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1.
J Exp Clin Cancer Res ; 43(1): 104, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576051

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) comprises a heterogeneous group of biliary tract cancer. Our previous CCA mutation pattern study focused on genes in the post-transcription modification process, among which the alternative splicing factor RBM10 captured our attention. However, the roles of RBM10 wild type and mutations in CCA remain unclear. METHODS: RBM10 mutation spectrum in CCA was clarified using our initial data and other CCA genomic datasets from domestic and international sources. Real-time PCR and tissue microarray were used to detect RBM10 clinical association. Function assays were conducted to investigate the effects of RBM10 wild type and mutations on CCA. RNA sequencing was to investigate the changes in alternative splicing events in the mutation group compared to the wild-type group. Minigene splicing reporter and interaction assays were performed to elucidate the mechanism of mutation influence on alternative splicing events. RESULTS: RBM10 mutations were more common in Chinese CCA populations and exhibited more protein truncation variants. RBM10 exerted a tumor suppressive effect in CCA and correlated with favorable prognosis of CCA patients. The overexpression of wild-type RBM10 enhanced the ASPM exon18 exon skipping event interacting with SRSF2. The C761Y mutation in the C2H2-type zinc finger domain impaired its interaction with SRSF2, resulting in a loss-of-function mutation. Elevated ASPM203 stabilized DVL2 and enhanced ß-catenin signaling, which promoted CCA progression. CONCLUSIONS: Our results showed that RBM10C761Y-modulated ASPM203 promoted CCA progression in a Wnt/ß-catenin signaling-dependent manner. This study may enhance the understanding of the regulatory mechanisms that link mutation-altering splicing variants to CCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Mutação , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Via de Sinalização Wnt , Ductos Biliares Intra-Hepáticos/metabolismo , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Isoformas de Proteínas , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
2.
World J Gastroenterol ; 30(9): 1018-1042, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577184

RESUMO

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Humanos , Tumor de Klatskin/terapia , Tumor de Klatskin/cirurgia , Resultado do Tratamento , Hepatectomia/métodos , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Ductos Biliares Intra-Hepáticos/patologia , Colangiopancreatografia Retrógrada Endoscópica , Drenagem
3.
BMC Pediatr ; 24(1): 243, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580968

RESUMO

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Cisto do Colédoco , Masculino , Humanos , Pré-Escolar , Cisto do Colédoco/complicações , Cisto do Colédoco/diagnóstico por imagem , Cisto do Colédoco/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia
4.
Chirurgia (Bucur) ; 119(Ahead of print): 1-13, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38484362

RESUMO

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


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Resultado do Tratamento , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia
5.
J Pharmacol Sci ; 154(4): 301-311, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38485348

RESUMO

Amino acid transporter LAT1 is highly upregulated in various cancer types, including cholangiocarcinoma (CHOL), and contributes to the rapid proliferation of cancer cells and disease progression. However, the molecular mechanisms underlying the pathological upregulation of LAT1 remain largely unknown. This study pursued the possibility of miRNA-mediated regulation of the LAT1 expression in CHOL cells. Using online target prediction methods, we extracted five candidate miRNAs commonly predicted to regulate the LAT1 expression. Three of them, miR-194-5p, miR-122-5p, and miR-126-3p, were significantly downregulated in CHOL cancer compared to normal tissues. Correlation analysis revealed weak-to-moderate negative correlations between the expression of these miRNAs and LAT1 mRNA in CHOL cancer tissues. We selected miR-194-5p and miR-122-5p for further analyses and found that both miRNAs functionally target 3'UTR of LAT1 mRNA by a luciferase-based reporter assay. Transfection of the miRNA mimics significantly suppressed the LAT1 expression at mRNA and protein levels and inhibited the proliferation of CHOL cells, with a trend of affecting intracellular amino acids and amino acid-related signaling pathways. This study indicates that the decreased expression of these LAT1-targeting tumor-suppressive miRNAs contributes to the upregulation of LAT1 and the proliferation of CHOL cells, highlighting their potential for developing novel cancer therapeutics and diagnostics.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Linhagem Celular Tumoral , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , RNA Mensageiro/genética , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética
6.
BMC Cancer ; 24(1): 358, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509498

