RESUMEN
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.
Asunto(s)
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/cirugíaRESUMEN
BACKGROUND: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking. METHODS: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing. RESULTS: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival. CONCLUSION: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.
Asunto(s)
Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Humanos , Masculino , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/genética , Adulto , PronósticoRESUMEN
BACKGROUND: This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR). METHODS: In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence. RESULTS: The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion. CONCLUSIONS: The predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels.
Asunto(s)
Neoplasias de los Conductos Biliares , Antígeno CA-19-9 , Colangiocarcinoma , Hepatectomía , Linfocitos , Recurrencia Local de Neoplasia , Neutrófilos , Humanos , Colangiocarcinoma/cirugía , Colangiocarcinoma/sangre , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Masculino , Femenino , Neutrófilos/patología , Persona de Mediana Edad , Pronóstico , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/sangre , Neoplasias de los Conductos Biliares/mortalidad , Estudios Retrospectivos , Linfocitos/patología , Antígeno CA-19-9/sangre , Anciano , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Adulto , Periodo Preoperatorio , Recuento de Linfocitos , Factores de RiesgoRESUMEN
PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC). METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs. CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Desoxicitidina , Gemcitabina , Compuestos de Fenilurea , Quinolinas , Humanos , Masculino , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/mortalidad , Femenino , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Persona de Mediana Edad , Anciano , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Estudios Retrospectivos , Infusiones Intraarteriales , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Arteria Hepática , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Compuestos OrganoplatinosRESUMEN
BACKGROUND: This study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA). METHODS AND RESULTS: The transcriptomic and whole-exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression-free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (p = 0.0287) and upregulation of genes associated with cancer-related transcriptional misregulation, chemokine signaling, and cytokine-cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (p = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer-related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti-tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients. CONCLUSIONS: In this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi-omics analysis.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Mutación , Humanos , Colangiocarcinoma/genética , Colangiocarcinoma/inmunología , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/inmunología , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Masculino , Pronóstico , Femenino , Persona de Mediana Edad , Factores de Riesgo , Regulación Neoplásica de la Expresión Génica , Anciano , Metástasis Linfática , Secuenciación del Exoma , Proteína p53 Supresora de Tumor/genética , Transcriptoma , Proteínas Filagrina , Biomarcadores de Tumor/genética , Linfocitos T CD8-positivos/inmunología , Perfilación de la Expresión Génica , Supervivencia sin Progresión , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismoRESUMEN
BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.
Asunto(s)
Conductos Biliares Extrahepáticos , Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/complicaciones , Masculino , Femenino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/complicaciones , Persona de Mediana Edad , Pronóstico , Conductos Biliares Extrahepáticos/cirugía , Conductos Biliares Extrahepáticos/patología , Trombosis/cirugía , Trombosis/etiología , Trombosis/patología , Estudios Retrospectivos , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/mortalidad , Anciano , AdultoRESUMEN
Intrahepatic bile duct mucinous adenocarcinoma (IHBDMAC) is a rare pathological subtype of intrahepatic cholangiocarcinoma (IHCC), and its tumor biological features and survival outcomes have rarely been explored, especially when compared to the most common subtype, intrahepatic bile duct adenocarcinoma (IHBDAC). Therefore, the aim of this study was to explore the clinical features and survival outcomes of IHBDAC and IHBDMAC using the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2021. A total of 1,126 patients were included, with 1,083 diagnosed with IHBDAC and 43 diagnosed with IHBDMAC. Patients with IHBDMAC presented with a more advanced T stage (55.8% vs. 36.9%, P = 0.012) and higher rate of lymph node metastasis (37.2% vs. 24.9%, P = 0.070). Cox regression identified advanced T stage, lymph node metastasis, and distant metastasis as poor survival predictors, while chemotherapy and surgery were protective factors. Survival analyses revealed significantly worse overall survival (OS) and cancer-specific survival (CSS) for IHBDMAC compared to IHBDAC (P < 0.05). Even after matching, patients with IHBDMAC still had a worse prognosis than those with IHBDAC. These findings highlight the aggressive nature of IHBDMAC and the need for tailored therapeutic strategies. Future research should focus on prospective studies and molecular insights to develop targeted treatments for IHBDMAC.
