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Endoscopy Dec 2024
Topics: Humans; Bile Duct Neoplasms; Cystic Duct; Endoscopy, Digestive System; Image-Guided Biopsy; Male; Aged; Female; Surgical Instruments
PubMed: 38759967
DOI: 10.1055/a-2313-9930 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Feb 2024Hepatic lymphoepithelioma-like carcinoma (LELC) is an extremely rare malignant tumor characterized by undifferentiated malignant epithelial cells and significant... (Review)
Review
Hepatic lymphoepithelioma-like carcinoma (LELC) is an extremely rare malignant tumor characterized by undifferentiated malignant epithelial cells and significant lymphatic infiltration. Hepatic LELC mainly includes lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) and lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEL-CC). Epstein-Barr virus (EBV) infection is considered as an important factor in LELC carcinogenesis. Since 2005, Xiangya Hospital of Central South University has treated a total of 3 patients with EBV-associated LEL-CC, which all showed liver masses by CT scans. After surgical resection, the EBV encoded RNA (EBER) and CK19 expression in all 3 patients were positive, and pathological examination confirmed EBV-associated LEL-CC. Two patients had a good postoperative prognosis, while 1 patient received relevant immunotherapy and chemotherapy after surgery. Based on the analysis of existing literature, the author believes that hepatic LELC can be included in the classification of liver tumors, which will provide new ideas for the accurate diagnosis and treatment of hepatic LELC.
Topics: Humans; Cholangiocarcinoma; Male; Bile Duct Neoplasms; Epstein-Barr Virus Infections; Middle Aged; Herpesvirus 4, Human; Bile Ducts, Intrahepatic; Female; Liver Neoplasms
PubMed: 38755729
DOI: 10.11817/j.issn.1672-7347.2024.230298 -
BMC Cancer May 2024With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence...
BACKGROUND
With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations.
METHODS AND RESULTS
We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28-84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT.
CONCLUSIONS
About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.
Topics: Humans; Middle Aged; Female; Male; Aged; Adult; Scotland; Aged, 80 and over; Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms; Chemotherapy, Adjuvant
PubMed: 38755562
DOI: 10.1186/s12885-024-12279-6 -
Journal of Experimental & Clinical... May 2024Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in...
BACKGROUND
Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in pancreatic and biliary tract cancers. The aim of this study is to characterize the cfDNA fragmentomics in biliopancreatic cancers and develop an accurate method for cancer detection.
METHODS
One hundred forty-seven patients with biliopancreatic cancers and 71 non-cancer volunteers were enrolled, including 55 patients with cholangiocarcinoma, 30 with gallbladder cancer, and 62 with pancreatic cancer. Low-coverage whole-genome sequencing (median coverage: 2.9 ×) was performed on plasma cfDNA. Three cfDNA fragmentomic features, including fragment size, end motif and nucleosome footprint, were subjected to construct a stacked machine learning model for cancer detection. Integration of carbohydrate antigen 19-9 (CA19-9) was explored to improve model performance.
RESULTS
The stacked model presented robust performance for cancer detection (area under curve (AUC) of 0.978 in the training cohort, and AUC of 0.941 in the validation cohort), and remained consistent even when using extremely low-coverage sequencing depth of 0.5 × (AUC: 0.905). Besides, our method could also help differentiate biliopancreatic cancer subtypes. By integrating the stacked model and CA19-9 to generate the final detection model, a high accuracy in distinguishing biliopancreatic cancers from non-cancer samples with an AUC of 0.995 was achieved.
CONCLUSIONS
Our model demonstrated ultrasensitivity of plasma cfDNA fragementomics in detecting biliopancreatic cancers, fulfilling the unmet accuracy of widely-used serum biomarker CA19-9, and provided an affordable way for accurate noninvasive biliopancreatic cancer screening in clinical practice.
Topics: Humans; Pancreatic Neoplasms; Biliary Tract Neoplasms; Male; Female; Cell-Free Nucleic Acids; Middle Aged; Aged; Biomarkers, Tumor; Adult
PubMed: 38750539
DOI: 10.1186/s13046-024-03067-y -
Journal of Clinical Pathology May 2024Intrahepatic cholangiocarcinoma (iCCA) is a diagnosis of exclusion that can pose a challenge to the pathologist despite thorough clinical workup. Although several...
Combined analysis of albumin in situ hybridisation and C reactive protein immunohistochemistry for the diagnosis of intrahepatic cholangiocarcinoma: towards a molecular classification paradigm.