RESUMO

BACKGROUND: The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients. METHODS: Patients who underwent curative - intent resection of ICC between 2011 and 2019 were identified from a large multi - institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence - free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage. RESULTS: A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 - year survival (both p < 0.001). As expected, patients with low CTC grade (i.e., low TBS/low CEA) were associated with the best OS as well as RFS, while high CTC grade (i.e., high TBS/high CEA) correlated to the worst outcomes. The model exhibited well performance in both the derivation cohort (area under the curve of 0.694) and the validation cohort (0.664). The predictive efficacy of the CTC grade system remains consistently stable across TNM stages I and III/IV. CONCLUSION: The CTC grade, a composite parameter derived from the combination of TBS and CEA levels, served as an easy - to - use tool and performed well in stratifying patients with ICC relative to OS and RFS.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Hepatectomia , Antígeno Carcinoembrionário , Carga Tumoral , Colangiocarcinoma/patologia , Prognóstico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Estudos Retrospectivos
7.
Ann Clin Lab Sci ; 54(1): 106-111, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38514067

RESUMO

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a liver tumor with features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It consists of intermingled malignant biliary and hepatic tissue and thus a distinct entity, rather than two separate coexisting malignancies. A 59-year-old female with a history of hepatitis C and cirrhosis presented with abdominal pain and altered mental status. She developed hematemesis, and despite extensive interventions, she expired one day after her initial presentation. At autopsy, the liver was diffusely and markedly fibrotic with numerous nodules of varying size with invasion into adjacent vasculature. Microscopic examination of the nodules revealed cHCC-CC with stem cell features, lymphovascular invasion, and tumor emboli scattered throughout the right lung. The patient had end-stage liver disease due to the accumulation of damage and consequent fibrosis. This led to portal hypertension with subsequent massive gastrointestinal bleeding, hemorrhagic shock, and death. cHCC-CC is a rare, aggressive primary liver tumor with a poor prognosis. It can present with a cirrhotomemetic pattern with small nodules that can evade clinical and radiographic detection. Autopsy findings can provide valuable insights into the pathogenesis and clinical course of cHCC-CC, highlight the aggressive nature of the disease, and may inform future diagnostic and therapeutic strategies. Accurate diagnosis of this tumor is important for patient management and prognostication.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/complicações , Colangiocarcinoma/patologia , Estudos Retrospectivos
8.
Cancer Rep (Hoboken) ; 7(3): e2029, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38517409

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA), as a rare malignancy of the biliary tree, has a poor prognosis most of the time. CCA is highly epigenetically regulated and several long non-coding RNAs (lncRNA) have been investigated to have a diagnostic and prognostic role in CCA. The current study aimed to assess the studies finding relevant lncRNAs in CCA systematically. METHODS: International databases, including PubMed, Cochrane Library, and Embase, were comprehensively searched in order to identify studies investigating any lncRNA in CCA. After screening by title/abstract and full-text, necessary data were extracted. Random-effect meta-analysis was performed for pooling the areas under the curve (AUCs), specificity, and sensitivity of lncRNAs for the diagnosis of CCA. RESULTS: A total of 33 studies were chosen to be included in the final analysis, comprised of 2677 patients. Meta-analysis of AUCs for evaluation of CCA resulted in pooled AUC of 0.79 (95% CI: 0.75-0.82; I2 = 69.11, p < .01). Additionally, overall sensitivity of 0.80 (95% CI 0.75-0.84) and specificity of 0.77 (95% CI: 0.68-0.84) were observed. Measurement of lncRANs in the assessment of CCA also improved overall survival significantly (effect size 1.61, 95% CI: 1.39-1.82). A similar result was found for progression-free survival (effect size 1.57, 95% CI: 1.20-1.93). CONCLUSION: Based on our findings, lncRNAs showed promising results as biomarkers in the diagnosis of CCA since they had acceptable sensitivity and specificity, in addition to the fact that improved survival in this poor prognosis cancer. Further studies might be needed to address this issue and find the best clinically useful lncRNA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Sensibilidade e Especificidade , Ductos Biliares Intra-Hepáticos/patologia
9.
Dig Surg ; 41(2): 92-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447545

