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Rare Cancer News & Clinical Trials » PubMed - Bile Duct Cancer
A Case of Erdheim-Chester Disease Causing Secondary Sclerosing Cholangitis
Fetched: January 27th, 2023, 5:01am GMT by Vijayvardhan Kamalumpundi
ACG Case Rep J. 2023 Jan 20;10(1):e00963. doi: 10.14309/crj.0000000000000963. eCollection 2023 Jan.
Erdheim-Chester disease (ECD) is an exceedingly rare and aggressive disease characterized by foamy CD68 + CDa-histiocytic infiltration into multiple tissues and organs. Only 1,500 cases have been diagnosed since 1930 when ECD was first described. Biliary tract involvement of ECD has only been reported in the literature once. We report a case of ECD causing extrahepatic biliary obstruction without significant bile duct dilation, mimicking primary sclerosing cholangitis or IgG4 disease.
PMID:36699184 | PMC:PMC9857465 | DOI:10.14309/crj.0000000000000963
Epigenetic dysregulation-mediated COL12A1 upregulation predicts worse outcome in intrahepatic cholangiocarcinoma patients
Fetched: January 27th, 2023, 5:01am GMT by Zengwei Tang
Clin Epigenetics. 2023 Jan 24;15(1):13. doi: 10.1186/s13148-022-01413-5.
BACKGROUND: Collagen type XII alpha 1 chain (COL12A1) is associated with human cancer progression. Nevertheless, the expression pattern and the function of COL12A1 in intrahepatic cholangiocarcinoma (iCCA) remain unknown. The present study was performed to assess the role of COL12A1 in iCCA.
RESULTS: A total of 1669 genes, differentially expressed between iCCA and nontumor liver tissue samples, were identified as potential tumor-specific biomarkers for iCCA patients. Of these, COL12A1 was significantly upregulated in clinical iCCA tissue samples and correlated with epithelial-mesenchymal transition gene set enrichment score and advanced tumor stage in clinical iCCA. COL12A1-high expression was associated with the poor prognoses of iCCA patients (n = 421) from four independent cohorts. Promoter hypermethylation-induced downregulation of miR-424-5p resulted in COL12A1 upregulation in clinical iCCA. Experimental knockout of COL12A1 inhibited the proliferation, invasiveness and growth of iCCA cells. MiR-424-5p had a therapeutic potential in iCCA via directly targeting COL12A1.
CONCLUSIONS: Promoter hypermethylation-induced miR-424-5p downregulation contributes to COL12A1 upregulation in iCCA. COL12A1 is a promising druggable target for epigenetic therapy of iCCA.
PMID:36694230 | PMC:PMC9875497 | DOI:10.1186/s13148-022-01413-5
Clonorchis sinensis aggravates biliary fibrosis through promoting IL-6 production via toll-like receptor 2-mediated AKT and p38 signal pathways
Fetched: January 27th, 2023, 5:01am GMT by Yuru Wang
PLoS Negl Trop Dis. 2023 Jan 24;17(1):e0011062. doi: 10.1371/journal.pntd.0011062. eCollection 2023 Jan.
Clonorchis sinensis is an important food-borne zoonotic parasite which has been linked to biliary fibrosis and cholangiocarcinoma. However, the details of the pathogenesis of C. sinensis were unclear. To explore the role and regulatory mechanism of toll-like receptor 2 (TLR2) in C. sinensis-induced biliary fibrosis, we established the C. sinensis-infected C57BL/6 mouse model with TLR2-/- and wild type (WT) mice. The mortality rate, liver lesions, TLR2 and TGF-β1 expression, phosphorylation of Smad2/3, AKT, p38, ERK and p65, and cytokine productions were analyzed. Furthermore, similar parameters were examined in mouse biliary epithelial cells (BECs) co-cultured with C. sinensis excretory/secretory proteins (ESPs). The results showed that TLR2 expression was enhanced significantly in C. sinensis-infected WT mice and mouse BECs. C. sinensis-infected TLR2-/- mice exhibited an increased weight and a decreased mortality rate; significantly alleviated liver lesions and biliary fibrosis, reduced numbers of myofibroblasts; decreased expression of TGF-β1 and phosphorylation level of AKT, p38 and Smad2/3; significantly decreased production of IL-6, TNF-α and IL-4, while increased production of IFN-γ compared with C. sinensis-infected WT mice. Furthermore, C. sinensis ESPs could activate TLR2-mediated AKT and p38 pathways to increase the production of IL-6 in mouse BECs. In conclusion, these data indicate that C. sinensis infection activated TGF-β1-Smad2/3 through TLR2-mediated AKT and p38 pathways to promote IL-6 production, which resulted in myofibroblast activation and aggravating biliary fibrosis in mice.
PMID:36693049 | PMC:PMC9873171 | DOI:10.1371/journal.pntd.0011062
Endoscopic Biliary Darinage (EBD) versus Percutaneous Transhepatic Biliary Drainage (PTBD) for biliary drainage in patients with Perihilar Cholangiocarcinoma (PCCA): A systematic review and meta-analysis
Fetched: January 27th, 2023, 5:01am GMT by Caroline Flaksbaum Moll
Clinics (Sao Paulo). 2023 Jan 19;78:100163. doi: 10.1016/j.clinsp.2022.100163. eCollection 2023.
Biliary drainage for Perihilar Cholangiocarcinoma (PCCA) can be performed either by endoscopic retrograde cholangiopancreatography or Percutaneous Transhepatic Biliary Drainage (PTBD). To date there is no consensus about which method is preferred. Taking that into account, the aim of this study is to compare Endoscopic Biliary Drainage (EBD) versus percutaneous transhepatic biliary drainage in patients with perihilar cholangiocarcinoma through a systematic review and metanalysis. A comprehensive search of multiple electronic databases was performed. Evaluated outcomes included technical success, clinical success, post drainage complications (cholangitis, pancreatitis, bleeding, and major complications), crossover, hospital length stay, and seeding metastases. Data extracted from the studies were used to calculate Mean Differences (MD). Seventeen studies were included, with a total of 2284 patients (EBD = 1239, PTBD = 1045). Considering resectable PCCA, the PTBD group demonstrated lower rates of crossover (RD = 0.29; 95% CI 0.07‒0.51; p = 0.009 I² = 90%), post-drainage complications (RD = 0.20; 95% CI 0.06‒0.33; p < 0.0001; I² = 78%), and post-drainage pancreatitis (RD = 0.10; 95% CI 0.05‒0.16; p < 0.0001; I² = 64%). The EBD group presented reduced length of hospital stay (RD = -2.89; 95% CI -3.35 ‒ -2,43; p < 0.00001; I² = 42%). Considering palliative PCCA, the PTBD group demonstrated a higher clinical success (RD = -0.19; 95% CI -0.27 ‒ -0.11; p < 0.00001; I² = 0%) and less post-drainage cholangitis (RD = 0.08; 95% CI 0.01‒0.15; p = 0.02; I² = 48%) when compared to the EBD group. There was no statistical difference between the groups regarding: technical success, post-drainage bleeding, major post-drainage complications, and seeding metastases.
PMID:36681067 | DOI:10.1016/j.clinsp.2022.100163
CCL3 secreted by hepatocytes promotes the metastasis of intrahepatic cholangiocarcinoma by VIRMA-mediated N6-methyladenosine (m6A) modification
Fetched: January 26th, 2023, 5:01am GMT by Shurui Zhou
J Transl Med. 2023 Jan 23;21(1):43. doi: 10.1186/s12967-023-03897-y.
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a malignant disease characterized by onset occult, rapid progression, high relapse rate, and high mortality. However, data on how the tumor microenvironment (TME) regulates ICC metastasis at the transcriptomic level remains unclear. This study aimed to explore the mechanisms and interactions between hepatocytes and ICC cells.
METHODS: We analyzed the interplay between ICC and liver microenvironment through cytokine antibody array analysis. Then we investigated the role of N6-methyladenosine (m6A) modification and the downstream target in vitro, in vivo experiments, and in clinical specimens.
RESULTS: Our study demonstrated that cytokine CCL3, which is secreted by hepatocytes, promotes tumor metastasis by regulating m6A modification via vir-like m6A methyltransferase associated (VIRMA) in ICC cells. Moreover, immunohistochemical analyses showed that VIRMA correlated with poor outcomes in ICC patients. Finally, we confirmed both in vitro and in vivo that CCL3 could activate VIRMA and its critical downstream target SIRT1, which fuels tumor metastasis in ICC.
CONCLUSIONS: In conclusion, our results enhanced our understanding of the interaction between hepatocytes and ICC cells, and revealed the molecular mechanism of the CCL3/VIRMA/SIRT1 pathway via m6A-mediated regulation in ICC metastasis. These studies highlight potential targets for the diagnosis, treatment, and prognosis of ICC.
PMID:36691046 | PMC:PMC9869516 | DOI:10.1186/s12967-023-03897-y
Hepatic artery resection in distal cholangiocarcinoma
Fetched: January 26th, 2023, 5:01am GMT by Tatsuaki Sumiyoshi
Langenbecks Arch Surg. 2023 Jan 23;408(1):58. doi: 10.1007/s00423-022-02749-5.
PURPOSE: This study aimed to elucidate the safety and oncological outcomes of surgery with hepatic artery resection (HAR) for patients with distal cholangiocarcinoma.
METHODS: The clinical data of patients with distal cholangiocarcinoma who underwent curative intent surgery at Hiroshima University between March 2009 and January 2021 were retrospectively analyzed. Eligible patients were classified according to the presence or absence of HAR (HAR and non-HAR group), and clinicopathological features and disease-free survival rates were compared between the two groups.
RESULTS: Among the 60 patients analyzed, eight patients had received HAR, and the remaining 52 patients had not. The rate of portal vein resection, T stage, and the number of metastasized lymph nodes in the HAR group were significantly greater than those in the non-HAR group (p < 0.001, p = 0.00695, and p = 0.0480, respectively). Postoperative severe complication was confirmed in one patient, and there were no in-hospital deaths in the HAR group. Seven of 8 patients in the HAR group showed recurrence during follow-up, and of those, six patients showed early recurrence within 1 year postoperatively. The disease-free survival time in the HAR group was significantly shorter than that in the non-HAR group (median: 7.4 m vs. 34.2 m, respectively) (p < 0.001). Multivariate analysis revealed that lymph node metastasis and HAR were significant risk factors for predicting the adverse disease-free survival time (hazard ratio (HR), 3.21; p = 0.0142; HR, 4.47; p = 0.0346, respectively).
CONCLUSIONS: Patients with distal cholangiocarcinoma who underwent surgery with HAR tended to show early recurrences, although HAR could be performed safely.
PMID:36688973 | DOI:10.1007/s00423-022-02749-5
Expression patterns and prognostic value of key regulators associated with m7G RNA modification based on all gene expression in colon adenocarcinoma
Fetched: January 25th, 2023, 5:01am GMT by Yuanchang Zhu
BMC Gastroenterol. 2023 Jan 21;23(1):22. doi: 10.1186/s12876-023-02657-y.
BACKGROUND: N7-methylguanosine (m7G) is present in a wide variety of organisms and has important roles. m7G has been reported to be involved in multiple biological processes, and recent studies have reported that changes in RNA modifications result in tumor cellular transformation and cancer, such as colon adenocarcinoma, lung cancer, and intrahepatic cholangiocarcinoma. However, little is known about the function of the m7G in colon adenocarcinoma.
METHODS: We established two clusters based on the expression of all genes associated with m7G to explore the expression pattern of 31 key regulatory factors of m7G RNA and assess the prognostic value of regulatory factors. Wilcoxon test and differential box line plots were applied for bioinformatics analysis. Receiver Operating and Kaplan‒Meier curves were utilized to evaluate the prognostic value. Finally, four genes' expression in the colon cancer cell line was confirmed by qRT-PCR.
RESULTS: From The Cancer Genome Atlas database, we found that the expression levels of 25 out of the 31 key N7-methylguanosine RNA modification regulators were significantly different in colon adenocarcinoma. According to 25 methylation regulators' expression, we identified two subgroups by consensus clustering, in which the prognosis was worse in Group 2 than in Group 1 and was significantly correlated with age. Cluster 2 was significantly enriched in tumor-associated pathways, and immune cells were highly infiltrated in Cluster 1 but weakly infiltrated in Cluster 2. Further results indicated that this risk profile may serve as a standalone predictive factor for colon adenocarcinoma, and the four genetic risk profiles' prognostic relatedness was successfully verified through Gene Expression Omnibus dataset. At last, A nomogram for prognosis was created according to age, sex, histological grading, clinicopathological staging, and hazard score to accurately predict patient prognosis in colon adenocarcinoma. We successfully validated the differential expression of four genes using qRT-PCR.
CONCLUSIONS: In the present study, we revealed the important contribution of key regulators associated with m7G RNA modifications based on all gene expression in colon adenocarcinoma and developed a signature of risk that serves as a promising prognostic marker for patients with colon adenocarcinoma.
ARHGAP21 Is Involved in the Carcinogenic Mechanism of Cholangiocarcinoma: A Study Based on Bioinformatic Analyses and Experimental Validation
Fetched: January 25th, 2023, 5:01am GMT by Zhihuai Wang
Medicina (Kaunas). 2023 Jan 10;59(1):139. doi: 10.3390/medicina59010139.
Background and Objectives: Rho GTPase-activating protein (RhoGAP) is a negative regulatory element of Rho GTPases and participates in tumorigenesis. Rho GTPase-activating protein 21 (ARHGAP21) is one of the RhoGAPs and its role in cholangiocarcinoma (CCA) has never been disclosed in any publications. Materials and Methods: The bioinformatics public datasets were utilized to investigate the expression patterns and mutations of ARHGAP21 as well as its prognostic significance in CCA. The biological functions of ARHGAP21 in CCA cells (RBE and Hccc9810 cell) were evaluated by scratch assay, cell counting kit-8 assay (CCK8) assay, and transwell migration assay. In addition, the underlying mechanism of ARHGAP21 involved in CCA was investigated by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the most significant signaling pathway was identified through gene set enrichment analysis (GSEA) and the Western blot method. The ssGSEA algorithm was further used to explore the immune-related mechanism of ARHGAP21 in CCA. Results: The ARHGAP21 expression in CCA tissue was higher than it was in normal tissue, and missense mutation was the main alteration of ARHGAP21 in CCA. Moreover, the expression of ARHGAP21 had obvious differences in patients with different clinical characteristics and it had great prognostic significance. Based on cell experiments, we further observed that the proliferation ability and migration ability of the ARHGAP21-knockdown group was reduced in CCA cells. Several pathological signaling pathways correlated with proliferation and migration were determined by GO and KEGG analysis. Furthermore, the PI3K/Akt signaling pathway was the most significant one. GSEA analysis further verified that ARHGAP21 was highly enriched in PI3K/Akt signaling pathway, and the results of Western blot suggested that the phosphorylated PI3K and Akt were decreased in the ARHGAP21-knockdown group. The drug susceptibility of the PI3K/Akt signaling pathway targeted drugs were positively correlated with ARHGAP21 expression. Moreover, we also discovered that ARHGAP21 was correlated with neutrophil, pDC, and mast cell infiltration as well as immune-related genes in CCA. Conclusions: ARHGAP21 could promote the proliferation and migration of CCA cells by activating the PI3K/Akt signaling pathway, and ARHGAP21 may participate in the immune modulating function of the tumor microenvironment.
PMID:36676763 | PMC:PMC9867224 | DOI:10.3390/medicina59010139
A Deep Learning Workflow for Mass-Forming Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma Classification Based on MRI
Fetched: January 25th, 2023, 5:01am GMT by Yangling Liu
Curr Oncol. 2022 Dec 30;30(1):529-544. doi: 10.3390/curroncol30010042.
OBJECTIVE: Precise classification of mass-forming intrahepatic cholangiocarcinoma (MF-ICC) and hepatocellular carcinoma (HCC) based on magnetic resonance imaging (MRI) is crucial for personalized treatment strategy. The purpose of the present study was to differentiate MF-ICC from HCC applying a novel deep-learning-based workflow with stronger feature extraction ability and fusion capability to improve the classification performance of deep learning on small datasets.
METHODS: To retain more effective lesion features, we propose a preprocessing method called semi-segmented preprocessing (Semi-SP) to select the region of interest (ROI). Then, the ROIs were sent to the strided feature fusion residual network (SFFNet) for training and classification. The SFFNet model is composed of three parts: the multilayer feature fusion module (MFF) was proposed to extract discriminative features of MF-ICC/HCC and integrate features of different levels; a new stationary residual block (SRB) was proposed to solve the problem of information loss and network instability during training; the attention mechanism convolutional block attention module (CBAM) was adopted in the middle layer of the network to extract the correlation of multi-spatial feature information, so as to filter the irrelevant feature information in pixels.
RESULTS: The SFFNet model achieved an overall accuracy of 92.26% and an AUC of 0.9680, with high sensitivity (86.21%) and specificity (94.70%) for MF-ICC.
