RESUMEN
This study demonstrates the potential of using biological nanoparticles to deliver RNA therapeutics targeting programmed death-ligand 1 (PD-L1) as a treatment strategy for cholangiocarcinoma (CCA). RNA therapeutics offer prospects for intracellular immune modulation, but effective clinical translation requires appropriate delivery strategies. Milk-derived nanovesicles were decorated with epithelial cellular adhesion molecule (EpCAM) aptamers and used to deliver PD-L1 small interfering RNA (siRNA) or Cas9 ribonucleoproteins directly to CCA cells. In vitro, nanovesicle treatments reduced PD-L1 expression in CCA cells while increasing degranulation, cytokine release, and tumor cell cytotoxicity when tumor cells were co-cultured with T cells or natural killer cells. Similarly, immunomodulation was observed in multicellular spheroids that mimicked the tumor microenvironment. Combining targeted therapeutic vesicles loaded with siRNA to PD-L1 with gemcitabine effectively reduced tumor burden in an immunocompetent mouse CCA model compared with controls. This proof-of-concept study demonstrates the potential of engineered targeted nanovesicle platforms for delivering therapeutic RNA cargoes to tumors, as well as their use in generating effective targeted immunomodulatory therapies for difficult-to-treat cancers such as CCA.
Asunto(s)
Antígeno B7-H1 , Colangiocarcinoma , Inmunoterapia , ARN Interferente Pequeño , Colangiocarcinoma/terapia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/inmunología , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Animales , Humanos , Ratones , Línea Celular Tumoral , Inmunoterapia/métodos , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/administración & dosificación , Nanopartículas/química , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/inmunología , Microambiente Tumoral/inmunología , Modelos Animales de Enfermedad , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , GemcitabinaRESUMEN
BACKGROUND: Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. METHODS: We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. RESULTS: Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. CONCLUSIONS: MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Inestabilidad de Microsatélites , Antígeno B7-H1/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Mutación , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/metabolismo , Inmunoterapia , Genómica , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: Most patients with intrahepatic cholangiocarcinoma (ICC) have developed distant metastasis at the time of diagnosis, while there is rear related nomogram to predict the prognosis. METHODS: Clinical data of patients pathologically diagnosed of ICC with distant metastasis were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2005 to 2019. Finally, patients diagnosed as ICC in the Second Affiliated Hospital of Nanchang University from 2014 to 2019 were collected for external verification. All data were divided into training cohort and validation cohort in a ratio of 7:3. The nomogram was established based on independent prognostic factors using Cox univariate and multivariate analyses. The area under the receiver operating characteristic (ROC) curves (AUC), the calibration curve and the decision curve analysis (DCA) were used to determine the prediction accuracy of the nomogram. RESULTS: This study finally included 572 ICC with distant metastasis patients, another 32 patients collected by the author's hospital were used as external verification. Results showed that age, surgery, radiotherapy and chemotherapy were independent prognostic factors, and nomogram was established. The AUC of predicting 3, 6, 9-month overall survival were 0.866, 0.841 and 0.786. The ROC curves and calibration curves showed that the nomogram had good predictive accuracy, and DCA showed that the nomogram had good clinical applicability. CONCLUSIONS: The nomogram has good accuracy in predicting prognosis of DM-ICC patients, which would be of good significance to improve the prognosis of these patients.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Nomogramas , Estudios Retrospectivos , Pronóstico , Colangiocarcinoma/terapia , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares IntrahepáticosRESUMEN
BACKGROUND: With the increasing of novel therapeutics for the treatment of Biliary Tract Cancers (BTC), and the need to assess their socio-economic impacts for national licence approvals, it is as important as ever to have real-life data in national populations. METHODS AND RESULTS: We performed an audit of the first 2 year-activity (Sep 2019-Sep 2021) of the centralized West-of-Scotland-BTC clinic. 122 patients accessed the service, including 68% with cholangiocarcinoma (CCA), 27% with gallbladder cancer (GBC), and 5% with ampulla of Vater carcinoma with biliary phenotype (AVC). Median age at diagnosis was 66 (28-84), with 30% of newly diagnosed patients being younger than 60 years-old. Thirty-five cases (29%) underwent surgery, followed by adjuvant-chemotherapy in 66%. 60% had recurrent disease (80% with distant relapse). Sixty-four patients (58%) started first-line Systemic-AntiCancer-Treatment (SACT). Of these, 37% received second line SACT, the majority of which had iCCA and GBC. Thirty-% of those who progressed received third line SACT. CONCLUSIONS: About 30% of BTC were eligible for curative surgery. Fifty-eight and twenty% of the overall cohort of advanced BTC patients received first and second line SACT. Our data suggest that reflex genomic profiling may not be cost-effective until molecularly driven strategies are limited to second line setting.
