. 2.9 months with BSC.ConclusionIn our study, the combination of gemcitabine/platinum derivate showed similar OS and PFS as randomized prospective phase II/III trials. Therapy regimen adaptions were needed in the majority of patients. However, individualized modifications of the therapy regimen allowed better tolerance as well as continuation of therapy and did not significantly influence median OS. Furthermore, our study revealed a potential survival benefit with 2L CT for selected patients.

The aim of this study is to investigate the role of CFHR1 in bile duct carcinoma (BDC) and its mechanism of action, and we hope that our analysis and research will contribute to a better understanding of cholangiocarcinoma (BDC) disease genesis, progression and the development of new therapeutic strategies. The prognostic receiver operating characteristic curve of CFHR1 was generated using survival ROC. The ROC curve for CFHR1 showed that there is a correlation between CFHR1 expression and clinicopathological parameters and has an impact on poor prognosis. STRING was used to predict the protein-protein interaction network of the identified genes, and the Microenvironment Cell Populations counter algorithm was used to analyze immune cell infiltration within the BDC. The combined analysis showed that CFHR1 was found to be upregulated in BDC tissues, along with a total of 20 related differentially expressed genes (DEGs) (8 downregulated and 12 upregulated genes). Also, the results showed that the expression of CFHR1 is correlated with immune cell infiltration in tumor and immune cell markers in BDC (P < 0.05). In addition, we have verified experimentally the biological function of CFHR1. These findings suggest that CFHR1 may be a prognostic marker and a potential therapeutic target for BDC. Information regarding the detailed roles of CFHR1 in BDC could be valuable for improving the diagnosis and treatment of this rare cancer. [Display omitted] • The role of CFHR1 and its mechanism of action in the context of bile duct carcinoma (BDC) were explored. • The expression of CFHR1 is correlated with immune cell infiltration in tumor and immune cell markers in BDC. • CFHR1 may be a prognostic marker and a potential therapeutic target for BDC. [ABSTRACT FROM AUTHOR]

Adenomyomatous hyperplasia (AH) is a tumor-like inflammatory hyperplastic lesion. In the biliary system, AH commonly arises in the gallbladder, but AH of the extrahepatic bile duct is extremely rare. AH usually develops and is found with symptoms related to biliary stenosis or obstruction, but there are few disease-specific manifestations. It is difficult to make a definitive diagnosis by imaging or cytopathological examination; thus, surgical resections were performed in all past reported cases. The pathophysiological etiology of AH is unknown, but it is considered to be associated with chronic inflammation. According to the epidemiological findings of cases reported to date, the possibility of malignant transformation is considered to be negative. However, the symptoms and imaging findings of AH are difficult to distinguish from those of early-stage bile duct carcinoma. In the current review, we discuss the epidemiology, pathophysiology, diagnosis, and management of AH of the bile duct. [ABSTRACT FROM AUTHOR]

Background/Aims: Bile duct cancer, although not among the most common tumors, still accounts for more and more worldwide deaths each year. By attempting to verify an overexpression of ALDOA in cholangiocarcinoma tissues and cells and explore the underlying molecular mechanism regulated by miR-122-5p, this study was designed to provide a potential molecular target in bile duct cancer treatment. Methods: Western blot and immunohistochemistry were performed to detect the ALDOA protein level in duct carcinoma tissues. The transfection efficiency was confirmed by western blot and/or RT-qPCR assay. The proliferation of bile duct carcinoma cells was determined by MTT and colony formation assay. The invasion ability of bile duct carcinoma cells was evaluated with Transwell invasion assay. Flow cytometry detected cell apoptosis of bile duct carcinoma cells. The miRNAs which modulate ALDOA were filtrated from bioinformatics software and clinical specimens. The target relationship was confirmed by dual luciferase reporter assay. Furthermore, a xenograft model was completed to verify the impact of miRNA on inhibition growth of bile duct carcinoma cells. Results: ALDOA was found up-regulated in bile duct carcinoma tissues and cells. Knockdown of ALDOA promoted the apoptosis of cells and inhibited the proliferation and invasion of bile duct carcinoma cells. Bioinformatics and clinical specimens indicated the negative correlation and targeted regulation between miR-122-5p and ALDOA. By down-regulating ALDOA, overexpression of miR-122-5p appeared to promote cell apoptosis and significantly inhibit cell proliferation, invasion in vitro and suppress the tumor growth in vivo. Conclusion: miR-122-5p inhibited proliferation and invasion of bile duct carcinoma cells and promoted cell apoptosis by targeting ALDOA expression.