CONCLUSION: In this paper, we proposed a specifically designed Semi-SP method and SFFNet model to differentiate MF-ICC from HCC. This workflow achieves good MF-ICC/HCC classification performance due to stronger feature extraction and fusion capabilities, which provide complementary information for personalized treatment strategy.
PMID:36661691 | PMC:PMC9857958 | DOI:10.3390/curroncol30010042
Pathology of Cholangiocarcinomas
Fetched: January 25th, 2023, 5:01am GMT by Nathalie Guedj
Cholangiocarcinomas (CCA) are heterogeneous tumors that arise from epithelial cells of the biliary tract. They represent the second primary liver malignancy, after hepatocellular carcinoma. Recent epidemiological data show an increased incidence of intrahepatic CCA without any identified causes. According to their location on the biliary tract, intrahepatic, perihilar (p) and distal (d) CCA can be individualized. Intrahepatic CCA (iCCA) are subdivided into small duct type iCCA and large duct type iCCA, according to the level or size of the biliary duct affected. These two subgroups are characterized by distinct risk factors, gross aspect, histopathological and molecular features, and therapeutic management. The role of biopsy in iCCA is to confirm the diagnosis and to eliminate various differential diagnostics, in particular, metastases. In p/d CCA, biopsy requires more invasive approaches, and tissue samples are difficult to obtain, leading to a high rate of false negatives. In this review, we will discuss the different classifications of CCA (anatomical and macroscopic). We will describe the various microscopic and phenotypic subtypes of CCA. Finally, we will deal with their mode of extension, the role of biopsy and pre-neoplastic lesions.
Effectiveness of public health interventions in reducing the prevalence of Opisthorchis viverrini: a protocol for systematic review and network meta-analysis
Fetched: January 24th, 2023, 5:00am GMT by Pornphutthachat Sota
BMJ Open. 2022 Sep 8;12(9):e064573. doi: 10.1136/bmjopen-2022-064573.
INTRODUCTION: The carcinogenic liver fluke Opisthorchis viverrini is a major public health problem in the Mekong basin region. The liver flukes can induce cholangiocarcinoma, a bile duct cancer that causes a significant burden of mortality and economic loss. Various public health interventions have been conducted to reduce opisthorchiasis but the prevalence of O. viverrini remains high in endemic regions. The aim is to quantify the effectiveness of public health interventions in reducing the prevalence of O. viverrini infection.
METHODS AND ANALYSIS: Seven databases (including PubMed, SCOPUS, Web of Science, EMBASE, ScienceDirect, Thai thesis database and TCI (Thai journals online)) will be searched from initiation through to 2022 to identify studies of interventions to reduce the prevalence of O. viverrini infection. The prevalence, incidence or number of O. viverrini-infected people will be used as the source of O. viverrini prevalence data. A conventional meta-analysis and a Bayesian network meta-analysis will be conducted to undertake direct and indirect comparisons of different interventions. Meta-regression will be used to determine the effect of each intervention. The risk of bias will be assessed using the Cochrane Collaboration's risk of bias tool. Heterogeneity between studies will be determined by forest plots and I2 and publication bias investigated with funnel plots and the Egger's test.
ETHICS AND DISSEMINATION: Ethical approval will not be required because this study will only use published data. The final report of this review will be disseminated through publication in a peer-reviewed scientific journal and will also be presented at relevant conferences.
PROSPERO REGISTRATION NUMBER: CRD42022323066.
PMID:36691213 | PMC:PMC9462107 | DOI:10.1136/bmjopen-2022-064573
Mixed neuroendocrine-non-neuroendocrine neoplasm with mucinous adenocarcinoma and amphicrine carcinoma components in the bile duct: an autopsy case
Fetched: January 24th, 2023, 5:00am GMT by Toji Murabayashi
Clin J Gastroenterol. 2023 Jan 23. doi: 10.1007/s12328-023-01763-4. Online ahead of print.
We report the first case of bile duct mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) that had a mucinous carcinoma component. An 88-year-old man with biliary obstruction was diagnosed as having distal bile duct cancer using imaging examinations and endoscopic biopsy. The patient received the best supportive care without surgical resection for 13 months until death. An autopsy revealed a bulky mass involving the distal bile duct and multiple metastases in intra-abdominal lymph nodes, the liver, and the lungs. The primary cancer was microscopically diagnosed as a MiNEN, which consisted of mucinous adenocarcinoma and large cell-type neuroendocrine carcinoma (NEC) components. Metastatic lesions in the liver and lungs were composed of only NEC with rich extracellular mucin without adenocarcinoma cells. Using electron microscopy and immunohistochemistry, it was proved that all NEC cells in both primary and metastatic lesions had amphicrine features. On the basis of pathological findings, we thought that the MiNEN was initially derived from a mucinous adenocarcinoma that dedifferentiated to amphicrine NEC cells with mucin production.
Treatment of obstructive jaundice induced by non-hodgkin lymphoma with EUS-guided transgastric anterograde common bile duct stenting: Technical case report and literature review
Fetched: January 24th, 2023, 5:00am GMT by Lingzhi Yuan
Front Surg. 2023 Jan 6;9:1031718. doi: 10.3389/fsurg.2022.1031718. eCollection 2022.
BACKGROUND: Non-Hodgkin lymphoma (NHL) is a rare cause of biliary obstruction. The optimum treatment for these patients is unclear. Lymphoma-associated obstructive jaundice is generally managed with open surgery, Endoscopic retrograde cholangiopancreatography (ERCP), or Percutaneous transhepatic biliary drainage. Here, we present the first description of EUS-guided anterograde common bile duct stenting via the stomach for obstructive jaundice associated with NHL.
PATIENT AND METHODS: A 58-year-old male patient who had been undergoing chemotherapy for NHL was admitted to our institution for severe obstructive jaundice. The patient's hepatic function indicators were: alanine aminotransferase 211 U/L, aspartate aminotransferase 301 U/L, total bilirubin 485.6 μmol/L, and direct bilirubin 340.2 μmol/L. Abdominal magnetic resonance imaging showed massive lymphomatous lesions filling the peritoneal cavity. Magnetic resonance cholangiopancreatography revealed an external compressive stricture in the superior middle common bile duct and dilation of the intrahepatic and extrahepatic ducts. ERCP was performed unsuccessfully, due to the stricture at the descending junction of the duodenal bulb caused by lymphoma infiltration. So, EUS-guided anterograde common bile duct stenting via the stomach was performed.
RESULTS: The patient's bilirubin level decreased significantly in the postoperative period, and no adverse reaction was observed. Computed tomography showed marked shrinking of the abdominal mass after targeted therapy.
CONCLUSIONS: Our report suggests that early relief of biliary obstruction may be more beneficial to subsequent chemotherapy when symptoms of lymphoma-associated jaundice are persistently aggravating. Endoscopic ultrasound-guided biliary drainage is a safe, effective and timely alternative approach to treat biliary obstruction when ERCP fails, especially in cases of malignancy caused by extrahepatic bile duct space-occupying lesions.
PMID:36684212 | PMC:PMC9852524 | DOI:10.3389/fsurg.2022.1031718
The influence of resection margin width in patients with intrahepatic cholangiocarcinoma: a meta-analysis
Fetched: January 24th, 2023, 5:00am GMT by Yu-Shi Dai
World J Surg Oncol. 2023 Jan 20;21(1):16. doi: 10.1186/s12957-023-02901-5.
BACKGROUND: Some studies have pointed out that a wide resection margin can improve the prognosis of intrahepatic cholangiocarcinoma, but some researchers disagree and believe that a wide margin may increase complications. The optimal margin length of intrahepatic cholangiocarcinoma is controversial.
METHOD: The literature was searched in PubMed, MedLine, Embase, the Cochrane Library, and Web of Science until December 31, 2021, to evaluate the postoperative outcomes of patients with different margin width after resection. Odds ratios (ORs) with 95% confidence intervals were used to determine the effect size.
RESULT: A total of 11 articles were included in this meta-analysis, including 3007 patients. The narrow group had significantly lower 1-, 3-, and 5-year overall survival rates and recurrence-free survival rates than the wide group. Postoperative morbidity and prognostic factors were also evaluated.
CONCLUSION: A resection margin width of over 10 mm is recommended in intrahepatic cholangiocarcinoma patients, especially in patients with negative lymph node and early tumor stage. When the resection margin width cannot be greater than 10 mm, we should ensure that the resection margin width is greater than 5 mm.
The Sympathetic Ampulla
Fetched: January 24th, 2023, 5:00am GMT by James Gauci
Turk J Gastroenterol. 2023 Jan;34(1):87-88. doi: 10.5152/tjg.2020.18997.
PMID:36656081 | DOI:10.5152/tjg.2020.18997
The Fibrotic Effects of LINC00663 in Human Hepatic Stellate LX-2 Cells and in Bile Duct-Ligated Cholestasis Mice Are Mediated through the Splicing Factor 2-Fibronectin
Fetched: January 22nd, 2023, 5:01am GMT by Yang Chu
Cells. 2023 Jan 4;12(2):215. doi: 10.3390/cells12020215.
Hepatic fibrosis can develop into cirrhosis or even cancer without active therapy at an early stage. Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of a wide variety of important biological processes. However, lncRNA mechanism(s) involved in cholestatic liver fibrosis remain unclear. RNA sequence data of hepatic stellate cells from bile duct ligation (BDL) mice or controls were analyzed by weighted gene co-expression network analysis (WGCNA). Based on WGCNA analysis, a competing endogenous RNA network was constructed. We identified LINC00663 and evaluated its function using a panel of assays, including a wound healing assay, a dual-luciferase reporter assay, RNA binding protein immunoprecipitation and chromatin immunoprecipitation. Functional research showed that LINC00663 promoted the activation, migration and epithelial-mesenchymal transition (EMT) of LX-2 cells and liver fibrosis in BDL mice. Mechanistically, LINC00663 regulated splicing factor 2 (SF2)-fibronectin (FN) alternative splicing through the sponging of hsa-miR-3916. Moreover, forkhead box A1 (FOXA1) specifically interacted with the promoter of LINC00663. In summary, we elaborated the fibrotic effects of LINC00663 in human hepatic stellate LX-2 cells and in bile duct-ligated cholestasis mice. We established a FOXA1/LINC00663/hsa-miR-3916/SF2-FN axis that provided a potential target for the diagnosis and targeted therapy of cholestatic liver fibrosis.
PMID:36672150 | PMC:PMC9857260 | DOI:10.3390/cells12020215
Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma
Fetched: January 21st, 2023, 5:00am GMT by Lipika Goyal
N Engl J Med. 2023 Jan 19;388(3):228-239. doi: 10.1056/NEJMoa2206834.
BACKGROUND: Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.
METHODS: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors). The patients received oral futibatinib at a dose of 20 mg once daily in a continuous regimen. The primary end point was objective response (partial or complete response), as assessed by independent central review. Secondary end points included the response duration, progression-free and overall survival, safety, and patient-reported outcomes.
RESULTS: Between April 16, 2018, and November 29, 2019, a total of 103 patients were enrolled and received futibatinib. A total of 43 of 103 patients (42%; 95% confidence interval, 32 to 52) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations. At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months. Common treatment-related grade 3 adverse events were hyperphosphatemia (in 30% of the patients), an increased aspartate aminotransferase level (in 7%), stomatitis (in 6%), and fatigue (in 6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2% of the patients. No treatment-related deaths occurred. Quality of life was maintained throughout treatment.
CONCLUSIONS: In previously treated patients with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to measurable clinical benefit. (Funded by Taiho Oncology and Taiho Pharmaceutical; FOENIX-CCA2 ClinicalTrials.gov number, NCT02052778.).
PMID:36652354 | DOI:10.1056/NEJMoa2206834
Hemoglobin and Neutrophil Count as Prognostic Factors in Cholangiocarcinoma Patients in 2nd Line Treatment Setting: Results from a Small Monocentric Retrospective Study
Fetched: January 21st, 2023, 5:00am GMT by Carolina Liguori
Curr Oncol. 2023 Jan 11;30(1):1032-1045. doi: 10.3390/curroncol30010079.
BACKGROUND: Unresectable cholangiocarcinoma prognosis can be extremely variable due to different symptoms and sites of disease involvement at diagnosis and unpredictable chemotherapy response rates. Most patients will usually receive 1st line palliative chemotherapy with platinum compounds and Gemcitabine or Gemcitabine alone. Only a few patients maintain adequate performance status after first-line treatment failure: second-line treatment with FOLFOX or FOLFIRI chemotherapy has been used in this setting with modest overall survival improvement. There is a lack of data concerning whether laboratory findings might help clinicians in identifying those patients with the highest likelihood of benefiting from 2nd line treatment. The aim of this analysis is to assess the prognostic role of a series of easily available laboratory tests in patients with bile duct cancer who received 2nd line chemotherapy.
PATIENTS AND METHODS: Patients with unresectable bile duct cancer treated in 2nd-line setting with platinum-based chemotherapy doublet or FOLFIRI were enrolled. The primary objective of the analysis was to assess overall survival (OS) differences among patients based on the results of lab tests. Serum hemoglobin, neutrophil, lymphocyte, monocyte, platelet absolute count, creatinine, total bilirubin, albumin, LDH, circulating CEA and CA19.9 values were collected at the start of 2nd line treatment. Cut-off values for all lab tests were set by ROC curve analysis. Survival was calculated by the Kaplan-Meier method and differences in survival among stratification factors were assessed by Log-rank test. Cox-proportional-hazard regression was used for multivariate analysis. Level of statistical significance p was set at 0.05 for all tests. Correction for false discovery error rate was performed by Holm's stepdown procedure.
RESULTS: A total of 46 patients were eligible. Median overall survival of the entire cohort was 8.98 months (95%CI: 6.68-13.93) while mean OS was 17.10 months (standard error: 3.16). Using 6.2 months OS landmark as classification variable for ROC curve analysis, only serum hemoglobin (cut-off: >10 g/dL), albumin (cut-off: >3.5 mg/dL), CA19.9 (cut-off: ≤668 UI/mL), monocyte (cut-off: ≤510/mmc) and neutrophil count (cut-off: ≤5140/mmc) were significantly associated with the chosen end-point. Multivariate analysis confirmed an independent statistically significant impact on overall survival only for hemoglobin (Exp(b): 0.12, p = 0.0023) and neutrophil count (Exp(b): 0.30, p = 0.0039). Based on these results, using both hemoglobin and neutrophil count, three prognostic groups were defined: patients with both favorable factors had 12.63 months median OS vs. 6.75 months of patients with only one favorable factor vs. 1.31 months of those with neither. The difference between these three groups of patients was statistically significant (p < 0.0001).
DISCUSSION: Second-line palliative chemotherapy can be a potentially useful option for a few patients with unresectable/metastatic bile duct cancer. Even though assessment of patients' prognosis might be difficult due to the complex behavior of this disease, a series of easily available laboratory tests might be used for these means: serum hemoglobin and neutrophil count we0re able to define subsets of patients with entirely different prognoses. It is hoped that this score will be prospectively validated in a larger group of patients in order to improve treatment decisions in patients with unresectable bile duct cancer candidate to receive palliative 2nd line chemotherapy.
Clinicopathological Features and Prognosis Analysis of Primary Bile Duct and Ampullary Neuroendocrine Neoplasms: A Population-Based Study from 1975 to 2016
Fetched: January 21st, 2023, 5:00am GMT by Yijun Li
BACKGROUND: The main purpose of this study is to analyze the clinicopathological features and prognosis factors of bile duct and ampullary neuroendocrine neoplasms (NENs).
METHODS: The relevant data were collected from the SEER database from 1975 to 2016. The Kaplan-Meier curve and Cox model were used for survival analysis. The nomogram was drawn to predict the survival rate. The calibration, discrimination and clinical utility of the nomogram were evaluated by calibration curve, the concordance index (C-index) and decision curve analysis (DCA).
RESULTS: A total of 340 cases were included in our research. According to Kaplan-Meier analysis, 1-year, 3-year and 5-year of overall survival (OS) were 77.3%, 61.9% and 58.4%, while 1-year, 3-year and 5-year of the disease-specific survival (DSS) were 82.7%, 69.3% and 66.9%, respectively. The multivariable analysis results showed that age, histological grade, SEER stage and surgery were independent predictors for either OS or DSS. The calibration curve and the C-index value indicated that the nomogram was well calibrated and had good discrimination. DCA showed that the model had ideal net benefits.
CONCLUSIONS: The age, histological grade, SEER stage and surgery were identified as independent prognostic variables for OS and DSS. After verification, nomogram has good predictive ability and clinical application value.
13‑cis‑retinoic acid inhibits the self‑renewal, migration, invasion and adhesion of cholangiocarcinoma cells
Fetched: January 21st, 2023, 5:00am GMT by Siriwoot Butsri
Int J Mol Med. 2023 Mar;51(3):20. doi: 10.3892/ijmm.2023.5223. Epub 2023 Jan 20.