RESUMO

BACKGROUND: Prognosis of perihilar cholangiocarcinoma (PHCC) is poor, and curative-intent resection is the most effective treatment associated with long-term survival. Surgery is technically demanding since it involves a major hepatectomy with en bloc resection of the caudate lobe and extrahepatic bile duct. Furthermore, to achieve negative margins, it may be necessary to perform concomitant vascular resection or pancreatoduodenectomy. Despite this aggressive approach, recurrence is often observed, considering 5-year recurrence-free survival below 15% and 5-year overall survival that barely exceeds 40%. SUMMARY: The literature reports that survival rates are better in patients with negative margins, and surprisingly, R0 resections range between 19% and 95%. This variability is probably due to different surgical strategies and the pathologist's expertise with specimens. In fact, a proper pathological examination of residual disease should take into consideration both the ductal and the radial margin (RM) status. Currently, detailed pathological reports are lacking, and there is a likelihood of misinterpreting residual disease status due to the missing of RM description and the utilization of various definitions for surgical margins. KEY MESSAGES: The aim of PHCC surgery is to achieve negative margins including RM. More clarity in reporting on RM is needed to define true radical resection and consistent design of oncological studies for adjuvant treatments.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Humanos , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Margens de Excisão , Análise de Sobrevida , Estudos Retrospectivos , Hepatectomia , Neoplasias dos Ductos Biliares/patologia
10.
Cancer Lett ; 588: 216799, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38479553

RESUMO

As two major types of primary liver cancers, the tumor immune microenvironment (TIME) of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have been well studied separately. However, a systemic assessment of the similarities and differences between the TIME of HCC and ICC is still lacking. In this study, we pictured a landscape of combined TIME of HCC and ICC by sequencing and integrating 41 single-cell RNA-seq samples from four different tissue types of both malignancies. We found that T cells in HCC tumors generally exhibit higher levels of immunosuppression and exhaustion than those in ICC tumors. Myeloid cells in HCC and ICC tumors also exhibit distinct phenotypes and may serve as a key factor driving the differences between their TIMEs. Besides, we identified a cluster of EGR1+ macrophages specifically enriched in HCC tumors. Together, our study provides new insights into cellular composition, states and interactions in the TIMEs of HCC and ICC, which could pave the way for the development of future therapeutic targets for liver cancers.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/patologia , Microambiente Tumoral
11.
Zhonghua Wai Ke Za Zhi ; 62(4): 290-301, 2024 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-38432670

RESUMO

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Masculino , Feminino , Humanos , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/patologia , Estudos de Coortes , Resultado do Tratamento , Estudos Retrospectivos , Bismuto , Prognóstico , Hepatectomia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Bilirrubina
12.
Zhonghua Wai Ke Za Zhi ; 62(4): 346-352, 2024 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-38432677

RESUMO

Intrahepatic cholangiocarcinoma(ICC) refers to cholangiocarcinomas originating from the secondary bile ducts within the liver and their branches.As a prevalent malignancy of the liver,the diagnosis and treatment of ICC pose significant challenges due to the high heterogeneity of the tumor and its propensity to develop drug resistance.Traditional drug screening and tumor mechanism studies have been confined to two-dimensional cell line cultures and patient-derived xenograft(PDX) models.However,cell lines cannot fully recapitulate the tumor heterogeneity,and PDX models have limitations such as high costs and time consumption,making them less practical for widespread clinical application.To address the limitations of these models,organoid models have been developed based on two-dimensional cell cultures.Organoid models combine the advantages of both aforementioned culture methods and offer unique strengths in cancer research.They provide a new perspective for studying the development and treatment of tumors. In this review, the focus is primarily on the latest advances in the field of organoids of ICC,with a particular emphasis on existing culture protocols and their potential applications in precision medicine and the establishment of biobanks.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Animais , Humanos , Colangiocarcinoma/patologia , Fígado/patologia , Modelos Animais de Doenças , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/patologia , Organoides/metabolismo , Organoides/patologia
13.
Zhonghua Wai Ke Za Zhi ; 62(4): 331-337, 2024 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-38432675