Asunto(s)
Adenocarcinoma Mucinoso , Neoplasias de los Conductos Biliares , Programa de VERF , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Anciano , Pronóstico , Metástasis Linfática/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Estadificación de Neoplasias , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Conductos Biliares Intrahepáticos/patologíaRESUMEN
BACKGROUND: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a cancer stem cell (CSC) marker of colorectal cancer and may be a CSC marker of other cancer types. Few studies have been conducted on LGR5 expression in extrahepatic cholangiocarcinoma (ECC). METHODS: We analyzed LGR5 expression using RNAscope, a highly sensitive RNA in situ hybridization technique. Fifty-three ECCs were selected from the medical archives at Shinshu University Hospital and analyzed using a tissue microarray. LGR5 expression levels were divided into expression and no expression groups. LGR5 expression and clinicopathological characteristics were analyzed. RESULTS: Among 25 cases, no LGR5-positive dots were identified. Among 28 cases, some LGR5-positive dots were observed in carcinoma cells, together with a wide range of LGR5-positive cells. LGR5 expression was conspicuous in glandular duct formations. Well- to moderately differentiated types showed significantly higher LGR5 expression than the poorly differentiated type (p = 0.0268). LGR5 expression was associated with good overall survival (p = 0.0219) and good disease-free survival (DFS) (p = 0.0228). High LGR5 expression was associated with well- to moderately-differentiated types, indicating a favorable prognosis. In terms of DFS, multivariate analysis showed that high LGR5 expression was an independent favorable prognostic factor (p = 0.0397). CONCLUSIONS: These findings suggest that LGR5 is a promising, novel prognostic marker.
Asunto(s)
Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Colangiocarcinoma , Receptores Acoplados a Proteínas G , Humanos , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Colangiocarcinoma/metabolismo , Colangiocarcinoma/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/análisis , Receptores Acoplados a Proteínas G/genética , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/genética , Masculino , Biomarcadores de Tumor/análisis , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Supervivencia sin Enfermedad , Anciano de 80 o más Años , AdultoRESUMEN
Intrahepatic cholangiocarcinoma (ICC) is the second commonly-seen liver malignancy and one of the most fatal cancers in Taiwan. Survival after diagnosis of ICC remains poor. This study aimed to investigate the survival and prognostic factors in patients with ICC. All patients with newly diagnosed ICC during 2004 to 2018 were identified from a national cancer database and followed until December 2020. Estimates of overall survival (OS) were conducted using the Kaplan-Meier method and Cox proportional hazards model. Hazard ratios with 95% confidence intervals were calculated. Initially, 7940 patients with ICC disease (stage IV: 55.6%, 4418/7940) were eligible for this study. Only 32.3% (2563/7940) patients with ICC underwent liver resection. After Propensity score matching, 969 pairs (N = 1938) of patients were matched and selected (mean age 62.8 ± 11.0 years, 53.1% were male, 29.7% had cirrhosis). The median follow-up time was 80.0 months (range 25-201 months). The 3-, 5-year OS rates were 44.0%, 36.4% in the surgical group and 26.0%, 23.7% in the non-surgical group, respectively. Surgery, young patients (≤ 54 years), small tumor size, no vascular invasion and chemotherapy were associated with better OS in patients with stages I-III disease. Surgery benefit was maximum in stage I disease followed by stage II. In patients with stage IV disease, factors such as surgery, young patients (≤ 64 years), single tumor, and no vascular invasion were associated with better OS. Chemotherapy was insignificantly associated with better OS. Long-term survival in patients with ICC is very poor. Compared to non-surgical patients, surgery conveys approximately 18% and 12% better OS rates at 3-year and 5-year, respectively. Early detection and surgical intervention may improve OS substantially in patients with ICC.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Colangiocarcinoma/terapia , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/terapia , Pronóstico , Anciano , Taiwán/epidemiología , Tasa de Supervivencia , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Puntaje de Propensión , Estadificación de Neoplasias , HepatectomíaAsunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Radiómica , Tomografía Computarizada por Rayos X , Humanos , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Pronóstico , Tasa de Supervivencia , Tomografía Computarizada por Rayos X/métodosRESUMEN
Background/Aims: Bile duct invasion (BDI) is rarely observed in patients with advanced hepatocellular carcinoma (HCC), leading to hyperbilirubinemia. However, the efficacy of pretreatment biliary drainage for HCC patients with BDI and obstructive jaundice is currently unclear. Thus, the aim of this study was to assess the effect of biliary drainage on the prognosis of these patients. Methods: We retrospectively enrolled a total of 200 HCC patients with BDI from multicenter cohorts. Patients without obstructive jaundice (n=99) and those who did not undergo HCC treatment (n=37) were excluded from further analysis. Finally, 64 patients with obstructive jaundice (43 subjected to drainage and 21 not subjected to drainage) were included. Propensity score matching was then conducted. Results: The biliary drainage group showed longer overall survival (median 10.13 months vs 4.43 months, p=0.004) and progression-free survival durations (median 7.00 months vs 1.97 months, p<0.001) than the non-drainage group. Multivariate analysis showed that biliary drainage was a significantly favorable prognostic factor for overall survival (hazard ratio, 0.42; p=0.006) and progression-free survival (hazard ratio, 0.30; p<0.001). Furthermore, in the evaluation of first response after HCC treatment, biliary drainage was beneficial (p=0.005). Remarkably, the durations of overall survival (p=0.032) and progression-free survival (p=0.004) were similar after propensity score matching. Conclusions: Biliary drainage is an independent favorable prognostic factor for HCC patients with BDI and obstructive jaundice. Therefore, biliary drainage should be contemplated in the treatment of advanced HCC with BDI to improve survival outcomes.