13‑cis‑retinoic acid (13CRA), a Food and Drug Administration‑approved drug for severe acne, is currently being investigated for its potential use in skin cancer prevention. 13CRA has been reported to exhibit antitumor effects against various types of cancer cells, both in vitro and in vivo. However, to the best of our knowledge, no information is yet available regarding the effects of 13CRA on cholangiocarcinoma (CCA), a malignancy of the bile duct epithelia. Currently, there are no reliably effective therapeutic options for metastatic CCA. The present study thus aimed to evaluate the effects of 13CRA on the self‑renewal, migration, invasion and adhesion of CCA cells, and also investigated the underlying mechanisms. The results revealed that 13CRA suppressed cell proliferation via the inhibition of the self‑renewal ability of CCA cells. 13CRA induced cell cycle arrest at the G2/M phase in KKU‑100 and KKU‑213B CCA cells through the regulation of cell cycle‑regulatory genes and proteins. 13CRA reduced the cell migratory ability of both cell lines via the modulation of the genes and proteins associated with epithelial‑mesenchymal transition. 13CRA also inhibited the invasive and adhesive abilities of CCA cells via the suppression of genes and proteins associated with the invasion and adhesion of CCA cells. On the whole, these results suggested that 13CRA exerts suppressive effects on CCA cell proliferation, migration, adhesion and invasion.
PMID:36660943 | DOI:10.3892/ijmm.2023.5223
Severe biliary hemorrhage after metal stent placement into the bile duct
Fetched: January 21st, 2023, 5:00am GMT by Akio Sugimoto
J Hepatobiliary Pancreat Sci. 2023 Jan 19. doi: 10.1002/jhbp.1304. Online ahead of print.
PMID:36660792 | DOI:10.1002/jhbp.1304
Hepatic ribosomal protein S6 (Rps6) insufficiency results in failed bile duct development and loss of hepatocyte viability; a ribosomopathy-like phenotype that is partially p53-dependent
Fetched: January 20th, 2023, 5:01am GMT by Sarah A Comerford
PLoS Genet. 2023 Jan 19;19(1):e1010595. doi: 10.1371/journal.pgen.1010595. Online ahead of print.
Defective ribosome biogenesis (RiBi) underlies a group of clinically diverse human diseases collectively known as the ribosomopathies, core manifestations of which include cytopenias and developmental abnormalities that are believed to stem primarily from an inability to synthesize adequate numbers of ribosomes and concomitant activation of p53. The importance of a correctly functioning RiBi machinery for maintaining tissue homeostasis is illustrated by the observation that, despite having a paucity of certain cell types in early life, ribosomopathy patients have an increased risk for developing cancer later in life. This suggests that hypoproliferative states trigger adaptive responses that can, over time, become maladaptive and inadvertently drive unchecked hyperproliferation and predispose to cancer. Here we describe an experimentally induced ribosomopathy in the mouse and show that a normal level of hepatic ribosomal protein S6 (Rps6) is required for proper bile duct development and preservation of hepatocyte viability and that its insufficiency later promotes overgrowth and predisposes to liver cancer which is accelerated in the absence of the tumor-suppressor PTEN. We also show that the overexpression of c-Myc in the liver ameliorates, while expression of a mutant hyperstable form of p53 partially recapitulates specific aspects of the hepatopathies induced by Rps6 deletion. Surprisingly, co-deletion of p53 in the Rps6-deficient background fails to restore biliary development or significantly improve hepatic function. This study not only reveals a previously unappreciated dependence of the developing liver on adequate levels of Rps6 and exquisitely controlled p53 signaling, but suggests that the increased cancer risk in ribosomopathy patients may, in part, stem from an inability to preserve normal tissue homeostasis in the face of chronic injury and regeneration.
PMID:36656901 | DOI:10.1371/journal.pgen.1010595
Curcumin analog WZ26 induces ROS and cell death via inhibition of STAT3 in cholangiocarcinoma
Fetched: January 19th, 2023, 5:01am GMT by Minxiao Chen
Cancer Biol Ther. 2023 Dec 31;24(1):2162807. doi: 10.1080/15384047.2022.2162807.
Cholangiocarcinoma (CCA) is an aggressive biliary epithelial tumor with limited therapeutic options and poor prognosis. Curcumin is a promising active natural compound with several anti-cancer properties, though its clinical uses remain hindered due to its poor bioavailability. We recently synthesized curcumin analogs with multifunctional pharmacological and bioactivities with enhanced bioavailability. Among these novel curcumin analogs, WZ26 is a representative molecule. However, the anti-tumor effect of WZ26 against CCA is unclear. In this study, we evaluated the anti-tumor effect of WZ26 in both CCA cells and CCA xenograft mouse model. The underlying molecular anti-cancer mechanism of WZ26 was also studied. Our results show that WZ26 significantly inhibited cell growth and induced mitochondrial apoptosis in CCA cell lines, leading to significant inhibition of tumor growth in xenograft tumor mouse model. Treatment of WZ26 increased reactive oxygen species (ROS) generation, subsequently decreased mitochondrial membrane potential and inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inducing G2/M cell cycle arrest and cell apoptosis. Pretreatment of N-acetyl cysteine (NAC), an antioxidant agent, could fully reverse the WZ26-induced ROS-mediated changes in CCA cells. Our findings provide experimental evidence that curcumin analog WZ26 could be a potential candidate against CCA via enhancing ROS induction and inhibition of STAT3 activation.
PMID:36647192 | PMC:PMC9851268 | DOI:10.1080/15384047.2022.2162807
Secondary Budd-Chiari syndrome occurred after adjuvant radiotherapy for perihilar cholangiocarcinoma: a case report
Fetched: January 19th, 2023, 5:01am GMT by Yuya Miura
World J Surg Oncol. 2023 Jan 16;21(1):9. doi: 10.1186/s12957-023-02890-5.
BACKGROUND: Budd-Chiari syndrome (BCS) is a rare vascular disorder of the liver, and acute and secondary BCS is even rarer.
CASE PRESENTATION: A 62-year-old man with perihilar cholangiocarcinoma of Bismuth type IIIa underwent right hemi-hepatectomy with caudate lobectomy and pancreatoduodenectomy. Adjuvant chemoradiotherapy was performed due to a positive hepatic ductal margin. Subsequently, the disease passed without recurrence. The patient visited for acute onset abdominal pain at the 32nd postoperative month. Multidetector-row computed tomography (MDCT) showed stenosis of the left hepatic vein (LHV) root, which was the irradiated field, and thrombotic occlusion of the LHV. The patient was diagnosed with acute BCS caused by adjuvant radiotherapy. Although anticoagulation therapy was performed, the patient complained of sudden upper abdominal pain again. MDCT showed an enlarged LHV thrombus and hepatomegaly. The patient was diagnosed with exacerbated acute BCS, and stenting for the stenotic LHV root was performed with a bare stent. Although stenting for the LHV root was very effective, restenosis occurred twice due to thrombus in the existing stent, so re-stenting was performed twice. The subsequent clinical course was acceptable without recurrence or restenosis of the LHV root as of 6 months after the last stenting using a stent graft.
CONCLUSION: Although no case of BCS caused by radiotherapy has yet been reported, the present case showed that late side effect of radiotherapy can cause hepatic vein stenosis and secondary BCS.
Integrative analysis of multiple genomic data from intrahepatic cholangiocarcinoma organoids enables tumor subtyping
Fetched: January 19th, 2023, 5:01am GMT by Hee Seung Lee
Nat Commun. 2023 Jan 16;14(1):237. doi: 10.1038/s41467-023-35896-4.
As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. Here, we verify the recently suggested two subgroups of ICC in the organoids model, compare the characteristics between types. ICC patients are subclassified into small-duct (SD) and large-duct (LD) subtype according to histological characteristics. ICC organoids are established, and unsupervised principal component analysis clustering separates each type of ICC. Differential gene expression reveals enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type (P < 0.05). Gene set enrichment analysis demonstrates that the cholangiocarcinoma class 2 signature, defined by Andersen et al., is enriched in the LD-type (enrichment Score = 2.19, P < 0.001). A protein-protein interaction network analysis identifies ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We perform prospective modeling of histological subtype using patient-derived organoids. Moreover, gene expression profiling of ICC organoids enables identification of type-specific targetable pathways.
Bilateral stent-in-stent placement of biliary metal stents with a slim delivery system through an ultraslim endoscope
Fetched: January 19th, 2023, 5:01am GMT by Koichiro Mandai
Endoscopy. 2023 Dec;55(S 01):E356-E357. doi: 10.1055/a-1997-0503. Epub 2023 Jan 16.
PMID:36646124 | PMC:PMC9842437 | DOI:10.1055/a-1997-0503
How we treat advanced biliary tract cancers in the second-line setting
Fetched: January 18th, 2023, 5:01am GMT by Haley Ellis
Clin Adv Hematol Oncol. 2023 Jan;21(1):35-42.
Tumor budding may be a promising prognostic indicator in intrahepatic cholangiocarcinoma: A multicenter retrospective study
Fetched: January 17th, 2023, 5:01am GMT by Hisashi Kosaka
Ann Gastroenterol Surg. 2022 Jul 30;7(1):138-146. doi: 10.1002/ags3.12605. eCollection 2023 Jan.
PURPOSE: This retrospective study evaluated our hypothesis that high tumor budding (≥10 buds) may help determine the appropriate T category for more accurate staging of intrahepatic cholangiocarcinoma (ICC).
METHODS: We analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals in the Kansai region of Japan between January 2009 and December 2020. ICC staging was based on the Liver Cancer Study Group of Japan (LCSGJ) staging system, 6th edition.
RESULTS: Patients with ICC with high budding showed significantly shorter disease-specific survival (DSS) and disease-free survival (DFS) than patients with low/intermediate budding. Cox proportional hazards regression analysis showed a hazard ratio of 2.2-2.3 (P < 0.05) for high budding. Based on these results, we modified the T category of ICC in the LCSGJ staging system by adding severity of tumor budding as a fourth determinant. This proposed staging system for ICC has significantly improved the prognostic accuracy for both DSS and DFS (both: P < 0.05).
CONCLUSIONS: High tumor budding is a new candidate for an additional determinant of the T category in staging ICC. An LCSGJ staging system containing an additional evaluation of tumor budding may lead to improved staging accuracy.
PMID:36643363 | PMC:PMC9831894 | DOI:10.1002/ags3.12605
Are the Immunohistochemistry-Based Biomarkers Helpful for Predicting Prognosis in Patients with Surgically Resected Cholangiocarcinoma?
Fetched: January 17th, 2023, 5:01am GMT by Dong Uk Kim
Gut Liver. 2023 Jan 15;17(1):10-11. doi: 10.5009/gnl220542.
PMID:36636886 | DOI:10.5009/gnl220542
CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export
Fetched: January 17th, 2023, 5:01am GMT by Xiaopeng Yu
Cell Death Dis. 2023 Jan 12;14(1):20. doi: 10.1038/s41419-022-05540-y.
The carcinogenic role of FASN by regulating lipid metabolism reprogramming has been well-established in multiple tumors. However, whether mechanisms during intrahepatic cholangiocarcinoma (ICC) progression, such as circRNAs, regulate FASN expression remains unknown. Here we demonstrate a lipid metabolism-related circRNA, circMBOAT2 (hsa_circ_0007334 in circBase), frequently upregulated in ICC tissues, and positively correlated with ICC malignant features. CircMBOAT2 knockdown inhibits the growth and metastasis of ICC cells. Mechanistically, circMBOAT2 combines with PTBP1 and protects PTBP1 from ubiquitin/proteasome-dependent degradation, impairing the function of PTBP1 to transfer FASN mRNA from the nucleus to the cytoplasm. Moreover, circMBOAT2 and FASN have the same effect on fatty acid profile, unsaturated fatty acids instead of saturated fatty acids are primarily regulated and associated with malignant behaviors of ICC cells. The levels of lipid peroxidation and ROS were significantly higher when FASN was knocked down and recovered when circMBOAT2 was overexpressed. Our results identified that circMBOAT2 was upregulated in ICC and promoted progression by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export, which altered lipid metabolic profile and regulated redox homeostasis in ICC, suggesting that circMBOAT2 may serve as an available therapeutic target for ICC with active lipid metabolism.
Oncogenic RAS Drives Resistance to Pemigatinib in Cholangiocarcinoma Harboring a FGFR2 Delins Disrupting Ligand Binding
Fetched: January 17th, 2023, 5:01am GMT by Mir Lim
JCO Precis Oncol. 2023 Jan;7:e2200340. doi: 10.1200/PO.22.00340.
PMID:36634295 | DOI:10.1200/PO.22.00340
Detection and endoscopic classification of intraductal neoplasms of the bile duct by peroral cholangioscopy with narrow-band imaging (with videos)
Fetched: January 16th, 2023, 5:01am GMT by Il Sang Shin
Gastrointest Endosc. 2023 Jan 12:S0016-5107(23)00011-1. doi: 10.1016/j.gie.2023.01.008. Online ahead of print.
BACKGROUND AND AIMS: Indirect diagnostic modalities are unsatisfactory for detecting intraductal neoplasm of the bile duct (IN-B), which can be detected by peroral cholangioscopy (POC) with narrow-band imaging (NBI). We investigated the POC findings of IN-B and developed a feasible endoscopic classification system.
METHODS: A total of 471 patients who underwent direct POC from April 2008 to July 2020 were enrolled. Intraductal superficial lesions of the bile duct (ISL-Bs) were classified according to surface structure and microvascular pattern on POC with NBI and correlated to histologic findings after POC-guided forceps biopsy (POC-FB) or surgery. The primary outcome was the detection rate of IN-Bs, and the secondary outcomes were the associations of POC findings with IN-B, the technical success rates of POC and POC-FB, and adverse events (AEs).
RESULTS: Direct POC was successful in 458 of 471 patients (97.2%). Among the patients, 131 (27.8%) exhibited ISL-Bs. The technical success rate of POC-FB was 94.7% (124 of 131). Among the 124 patients who underwent POC-FB, IN-B was revealed in 54 (43.5%), for a detection rate of 11.8% (54 of 458). Papillary lesion (P = 0.041), nodular lesion (P = 0.044), and irregularly or regularly dilated and tortuous vessels (P = 0.004; P = 0.006) were POC findings associated with IN-B. The area under the receiver operating characteristic curve of the novel classification system was 0.899.
CONCLUSIONS: POC with NBI can be useful for the detection of IN-Bs. Our novel classification system based on both surface structure and microvascular pattern may allow differentiation of IN-B from ISL-Bs.
PMID:36642196 | DOI:10.1016/j.gie.2023.01.008
Clinical outcomes of second‑line chemotherapy after gemcitabine and cisplatin plus S‑1 treatment for patients with advanced biliary tract cancer in the KHBO1401‑3A study
Fetched: January 13th, 2023, 2:07pm GMT by Yoshitaro Shindo
Oncol Rep. 2023 Feb;49(2):41. doi: 10.3892/or.2023.8478. Epub 2023 Jan 12.
Since the completion of the KHBO1401 study, which evaluated the efficacy of the combination of gemcitabine (GEM) and cisplatin (GC) compared with GC plus S‑1 (GCS), GCS has become a standard chemotherapy for patients with advanced biliary tract cancer (BTC). However, there are currently no data revealing second‑line therapy options after GCS. The present study aimed to evaluate the survival outcomes of patients receiving second‑line chemotherapy for advanced BTC, refractory or intolerant to GCS, using data from the KHBO1401 study. Patients who received a second‑line treatment after GCS chemotherapy between July 2014 and February 2016 were retrospectively studied. Overall survival (OS) was calculated from the day of GCS treatment failure or the first day of second‑line chemotherapy to the final follow‑up date or until death from any cause. Among 83 patients refractory or intolerant to GCS chemotherapy, 51 (61%) received second‑line chemotherapy, including GCS (n=8), GC (n=15), GEM (n=6), GEM plus S‑1 (GS) (n=4) and S‑1 (n=18). The 6‑ and 12‑month OS rates were 66.7 and 44.4%, respectively, following second‑line chemotherapy, and 6.3 and 3.1%, respectively, in the best supportive care group (P<0.0001). In addition, the 12‑ and 24‑month OS rates were 59.3 and 36.2%, respectively, in the multidrug chemotherapy group, and 26.9 and 9.0%, respectively, in the single‑agent chemotherapy group (P=0.0191). These results suggested that second‑line combination chemotherapy is a viable treatment option for patients with advanced BTC that is refractory or intolerant to first‑line GCS therapy.
PMID:36633148 | DOI:10.3892/or.2023.8478
Pre-surgical diagnosis of neuroendocrine carcinoma of the extrahepatic bile duct: a case study
Fetched: January 13th, 2023, 2:07pm GMT by Mari Tajima
Nihon Shokakibyo Gakkai Zasshi. 2023;120(1):96-103. doi: 10.11405/nisshoshi.120.96.