Background and Aims: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome. Methods: In a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity. Results: A total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18‐70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30‐day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later. Conclusions: In a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%). [ABSTRACT FROM AUTHOR]

In the present study, we aimed to identify specific lncRNAs and miRNAs, as well as mRNAs, involved in bile duct carcinoma (BDC) and to further explore the way in which lncRNA UCA1 regulates cell metastasis ability. Differentially expressed RNAs were screened out from the TCGA database. In in vitro experiments, qRT-PCR was used to measure lncRNA UCA1, miR-122 and CLIC1 expression. We performed a dual luciferase assay to validate the target relationships among UCA1, CLIC1 and miR-122. The cell migration ability was measured by a wound healing assay, and Transwell assays were applied to detect cell invasive ability. Western blot analysis was employed to detect the expression of related proteins in the MAPK signaling pathway. According to the bioinformatics analysis, lncRNA UCA1 and CLIC1 were both significantly upregulated in BDC, while the expression of miR-122 declined compared with the normal group. The target relationship among UCA1, CLIC1 and miR-122 was verified. UCA1 promoted BDC cell migration and invasiveness, while miR-122 inhibited their progression. CLIC1 served as the downstream target gene of miR-122 and had opposite effects. The ERK/MAPK signaling pathway was activated after upregulating UCA1. LncRNA-UCA1 promoted the metastasis of BDC cells by regulating the expression of miR-122 and its downstream gene mRNA CLIC1 and promoted the activation of the ERK/MAPK pathway, which expanded the horizons of targeted therapy of cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an effective local treatment modality as a cancer-specific laser ablation in malignancy of some organs including digestive tracts or bile duct. In Japan, PDT has been applied at the early period after the first clinical induction in 1980’s. Although the useful efficacy was clarified, PDT has not been fully applied because of the phototoxicity of the porfimer sodium. The next generated talaporfin-sodium was used for PDT, in which phototoxicity was reduced and, however, the clinical efficacy for digestive tract malignancy has not yet been clarified. By proceeding the experimental and clinical trials, it is necessary to clarify the evidence of efficacy as a local powerful treatment with the conventional surgery, brachiotherapy and chemotherapy in the future step.

Abstract Notch signaling is involved in both differentiation of hepatocyte progenitors and hepatocellular carcinoma (HCC). The mechanism whereby Notch signaling regulates cellular transformation in hepatocytes is still controversial. This study investigated the impact of overexpressing truncated intracellular Notch1 (NICD1) on transcriptomic profiles of immortalized human hepatocytes. RNA sequencing and gene ontology enrichment analysis revealed that extracellular matrix organization and hyaluronan biosynthesis process gene sets are among those affected by Notch hyperactivation. The relationship between Notch signaling and periostin, an extracellular matrix protein highly expressed in HCC, were further studied. Modulating Notch signaling through NICD1 overexpression or treatment with a gamma secretase inhibitor resulted in increased or decreased periostin expression, respectively, in HCC and liver bile duct carcinoma cell lines. Based on The Cancer Genome Atlas database, mRNA levels of NOTCH1 and POSTN are positively correlated in tumor tissues but not in nontumor tissues. Two consensus RBPJ binding motifs were identified in the −3932/-3921 and + 2522/+2533 bp of POSTN regulatory regions, and NOTCH1 is associated with these binding sites in a liver bile duct carcinoma cell line. Taken together, these results indicate that Notch signaling directly regulates transcription of POSTN in hepatocytes and liver cancer cell lines and may be a candidate for drug targeting in liver cancer. Highlights • Activation of Notch1 in hepatocytes increased level of extracellular matrix POSTN. • Modulating Notch signaling affected the level of POSTN in hepatocytes. • Periostin and Notch1 are expressed higher in tumor area in liver tumor biopsies. • Notch1 is associated with the promoter region of POSTN. [ABSTRACT FROM AUTHOR]