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Neoplasias del Sistema Biliar , Humanos , Persona de Mediana Edad , Femenino , Masculino , Anciano , Adulto , Escocia/epidemiología , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/terapia , Neoplasias del Sistema Biliar/epidemiología , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Neoplasias de la Vesícula Biliar/terapia , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/epidemiología , Quimioterapia AdyuvanteRESUMEN
BACKGROUND: Despite the recent advances in cancer treatment, the therapeutic options for patients with biliary tract cancer are still very limited and the prognosis very poor. More than 50% of newly diagnosed patients with biliary tract cancer are not amenable to curative surgical treatment and thus treated with palliative systemic treatment. Malignant bile duct obstructions in patients with perihilar and/or ductal cholangiocarcinoma (CCA) represents one of the most important challenges in the management of these patients, owning to the risk represented by developing life-threatening cholangitis which, in turn, limits the use of systemic treatment. For this reason, endoscopic stenting and/or bile duct decompression is the mainstay of treatment of these patients. Data on efficacy and safety of adding radiofrequency ablation (RFA) to biliary stenting is not conclusive. The aim of this multicenter, randomized trial is to evaluate the effect of intraductal RFA prior to bile duct stenting in patients with unresectable perihilar or ductal CCA undergoing palliative systemic therapy. METHODS/DESIGN: ACTICCA-2 is a multicenter, randomized, controlled, open-label, investigator-initiated trial. 120 patients with perihilar or ductal CCA with indication for biliary stenting and systemic therapy will be randomized 1:1 to receive either RFA plus bile duct stenting (interventional arm) or bile duct stenting alone (control arm). Patients will be stratified by trial site and tumor location (perihilar vs. ductal). Both arms receive palliative systemic treatment according to the local standard of care determined by a multidisciplinary tumorboard. The primary endpoint is time to first biliary event, which is determined by an increase of bilirubin to > 5 mg/dl and/or the occurrence of cholangitis leading to premature stent replacement and/or disruption of chemotherapy. Secondary endpoints include overall survival, safety according to NCI CTCAE v5, quality of life assessed by questionnaires (EORTC QLQ-C30 and QLQ-BIL21), clinical event rate at 6 months after RFA and total days of over-night stays in hospital. Follow-up for the primary endpoint will be 6 months, while survival assessment will be continued until end of study (maximum follow-up 30 month). All patients who are randomized and who underwent endoscopic stenting will be used for the primary endpoint analysis which will be conducted using a cause-specific Cox proportional hazards model with a frailty for trial site and fixed effects for the treatment group, tumor location, and stent material. DISCUSSION: ACTICCA-2 is a multicenter, randomized, controlled trial to assess efficacy and safety of adding biliary RFA to bile duct stenting in patients with CCA receiving palliative systemic treatment. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT06175845) and approved by the local ethics committee in Hamburg, Germany (2024-101232-BO-ff). This manuscript reflects protocol version 1 as of January 9th, 2024.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Ablación por Radiofrecuencia , Stents , Humanos , Colangiocarcinoma/terapia , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/terapia , Ablación por Radiofrecuencia/métodos , Ablación por Radiofrecuencia/efectos adversos , Cuidados Paliativos/métodos , Masculino , Femenino , Calidad de Vida , Ablación por Catéter/métodos , Resultado del Tratamiento , AncianoRESUMEN
BACKGROUND & AIMS: Accumulating data has shown the rising incidence and poor prognosis of early-onset gastrointestinal cancers, but few data exist on biliary tract cancers (BTC). We aimed to analyse the clinico-pathological, molecular, therapeutic characteristics and prognosis of patients with early onset BTC (EOBTC, age ≤50 years at diagnosis), versus olders. METHODS: We analysed patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma between 1 January 2003 and 30 June 2021. Baseline characteristics and treatment were described in each group and compared. Progression-free survival, overall survival and disease-free survival were estimated in each group using the Kaplan-Meier method. RESULTS: Overall, 1256 patients were included, 188 (15%) with EOBTC. Patients with EOBTC demonstrated fewer comorbidities (63.5% vs. 84.5%, p < .0001), higher tumour stage (cT3-4: 50.0% vs. 32.3%, p = .0162), bilobar liver involvement (47.8% vs. 32.1%, p = .0002), and metastatic disease (67.6% vs. 57.5%, p = .0097) compared to older. Patients with EOBTC received second-line therapy more frequently (89.5% vs. 81.0% non-EOBTC, p = .0224). For unresectable patients with BTC, median overall survival was 17.0 vs. 16.2 months (p = .0876), and median progression-free survival was 5.8 vs. 6.0 months (p = .8293), in EOBTC vs. older. In advanced stages, fewer actionable alterations were found in EOBTC (e.g., IDH1 mutations [7.8% vs. 16.6%]; FGFR2-fusion [11.7% vs. 8.9%]; p = .029). CONCLUSIONS: Patients with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage but show similar survival. A distinctive molecular profile enriched for FGRF2 fusions was found.