A 70-year-old woman presented to our hospital with jaundice. Abdominal ultrasonography showed biliary duct dilatation. Blood tests revealed elevated total bilirubin and hepatobiliary enzyme levels. A contrast-enhanced computed tomography of the abdomen showed bile duct thickening with wall enhancement. Transpapillary bile duct biopsy showed an invasive carcinoma proliferating in a follicular pattern. Pathology revealed positive synaptophysin and chromogranin A and a Ki67 index >40%, consistent with a diagnosis of neuroendocrine carcinoma (NEC). After confirming the absence of distant metastases, a subtotal stomach-preserving pancreaticoduodenectomy was performed. The result of the postoperative pathology was the same as the preoperative biopsy. According to previous reports, 7 out of 28 cases with NEC/mixed adenoneuroendocrine carcinoma could be diagnosed as NEC before surgery. However, biliary cytology and bile duct scraping cytology were used in many cases;only 11 cases underwent bile duct biopsy. For the latter, 5 out of 11 cases could be diagnosed preoperatively. NEC of the extrahepatic duct often exhibits a submucosal tumor-like morphology, which may result in a false negative result with biliary cytology or bile duct scraping cytology. In our case, the transpapillary bile duct biopsy sample was sufficient to diagnose NEC. This method could be an attractive option for the diagnosis of these tumors.
PMID:36631122 | DOI:10.11405/nisshoshi.120.96
Laparoscopic versus open oncological extended re-resection for incidental gallbladder adenocarcinoma: we can do more than T1/2
Fetched: January 13th, 2023, 5:01am GMT by Yan-Wen Jin
Surg Endosc. 2023 Jan 12. doi: 10.1007/s00464-022-09839-x. Online ahead of print.
BACKGROUND: The laparoscopic and open approaches have comparable safety and oncological efficacy to treat early (T1b or T2) stage incidental gallbladder cancer (IGBC). However, their effects on T3 stage or above tumors unclear.
METHODS: Data of IGBC patients who underwent radical re-resection were retrospectively analyzed. Demographic characteristics, surgical variables, and tumor characteristics were evaluated for association with survival.
RESULTS: We analyzed retrospectively 201 patients (72 men, 129 women; median age 63 years; range, 36-85 years). 84 underwent laparoscopic re-resection and 117 underwent open surgery. The 5-year OS post-resection was 74.7%, with a median survival of 74.52 months. The median OS (73.92 months vs. 77.04 months, P = 0.67), and disease-free survival (72.60 months vs. 71.09 months, P = 0.18) were comparable between the laparoscopic re-resection and open surgery groups. The survival of patients with T1/T2 (median: 85.50 months vs. 80.14 months; P = 0.67) and T3 (median: 68.56 months vs. 58.85 months; P = 0.36) disease were comparable between the open re-resection and laparoscopic re-resection groups even after PS matching. Open surgery group lost significantly more blood, while laparoscopic surgery took longer. The postsurgical stay in the laparoscopic re-resection group was significantly shorter. Combined extrahepatic bile duct resection, gallbladder perforation, pT, pStage, histological grade, microscopic liver invasion, status of the resected margin, and adjuvant therapy comprised significant independent prognostic indicators for IGBC.
CONCLUSIONS: Laparoscopic and open surgery can achieve similar short and long-term outcomes for T3 IGBC; however, careful surgical manipulation is necessary to avoid secondary injuries.
PMID:36635401 | DOI:10.1007/s00464-022-09839-x
Prognostic influence for hilar cholangiocarcinoma and comparisons of prognostic values of Mayo staging and TNM staging systems
Fetched: January 13th, 2023, 5:01am GMT by Zhaowei Sun
Medicine (Baltimore). 2022 Dec 9;101(49):e32250. doi: 10.1097/MD.0000000000032250.
The study was designed to discuss the effect of stratification factors in the Mayo staging on the prognosis of hilar cholangiocarcinoma (HCCA) patients, and to evaluate the predictive value of the Mayo staging on the prognosis. The Kaplan-Meier survival curve and Log-rank test were used to perform univariate analysis on each index and obtain statistically significant influencing factors. The Kaplan-Meier survival curve and Log-rank test were used to analyze the correlation between the two staging systems and the survival period. The receiver operating characteristic (ROC) curves were used for each single staging system trend analysis, and comparison of their curve area to determine prognosis prediction ability for patients with HCCA. According to Kaplan-Meier survival curve changes and Log-rank test results, it was found that both staging systems were correlated with the survival time of the patients (P < .001). Through a pairwise comparison within the stages, it was found that the heterogeneity between the stages within the Mayo staging is very good, which was better than the TNM staging. A single trend analysis of the prognostic assessment capabilities of the two systems found that the area under the ROC curve of Mayo staging system (AUC = 0.587) was the largest and better than the TNM staging system (AUC = 0.501). Mayo staging can be used for preoperative patient prognosis assessment which can provide better stratification ability based on a single-center small sample study, and the predictive value is better than TNM staging.
PMID:36626512 | PMC:PMC9750704 | DOI:10.1097/MD.0000000000032250
Triptolide inhibits intrahepatic cholangiocarcinoma growth by suppressing glycolysis via the AKT/mTOR pathway
Fetched: January 13th, 2023, 5:01am GMT by Li Li
Phytomedicine. 2023 Jan;109:154575. doi: 10.1016/j.phymed.2022.154575. Epub 2022 Nov 21.
BACKGROUND: High levels of glycolysis supply large quantities of energy and biological macromolecular raw materials for cell proliferation. Triptolide (TP) is a kind of epoxy diterpene lactone extracted from the roots, flowers, leaves, or grains of the Celastraceae plant, Tripterygium wilfordii. TP has multiple biological activities, including anti-inflammatory, immunologic suppression, and anti-cancer effects. Nevertheless, it is little known regarding its anti-intrahepatic cholangiocarcinoma (ICC) growth, and the mechanism still require exploration.
PURPOSE: This research explored the effect of TP on ICC growth and investigated whether TP inhibits glycolysis via the AKT/mTOR pathway.
METHODS: Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8), clonogenic assay, and flow cytometry. The underlying molecular mechanism was identified by determining glucose consumption, ATP production, lactate production, hexokinase (HK) and pyruvate kinase (PK) activity, and Western blot analysis. A rapid ICC model of AKT/YapS127A oncogene coactivation in mice was used to clarify the effect of TP treatment on tumor growth and glycolysis.
RESULTS: The results showed that TP treatment significantly inhibited ICC cell proliferation and glycolysis in a dose- and time-dependent manner(P < 0.05). Further analysis suggested that TP suppressed ICC cell glycolysis by targeting AKT/mTOR signaling. Additionally, we found that TP inhibits tumor growth and glycolysis in AKT/YapS127A mice(P < 0.05).
CONCLUSION: Taken together, we revealed that TP suppressed ICC growth by suppressing glycolysis via the AKT/mTOR pathway and may provide a potential therapeutic target for ICC treatment.
PMID:36610163 | DOI:10.1016/j.phymed.2022.154575
Tumor ratio of unsaturated to saturated sulfatide species is associated with disease-free survival in intrahepatic cholangiocarcinoma
Fetched: January 12th, 2023, 5:00am GMT by Lennart Huizing
Cell Oncol (Dordr). 2023 Jan 11. doi: 10.1007/s13402-022-00766-6. Online ahead of print.
PURPOSE: Cholangiocarcinoma (CCA) is a malignancy arising from the bile duct epithelium and has a poor outcome. Sulfatides are lipid components of lipid rafts, and are implicated in several cancer types. In the liver, sulfatides are specifically present in the bile ducts. Here, sulfatide abundance and composition were analyzed using mass spectrometry imaging in intrahepatic CCA (iCCA) tumor tissue, and correlated with tumor biology and clinical outcomes.
METHODS: Sulfatides were analyzed in iCCA (n = 17), hepatocellular carcinoma (HCC, n = 10) and colorectal liver metastasis (CRLM, n = 10) tumor samples, as well as tumor-distal samples (control, n = 16) using mass spectrometry imaging. Levels of sulfatides as well as the relative amount in structural classes were compared between groups, and were correlated with clinical outcomes for iCCA patients.
RESULTS: Sulfatide localization was limited to the respective tumor areas and the bile ducts. Sulfatide abundance was similar in iCCA and control tissue, while intensities were notably higher in CRLM in comparison with control (18-fold, P < 0.05) and HCC tissue (47-fold, P < 0.001). Considerable variation in sulfatide abundance was observed in iCCA tumors. A high ratio of unsaturated to saturated sulfatides was associated with reduced disease-free survival (10 vs. 20 months) in iCCA. The sulfatide pattern in HCC deviated from the other groups, with a higher relative abundance of odd- versus even-chain sulfatides.
CONCLUSION: Sulfatides were found in tumor tissue of patients with iCCA, with sulfatide abundance per pixel being similar to bile ducts. In this explorative study, sulfatide abundance was not related to overall survival of iCCA patients. A high ratio of unsaturated to saturated sulfatides was associated with earlier tumor recurrence in patients with iCCA.
A case of delayed pancreatic fistula after covered self-expandable metallic stent deployment for pancreatic head cancer
Fetched: January 11th, 2023, 5:00am GMT by Shogo Ota
A 69-year-old man was referred to our hospital with obstructive jaundice. A tumor with poor contrast enhancement was found in the pancreatic head, but there was no evidence of pancreatic atrophy, irregular stenosis, or dilation of the main pancreatic duct. He was diagnosed with borderline resectable pancreatic cancer with distal malignant biliary obstruction. After plastic stent placement, serum bilirubin levels improved, and chemotherapy was started. However, he developed cholangitis; thus, the plastic stent was replaced with a covered self-expandable metallic stent. He subsequently developed a delayed pancreatic fistula due to main pancreatic duct disruption. An endoscopic nasopancreatic duct drainage tube was placed to bridge the main pancreatic duct disruption after removing the covered self-expandable metallic stent. In addition, endoscopic ultrasound-guided transmural drainage was performed for the infected fluid collection caused by the pancreatic fistula, and the clinical symptoms quickly improved. This case presents the possibility of a delayed pancreatic fistula due to self-expandable metallic stent deployment. The need for considering such delayed complications when placing self-expanding metallic stents is highlighted.
Case report: A report of the complete pathological response of intrahepatic cholangiocarcinoma after conversion therapy
Fetched: January 11th, 2023, 5:00am GMT by Xi Zhang
Front Immunol. 2022 Dec 23;13:1051130. doi: 10.3389/fimmu.2022.1051130. eCollection 2022.
Cholangiocarcinoma (CCA) is a rare disease with poor prognosis, and surgery remains the only curative treatment option. However, surgery is inappropriate for the majority of patients with CCA. Conversion therapy may provide opportunities for the surgical treatment of these patients. Herein, we describe a patient with intrahepatic CCA who was first treated with albumin-bound paclitaxel, cisplatin, and gemcitabine in combination with camrelizumab. The patient then successfully underwent surgery and achieved pathological complete remission. This report can serve as a reference for clinicians regarding conversion therapy for intrahepatic CCA.
PMID:36618353 | PMC:PMC9816130 | DOI:10.3389/fimmu.2022.1051130
Research progress of potential factors influencing photodynamic therapy for Gastrointestinal Cancer
Fetched: January 10th, 2023, 5:01am GMT by Puyi He
Photodiagnosis Photodyn Ther. 2023 Jan 6;41:103271. doi: 10.1016/j.pdpdt.2022.103271. Online ahead of print.
Gastrointestinal cancer is a malignant tumor of the gastrointestinal tract and its associated digestive organs, including esophageal cancer, gastric cancer, carcinoma of the ampulla, pancreas, bile duct, intestines and rectal cancer. They account for about 30% of global cancer-related incidence and about 40% of mortality. Photodynamic therapy (PDT), as a treatment mode, has been applied to the treatment of gastrointestinal cancer due to potential advantages targeting and potentially lower toxic side effects. However, In the course of clinical treatment, we have found that different patients have various responsiveness to PDT, and even the same patients may have different clinical effects after receiving treatment in different time periods. For influencing factors, traditionally, we only focus on adjusting the dose of photosensitizer and the intensity and time of irradiation,while minimizing other potential factors.Therefore, this paper looks for factors that affect PDT from the patient's own conditions, tumor characteristics and tumor microenvironment(including:tumor acidic microenvironment,tumor hypoxic microenvironment, multi-drug resistance, different tumor characteristics and the immune status of patients) and summarizes how to potentially improve the curative effect of PDT.
PMID:36623701 | DOI:10.1016/j.pdpdt.2022.103271
Gastrointestinal and Pancratohepatobiliary Cancers: A Comprehensive Review on Epidemiology and Risk Factors Worldwide
Fetched: January 10th, 2023, 5:01am GMT by Ahmad Hormati
Middle East J Dig Dis. 2022 Jan;14(1):5-23. doi: 10.34172/mejdd.2022.251. Epub 2022 Jan 30.
A significant number of cancer cases are afflicted by gastrointestinal cancers annually. Lifestyle and nutrition have a huge effect on gastrointestinal function, and unhealthy habits have become quite widespread in recent decades, culminating in the rapid growth of gastrointestinal cancers. The most prevalent cancers are lip and mouth cancer, esophageal cancer, gastric cancer, liver and bile duct cancer, pancreatic cancer, and colorectal cancer. Risk factors such as red meat consumption, alcohol consumption, tea, rice, viruses such as Helicobacter pylori and Ebstein Bar Virus (EBV), along with reduced physical activity, predispose the gastrointestinal tract to damage and cause cancer. According to the rapid increase of cancer incidence and late diagnosis of gastrointestinal malignancies, further epidemiological researches remain necessary in order to make appropriate population-based preventive policies. In this study, we reviewed clinical symptoms, risk factors, preventative measures, as well as incidence and mortality rates of gastrointestinal malignancies worldwide with focus on Iranian population.
PMID:36619733 | PMC:PMC9489325 | DOI:10.34172/mejdd.2022.251
A retrospective multicenter study comparing the punctures to B2 and B3 in endoscopic ultrasound-guided hepaticogastrostomy
Fetched: January 10th, 2023, 5:01am GMT by Masanari Sekine
DEN Open. 2023 Jan 3;3(1):e201. doi: 10.1002/deo2.201. eCollection 2023 Apr.
OBJECTIVES: In recent years, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) has been performed as an important salvage option for failed endoscopic retrograde cholangiopancreatography for biliary drainage. However, technical issues, such as puncture site (bile duct of segment 3 [B3] or bile duct of segment 2 [B2]), dilation method, stent selection, and procedural safety, need to be resolved for the optimization of EUS-HGS. The present study was to compare the safety, difficulty, and technical and functional success between biliary access via B2 and B3 during EUS-HGS.
METHODS: We conducted a retrospective investigation of 161 consecutive EUS-HGS cases across a total of 6 facilities, including those at our hospital. The patients were divided into two groups according to the successful drainage route: the puncture to B2 (P-B2) or the puncture to B3 (P-B3). We compared the technical and functional success rates, technical difficulty, and adverse events between the two groups. We also conducted a subgroup analysis to show the factors related to the procedure time.
RESULTS: There were 92 cases in the P-B2 group and 69 cases in the P-B3 group. There were no significant differences in the technical success, functional success, or adverse events between the groups; however, the procedure time was significantly shorter in P-B2 cases than in P-B3 cases. The multivariate analysis showed that the puncture site was the only factor related to the procedure time.
CONCLUSIONS: Based on these findings, P-B2 appears useful and safe. P-B2 is as effective as P-B3 and was able to be performed in a shorter period of time. The B2 approach can be considered a useful option for EUS-HGS.
PMID:36618883 | PMC:PMC9810585 | DOI:10.1002/deo2.201
Circulating tumour DNA in gastrointestinal cancer in clinical practice: Just a dream or maybe not?
Fetched: January 10th, 2023, 5:01am GMT by Andrea Pretta
World J Clin Oncol. 2022 Dec 24;13(12):980-983. doi: 10.5306/wjco.v13.i12.980.
The evaluation of circulating tumor DNA (ctDNA) is increasingly integrated into the management of diagnosis and treatment of gastrointestinal cancer as it represents an innovative and minimally invasive biomarker that could allow us to reach clinical needs not met yet in randomized clinical trials. Recent research provided an interesting overview of the role of circulating tumor DNA in gastric, biliary, liver, pancreatic, and colorectal cancer. Data regarding upper gastrointestinal tumors are currently not practice changing. Tumor detection rates are low in the early stages, while in advanced stages ctDNA is useful for molecular tracking evaluation. Most of the evidence comes from colorectal cancer studies, where ctDNA was evaluated both in the early and advanced stages with the post-surgery minimal residual disease assessment and the response assessment, respectively. ctDNA qualifies as a promising tool in the era of precision medicine, with potential applications in the entire management of gastrointestinal cancer patients. Further evidence is needed to establish which setting may be influenced greatly by liquid biopsy in clinical practice.