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is a type of primary liver cancer, which has shown an increasing trend in incidence and mortality in recent years, with a poor prognosis. The clinical diagnosis and treatment of ICC currently face the challenges of low detection rate, high mortality rate, poor treatment outcome, and urgently need more in-depth research to promote the improvement of clinical diagnosis and treatment level. In recent years, ICC diagnosis and treatment related research has made new progress in many aspects, and the knowledge about these new clinical diagnosis and treatment advances should be updated in a timely manner. This article reviewed the latest research results in recent years, summarized some new views on ICC typing, prevention and diagnosis staging that have been proposed recently, as well as the new progress made in surgical treatment and systemic treatment, and briefly discussed the potential of ICC individualized precision treatment and the occurrence of rare complications caused by combined treatment.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Colangiocarcinoma/patologia , Resultado do Tratamento , Terapia Combinada , Ductos Biliares Intra-Hepáticos/patologia , Prognóstico
14.
J Pathol ; 263(1): 113-127, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38482714

RESUMO

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and ß-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Segunda Neoplasia Primária , Humanos , Segunda Neoplasia Primária/genética , Filogenia , Mutação , Ductos Biliares/patologia , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/cirurgia , Neoplasias dos Ductos Biliares/patologia
15.
Open Vet J ; 14(2): 664-673, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38549578

RESUMO

Background: Inflammation caused by Opisthorchis viverrini infection increases the risk of cholangitis, cholecystitis, and leads to bile duct cancer (cholangiocarcinoma or CCA). However, only certain infected individuals are susceptible to CCA, suggesting the involvement of host factors in cancer development. In addition, there are reports indicating differences in the locations of CCA. Aim: This study aims to investigate cellular inflammatory responses in the common bile duct (CB), intrahepatic bile duct (IHB), and gallbladder (GB) in susceptible and non-susceptible hosts following O. viverrini infection. Methods: Thirty Syrian golden hamsters (a susceptible host) and 30 BALB/c mice (a non-susceptible host) infected with O. viverrini were studied at six time points (five animals per group). Histopathological evaluations were conducted on samples from the IHB, CB, and GB. Inflammatory cell infiltration was quantitatively assessed and compared between groups and time points. Statistical analysis was performed using one-way ANOVA, with a significance level of p < 0.05. Results: Inflammation was significantly more pronounced in the IHB compared to the other two biliary locations. In comparison between susceptible and non-susceptible hosts, the intensity of inflammation was higher in the OV+H group than in the OV+M group (p < 0.05). Conclusion: This study highlights the association between host response to inflammation, tissue location, and host susceptibility, with the IHB showing particular susceptibility to inflammation and pathological changes. These findings contribute to our understanding of the increased risk of CCA in susceptible hosts.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Opistorquíase , Opisthorchis , Doenças dos Roedores , Cricetinae , Camundongos , Animais , Opistorquíase/complicações , Opistorquíase/patologia , Opistorquíase/veterinária , Opisthorchis/fisiologia , Ductos Biliares Intra-Hepáticos/patologia , Mesocricetus , Colangiocarcinoma/patologia , Colangiocarcinoma/veterinária , Inflamação/veterinária , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/veterinária
16.
JCO Precis Oncol ; 8: e2300544, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38547421

RESUMO

PURPOSE: Isocitrate dehydrogenase (IDH)1/2 genomic alterations (GA) occur in 20% of intrahepatic cholangiocarcinoma (iCCA); however, the immunogenomic landscape of IDH1-/2-mutated iCCA is largely unknown. METHODS: Comprehensive genomic profiling (CGP) was performed on 3,067 cases of advanced iCCA. Tumor mutational burden (TMB), PD-L1 expression (Dako 22C3), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) as a surrogate marker for homologous recombination deficiency were examined. RNA sequencing of 73 patient samples was analyzed for differences in stromal/immune cell infiltration, immune marker expression, and T-cell inflammation. Tissue microarray arrays were subjected to multiplex immunohistochemistry and colocalization analysis in 100 surgical samples. Retrospective clinical data were collected for 501 patients with cholangiocarcinoma to examine median overall survival (mOS) in IDH1/2+ versus IDHwt. RESULTS: Of 3,067 iCCA cases subjected to CGP, 426 (14%) were IDH1+ and 125 (4%) were IDH2+. IDH1 GA included R132C (69%) and R132L/G/S/H/F (16%/7%/4%/3%/<1%). IDH2 GA occurred at R172 (94.4%) and R140 (6.6%). No significant difference was seen in median gLOH between IDH1+ versus IDHwt iCCA (P = .37), although patterns of comutations differed. MSI-High (P = .009), TMB ≥10 mut/Mb (P < .0001), and PD-L1 positivity were lower in IDH1/2+ versus IDHwt iCCA. Resting natural killer cell population, CD70, and programmed cell death 1 expression were significantly higher in non-IDH1-mutated cases, whereas V-set domain containing T-cell activation inhibitor 1 (B7-H4) expression was significantly higher in IDH1+. No significant difference in mOS was observed between IDH1/2+ versus IDHwt patients. CONCLUSION: Significant differences in GA and immune biomarkers are noted between IDH1/2+ and IDHwt iCCA. IDH1-/2-mutated tumors appear immunologically cold without gLOH. These immunogenomic data provide insight for precision targeting of iCCA with IDH alterations.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Isocitrato Desidrogenase , Humanos , Antígeno B7-H1/genética , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Isocitrato Desidrogenase/genética , Mutação , Estudos Retrospectivos
17.
Parasit Vectors ; 17(1): 151, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519993