Asunto(s)
Neoplasias del Sistema Biliar , Colangiocarcinoma , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Colangiocarcinoma/mortalidad , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Adulto , Neoplasias del Sistema Biliar/mortalidad , Neoplasias del Sistema Biliar/patología , Neoplasias del Sistema Biliar/terapia , Anciano , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/terapia , Neoplasias de la Vesícula Biliar/patología , Edad de Inicio , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adenocarcinoma/patología , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Pronóstico , Estimación de Kaplan-Meier , Supervivencia sin ProgresiónRESUMEN
The recent Hot Topics section focuses on survival rates for patients with cholangiocarcinoma.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Terapia Neoadyuvante , Humanos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Terapia Neoadyuvante/métodos , Tasa de SupervivenciaRESUMEN
OPINION STATEMENT: Biliary tract cancers are molecularly and anatomically diverse cancers which include intrahepatic cholangiocarcinoma, extrahepatic (perihilar and distal) cholangiocarcinoma, and gallbladder cancer. While recognized as distinct entities, the rarer incidence of these cancers combined with diagnostic challenges in classifying anatomic origin has resulted in clinical trials and guideline recommended strategies being generalized patients with all types of biliary tract cancer. In this review, we delve into the unique aspects, subtype-specific clinical trial outcomes, and multidisciplinary management of patients with extrahepatic cholangiocarcinoma. When resectable, definitive surgery followed by adjuvant chemotherapy (sometimes with selective radiation/chemoradiation) is current standard of care. Due to high recurrence rates, there is growing interest in the use of upfront/neoadjuvant therapy to improve surgical outcomes and to downstage patients who may not initially be resectable. Select patients with perihilar cholangiocarcinoma are being successfully treated with novel approaches such as liver transplant. In the advanced disease setting, combination gemcitabine and cisplatin remains the standard base for systemic therapy and was recently improved upon with the addition of immune checkpoint blockade to the chemotherapy doublet in the recently reported TOPAZ-1 and KEYNOTE-966 trials. Second-line all-comer treatments for these patients remain limited in both options and efficacy, so clinical trial participation should be strongly considered. With increased use of molecular testing, detection of actionable mutations and opportunities to receive indicated targeted therapies are on the rise and are the most significant driver of improved survival for patients with advanced stage disease. Though these targeted therapies are currently reserved for the second or later line, future trials are looking at moving these to earlier treatment settings and use in combination with chemotherapy and immunotherapy. In addition to cross-disciplinary management with surgical, medical, and radiation oncology, patient-centered care should also include collaboration with advanced endoscopists, palliative care specialists, and nutritionists to improve global patient outcomes.