PMID:36618080 | PMC:PMC9813836 | DOI:10.5306/wjco.v13.i12.980
Selective Decontamination of the Digestive Tract in Pancreatic Head Resections-A Propensity Score-Matched Analysis
Fetched: January 9th, 2023, 5:01am GMT by Olga Radulova-Mauersberger
J Clin Med. 2022 Dec 29;12(1):250. doi: 10.3390/jcm12010250.
(1) Background: The postoperative morbidity rate after pancreatic head resection remains high, partly due to infectious complications. The primary aim of this study was to analyze the influence of selective decontamination of the digestive tract (SDD) on the postoperative infection rate after pancreatic surgery. (2) Methods: From January 2019, the standard of care for patients undergoing pancreatic head resections at the Department for Visceral, Thoracic, and Vascular Surgery, University Hospital Dresden was the preoperative oral administration of SDD. The influence of SDD was evaluated for patients operated on between January 2019 and June 2020 in comparison to a propensity score-matched cohort, extracted from an existing database including all pancreatic resections from 2012 to 2018. The primary endpoint of the study was the shift of the bacterial load on the intraoperative bile swab test. The secondary endpoint was the association of SDD with postoperative complications. (3) Results: In total, 200 patients either with SDD (n = 100; 50%) or without SDD (non-SDD, n = 100; 50%) were analyzed. In the patient group without a preoperative biliary stent, 44% (n = 11) of the non-SDD group displayed positive bacterial results, whereas that was the case for only 21.7% (n = 10) in the SDD group (p = 0.05). Particularly, Enterobacter species (spp.) were reduced from 41.2% (n = 14) (non-SDD group) to 23.5% (n = 12) (SDD group) (p = 0.08), and Citrobacter spp. were reduced by 13.7% (p = 0.09) from the non-SDD to the SDD cohort. In patients with a preoperative biliary stent, the Gram-negative Enterobacter spp. were significantly reduced from 52.2% (n = 12) in the non-SDD group to 26.8% (n = 11) in the SDD group (p = 0.04). Similarly, Citrobacter spp. decreased by 20.6% from 30.4% (n = 7) to 9.8% (n = 4) in the non-SDD compared to the SDD group (p = 0.04). In general, deep fluid collection and abscesses occurred more frequently in the non-SDD group (36%; n = 36 vs. 27%; n = 27; p = 0.17). (4) Conclusions: Adoption of SDD before pancreatic head surgery may reduce the bacterial load in bile fluid. SDD administration does not significantly affect the postoperative infectious complication rate after pancreatic head resections.
PMID:36615050 | PMC:PMC9820838 | DOI:10.3390/jcm12010250
Utilization of Cancer Cell Line Screening to Elucidate the Anticancer Activity and Biological Pathways Related to the Ruthenium-Based Therapeutic BOLD-100
Fetched: January 9th, 2023, 5:01am GMT by Brian J Park
Cancers (Basel). 2022 Dec 21;15(1):28. doi: 10.3390/cancers15010028.
BOLD-100 (sodium trans-[tetrachlorobis(1H indazole)ruthenate(III)]) is a ruthenium-based anticancer compound currently in clinical development. The identification of cancer types that show increased sensitivity towards BOLD-100 can lead to improved developmental strategies. Sensitivity profiling can also identify mechanisms of action that are pertinent for the bioactivity of complex therapeutics. Sensitivity to BOLD-100 was measured in a 319-cancer-cell line panel spanning 24 tissues. BOLD-100's sensitivity profile showed variation across the tissue lineages, including increased response in esophageal, bladder, and hematologic cancers. Multiple cancers, including esophageal, bile duct and colon cancer, had higher relative response to BOLD-100 than to cisplatin. Response to BOLD-100 showed only moderate correlation to anticancer compounds in the Genomics of Drug Sensitivity in Cancer (GDSC) database, as well as no clear theme in bioactivity of correlated hits, suggesting that BOLD-100 may have a differentiated therapeutic profile. The genomic modalities of cancer cell lines were modeled against the BOLD-100 sensitivity profile, which revealed that genes related to ribosomal processes were associated with sensitivity to BOLD-100. Machine learning modeling of the sensitivity profile to BOLD-100 and gene expression data provided moderative predictive value. These findings provide further mechanistic understanding around BOLD-100 and support its development for additional cancer types.
PMID:36612025 | PMC:PMC9817855 | DOI:10.3390/cancers15010028
In vivo detection of bile duct pre-cancer with endoscopic light scattering spectroscopy
Fetched: January 9th, 2023, 5:01am GMT by Douglas K Pleskow
Nat Commun. 2023 Jan 7;14(1):109. doi: 10.1038/s41467-022-35780-7.
Bile duct cancer is the second most common primary liver cancer, with most diagnoses occurring in the advanced stages. This leads to a poor survival rate, which means a technique capable of reliably detecting pre-cancer in the bile duct is urgently required. Unfortunately, radiological imaging lacks adequate accuracy for distinguishing dysplastic and benign biliary ducts, while endoscopic techniques, which can directly assess the bile duct lining, often suffer from insufficient sampling. Here, we report an endoscopic optical light scattering technique for clinical evaluation of the malignant potential of the bile duct. This technique employs an ultraminiature spatial gating fiber optic probe compatible with cholangioscopes and endoscopic retrograde cholangiopancreatography (ERCP) catheters. The probe allowed us to investigate the internal cellular composition of the bile duct epithelium with light scattering spectroscopy (LSS) and phenotypic properties of the underlying connective tissue with diffuse reflectance spectroscopy (DRS). In a pilot in vivo double-blind prospective study involving 29 patients undergoing routine ERCP procedures, the technique detected malignant transformation with 97% accuracy, showing that biliary duct pre-cancer can be reliably identified in vivo non-invasively.
Colorectal liver metastasis with bile duct tumor thrombus discovered 15 years post primary tumor resection: a case report and literature review
Fetched: January 7th, 2023, 5:01am GMT by Kazuya Kato
Int Cancer Conf J. 2022 Oct 26;12(1):75-80. doi: 10.1007/s13691-022-00583-6. eCollection 2023 Jan.
Colorectal liver metastasis (CRLM) appears in 25-50% of patients with colorectal cancer (CRC). However, CRLM with bile duct tumor thrombus (BDTT) is rare and often diagnosed after surgical resection. We report a case of CRLM associated with BDTT in a 79 year-old woman. She underwent sigmoid colectomy for sigmoid colon carcinoma at the age of 64. Fifteen years later, abdominal computed tomography revealed a liver tumor with a biliary tumor thrombus in segment IV/V and localized dilation of the intrahepatic bile duct. Additionally, magnetic resonance imaging confirmed a tumor in liver segment IV/V and mass in the bile duct (B4). Extended left hepatic lobectomy was performed under the diagnosis of intrahepatic cholangiocarcinoma or metastatic liver tumor with tumor development in the intrahepatic bile duct. The resected specimen showed significant cancer infiltration into the intrahepatic bile duct (B4), forming a tumor thrombus. The tumor was a moderately differentiated adenocarcinoma, histologically similar to sigmoid colon cancer. CRLM with BDTT may have a relatively low invasive potential of malignancy with a long interval after primary resection. When a patient with a history of CRC presents with BDTT, the possibility of CRLM with BDTT and surgical treatment should be considered, because resection could lead to a good prognosis. It is important to ensure a secure surgical margin in the bile ducts during surgery and anatomical hepatic resection should be considered.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-022-00583-6.
Effect of age on the prognosis of intrahepatic cholangiocarcinoma
Fetched: January 6th, 2023, 5:01am GMT by Jung Hun Kim
Korean J Intern Med. 2023 Jan;38(1):39-47. doi: 10.3904/kjim.2022.146. Epub 2022 Dec 21.
BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma and is the second- most-common primary hepatic tumor. Several predictive and prognostic factors have been analyzed; however, in this study we focused on the influence of age. Our aim was to use real-world results to determine the influence of age in iCCA patients.
METHODS: A retrospective analysis of patients treated between 2005 and 2016 at Konkuk University Medical Center. In total, 133 patients with iCCA were identified. The mass-forming, periductal-infiltrating, and intraductal-growth types were included; patients with extrahepatic or hilar-type cholangiocarcinoma were excluded. We defined two groups: a younger group, age < 65 years, and an older group, age ≥ 65 years. Statistical analyses using univariate and multivariate Cox regression analyses, including the Kaplan-Meier method, were conducted.
RESULTS: In total, 114 patients were enrolled. The two groups differed with regard to treatment options such as surgery with adjuvant chemotherapy or palliative chemotherapy (p = 0.012, p < 0.001). The younger group had significantly longer survival than the older group (p = 0.017). In the younger group, patients who received therapy had longer survival than those who did not (hazard ratio, 3.942; 95% confidence interval, 2.053 to 7.569; p < 0.001). Multivariate analysis indicated that younger age, lower bilirubin, low CA 19-9, and no lymph-node involvement were independent factors for improved survival.
CONCLUSION: Younger patients and those who underwent surgery with adjuvant chemotherapy had longer survival. The younger the patient, the more treatments received, including palliative chemotherapy.
PMID:36541019 | DOI:10.3904/kjim.2022.146
Primary Sclerosing Cholangitis- A Rare Cause of Obstructive Jaundice: A Case Report
Fetched: January 5th, 2023, 5:01am GMT by M M Chowdhury
Mymensingh Med J. 2023 Jan;32(1):257-260.
Diagnosis of primary sclerosing cholangitis (PSC) is often very difficult and may have a suspicion with altered liver functions. PSC is known to be associated with inflammatory bowel disease. This article presents a case study of a 70 years old male patient who presented with obstructive jaundice with recurrent episode of cholangitis in June 2019 at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Evaluation revealed beaded appearance in MRCP with positive relevant markers which raised suspicion of PSC and it was confirmed by biopsy and histopathology of the affected segment in biliary tree. The importance of early detection of primary sclerosing cholangitis in an effort to decrease the morbidity and mortality from cholangiocarcinoma will also be emphasized and our management according to local protocol and outcome of this patient.
High Level of Serum Coiled-coil Domain Containing 25 (CCDC25) as a Diagnostic Marker for Cholangiocarcinoma But Not for Other Cancers
Fetched: January 5th, 2023, 5:01am GMT by Apinya Jannawan
In Vivo. 2023 Jan-Feb;37(1):294-303. doi: 10.21873/invivo.13079.
BACKGROUND/AIM: Recently, we reported that coiled-coil domain containing 25 (CCDC25) protein is elevated in the sera of patients with cholangiocarcinoma (CCA) and is suggested to be a diagnostic biomarker for CCA. This study aimed to examine whether serum CCDC25 level can be a unique biomarker for CCA. Bioinformatic analyses using Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) indicated that CCDC25 protein and mRNA are expressed not only in CCA but also in other cancers, such as colorectal cancer (CRC), breast cancer (BC), and hepatocellular carcinoma (HCC), all of which are the top 5 cancers highly prevalent in Thailand.
MATERIALS AND METHODS: Using a quantitative dot blot assay, serum CCDC25 levels were measured for 30 healthy controls (HC), 34 CRC, 42 BC, 43 HCC, and 83 CCA.
RESULTS: The serum CCDC25 levels of CCA patients (0.193±0.039 ng/μl) were significantly higher than those of CRC (0.019±0.006 ng/μl), BC (0.036±0.015 ng/μl), HCC (0.035±0.016 ng/μl), and higher than those of HC (0.012±0.003 ng/μl). The serum CCDC25 level can discriminate CCA from the HC, CRC, BC, and HCC with a sensitivity of 100, 99, 94, and 94%, respectively, and specificity of 100, 100, 98, and 95%, respectively.
CONCLUSION: CCDC25 is a candidate diagnostic biomarker for CCA.
PMID:36593058 | DOI:10.21873/invivo.13079
Impact of the COVID-19 Pandemic on Liver Cancer Staging at a Multidisciplinary Liver Cancer Clinic
Fetched: January 3rd, 2023, 5:01am GMT by Daniel Li
Ann Surg Open. 2022 Oct 3;3(4):e207. doi: 10.1097/AS9.0000000000000207. eCollection 2022 Dec.
To compare liver cancer resectability rates before and during the COVID-19 pandemic.
BACKGROUND: Liver cancers usually present with nonspecific symptoms or are diagnosed through screening programs for at-risk patients, and early detection can improve patient outcomes. In 2020, the COVID-19 pandemic upended medical care across all specialties, but whether the pandemic was associated with delays in liver cancer diagnosis is not known.
METHODS: We performed a retrospective review of all patients evaluated at the Johns Hopkins Multidisciplinary Liver Cancer Clinic from January 2019 to June 2021 with a new diagnosis of suspected or confirmed hepatocellular carcinoma (HCC) or biliary tract cancer (BTC).
RESULTS: There were 456 liver cancer patients (258 HCC and 198 BTC). From January 2019 to March 2020 (pre-pandemic), the surgical resectability rate was 20%. The subsequent 6 months (early pandemic), the resectability rate decreased to 11%. Afterward from October 2020 to June 2021 (late pandemic), the resectability rate increased to 27%. The resectability rate early pandemic was significantly lower than that for pre-pandemic and later pandemic combined (11% lower; 95% confidence interval [CI], 2%-20%). There was no significant difference in resectability rates pre-pandemic and later pandemic (7% difference; 95% CI, -3% to 16%). In subgroup analyses, the early pandemic was associated with a larger impact in BTC resectability rates than HCC resectability rates. Time from BTC symptom onset until Multidisciplinary Liver Clinic evaluation increased by over 6 weeks early pandemic versus pre-pandemic (Hazard Ratio, 0.63; 95% CI, 0.44-0.91).
CONCLUSIONS: During the early COVID-19 pandemic, we observed a drop in the percentage of patients presenting with curable liver cancers. This may reflect delays in liver cancer diagnosis and contribute to excess mortality related to the COVID-19 pandemic.
PMID:36590894 | PMC:PMC9782462 | DOI:10.1097/AS9.0000000000000207
The epidemiological trends of biliary tract cancers in the United States of America
Fetched: January 3rd, 2023, 5:01am GMT by Yong Jiang
BMC Gastroenterol. 2022 Dec 29;22(1):546. doi: 10.1186/s12876-022-02637-8.
BACKGROUND: Biliary tract cancers (BTCs) are a series of heterogeneous malignancies that are broadly grouped based on the anatomical site where they arise into subtypes including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC).
METHODS AND RESULTS: The present study provides an overview of the epidemiology of the various BTCs based on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2018. Distinct differences in both incidence and mortality rates were observed for these BTCs as a function of age, sex, ethnicity, and calendar year. In 2018, BTCs emerged as the fifth most prevalent form of alimentary tract cancer in the USA. While the incidence and mortality of ICC appear to be increasing, the incidence rates of GBC, ECC, and AVC have remained stable, as have the corresponding mortality rates. The most common and deadliest BTCs in 2018 were ICC and GBC among males and females, respectively. The ethnic groups exhibiting the highest incidence rates of these different BTCs were American Indians and Alaska Natives for GBC, and Asian and Pacific Islanders for ICC, ECC, and AVC. The incidence of all of these forms of BTC rose with age. There were some variations in BTCs in terms of staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes from 2000 to 2018.
CONCLUSIONS: The epidemiological characteristics, staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes were distinct for each of these BTCs.
Survival analysis of extrahepatic cholangiocarcinoma based on surveillance, epidemiology, and end results database
Fetched: January 2nd, 2023, 5:00am GMT by Hassam Ali
Ann Hepatobiliary Pancreat Surg. 2023 Jan 2. doi: 10.14701/ahbps.22-090. Online ahead of print.
BACKGROUNDS/AIMS: Cholangiocarcinoma (CCA) can be classified as intrahepatic CCA or extrahepatic CCA (eCCA). We intended to analyze and reports the survival outcomes for eCCA.
METHODS: Surveillance, epidemiology, and end results (SEER) registry, site recode C24.0, was used to select cases of eCCA from 2000 to 2018. Patients with incomplete data or ages <18 years were excluded.
RESULTS: Male (52.69%) and White race (77.99%) predominated. Compared with 2000-2006, survival increased in 2013 (adjusted hazard ratio [HRadj]: 0.68, 95% confidence interval [CI] 0.58-0.70; p < 0.01). Surgery with chemoradiotherapy (HRadj: 0.69, 95% CI 0.60-0.7; p < 0.01) and surgery with chemotherapy (HRadj: 0.72, 95% CI 0.62-0.83; p < 0.01) improved survival over surgery alone. Compared with surgery without lymph node (LN) removal, surgery of four or more regional LN reduced the risk of death by 58% (HRadj: 0.42, 95% CI 0.36-0.51; p < 0.01). Compared with patients without surgery, patients who underwent bile duct excision (HRadj: 0.82, 95% CI 0.72-0.94; p < 0.01), simple or extended lobectomy (HRadj: 0.85, 95% CI 0.75-0.95; p = 0.009), and hepatectomy (HRadj: 0.80, 95% CI 0.72-0.88; p < 0.01) significantly improved survival. Patients with distal CCA had a 17% higher survival than perihilar CCA (HRadj: 0.83, 95% CI 0.74-0.92; p < 0.01) and LN dissection was equally beneficial for both subgroups (p < 0.01).