RESUMO

ABSTRACT: BACKGROUND: Clonorchis sinensis infection is one of the risk factors that provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis and even cholangiocarcinoma (CCA). Disrupted or aberrant intercellular communication among liver-constituting cells leads to pathological states that cause various hepatic diseases. This study was designed to investigate the pathological changes caused by C. sinensis excretory-secretory products (ESPs) in non-cancerous human cell lines (cholangiocytes [H69 cell line] and human hepatic stellate cells [LX2 cell line]) and their intercellular crosstalk, as well the pathological changes in infected mouse liver tissues. METHODS: The cells were treated with ESPs, following which transforming growth factor beta 1 (TGF-ß1) and interleukin-6 (IL-6) secretion levels and epithelial-mesenchymal transition (EMT)- and fibrosis-related protein expression were measured. The ESP-mediated cellular motility (migration/invasion) between two cells was assessed using the Transwell and three-dimensional microfluidic assay models. The livers of C. sinensis-infected mice were stained using EMT and fibrotic marker proteins. RESULTS: Treatment of cells with ESPs increased TGF-ß1 and IL-6 secretion and the expression of EMT- and fibrosis-related proteins. The ESP-mediated mutual cell interaction further affected the cytokine secretion and protein expression levels and promoted cellular motility. N-cadherin overexpression and collagen fiber deposition were observed in the livers of C. sinensis-infected mice. CONCLUSIONS: These findings suggest that EMT and biliary fibrosis occur through intercellular communication between cholangiocytes and hepatic stellate cells during C. sinensis infection, promoting malignant transformation and advanced hepatobiliary abnormalities.


Assuntos
Neoplasias dos Ductos Biliares , Clonorquíase , Clonorchis sinensis , Humanos , Animais , Camundongos , Clonorquíase/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Clonorchis sinensis/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Células Estreladas do Fígado/metabolismo , Fibrose , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Transição Epitelial-Mesenquimal
18.
Surg Oncol ; 53: 102058, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431994

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma with an increasing incidence worldwide. Surgical resection is still the only potential cure, and survival rates are dismal due to disease relapse after resection and/or metastatic disease. Positive resection margins are associated with recurrence, with conflicting studies regarding the benefits of wide resection margins to reduce recurrence rates. METHODS: 126 patients with an R0 resection treated with hepatic surgery for intrahepatic cholangiocarcinoma at the Surgical Department at the Medical University Centre Essen, Germany were identified in a database and retrospectively analysed. Patients were grouped into three groups according to margin width, <1 mm (very narrow margin width) 1-5 mm (narrow margin width) and >5 mm (wide margin width). Epidemiological as well as perioperative data was analysed, and a univariate analysis as well as Kaplan-Meier plots carried out to investigate recurrence-free and overall survival. RESULTS: Wider resection margins did not lead to better recurrence-free survival. A wider resection margin >5 mm was not significantly associated with improved overall survival. Positive lymph nodes (HR 2.50, 95% CI 1.11-5.61, p=0.027) and non-anatomic resections (HR 2.06, 95% CI 1.13-3.75, p=0.019) are significantly associated with poorer overall survival. Regarding recurrence-free survival, V2 vascular invasion was the only risk factor statistically significantly associated with poorer recurrence-free survival (HR 8.83, 95% CI 0.85-2.83, p=0.005). CONCLUSION: Resection margins did not have a significant impact on disease free survival or overall survival following hepatic resection for intrahepatic cholangiocarcinoma. Non-anatomical resections, lymph node and vascular invasion all significantly impacted oncological outcomes.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Margens de Excisão , Estudos Retrospectivos , Colangiocarcinoma/patologia , Neoplasias Hepáticas/patologia , Hepatectomia/métodos , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/cirurgia
19.
Cells ; 13(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38474330