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Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Humanos , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Neoplasias del Sistema Biliar/patología , Gemcitabina , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patologíaRESUMEN
PURPOSE: Systemic chemotherapy (SYS) is the first-line treatment of unresectable intrahepatic cholangiocarcinoma (ICC). However, the survival benefit of SYS is still limited. This study compared the efficacy and safety of patients with unresectable ICC treated with transarterial chemoembolization (TACE) plus SYS to SYS alone. MATERIAL AND METHODS: The multicenter retrospective cohort study included patients aged ≥ 18 years old with pathologically diagnosed ICC. Patients with unmeasurable lesions, not receiving SYS treatment, Child-Pugh grade C, Eastern Cooperative Oncology Group performance status score of 3 or higher, prior liver resection, incomplete medical information, or discontinuation of the first SYS treatment were excluded. Data collection was mainly from the hospital system, and the survival outcome of patients was obtained through follow-up. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Propensity score matching at a 1:1 ratio using the nearest neighbor matching algorithm was performed to reduce selection bias between the TACE plus SYS and SYS alone groups. The Cox proportional hazards model was used to identify prognostic factors associated with OS and to estimate their hazard ratios. Modified Response Evaluation Criteria in Solid Tumors criteria were utilized to evaluate the response of tumors to therapy. RESULTS: Between June 2016 and February 2023, 118 unresectable ICC patients from three hospitals were included in this study. Of them, 37 were in the TACE plus SYS group and 81 were in the SYS alone group. The median OS in the combination group was 11.3 months, longer than the 6.4 months in the SYS alone group (P = 0.011). A greater objective response rate (ORR) and disease control rate (DCR) were observed in the combination group than in the SYS alone group (ORR, 48.65 vs. 6.17%, P < 0.001; DCR, 89.19 vs. 62.96%, P = 0.004). There were 16 patients in each group after matching, and the matched results remained consistent regarding OS and tumor response. Adverse events (AEs) were similar in the two groups after matching. CONCLUSION: Compared to SYS alone, the combination treatment of TACE plus SYS was more effective than SYS alone in improving OS, ORR, and DCR without any significant increase in AEs. TACE plus SYS may be a viable treatment option for patients with unresectable ICC.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/métodos , Colangiocarcinoma/terapia , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Resultado del Tratamiento , AdultoRESUMEN
BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA. METHODS: iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas. RESULTS: 47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first. DISCUSSION: In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Terapia Neoadyuvante , Humanos , Colangiocarcinoma/terapia , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Hepatectomía , Resultado del TratamientoRESUMEN
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.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Colangiocarcinoma/patología , Resultado del Tratamiento , Terapia Combinada , Conductos Biliares Intrahepáticos/patología , PronósticoRESUMEN
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.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Pronóstico , Factores de Riesgo , Márgenes de Escisión , Estadificación de Neoplasias , Factores Socioeconómicos , Resultado del Tratamiento , Conductos Biliares Intrahepáticos/patología , Conductos Biliares Intrahepáticos/cirugíaAsunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Recurrencia Local de Neoplasia , Humanos , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Colangiocarcinoma/mortalidad , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/mortalidad , Recurrencia Local de Neoplasia/patología , Tasa de Supervivencia , Pronóstico , Manejo de la EnfermedadRESUMEN
BACKGROUND: Molecular profiling of intrahepatic cholangiocarcinoma (ICC) can detect actionable molecular alterations and guide targeted therapies. We explore the clinical use of molecular profiling of ICC in our comprehensive multidisciplinary clinic. STUDY DESIGN: Patients with a tissue diagnosis of ICC seen between 2019 and 2023 were identified. A retrospective review was performed to identify their molecular profiles and targeted therapy. The association between the detection of actionable molecular alterations and overall survival (OS) from the first clinic visit date was studied. Patients with an OS of less than 2 months were excluded. RESULTS: Among 194 patients with ICC, 125 had molecular profiling. Actionable molecular alterations were detected in 56 (45%) patients, including microsatellite instability (n = 3), high tumor mutational burden (>10 muts/mb; n = 5), isocitrate dehydrogenase 1 and 2 mutations (n = 22 and 6, respectively), BRAF V600E mutations (n = 2), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha mutations (n = 7), breast cancer 1 and breast cancer 2 mutations (n = 5), mesenchymal epithelial transition amplification (n = 2), fibroblast growth factor receptor 2 and 3 fusions (n = 13), erb-b2 receptor tyrosine kinase 2 overexpression (n = 6), and receptor tyrosine kinase 1 fusion (n = 1). Twenty-one patients received targeted therapies during their treatment course. Survival analysis revealed that for 120 patients with molecular profiling, the detection of an actionable molecular alteration was associated with improved mean OS (34.1 vs 23.6 months, p = 0.008). Among 70 patients with nonmetastatic ICC, the detection of an actionable molecular alteration was associated with improved mean OS (32.1 vs 27.5 months, p = 0.02). CONCLUSIONS: Actionable molecular alterations were frequently observed in patients with ICC. Detection of actionable alterations was associated with improved OS. The role of targeted therapy needs further exploration in prospective multicenter studies.