CONCLUSIONS: Surgery with chemoradiotherapy has a proven increase in the 5-year survival of the eCCA. LN resection, bile duct excision, lobectomy, and hepatectomy have better outcomes.
PMID:36588169 | DOI:10.14701/ahbps.22-090
"Infiltrative" Versus "Mass-Forming" Pancreatic Cancer: A New Radiological Classification System for Pancreatic Head Ductal Carcinoma and Its Pathological Correlation
Fetched: December 31st, 2022, 5:01am GMT by Muhammad B Darwish
J Pancreat Cancer. 2022 Oct 5;8(1):9-14. doi: 10.1089/pancan.2022.0003. eCollection 2022.
PURPOSE: Resectability in localized pancreatic ductal adenocarcinoma (PDAC) is deemed through radiological criteria. Despite initial evaluation classifying tumors as "resectable," they often have ill-defined borders that can result in more extensive cancer than predicted on final pathology analysis. We attempt to categorize these tumors radiologically and define them as "infiltrative" and contrast them to more well-defined or "mass-forming" tumors and assess their correlation with surgical oncological outcomes. We hypothesize that mass-forming lesions will result in fewer positive resection margins.
METHODS: Patients diagnosed with PDAC of the head of the pancreas and who underwent subsequent curative intent resection between 2016 and 2018 were included. A retrospective chart review of patients was conducted and computed tomography images at the time of diagnosis were reviewed by two radiologists and scored as "mass forming" or "infiltrative" using a newly developed classification system. These classifications were then correlated with margin status.
RESULTS: Sixty-eight consecutive pancreatoduodenectomies performed for PDAC from 2016 to 2018 were identified. After screening, 54 patients were eligible for inclusion. Radiologically defined mass-forming lesions had a trend toward a lower rate of positive resection margins (35.7% vs. 50.0%; p = 0.18), specifically the bile duct margin and pancreas margin as well as an overall larger size (4.03 cm vs. 3.25 cm, p = 0.02) compared with infiltrative lesions.
CONCLUSION: We propose a new radiological definition of PDAC into "mass forming" and "infiltrative," a nomenclature that resonates with other tumor sites. Infiltrative lesions trended toward a higher rate of positive resection margins. This classification may help tailor therapy for infiltrative tumors toward a neoadjuvant approach even if they appear resectable.
PMID:36583028 | PMC:PMC9786088 | DOI:10.1089/pancan.2022.0003
Intraductal oncocytic papillary neoplasm arising in Peutz-Jeghers Syndrome bile duct: a unique case report
Fetched: December 31st, 2022, 5:01am GMT by Qingyue Liu
Diagn Pathol. 2022 Dec 28;17(1):96. doi: 10.1186/s13000-022-01275-8.
BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant disorder caused by germline mutations of STK11/LKB1, with an increased risk of tumors at multiple sites. Intraductal oncocytic papillary neoplasm (IOPN) is a unique subtype of intraductal papillary neoplasm of the bile duct (IPNB) defined by a premalignant neoplasm with intraductal papillary or villous growth of biliary-type epithelium. IOPN has a distinct mutation profile compared with both IPNB and intraductal papillary mucinous neoplasm (IPMN).
CASE PRESENTATION: We herein describe the case of a 44-year-old woman who presented as polyps in the intestinal lumen of sigmoid colon and a 3.1 × 2.1 cm mass in the left lobe of liver. Gross feature revealed a cystic papillary mass and the neoplasm had a clear boundary with the surrounding liver tissue. Histology revealed complex papillary structures, a small amount of fine fibrovascular cores and immunohistochemistry showed extensive positive for MUC5AC, MUC6, CD117. Therefore, histological and immunohistochemical examination of the liver tumor suggested the diagnosis of IOPN. Next-generation sequencing (NGS) revealed other than STK11 germline mutation, the tumor also harbors GNAS somatic mutation at codon 478 and EGFR amplification.
CONCLUSION: To our knowledge, this is the first report of IOPN arising in PJS. This case enlarges the spectrum of PJS related tumors and genetic rearrangements in IOPN.
Molecular profiling in daily practice for cholangiocarcinoma
Fetched: December 31st, 2022, 5:01am GMT by J Selves
Ann Pathol. 2022 Dec;42(6S):6S5-6S7. doi: 10.1016/S0242-6498(22)00212-7.
PMID:36577541 | DOI:10.1016/S0242-6498(22)00212-7
Cholangiocarcinoma: Description and classification
Fetched: December 31st, 2022, 5:01am GMT by V Paradis
iCCA: a new diagnostic approach for a new therapeutic management!
Fetched: December 31st, 2022, 5:01am GMT by J-C Sabourin
Feasibility of machine learning-based modeling and prediction using multiple centers data to assess intrahepatic cholangiocarcinoma outcomes
Fetched: December 31st, 2022, 5:01am GMT by Shuang-Nan Zhou
Ann Med. 2023 Dec;55(1):215-223. doi: 10.1080/07853890.2022.2160008.
BACKGROUND AND AIMS: Currently, there are still no definitive consensus in the treatment of intrahepatic cholangiocarcinoma (iCCA). This study aimed to build a clinical decision support tool based on machine learning using the Surveillance, Epidemiology, and End Results (SEER) database and the data from the Fifth Medical Center of the PLA General Hospital in China.
METHODS: 4,398 eligible patients from the SEER database and 504 eligible patients from the hospital data, who presented with histologically proven iCCA, were enrolled for modeling by cross-validation based on machine learning. All the models were trained using the open-source Python library scikit-survival version 0.16.0. Shapley additive explanations method was used to help clinicians better understand the obtained results. Permutation importance was calculated using library ELI5.
RESULTS: All involved treatment modalities could contribute to a better prognosis. Three models were derived and tested using different data sources, with concordance indices of 0.67, 0.69, and 0.73, respectively. The prediction results were consistent with those under actual situations involving randomly selected patients. Model 2, trained using the hospital data, was selected to develop an online tool, due to its advantage in predicting short-term prognosis.
CONCLUSION: The prediction model and tool established in this study can be applied to predict the prognosis of iCCA after treatment by inputting the patient's clinical parameters or TNM stages and treatment options, thus contributing to optimal clinical decisions.KEY MESSAGESA prognostic model related to disease staging and treatment mode was conducted using the method of machine learning, based on the big data of multi centers.The online calculator can predict the short-term survival prognosis of intrahepatic cholangiocarcinoma, thus, help to make the best clinical decision.The online calculator built to calculate the mortality risk and overall survival can be easily obtained and applied.
Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma
Fetched: December 30th, 2022, 5:01am GMT by Chotirat Rattanasinchai
Sci Rep. 2022 Dec 27;12(1):22429. doi: 10.1038/s41598-022-26747-1.
Intrahepatic cholangiocarcinoma (iCCA) arises along the peripheral bile ducts and is often accompanied by a tumor microenvironment (TME) high in extracellular matrices (ECMs). In this study, we aimed to evaluate whether an ECM-rich TME favors iCCA progression. We identified ITGA2, which encodes collagen-binding integrin α2, to be differentially-expressed in iCCA tumors compared with adjacent normal tissues. Elevated ITGA2 is also positively-correlated with its ligand, collagen type I. Increased ITGA2 expression and its role in collagen type I binding was validated in vitro using four iCCA cell lines, compared with a non-cancerous, cholangiocyte cell line. Robust interaction of iCCA cells with collagen type I was abolished by either ITGA2 depletion or integrin α2β1-selective inhibitor treatment. In a phenotypic study, collagen type I significantly enhances clonogenic growth of HuCCA-1 and HuCCT-1 cells by three and sixfold, respectively. Inhibition of integrin α2 expression or its activity significantly blocks collagen type I-induced colony growth in both cell lines. Taken together, our data provide mechanistic evidence that collagen type I promotes growth of iCCA colonies through integrin α2 suggesting that the collagen type I-integrin α2 axis could be a promising target for cancer prevention and a therapeutic opportunity for this cancer.
Rare cause of obstructive icterus in a young patient
Fetched: December 30th, 2022, 5:01am GMT by Marie Kundratová
Vnitr Lek. 2022 Winter;68(E-8):18-22. doi: 10.36290/vnl.2022.117.
In this case report is discussed the diagnosis of papillary carcinoma in the case of a patient in whose age the occurrence of the disease is very rare. The patient underwent a series of non-invasive and invasive examinations, the results of which eventually led to a surgical solution of the suspected lesion (Wipples procedure). Histological examination of the resection confirmed mixed type ampular adenocarcinoma. In the context of this finding, the results of the examination, their information value, interpretation and mutual interaction are discussed. In the postoperative period, the patient suffered from gastrointestinal bleeding, subileum and poor postoperative healing. After hospitalization, the patient was transferred to oncology care and indicated for genetic testing.
PMID:36575062 | DOI:10.36290/vnl.2022.117
Early postoperative decrease of skeletal muscle mass predicts recurrence and poor survival after surgical resection for perihilar cholangiocarcinoma
Fetched: December 29th, 2022, 5:01am GMT by Sho Yasuta
BMC Cancer. 2022 Dec 28;22(1):1358. doi: 10.1186/s12885-022-10453-2.
BACKGROUND: Preoperative sarcopenia is a predictor of poor survival in cancer patients. We hypothesized that sarcopenia could progress as occult metastasis arose, especially after highly invasive surgery for highly aggressive malignancy. This study aimed to evaluate the associations of postoperative changes in skeletal muscle mass volume with survival outcomes in patients who underwent surgery for perihilar cholangiocarcinoma.
METHODS: Fifty-six patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar cholangiocarcinoma were studied. The skeletal muscle index (SMI) at the third lumbar vertebra was calculated from axial computed tomography images taken preoperatively and 3-6 months postoperatively (early postoperative period). The associations of clinicopathological variables, including changes of SMI after surgery, with overall survival and recurrence-free survival were evaluated. Moreover, the associations of decreased SMI and elevated serum carbohydrate antigen 19-9 level with early recurrence and poor survival was compared.
RESULTS: Among 56 patients, 26 (46%) had sarcopenia preoperatively and SMI decreased in 29 (52%) in the early postoperative period. During the median follow-up of 57.9 months, 35 patients (63%) developed recurrence and 29 (50%) died. Decreased SMI in the early postoperative period was independently associated with a shorter overall survival (hazard ratio, 2.39; 95% confidence interval, 1.00-6.18; P = 0.049) and a shorter recurrence-free survival (hazard ratio, 2.14; 95% confidence interval, 1.04-4.57; P = 0.039), whereas elevated carbohydrate antigen 19-9 level was not.
CONCLUSIONS: Decreased SMI in the early postoperative period may be used as a predictor for recurrence and poor survival in patients undergoing surgery for perihilar cholangiocarcinoma.
Endoscopic ultrasound-guided hepaticogastrostomy in a patient with post esophagectomy and gastric tube reconstruction: a case report
Fetched: December 29th, 2022, 5:01am GMT by Hau-Jyun Su
Clin J Gastroenterol. 2022 Dec 28. doi: 10.1007/s12328-022-01748-9. Online ahead of print.
A 54-year-old woman with a history of esophageal adenocarcinoma suffered from obstructive jaundice after completing esophagectomy with gastric tube reconstruction and adjuvant concurrent chemoradiotherapy 1 year. An abdominal computed tomography showed that the common bile duct was compressed by metastatic lymphadenopathy. She received endoscopic retrograde cholangiopancreatography first but it was failed in cannulation. Then, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) was performed with a partially covered metallic stent placed from the stomach to the left intrahepatic duct. Though aspiration pneumonia occurred after the procedure, she recovered on the next day. She resumed oral intake since the third day without fever or abdominal pain and she was discharged on the seventh day after the procedure. This is the second case report of placing a partially covered metallic stent through EUS-HGS in a patient with post esophagectomy and gastric tube reconstruction and it can be an alternative treatment.
What is the management of resected cholangiocarcinoma in terms of intra- and postoperative status of tumor margins and lymph nodes? A current view
Fetched: December 28th, 2022, 5:01am GMT by Konstantin Schlick
Expert Rev Gastroenterol Hepatol. 2022 Nov-Dec;16(11-12):1019-1022. doi: 10.1080/17474124.2022.2155633. Epub 2022 Dec 13.
PMID:36472068 | DOI:10.1080/17474124.2022.2155633
Pan-tumor landscape of fibroblast growth factor receptor 1-4 genomic alterations
Fetched: December 28th, 2022, 5:01am GMT by K Murugesan
ESMO Open. 2022 Dec;7(6):100641. doi: 10.1016/j.esmoop.2022.100641. Epub 2022 Nov 30.
BACKGROUND: Selective tyrosine kinase inhibitors targeting fibroblast growth factor receptor (FGFR) 1-4 genomic alterations are in development or have been approved for FGFR-altered cancers (e.g. bladder cancer and advanced intrahepatic cholangiocarcinoma). Understanding FGFR inhibitor-resistance mechanisms is increasingly relevant; we surveyed the pan-tumor landscape of FGFR1-4 genomic alterations [short variants (SVs), gene rearrangements (REs), and copy number alterations (CNAs)], including their association with tumor mutational burden (TMB) and the genomic comutational landscape.
PATIENTS AND METHODS: Comprehensive genomic profiling of 355 813 solid tumor clinical cases was performed using the FoundationOne and FoundationOne CDx assays (Foundation Medicine, Inc.) to identify genomic alterations in >300 cancer-associated genes and TMB (determined on ≤1.1 megabases of sequenced DNA).
RESULTS: FGFR1-4 SVs and REs occurred in 9603/355 813 (2.7%), and CNAs in 15 078/355 813 (4.2%) samples. Most common FGFR alterations for bladder cancer, intrahepatic cholangiocarcinoma, and glioma were FGFR3 SVs (1051/7739, 13.6%), FGFR2 REs (618/6641, 9.3%), and FGFR1 SVs (239/11 550, 2.1%), respectively. We found several, potentially clinically relevant, tumor-specific associations between FGFR1-4 genomic alterations and other genomic markers. FGFR3 SV-altered bladder cancers and FGFR1 SV-altered gliomas were significantly less likely to be TMB-high versus unaltered samples. FGFR3 SVs in bladder cancer significantly co-occurred with TERT and CDKN2A/B alterations; TP53 and RB1 alterations were mutually exclusive. In intrahepatic cholangiocarcinoma, FGFR2 REs significantly co-occurred with BAP1 alterations, whereas KRAS, TP53, IDH1, and ARID1A alterations were mutually exclusive. FGFR1 SVs in gliomas significantly co-occurred with H3-3A and PTPN11 alterations, but were mutually exclusive with TERT, EGFR, TP53, and CDKN2A/B alterations.
CONCLUSIONS: Overall, our hypothesis-generating findings may help to stratify patients in clinical trials and guide optimal targeted therapy in those with FGFR alterations.
PMID:36462464 | DOI:10.1016/j.esmoop.2022.100641
Oncologic safety of Carrel patch hepaticojejunostomy for treating cystic-type choledochal cyst in children based on 20-plus years follow-up
Fetched: December 28th, 2022, 5:01am GMT by Junya Ishii
Pediatr Surg Int. 2022 Dec 27;39(1):65. doi: 10.1007/s00383-022-05339-0.
AIM: During choledochal cyst (CC) excision, the hepaticojejunostomy anastomosis (HJA) can be performed conventionally (CHJA) or with a Carrel patch (CPA). CPA can increase CHD diameter to 10-13 mm, preventing anastomotic stenosis and intrahepatic bile duct (IHBD) stones but may be at risk for malignant transformation.
METHODS: The medical records of 83 cystic-type CC with CHD ≤ 9 mm followed up for at least 20 years were reviewed retrospectively. Available excised CC specimens (70/83) were re-examined blindly for pre-malignant changes. A questionnaire about suturing narrow lumens was conducted.
RESULTS: All 83 had pancreaticobiliary maljunction. Group data were similar. Anastomoses were CPA (n = 43) and CHJA (n = 40). Mean diameter for CPA was 11.4 mm (range: 10-13 mm); for CHJA was 7.4 mm (range: 5-9 mm). Mean follow-up was 27.7 years (range: 20-42). Postoperative anastomotic stenoses were less after CPA: 1/43 (2.3%) versus 5/40 (12.5%) (p = 0.10), but CHJA had significantly more postoperative IHBD stones: 0% versus 4/40 (10.0%) (p < 0.05). All IHBD stone patients had anastomotic stenosis. Excised specimens showed no pre-malignant cytology. Lumen diameter ≤ 9 mm was considered challenging by 10/10 surgical trainees and ≤ 7 mm by 16/22 pediatric surgeons.
CONCLUSIONS: CPA appears to be oncologically safe because of the absence of malignant transformation for at least 20 years.