AIMS
Intrahepatic cholangiocarcinoma (iCCA) is a diagnosis of exclusion that can pose a challenge to the pathologist despite thorough clinical workup. Although several immunohistochemical markers have been proposed for iCCA, none of them reached clinical practice. We here assessed the combined usage of two promising diagnostic approaches, albumin in situ hybridisation (Alb-ISH) and C reactive protein (CRP) immunohistochemistry, for distinguishing iCCA from other adenocarcinoma primaries.
METHODS
We conducted Alb-ISH and CRP immunohistochemistry in a large European iCCA cohort (n=153) and compared the results with a spectrum of other glandular adenocarcinomas of different origin (n=885). In addition, we correlated expression patterns with clinicopathological information and mutation data.
RESULTS
Alb-ISH was highly specific for iCCA (specificity 98.8%) with almost complete negativity in perihilar CCA and only rare positives among other adenocarcinomas (sensitivity 69.5%). CRP identified the vast majority of iCCA cases (sensitivity 84.1%) at a lower specificity of 86.4%. Strikingly, the combination of CRP and Alb-ISH boosted the diagnostic sensitivity to 88.0% while retaining a considerable specificity of 86.1%. Alb-ISH significantly correlated with CRP expression, specific tumour morphologies and small or large duct iCCA subtypes. Neither Alb-ISH nor CRP was associated with iCCA patient survival. 16 of 17 recurrent mutations in either IDH1, IDH2 and FGFR2 affected Alb-ISH positive cases, while the only KRAS mutation corresponded to an Alb-ISH negative case.
CONCLUSIONS
In conclusion, we propose a sequential diagnostic approach for iCCA, integrating CRP immunohistochemistry and Alb-ISH. This may improve the accuracy of CCA classification and pave the way towards a molecular-guided CCA classification.
PubMed: 38749660
DOI: 10.1136/jcp-2024-209429 -
BMC Gastroenterology May 2024The liver regeneration is a highly complicated process depending on the close cooperations between the hepatocytes and non-parenchymal cells involving various...
BACKGROUND
The liver regeneration is a highly complicated process depending on the close cooperations between the hepatocytes and non-parenchymal cells involving various inflammatory cells. Here, we explored the role of myeloid-derived suppressor cells (MDSCs) in the processes of liver regeneration and liver fibrosis after liver injury.
METHODS
We established four liver injury models of mice including CCl-induced liver injury model, bile duct ligation (BDL) model, concanavalin A (Con A)-induced hepatitis model, and lipopolysaccharide (LPS)-induced hepatitis model. The intrahepatic levels of MDSCs (CD11bGr-1) after the liver injury were detected by flow cytometry. The effects of MDSCs on liver tissues were analyzed in the transwell co-culture system, in which the MDSCs cytokines including IL-10, VEGF, and TGF-β were measured by ELISA assay and followed by being blocked with specific antibodies.
RESULTS
The intrahepatic infiltrations of MDSCs with surface marker of CD11bGr-1 remarkably increased after the establishment of four liver injury models. The blood served as the primary reservoir for hepatic recruitment of MDSCs during the liver injury, while the bone marrow appeared play a compensated role in increasing the number of MDSCs at the late stage of the inflammation. The recruited MDSCs in injured liver were mainly the M-MDSCs (CD11bLy6GLy6C) featured by high expression levels of cytokines including IL-10, VEGF, and TGF-β. Co-culture of the liver tissues with MDSCs significantly promoted the proliferation of both hepatocytes and hepatic stellate cells (HSCs).
CONCLUSIONS
The dramatically and quickly infiltrated CD11bGr-1 MDSCs in injured liver not only exerted pro-proliferative effects on hepatocytes, but also accounted for the activation of profibrotic HSCs.
Topics: Animals; Myeloid-Derived Suppressor Cells; Mice; Liver Cirrhosis; Liver Regeneration; CD11b Antigen; Male; Mice, Inbred C57BL; Disease Models, Animal; Liver; Vascular Endothelial Growth Factor A; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Concanavalin A; Ligation; Lipopolysaccharides; Interleukin-10; Transforming Growth Factor beta; Hepatic Stellate Cells; Coculture Techniques; Hepatocytes; Bile Ducts
PubMed: 38745150
DOI: 10.1186/s12876-024-03245-4 -
Communications Biology May 2024Circular RNAs (circRNAs) have recently been suggested as potential functional modulators of cellular physiology processes in gastric cancer (GC). In this study, we...
Circular RNAs (circRNAs) have recently been suggested as potential functional modulators of cellular physiology processes in gastric cancer (GC). In this study, we demonstrated that circFOXP1 was more highly expressed in GC tissues. High circFOXP1 expression was positively associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis in patients with GC. Cox multivariate analysis revealed that higher circFOXP1 expression was an independent risk factor for disease-free survival (DFS) and overall survival (OS) in GC patients. Functional studies showed that increased circFOXP1 expression promoted cell proliferation, cell invasion, and cell cycle progression in GC in vitro. In vivo, the knockdown of circFOXP1 inhibited tumor growth. Mechanistically, we observed ALKBH5-mediated m6A modification of circFOXP1 and circFOXP1 promoted GC progression by regulating SOX4 expression and sponging miR-338-3p in GC cells. Thus, our findings highlight that circFOXP1 could serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for GC.