A 73-year-old woman was admitted because of obstructive jaundice. Computed tomography revealed a stricture in the lower bile duct with enhanced bile duct wall. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a tapering stenosis at the lower bile duct. Transpapillary histological biopsy using biopsy forceps through ERCP was performed; the diagnosis of signet ring cell carcinoma (SRCC) of the bile duct was established. Regional lymph node enlargement and distant metastases were not detected on diagnostic imaging. Pancreaticoduodenectomy with pylorus preservation was performed. Histological examination of the resected specimen confirmed SRCC of the extrahepatic bile duct coexisting with adenocarcinoma (ADC) of the extrahepatic bile duct with negative resection margins. However, tumor cells directly invaded the pancreatic parenchyma and the muscle layer of the duodenum, prompting us to administer adjuvant chemotherapy to the patient, with no sign of tumor recurrence at 1-year follow-up. Almost all tumors originating from the extrahepatic bile duct are ADC and other histological variants are rare. Of these, SRCC is extremely rare and only four cases have been reported. Furthermore, to the best of our knowledge, this is the first case report regarding the preoperative diagnosis of SRCC of the bile duct. Current reports indicate that younger age and Asian ethnicity are the clinical features of SRCC of the extrahepatic bile duct. Immunohistochemical staining of CK7, CK20 and MUC2 may be useful for predicting prognosis. Chemotherapy has not resulted in increased survival rates and only surgical resection currently serves as a curative treatment.

OBJECTIVE: We investigated the expression of annexin A5 (ANXA5) in human cholangiocarcinoma (CCA) cell line and its effect on proliferation, migration, and apoptosis of human CCA cells. MATERIALS AND METHODS: Expression of ANXA5 was detected by fluorescent quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting method in 2 human CCA cell lines, QBC939 and RBE. 3 shRNA plasmids for ANXA5 silencing (ANXA5-sh1, ANXA5-sh2, ANXA5-sh3) and 1 negative control plasmid were constructed to infect QBC939 cells. The infection efficiency, expression of ANXA5, apoptosis and cell cycle of QBC939 cell were measured separately. RESULTS: The expression of ANXA5 in QBC939 cell was significantly higher than RBE cell. Expressed ANXA5 protein in the QBC939-KD cell (QBC939 cell treated by RNAi) was significantly lower than QBC939-BC (QBC939 cell) and QBC939-NC cells (QBC939 cell treated by scramble plasmid). The ratio of G0/1 phase cells and apoptosis rate increased in QBC939-KD cell. The proliferation activity and invasion ability decreased in QBC939-KD cell compared with QBC939-NC and QBC939-BC cells. CONCLUSIONS: ANXA5 play important role in the migration and apoptosis of CCA cells. Inhibiting the expression of ANXA5 significantly reduce the proliferation, migration and invasion ability of QBC939 cells, and increase the apoptosis of QBC939 cells. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor modified T cell-based immunotherapy is revolutionizing the field of cancer treatment. However, its potential in treating bile duct carcinoma has not been fully explored. Herein, we developed the secondgeneration mesothelin-targeting chimeric antigen receptor-modified T cells with the 4-1BB co-stimulatory module by the piggyBac transposon system. Mesothelin-targeting chimeric antigen receptor was expressed by 66.0% of mesothelintargeting chimeric antigen receptor-modified T cells post electrophoretic transfection and stimulation with K562-meso cells; the expressions of activation markers were tested by flow cytometry assay and showed greater activation of mesothelin-targeting chimeric antigen receptor-modified T cells than control T cells (CD107α: 71.9% vs 48.6%; CD27: 92.1% vs 61.8%; CD137: 55.5% vs 8.4%; CD28: 98.0% vs 82.1%; CD134: 37.5% vs 10.4%). Furthermore, mesothelintargeting chimeric antigen receptor-modified T cells exerted cytotoxicity toward mesothelin-expressing EH-CA1b and EH-CA1a cells in an effector-to-target ratio-dependent manner, while leaving mesothelin-negative GSC-SD and EH-GB1 cells and normal liver L02 cells almost unharmed. Mesothelin-targeting chimeric antigen receptor-modified T cells secreted cytokines at higher levels when co-cultured with mesothelin-positive EH-CA1a and EH-CA1b cells than with mesothelin-negative GSC-SD and EH-GB1 cells. Enhanced cytotoxicity and cytokine secretion of mesothelintargeting chimeric antigen receptor-modified T cells compared to control T cells were also observed when co-cultured with 293-meso cells (interferon γ: 85.1% ± 1.47% vs 8.3% ± 2.50%, p = 0.000; tumor necrosis factor α: 90.9% ± 4.67% vs 18.5% ± 3.62%, p = 0.0004; interleukin 2: 60.8% ± 2.00% vs 15.6% ± 2.06%, p = 0.002; interleukin 6: 6.4% ± 2.95% vs 1.7% ± 0.63%, p = 0.055). In addition, mesothelin-targeting chimeric antigen receptor-modified T cells showed greater inhibitory and proliferative capability than control T cells within EH-CA1a cell xenografts. This study shows the potential of mesothelin-targeting chimeric antigen receptor-modified T cells in treating bile duct carcinoma. [ABSTRACT FROM AUTHOR]