The use of histopathological subtyping in patients with ampullary cancer: a nationwide analysis
Fetched: December 28th, 2022, 5:01am GMT by Jacob de Bakker
World J Surg Oncol. 2022 Dec 24;20(1):406. doi: 10.1186/s12957-022-02873-y.
BACKGROUND: Recent guidelines advise to subtype adenocarcinoma at the ampulla and papilla of Vater (here: ampullary cancer) as intestinal, pancreatobiliary, and mixed, because this has consequences for both prognosis and treatment. This nationwide study aimed to investigate how often histopathological subtyping is performed in daily clinical practice in patients with ampullary cancer.
METHODS: Pathology reports of all patients with ampullary cancer were retrieved from the Dutch nationwide pathology database (PALGA, 1991-2020). Reports were assessed for the presence and methods used for the classification of these tumors into intestinal, pancreatobiliary, and mixed subtypes. The use of immunohistochemical markers was recorded.
RESULTS: Overall, 5246 patients with ampullary cancer were included. In 1030 (19.6%) patients, a distinction between intestinal, pancreatobiliary, and mixed subtypes was made. Use of subtyping increased from 3% in 1991-1993 to 37% in 2018-2020. In 274 of the 1030 (26.6%) patients, immunohistochemistry was used to make this distinction. A gradual increase in the use of various immunohistochemical markers was seen over time since 2008, with cytokeratin 7, cytokeratin 20, and CDX2 being the most common. Staining of DPC4/SMAD4 was increasingly used since 2012.
CONCLUSION: Despite recent improvements in the use of subtyping in ampullary cancer, the distinction between intestinal, pancreatobiliary, and mixed subtypes is only made in a minority of patients. Nationwide efforts are required to standardize the pathological distinction of the various subtypes of ampullary cancer.
Intratumor microbiome features reveal antitumor potentials of intrahepatic cholangiocarcinoma
Fetched: December 28th, 2022, 5:01am GMT by Xiaoqiang Chai
Gut Microbes. 2023 Jan-Dec;15(1):2156255. doi: 10.1080/19490976.2022.2156255.
Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with a high prevalence in China. This study aimed to characterize the ICC tissues' bacterial metagenomics signature and explore its antitumor potential for cancer. In this study, 16S rRNA sequencing was carried out on 99 tissues to characterize the features of intratumoral microbiota, followed by single-cell RNA sequencing (scRNA-seq) and multilevel validation. The presence of microbial DNA in tissues was determined using staining, fluorescence in situ hybridization (FISH), and transmission electron microscopy (TEM). A Gram-positive aerobic bacterium, identified as Staphylococcus capitis, was cultured from fresh tissues. Meanwhile, scRNA-seq showed that intratumoral bacteria could be present in multiple cell types. Using 16S rRNA sequencing, we identified a total of 2,320,287 high-quality reads corresponding to 4,594 OTU (operational taxonomic units) sequences. The most abundant bacterial orders include Burkholderiales, Pseudomonadales, Xanthomonadales, Bacillales and Clostridiales. Alpha and Beta diversity analysis revealed specific features in different tissues. In addition, the content of Paraburkholderia fungorum was significantly higher in the paracancerous tissues and negatively correlated with CA199 (Carbohydrate antigen199) levels. The results of in vitro and in vivo experiments suggest that P. fungorum possesses an antitumor activity against tumors. Metabolomics and transcriptomics showed that P. fungorum could inhibit tumor growth through alanine, aspartate and glutamate metabolism. We determined the characteristic profile of the intratumoral microbiota and the antitumor effect of P. fungorum in ICC.
Klatskin Tumor: A Survival Analysis According to Tumor Characteristics and Inflammatory Ratios
Fetched: December 27th, 2022, 5:01am GMT by Vlad-Ionuţ Nechita
Medicina (Kaunas). 2022 Dec 5;58(12):1788. doi: 10.3390/medicina58121788.
Background and Objectives: The aim was to evaluate the association of inflammatory biomarkers with resectability and overall survival in hilar cholangiocarcinoma. Materials and Methods: We conducted a retrospective cohort study over 72 consecutive surgical cases of Klatskin tumor over an 11-year period. The sample was divided into two groups: 42 surgical resection cases and 30 unresectable tumors. Values of inflammatory ratios were compared according to the resectability. Log-rank test, univariate, and multivariate Cox proportional hazards models were used to evaluate the overall survival. Results: Subjects were between 42-87 years old (average age of 64.91 ± 9.15 years). According to the procedure: 58.33% benefited from resection (with a 30.95% R0 resection rate) and 41.66% had palliative surgery. Elevated NLR (neutrophil to lymphocyte ratio), PLR (platelet to lymphocyte ratio), and SII (systemic immune-inflammation index), and lower LMR (lymphocyte to monocyte ratio) at admission were associated with unresectable tumors (p < 0.01). For the multivariate Cox proportional hazard models, increased absolute values of NLR, PLR, and SII were associated with lower survival; no differences were observed for LMR absolute value. The cut-off value of NLR ≥ 6 was associated with lower survival. The median survival time for all subjects was 442 days, with 774 days for the resection group and 147 days for the group with palliative surgery. Conclusions: In hilar cholangiocarcinoma, inflammatory ratios are associated with tumor resectability. Tumor excision conferred an important advantage in survival. Elevated NLR, PLR, and SII values at admission significantly increased the hazard ratio. LMR had no influence on survival.
Disparities in the Diagnosis and Treatment of Bile Duct Cancer in People with Disabilities: A National Cohort Study in South Korea
Fetched: December 24th, 2022, 5:01am GMT by Seon Mee Park
Int J Environ Res Public Health. 2022 Dec 10;19(24):16625. doi: 10.3390/ijerph192416625.
We aimed to evaluate the impacts of disability on the diagnosis, treatment, and prognosis of bile duct cancer (BDC) according to the severity and type of disability. Patients diagnosed with BDC were selected from an age- and sex-matched population (1:3 ratio) with or without disabilities from the National Disability Database, the Korean Central Cancer Registry, and the Korean National Health Insurance claims database. The cohort included 15,065 patients with BDC, with a significantly lower rate in those with severe disabilities than in people without or with mild disabilities (110.6 vs. 136.5 vs. 147.6 per 105 persons, respectively). People with severe disabilities were diagnosed with BDC at an earlier age but were less likely to undergo surgery (adjusted odds ratio (aOR) = 0.52, 95% confidence interval (CI): 0.45-0.61) or chemotherapy (aOR = 0.76, 95% CI: 0.61-0.95) compared to those without disabilities. This trend was more evident in patients with mental disabilities. The overall and cancer-specific mortality rates were higher in patients (especially women) with disabilities than in those without. There needs systemic approach to ensure equal access to quality cancer care for people with disabilities.
PMID:36554502 | PMC:PMC9779117 | DOI:10.3390/ijerph192416625
Synchronous Primary Adenocarcinoma of Distal Common Bile Duct and Gall bladder
Fetched: December 24th, 2022, 5:01am GMT by Tanka Prasad Bohara
J Nepal Health Res Counc. 2022 Nov 3;20(2):558-560. doi: 10.33314/jnhrc.v20i02.4033.
Synchronous primary cancer of the gall bladder and distal common bile duct is rare. There are only few case reports and case series available of these synchronous cancers. Management of this tumor is individualized in these case reports and series based upon the presentation. We present a case of a patient who had multifocal adenocarcinoma involving distal common bile duct and gall bladder. Keywords: Distal common bile duct cancer; gall bladder cancer; synchronous primary.
PMID:36550745 | DOI:10.33314/jnhrc.v20i02.4033
Vascular resection for distal cholangiocarcinoma
Fetched: December 23rd, 2022, 5:00am GMT by Ryusei Yamamoto
Surg Today. 2022 Dec 23. doi: 10.1007/s00595-022-02634-0. Online ahead of print.
PURPOSE: Vascular resection (VR) is extended surgery to attain a negative radial margin (RM) for distal cholangiocarcinoma (DCC). The present study explored the significance of VR for DCC, focusing on VR, RM, and findings suggestive of vascular invasion on multidetector-row computed tomography (MDCT).
METHODS: Patients with DCC who underwent resection between 2002 and 2019 were reviewed.
RESULTS: Among 230 patients, 25 received VR. The overall survival (OS) in the VR group was significantly worse than in the non-VR group (16.7% vs. 50.7% at 5 years, P < 0.001). Patients who underwent VR with a negative RM failed to show a better OS than those who did not undergo VR with a positive RM (19.7% vs. 35.7% at 5 years, P = 0.178). Of the 30 patients who were suspected of having vascular invasion on MDCT, 11 did not receive VR because the vessels were freed from the tumor; these patients had a significantly better OS (57.9% at 5 years) than those who underwent VR.
CONCLUSIONS: VR for DCC was associated with a poor prognosis, even if a negative RM was obtained. VR is not necessary for DCC when the vessels are detachable from the tumor.
Nomenclature and Lymphatic Drainage Patterns of Abdominal Lymph Nodes
Fetched: December 23rd, 2022, 5:00am GMT by Hyun Seok Cho
J Korean Soc Radiol. 2022 Nov;83(6):1240-1258. doi: 10.3348/jksr.2021.0189. Epub 2022 May 23.
The lymphatic system provides a route for the spread of inflammation and malignancies. The identification of nodal stations and lymphatic pathways of tumor spread is important for tumor staging, choice of therapy, and the prediction of the prognosis of patients with malignant diseases. Because lymph node metastasis is common in primary intra-abdominal malignant tumors, its detection is essential for radiologists to understand the pattern of disease spread. Using schematic pictures and color-coded CT images, this pictorial essay describes the locations and nomenclature of the abdominal lymph nodes. Furthermore, the lymphatic drainage pathways of the upper and lower gastrointestinal tracts, liver, gallbladder, bile duct, and pancreas have been highlighted. In addition, lymph nodes belonging to the regional lymph nodes in malignant tumors arising from each organ are described, and certain cases are presented with images from patients.
PMID:36545415 | PMC:PMC9748447 | DOI:10.3348/jksr.2021.0189
Ethanolic extract of Ya-nang (Tiliacora triandra) leaf powder induces apoptosis in cholangiocarcinoma cell lines via induction of hyperacetylation and inhibition of growth signaling
Fetched: December 23rd, 2022, 5:00am GMT by Arunta Samankul
PeerJ. 2022 Dec 15;10:e14518. doi: 10.7717/peerj.14518. eCollection 2022.
OBJECTIVE: To develop alternative medicine for reducing undesired side effects of chemotherapy in CCA patients, the anticancer activity of Tiliacora triandra leaf powder ethanolic (TLPE) extract against cholangiocarcinoma cell lines was investigated.
METHODS: Antiproliferation was studied using the MTT assay while apoptosis induction and cell cycle arrest were analyzed by flow cytometry. The levels of key proteins and phenolic acid content were analyzed by western blotting and reversed-phase HPLC, respectively.
RESULTS: TLPE extract inhibited CCA cell growth in a dose- and time-dependent manner, with IC50 values of 7.86 ± 0.05 µg/ml for KKU-M213B cells and 8.59 ± 0.36 µg/ml for KKU-100 cells at an exposure time of 72 h. TLPE extract inhibited the growth of CCA cell lines by inducing apoptosis of both cell lines and causing an increased population of KKU-100 cells at G0/G1 phase. TLPE extract up-regulated Ac-H3 but down-regulated p-ERK, p53, Bax, CDK4 and Bcl2 expressions in KKU-M213B cells. TLPE extract up-regulated Ac-H3, p21 and Bax but down-regulated p-ERK, p53, CDK4 and Bcl2 expressions in KKU-100 cells. Additionally, phenolic acids including p-hydroxybenzoic, vanillic, syringic, p-coumaric, ferulic and sinapinic acids were identified.
CONCLUSION: These results suggest the possibility of developing T. triandra leaf powder ethanolic extract as a chemotherapeutic or chemoprevention agent for cholangiocarcinoma.
PMID:36540797 | PMC:PMC9760018 | DOI:10.7717/peerj.14518
Pancreatic follicular dendritic cell sarcoma: one case report and literature review
Fetched: December 23rd, 2022, 5:00am GMT by Xiangyu Lu
J Int Med Res. 2022 Dec;50(12):3000605221142401. doi: 10.1177/03000605221142401.
Pancreatic follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with unclear pathological characteristics. In this study, we report one case of pancreatic FDCS and review published cases to summarize the characteristics and treatment of pancreatic FDCS. A man in his early 30 s was admitted for jaundice, abdominal fullness, and weight loss for 15 days. Computed tomography revealed a large capsule solid mass in the pancreatic head together with a dilated bile duct and enlarged retroperitoneal lymph nodes. Serum biochemistry revealed high total bilirubin levels (313.9 μmol/L) and normal tumor marker levels. Pancreatoduodenectomy was performed, but no chemotherapy was administrated at the patient's behest. The pathologic diagnosis was pancreatic FDCS infiltrating the duodenal seromuscular layer and common bile duct. The patient presented with liver metastasis 3 months after surgery and died 8 months after surgery from multiorgan failure. Pancreatic FDCS is a rare disease with high invasiveness. Our previous case exhibited paraneoplastic syndrome together with this disease, and further investigation is needed to confirm whether paraneoplastic syndrome is a typical syndrome of pancreatic FDCS.
PMID:36539966 | PMC:PMC9791293 | DOI:10.1177/03000605221142401
Impact of early detection on cancer curability: A modified Delphi panel study
Fetched: December 22nd, 2022, 5:01am GMT by Lee Schwartzberg
PLoS One. 2022 Dec 21;17(12):e0279227. doi: 10.1371/journal.pone.0279227. eCollection 2022.
Expert consensus on the potential benefits of early cancer detection does not exist for most cancer types. We convened 10 practicing oncologists using a RAND/UCLA modified Delphi panel to evaluate which of 20 solid tumors, representing >40 American Joint Committee on Cancer (AJCC)-identified cancer types and 80% of total cancer incidence, would receive potential clinical benefits from early detection. Pre-meeting, experts estimated how long cancers take to progress and rated the current curability and benefit (improvement in curability) of an annual hypothetical multi-cancer screening blood test. Post-meeting, experts rerated all questions. Cancers had varying estimates of the potential benefit of early cancer detection depending on estimates of their curability and progression by stage. Cancers rated as progressing quickly and being curable in earlier stages (stomach, esophagus, lung, urothelial tract, melanoma, ovary, sarcoma, bladder, cervix, breast, colon/rectum, kidney, uterus, anus, head and neck) were estimated to be most likely to benefit from a hypothetical screening blood test. Cancer types rated as progressing quickly but having comparatively lower cure rates in earlier stages (liver/intrahepatic bile duct, gallbladder, pancreas) were estimated to have medium likelihood of benefit from a hypothetical screening blood test. Cancer types rated as progressing more slowly and having higher curability regardless of stage (prostate, thyroid) were estimated to have limited likelihood of benefit from a hypothetical screening blood test. The panel concluded most solid tumors have a likelihood of benefit from early detection. Even among difficult-to-treat cancers (e.g., pancreas, liver/intrahepatic bile duct, gallbladder), early-stage detection was believed to be beneficial. Based on the panel consensus, broad coverage of cancers by screening blood tests would deliver the greatest potential benefits to patients.
PMID:36542647 | PMC:PMC9770338 | DOI:10.1371/journal.pone.0279227
A Rare Case of Metastasis to the Pancreas From a Primary Transitional-Cell Urinary Bladder Carcinoma
Fetched: December 22nd, 2022, 5:01am GMT by Labdhi H Rathod
Cureus. 2022 Nov 16;14(11):e31580. doi: 10.7759/cureus.31580. eCollection 2022 Nov.
Pancreatic cancer (PC) occurs when changes (mutations) in the pancreas cells lead them to multiply out of control. A mass of tissue can result. Sometimes, this mass is benign (not cancerous). In PC, however, the mass is malignant (cancerous). A 79-year-old male presents to the emergency department with complaints of yellow discoloration of the eyes and body as well as itching all over the body. On general examination, his vitals were normal. Laboratory investigations showed raised levels of bilirubin and hepatic enzymes. The CT abdomen study revealed abnormal enhancing soft tissue density in the pancreatic head region obstructing the pancreatic duct and common bile duct leading to its proximal gross with upstream dilatation. The lesion described lesion in the pancreatic head region is of a malignant neoplastic etiology and needed to be evaluated with endoscopic retrograde cholangiopancreatography (ERCP), biopsy, and histopathology correlation. Associated pancreatic parenchymal atrophy was also seen along with gross dilatation of the extrahepatic and intrahepatic biliary system. There were no associated enlarged draining lymph nodes and minimal free fluid was seen in the peritoneal cavity. Following the deployment of a stent in the common bile duct, the patient was discharged. The patient prognosis was good and the patient was scheduled for routine blood work after four weeks to assess bilirubin levels and hepatic enzymes.