Topics: Humans; Stomach Neoplasms; MicroRNAs; SOXC Transcription Factors; Forkhead Transcription Factors; Male; RNA, Circular; Female; Gene Expression Regulation, Neoplastic; AlkB Homolog 5, RNA Demethylase; Middle Aged; Disease Progression; Cell Line, Tumor; Animals; Mice; Cell Proliferation; Mice, Nude; Prognosis; Mice, Inbred BALB C
PubMed: 38745044
DOI: 10.1038/s42003-024-06274-7 -
Infection and Drug Resistance 2024This research aimed to analyze the clinical characteristics, prognosis, and antimicrobial treatment of bloodstream infections (BSI) caused by complex (ECC).
OBJECTIVE
This research aimed to analyze the clinical characteristics, prognosis, and antimicrobial treatment of bloodstream infections (BSI) caused by complex (ECC).
METHODS
The clinical data of patients with bloodstream infections caused by complex from April 2017 to June 2023 were collected retrospectively. These data were then analyzed in subgroups based on the detection results of extended-spectrum β-lactamase (ESBL), 30-day mortality, and the type of antimicrobial agent used (β-lactam/β-lactamase inhibitor combinations (BLICs) or carbapenems).
RESULTS
The proportion of ESBL-producing complex was 32.5% (37/114). Meanwhile, ICU admission, receiving surgical treatment within 3 months, and biliary tract infection were identified as risk factors for ESBL-producing ECC-BSI. Additionally, immunocompromised status and Sequential Organ Failure Assessment (SOFA) score ≥ 6.0 were identified as independent risk factors of 30-day mortality in patients with ECC-BSI (n = 108). Further analysis in BSI patients caused by non-ESBL-producing ECC revealed that patients treated with BLICs (n = 45) had lower SOFA scores and lower incidence of hypoproteinemia and sepsis compared with patients treated with carbapenems (n = 20). Moreover, in non-ESBL-producing ECC-BSI patients, the univariate Cox regression analysis indicated a significantly lower 30-day mortality rate in patients treated with BLICs compared to those treated with carbapenems (hazard ratios (HR) [95% CI] 0.190 [0.055-0.662], = 0.009; adjusted HR [95% CI] 0.106 [0.013-0.863], = 0.036).
CONCLUSION
This study investigated the factors influencing the susceptibility to infection by ESBL-producing strains and risk factors for 30-day mortality in ECC-BSI patients. The results revealed that ESBL-negative ECC-BSI patients treated with BLICs exhibited significantly lower 30-day mortality compared to those treated with carbapenems. BLICs were found to be more effective in ECC-BSI patients with milder disease (ESBL-negative and SOFA ≤6.0).
PubMed: 38741943
DOI: 10.2147/IDR.S460744 -
Polish Journal of Pathology : Official... 2024A 27-year-old woman with jaundice and abdominal pain was admitted to an emergency ward. The diagnostic process showed that gallstones were causing her symptoms.... (Review)
Review
A 27-year-old woman with jaundice and abdominal pain was admitted to an emergency ward. The diagnostic process showed that gallstones were causing her symptoms. The patient was treated via endoscopic retrograde cholangiopancreatography (ERCP), and during the procedure she suffered a cardiac arrest. Autopsy findings included multiple pulmonary bile emboli as well as features of disseminated intravascular coagulation. Among 22 thus far described cases of bile pulmonary embolism, 13 were associated with medical procedures involving the liver and biliary tract. We present the case report of a pulmonary bile embolism associated with acute pancreatitis treated via ERCP in a woman with gallbladder bile stones.
Topics: Humans; Female; Adult; Pulmonary Embolism; Pancreatitis; Fatal Outcome; Acute Disease; Gallstones; Cholangiopancreatography, Endoscopic Retrograde; Bile
PubMed: 38741429
DOI: 10.5114/pjp.2024.135762 -
Clinical and Translational Medicine May 2024Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection...
BACKGROUND
Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC.
METHODS
A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP).
RESULTS
Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001).
CONCLUSIONS
HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Female; Male; DNA Methylation; Middle Aged; Prognosis; Early Detection of Cancer; Circulating Tumor DNA; Cohort Studies; Biomarkers, Tumor; Aged; Adult
PubMed: 38741204
DOI: 10.1002/ctm2.1652