RESUMO

The term cholangiocarcinoma (CCA) defines a class of epithelial malignancies originating from bile ducts. Although it has been demonstrated that CCA patients with perineural invasion (PNI) have a worse prognosis, the biological features of this phenomenon are yet unclear. Our data show that in human intrahepatic CCA specimens with documented PNI, nerve-infiltrating CCA cells display positivity of the epithelial marker cytokeratin 7, lower with respect to the rest of the tumor mass. In an in vitro 3D model, CCA cells move towards a peripheral nerve explant allowing contact with Schwann cells (SCs) emerging from the nerve. Here, we show that SCs produce soluble factors that favor the migration, invasion, survival and proliferation of CCA cells in vitro. This effect is accompanied by a cadherin switch, suggestive of an epithelial-mesenchymal transition. The influence of SCs in promoting the ability of CCA cells to migrate and invade the extracellular matrix is hampered by a specific TGFß receptor 1 (TGFBR1) antagonist. Differential proteomic data indicate that the exposure of CCA cells to SC secreted factors induces the upregulation of key oncogenes and the concomitant downregulation of some tumor suppressors. Taken together, these data concur in identifying SCs as possible promoters of a more aggressive CCA phenotype, ascribing a central role to TGFß signaling in regulating this process.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Fenótipo , Proteômica , Células de Schwann/patologia , Fator de Crescimento Transformador beta/genética , Invasividade Neoplásica
20.
J Gastrointest Surg ; 28(1): 18-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38353070

RESUMO

BACKGROUND: Early-stage intrahepatic cholangiocarcinoma (ICC) is often an indication of curative-intent resection. Although patients with early-stage ICC generally have a better prognosis than individuals with advanced ICC, the incidence and risk factors of recurrence after early-stage ICC remain unclear. METHODS: A multi-institutional database was used to identify patients who underwent surgery between 2000 and 2018 for ICC with pathologically confirmed stage I disease. Cox regression analysis was used to identify clinicopathological factors associated with recurrence, and an online prediction model was developed and validated. RESULTS: Of 430 patients diagnosed with stage I ICC, approximately one-half of patients (n = 221, 51.4%) experienced recurrence after curative-intent resection. Among patients with a recurrence, most (n = 188, 85.1%) experienced it within 12 months. On multivariable analysis, carcinoembryonic antigen (hazard ratio [HR], 1.011; 95% CI, 1.004-1.018), systemic immune-inflammation index (HR, 1.036; 95% CI, 1.019-1.056), no lymph nodes evaluated (HR, 1.851; 95% CI, 1.276-2.683), and tumor size (HR, 1.101; 95% CI, 1.053-1.151) were associated with greater hazards of recurrence. A predictive model that included these weighted risk factors demonstrated excellent prognostic discrimination in the test (12-month recurrence-free survival [RFS]: low risk, 80.1%; intermediate risk, 60.3%; high risk, 37.7%; P = .001) and validation (12-month RFS: low risk, 84.5%; intermediate risk, 63.5%; high risk, 47.1%; P = .036) datasets. The online predictive model was made available at https://ktsahara.shinyapps.io/stageI_icc/. CONCLUSIONS: Patients with stage I ICC without vascular invasion or lymph node metastasis had a relatively high incidence of recurrence. An online tool can risk stratify patients relative to recurrence risk to identify individuals best suited for alternative treatment approaches.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Hepatectomia/efeitos adversos , Recidiva Local de Neoplasia/patologia , Prognóstico , Ductos Biliares Intra-Hepáticos/cirurgia , Neoplasias dos Ductos Biliares/patologia , Estudos Retrospectivos
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