PMID:36540441 | PMC:PMC9757765 | DOI:10.7759/cureus.31580
Cholangiocarcinomes avancés et gènes de fusion
Fetched: December 22nd, 2022, 5:01am GMT by Léo Mas
Bull Cancer. 2022 Nov;109(11S):11S28-11S34. doi: 10.1016/S0007-4551(22)00466-0.
Advanced cholangiocarcinoma and gene fusions Cholangiocarcinomas (CCAs) are rare digestive tumors classified as intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) CCAs. These tumors are most often diagnosed at an advanced stage, unresectable or metastatic, and associated with a poor prognosis. The identification in recent years of multiple molecular alterations of interest, particularly in iCCA, has nevertheless allowed the development of new targeted therapeutic options for a significant proportion of patients. Gene fusions are among the most frequent alterations, involving FGFR2 in 10-15% of iCCAs in particular, and NTRK genes at a lower frequency (<1%). A dedicated analysis, most often based on RNA sequencing, is required to identify such alterations. Three FGFR inhibitors, pemigatinib, infigratinib and futinatinib, have recently received FDA approval for use in pre-treated patients. These compounds are currently being evaluated as first-line therapy in several phase III trials. Promising results have also been reported with new-generation inhibitors such as RLY-4008, which may soon constitute new therapeutic options. In the case of NTRK fusion, larotrectinib and entrectinib have also demonstrated their efficacy. The objectives of this review are to clarify the specific diagnostic modalities for gene fusions and to summarize the results of the main trials and developments underway for the management of advanced CCA with gene fusions.
Mutations de l'ADN dans les cholangiocarcinomes : cibler IDH1 et autres mutations
Fetched: December 22nd, 2022, 5:01am GMT by Marine Valéry
DNA mutations in cholangiocarcinoma: targeting IDH1 and other mutations Biliary tract cancers (BTC) are rare cancers with a poor prognosis, particularly at the metastatic stage, with a 5-year survival rate not exceeding 7%. Two lines of chemotherapy are currently recommended in France, with cisplatin-gemcitabine and 5 FU-oxaliplatin as first and second-line treatment respectively, allowing a median survival of approximately one year. However, many studies have shown that BTC, and more particularly intrahepatic cholangiocarcinoma, have a high somatic alteration rate (mutations, fusions, or amplifications). Some of these alterations are potential therapeutic targets. To date, only ivosidenib and pemigatinib, targeting IDH1 mutations and FGFR2 fusions respectively, are approved in France for pre-treated patients with these molecular alterations. Many other potentially targetable alterations are found in BTC, including mutations in genes involved in DNA repair, BRAF, HER2 and the recently exploited KRASG12C mutation. This review will focus on targetable mutations in BTC and develop the main molecules that can be used in BTC with these actionable alterations, offering new therapeutic perspectives for these patients, with the ultimate goal of improving their prognosis.
Apport de l'immunothérapie dans le traitement des cancers des voies biliaires avancés
Fetched: December 22nd, 2022, 5:01am GMT by Matthieu Delaye
Contribution of immunotherapy in the treatment of advanced biliary tract cancer Biliary tract cancers (BTC) are rare tumors with a poor prognosis. Their treatment, at an advanced stage, relies on combinations of chemotherapies, which have a limited range and duration of benefit. Immunotherapy has emerged in recent years as a new therapeutic approach for BTC. However, the benefit with currently available treatments seems more modest than in other tumor locations and the predictive markers of response to these treatments remain to be identified. This review article summarizes the rationale, current data, and prospects and challenges for the development of immunotherapy in BTC.
Serum microRNAs as new criteria for referral to early palliative care services in treatment-naïve advanced cancer patients
Fetched: December 19th, 2022, 5:00am GMT by Tomofumi Miura
Oncotarget. 2022 Dec 17;13:1341-1349. doi: 10.18632/oncotarget.28327.
A major obstacle to the implementation of early palliative care (EPC) is the lack of objective criteria for referral to EPC. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers. The present study investigated objective definitions for referral to EPC using microRNA. A total of 178 serum samples were obtained from patients with lung, gastrointestinal, colorectal, bile duct, pancreas and bladder cancers who were treatment-naïve and received chemotherapy between January 2011 and December 2013 at National Cancer Center Hospital East. We investigated expression levels of miRNAs using microarrays. The primary outcome was prediction of admission to a palliative care unit ≤6 months after first visit. Diagnostic models using clinical characteristics, miRNAs and combinations of both were constructed. The miRNA models were constructed using 6 miRNA levels. The best areas under the receiver operating characteristic curve (AUCs) of the clinical model was 0.741, while the average AUCs of miRNA-based models and combination models were 0.769 and 0.806, respectively. Combination models showed higher AUCs than the clinical model (p < 0.023). The present combination models might offer new objective definitions for referral to EPC and thus contribute to real-world implementation of EPC.
PMID:36528878 | PMC:PMC9760266 | DOI:10.18632/oncotarget.28327
Bile Proteome Analysis by High-Precision Mass Spectrometry to Examine Novel Biomarkers of Primary Sclerosing Cholangitis
Fetched: December 19th, 2022, 5:00am GMT by Motoyasu Kan
J Hepatobiliary Pancreat Sci. 2022 Dec 17. doi: 10.1002/jhbp.1299. Online ahead of print.
BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of unknown etiology that affects the intra- and extrahepatic bile ducts. The present study examined the utility of a bile proteome analysis using a high-sensitivity mass spectrometer to comprehensively screen for novel PSC biomarkers.
METHODS: Bile endoscopically collected from patients with PSC, common bile duct stones, and biliary tract cancer were subjected to high-precision liquid chromatography/mass spectrometry. Some of the proteins specifically up-regulated in the bile of the PSC group were re-examined by an enzyme-linked immunosorbent assay.
RESULTS: A total of 8094 proteins were successfully identified and 332 were specifically up-regulated in the PSC group. The bioinformatics analysis showed that proteins involved in the proliferation and activation of diverse inflammatory cells were up-regulated in the PSC group. A receiver operating characteristic curve analysis showed good area under the curve values for interleukin-8 and annexin A1 (ANXA1) (0.836 and 0.914, respectively). Immunostaining for ANXA1 revealed its strong expression in inflammatory cells infiltrating the peripheral biliary tract in PSC livers.
CONCLUSION: A bile proteome analysis is a useful tool for elucidating the pathogenesis of PSC and developing new diagnostic approaches. Therefore, ANXA1 has potential as a bile biomarker for PSC.
Regenerative failure of intrahepatic biliary cells in Alagille syndrome rescued by elevated Jagged/Notch/Sox9 signaling
Fetched: December 16th, 2022, 5:01am GMT by Chengjian Zhao
Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2201097119. doi: 10.1073/pnas.2201097119. Epub 2022 Dec 5.
Despite the robust healing capacity of the liver, regenerative failure underlies numerous hepatic diseases, including the JAG1 haploinsufficient disorder, Alagille syndrome (ALGS). Cholestasis due to intrahepatic duct (IHD) paucity resolves in certain ALGS cases but fails in most with no clear mechanisms or therapeutic interventions. We find that modulating jag1b and jag2b allele dosage is sufficient to stratify these distinct outcomes, which can be either exacerbated or rescued with genetic manipulation of Notch signaling, demonstrating that perturbations of Jag/Notch signaling may be causal for the spectrum of ALGS liver severities. Although regenerating IHD cells proliferate, they remain clustered in mutants that fail to recover due to a blunted elevation of Notch signaling in the distal-most IHD cells. Increased Notch signaling is required for regenerating IHD cells to branch and segregate into the peripheral region of the growing liver, where biliary paucity is commonly observed in ALGS. Mosaic loss- and-gain-of-function analysis reveals Sox9b to be a key Notch transcriptional effector required cell autonomously to regulate these cellular dynamics during IHD regeneration. Treatment with a small-molecule putative Notch agonist stimulates Sox9 expression in ALGS patient fibroblasts and enhances hepatic sox9b expression, rescues IHD paucity and cholestasis, and increases survival in zebrafish mutants, thereby providing a proof-of-concept therapeutic avenue for this disorder.
PMID:36469766 | DOI:10.1073/pnas.2201097119
Durable response to the combination of pembrolizumab and nab-paclitaxel in a metastatic extrahepatic cholangiocarcinoma: A case report and literature review
Fetched: December 16th, 2022, 5:00am GMT by Sirui Tan
Front Pharmacol. 2022 Nov 28;13:1037646. doi: 10.3389/fphar.2022.1037646. eCollection 2022.
Background: Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor with poor overall survival. Although the first-line standard chemotherapy (gemcitabine plus cisplatin) combined with immunotherapy has yielded positive results with survival prolongation, the efficacy remains unsatisfactory, and new treatment modalities need to be explored. Case presentation: We report the case of a patient with metastatic extrahepatic CCA who achieved a durable response and good tolerance to the combination treatment of pembrolizumab and nab-paclitaxel following progression on gemcitabine plus capecitabine chemotherapy. The tumor samples of the patient revealed low TMB, MSS, negative PD-L1 expression, and negative CD8+ TIL expression. This patient was treated with 3 cycles of pembrolizumab plus nab-paclitaxel and cisplatin, followed by 5 cycles of pembrolizumab plus nab-paclitaxel. Finally, 10 cycles of pembrolizumab monotherapy were administered. The patient survived for over 27 months after the initiation of combined therapy and was still in continuous remission at the last follow-up. Conclusion: As far as we know, this is the first report that pembrolizumab plus nab-paclitaxel successfully treated a patient with advanced CCA. This combination therapy might be a potential treatment option for patients with cholangiocarcinoma, and further clinical trials are needed to explore the outcomes.
PMID:36518664 | PMC:PMC9742598 | DOI:10.3389/fphar.2022.1037646
Drainage of Afferent Limb Obstruction via the Trans-gastric-bile Duct Formed after Endoscopic Ultrasound-guided Hepaticogastrostomy in a Patient with Pancreatic Cancer
Fetched: December 16th, 2022, 5:00am GMT by Masatoshi Mabuchi
Intern Med. 2022 Dec 14. doi: 10.2169/internalmedicine.1002-22. Online ahead of print.
A 63-year-old man with advanced pancreatic cancer and pyloric obstruction underwent surgical gastrojejunostomy. Malignant biliary obstruction appeared eight months after surgery and was managed with endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS). Subsequently, afferent limb obstruction caused by cancer invasion occurred. Although an intestinal metal stent could not be placed, a biliary metal stent was deployed via the HGS route, which successfully decompressed the afferent limb; the abdominal symptoms subsequently disappeared. In future similar cases, decompression of the dilated intestine through the HGS and biliary stent might be a viable treatment option.
PMID:36517033 | DOI:10.2169/internalmedicine.1002-22
The World Health Organization Reporting System for Pancreaticobiliary Cytopathology
Fetched: December 16th, 2022, 5:00am GMT by Martha B Pitman
Acta Cytol. 2022 Dec 14:1-17. doi: 10.1159/000527912. Online ahead of print.
The World Health Organization (WHO), the International Academy of Cytology, and the International Agency for Research on Cancer, with expert contributors from around the world, present an international approach to standardized reporting of pancreaticobiliary cytopathology. This reporting system is one of the first in a series from various body sites that mirror the WHO Classification of Tumours series and provides an evidence-based terminology system with associated risk of malignancy and diagnostic management recommendation per diagnostic category. The WHO Reporting System for Pancreaticobiliary Cytopathology (WHO system) revises the Papanicolaou Society of Cytopathology (PSC) system for Reporting Pancreaticobiliary Cytology published in 2015 and replaces the six-tiered system with a seven-tiered system: "insufficient/inadequate/nondiagnostic"; "benign (negative for malignancy)," "atypical," "pancreaticobiliary neoplasm of low risk/low grade," "pancreatic neoplasm of high risk/high grade," "suspicious for malignancy," and "malignant." The principal differences between the WHO and the PSC systems revolve around the classification of neoplasia. In the PSC system, there was a single category for "neoplastic" lesions that includes two groups, one for "benign neoplasms" [primarily serous cystadenoma] and one named "other," dominated by premalignant intraductal neoplasms (primarily intraductal papillary mucinous neoplasms) and low-grade malignant neoplasms [pancreatic neuroendocrine tumors (PanNETs) and solid pseudopapillary neoplasms (SPNs)]. In the WHO system, benign neoplasms with virtually no risk of malignancy are included in the "benign" category and low-grade malignancies (PanNET and SPN) are included in the "malignant" category, as per the WHO Classification of Digestive System Tumours, thus leaving in the "neoplasm" category primarily those noninvasive premalignant lesions of the ductal system. These neoplasms are divided by the cytomorphological grade of the epithelium into low risk/low-grade and high risk/high-grade, with distinctly different risks of malignancy. As with the PSC system, the WHO system advocates close correlation with imaging and encourages incorporation of ancillary testing into the final diagnosis, such as biochemical (CEA and amylase) and molecular testing of cyst fluid and bile duct brushings. Key diagnostic cytopathological features of specific lesions or neoplasms, ancillary studies for diagnostic and prognostic evaluation, and implications of diagnosis for patient care and management are discussed. In addition, the WHO system includes reporting and diagnostic management options that recognize the variations in the availability of diagnostic and prognostic ancillary testing modalities in low- and middle-income countries, where cytopathology is particularly useful and is increasingly available in the absence of histopathological services.
PMID:36516741 | DOI:10.1159/000527912
Preoperative skeletal muscle fat infiltration is a strong predictor of poorer survival in gallbladder cancer underwent surgery
Fetched: December 16th, 2022, 5:00am GMT by Ryo Ashida
Clin Nutr ESPEN. 2022 Dec;52:60-67. doi: 10.1016/j.clnesp.2022.10.003. Epub 2022 Oct 13.
BACKGROUND & AIMS: Recently, a decrease in skeletal muscle, termed sarcopenia, has been reported to be associated with poorer survival of patients in several types of cancer. However, few studies have investigated the association between sarcopenia and the survival of patients with gallbladder cancer.
METHODS: A total of 88 patients undergoing curative resection for advanced gallbladder cancer were included in this study. The quality of skeletal muscle was assessed by the intramuscular adipose tissue content (IMAC), and the quantity of skeletal muscle was assessed by the psoas muscle index (PMI), measured on preoperative computed tomography. The optimum cutoff values for IMAC and PMI for predicting the overall survival in each sex were determined using a minimum p value approach. Clinicopathological factors, IMAC and PMI were retrospectively analyzed to identify the predictors of overall survival (OS).
RESULTS: The cutoff values for IMAC were -0.3 in males and 0.04 in females. The numbers of patients with low IMAC and high IMAC were 42 and 46, respectively. The cutoff values for PMI were 7.3 cm2/m2 in males and 5.0 cm2/m2 in females. The numbers of patients with low PMI and high PMI were 22 and 66, respectively. A multivariate analysis revealed that pT stage (pT3/4, hazard ratio [HR] = 6.72, p = 0.004), high IMAC (HR = 4.12, p < 0.001), Bile duct infiltration (present, HR = 2.82, p = 0.046), high age (≥72 years old, HR = 2.64, p = 0.010), major hepatectomy (performed, HR = 2.50, p = 0.031) and pN1/2 (HR = 2.17, p = 0.010) as independent prognostic factors.
CONCLUSION: IMAC was independent prognostic factor for resected advanced gallbladder cancer, so the quality of skeletal muscle more strongly predicted survival than the quantity of skeletal muscle.
PMID:36513487 | DOI:10.1016/j.clnesp.2022.10.003
Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma in patients aged 60 and older: a retrospective cohort study
Fetched: December 16th, 2022, 5:00am GMT by Jianlei Wang
World J Surg Oncol. 2022 Dec 13;20(1):396. doi: 10.1186/s12957-022-02870-1.
Objective laparoscopic surgical excision is the recommended treatment for liver cancers, yet its benefits in patients aged 60 and older remain poorly understood. Thus, this study evaluated the feasibility, safety, and clinical outcomes of laparoscopic hepatectomy for patients aged 60 and older with intrahepatic cholangiocarcinoma (ICC).MethodsAfter screening, 107 patients who underwent hepatectomy for ICC were enrolled and grouped into either laparoscopic (LH) or open hepatectomy (OH) groups. Baseline characteristics, pathological findings, and long-term outcomes were compared between the two groups. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using univariate and multivariate analyses.ResultsAmong baseline characteristics and pathological findings, only pre-operative albumin was higher in the LH group. The LH group had more favorable short-term outcomes such as incision length, level of postoperative total bilirubin, and length of postoperative stays than the OH group. The postoperative complication, lymph node dissection and R0 resection rate, and long-term outcomes including OS and DFS were not significantly different between the two groups. Cancer Antigen-19-9(CA-19-9) and pathological differentiation were independent prognostic factors for OS, whereas CA-19-9 and neutrophil count were independent prognostic factors for DFS.ConclusionLH is safe, reliable, and feasible for treatment of ICC patients aged 60 and older as it had better short-term clinical outcomes than OH and achieved long-term prognoses that were comparable to those of OH.
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