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Estudios Prospectivos , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Mutación , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patologíaRESUMEN
BACKGROUND AND STUDY AIMS: Drug-eluting bead transarterial chemoembolization (DEB-TACE) causes serious complications, including liver abscess and biloma formation. This study aimed to investigate the frequency and risk factors of liver abscess and biloma formation after dug-eluting bead transarterial chemoembolization for unresectable intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: 152 unresectable ICC patients received 241 DEB-TACE procedures from February 2018 to November 2022 were studied retrospectively. Patients were evaluated for the presence of liver abscess and biloma formation after DEB-TACE. The medical records, including baseline demographic data, preoperative imaging data, DEB-TACE details, and postoperative management, were reviewed to search for risk factors of liver abscess and biloma formation. RESULTS: Liver abscesses developed in 11 cases, with an incidence rate of 7.2 % (11/152) per patient and 4.6 % (11/241) per procedure. In the 11 patients with abscesses, the incidence of biloma formation was 36.4 % (n = 4). The binary logistic regression analysis showed that diabetes mellitus (OR 7.967, 95 % CI 1.491-42.571, p = 0.015), bilioenterostomy or biliary stent implantation (OR 18.716, 95 % CI 1.006-348.049, p = 0.049) and grade 1 arterial occlusion (OR 9.712, 95 % CI 1.054-89.484, p = 0.045) were independent risk factors for liver abscess and biloma formation. CONCLUSION: Liver abscesses and biloma formation induced by DEB-TACE are associated with various factors. Diabetes mellitus, bilioenterostomy or biliary stent implantation, and grade 1 artery occlusion were all associated with liver abscess and biloma formation after DEB-TACE for unresectable ICC. In patients with these risk factors, the DEB-TACE procedure should be finely designed and manipulated with more caution.
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Neoplasias de los Conductos Biliares , Quimioembolización Terapéutica , Colangiocarcinoma , Absceso Hepático , Humanos , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/métodos , Masculino , Colangiocarcinoma/terapia , Femenino , Absceso Hepático/etiología , Factores de Riesgo , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/terapia , Estudios Retrospectivos , Anciano , Adulto , Bilis , Incidencia , Anciano de 80 o más AñosRESUMEN
PURPOSE: The efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional TACE (c-TACE) in the treatment of patients with unresectable intrahepatic cholangiocarcinoma (ICC) remained controversial. Therefore, we aimed to compare the efficacy and safety between c-TACE and DEB-TACE among patients with ICC. METHOD: Between June 10, 2016 and November 19, 2022, consecutive patients with pathological diagnoses of ICC were divided into the DEB-TACE group and the c-TACE group based on the type of TACE treatment they received. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) between the two groups. Propensity score matching (PSM) was used to balance the characteristics between the c-TACE group and the DEB-TACE group. RESULTS: A total of 132 patients were included in this study, with 64 patients in the c-TACE group and 68 patients in the DEB-TACE group. The median OS for c-TACE and DEB-TACE was 5 and 12 months, respectively. The objective response rate (ORR) for c-TACE and DEB-TACE was 0 % and 66.2 %, respectively; the disease control rate (DCR) was 37.5 % and 91.2 %. There were no significant differences between c-TACE and DEB-TACE among adverse effects at 3 months after treatment (P > 0.05). The results remained consistent after PSM. The Cox regression demonstrated that the DEB-TACE was an independent protective factor for OS. CONCLUSIONS: Patients in the DEB-TACE group had longer OS and higher ORR and DCR than those in the c-TACE group, but no significant difference was observed between the two groups regarding adverse effects.
Asunto(s)
Neoplasias de los Conductos Biliares , Quimioembolización Terapéutica , Colangiocarcinoma , Humanos , Masculino , Femenino , Colangiocarcinoma/terapia , Quimioembolización Terapéutica/métodos , Neoplasias de los Conductos Biliares/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Puntaje de Propensión , Tasa de Supervivencia , Estudios de Cohortes , Antineoplásicos/administración & dosificaciónRESUMEN
Background: Clinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis. Methods: Data of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups' clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients' prognosis. Results: There was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70-0.87; CSS: AUC 0.74-0.89). Conclusion: Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.