Asunto(s)
Carcinoma Hepatocelular , Drenaje , Ictericia Obstructiva , Neoplasias Hepáticas , Invasividad Neoplásica , Puntaje de Propensión , Humanos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Masculino , Femenino , Drenaje/métodos , Estudios Retrospectivos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Persona de Mediana Edad , Ictericia Obstructiva/etiología , Ictericia Obstructiva/terapia , Ictericia Obstructiva/mortalidad , Pronóstico , Anciano , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares/patologíaRESUMEN
BACKGROUND: The prognosis of Klatskin tumors is poor, and radical surgery with disease-free surgical margins (R0) represents the treatment capable of ensuring the best long-term outcomes. In patients with Klatskin tumors, both right hepatectomy and left hepatectomy might achieve R0 surgical margins. This systematic review concentrated on a comparative investigation between left hepatectomy and right hepatectomy, aiming to furnish clinical evidence and to aid in surgical decision-making for Klatskin tumor depending on its spread within the bile duct tree. METHODS: The eligible articles in the study were obtained from PubMed, Medline, and Scopus databases, following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis, and they were categorized according to the type of Klatskin tumor treated with right hepatectomy or left hepatectomy. The studies that analyzed the outcomes related to the 2 surgical techniques without focusing on the type of Klatskin tumor were included in a separate paragraph and table. RESULTS: In total, 21 studies were included. Four studies reported outcomes of right hepatectomy or left hepatectomy for Klatskin type I/II tumor, 2 for Klatskin type II/IV tumor, 2 for Klatskin type III tumor, and 2 for Klatskin type IV. Eleven studies included the outcomes of right hepatectomy and left hepatectomy for hilar cholangiocarcinoma without specifying the type of Klatskin tumor. Although long-term oncologic outcomes seem comparable between right hepatectomy and left hepatectomy when achieving R0 resection for Klatskin type III/IV tumors, there may exist a marginal oncologic edge and reduced complication rates favoring left hepatectomy in individuals with Klatskin type I/II tumors. DISCUSSION: Right hepatectomy traditionally has played a central role in treating Klatskin tumor, but recent studies have questioned its oncologic efficacy and surgical risks. Currently, there is a lack of evidence regarding the ideal surgical approach for each type of Klatskin tumor, and surgical strategy relies heavily on the individual surgeon's experience and technical skills. The management of Klatskin tumors necessitates specialized hepatobiliary surgical centers capable of conducting major hepatectomy with thorough lymphadenectomy, biliary, and vascular reconstructions. There is a need for studies with larger sample sizes to achieve a wide consensus about the superiority of one surgical technique over the other in cases in which both right hepatectomy and left hepatectomy can achieve an R0 margin.
Asunto(s)
Neoplasias de los Conductos Biliares , Hepatectomía , Tumor de Klatskin , Humanos , Hepatectomía/métodos , Tumor de Klatskin/cirugía , Tumor de Klatskin/patología , Tumor de Klatskin/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Conducto Hepático Común/cirugía , Márgenes de Escisión , Resultado del TratamientoRESUMEN
INTRODUCTION: The treatment of perihilar Cholangiocarcinoma (pCCA) poses specific challenges not only due to its high perioperative complication rates but also due its dismal long-term prognosis with only a few long-term survivors (LTS) among the patients. Therefore, in this analysis characteristics and predictors of LTS in pCCA patients are investigated. MATERIAL AND METHODS: In this single center analysis, patients undergoing curative-intent liver resection for pCCA between 2010 and 2022 were categorized into long-term and short-term survivors (STS) excluding perioperative mortality. Binary logistic regression was used to determine key differences between the groups and to develop a prognostic composite variable. This composite variable was subsequently tested in the whole cohort of surgically treated pCCA patients using Cox Regression analysis for cancer-specific survival (CSS). RESULTS: Within a cohort of 209 individuals, 27 patients were identified as LTS (median CSS = 125 months) and 55 patients as STS (median CSS = 16 months). Multivariable analysis identified preoperative portal vein infiltration (OR = 5.85, p = 0.018) and intraoperative packed red blood cell (PRBC) transfusions (OR = 10.29, p = 0.002) as key differences between the groups. A prognostic composite variable based on these two features was created and transferred into a Cox regression model of the whole cohort. Here, the composite variable (HR = 0.35, p<0.001), lymph node metastases (HR = 2.15, p = 0.001) and postoperative complications (HR = 3.06, p<0.001) were identified as independent predictors of CSS. CONCLUSION: Long-term survival after surgery for pCCA is possible and is strongly negatively associated with preoperative portal vein infiltration and intraoperative PRBC transfusion. As these variables are part of preoperative staging or can be modulated by intraoperative technique, the proposed prognostic composite variable can easily be transferred into clinical management to predict the oncological outcome of patients undergoing surgery for pCCA.
Asunto(s)
Neoplasias de los Conductos Biliares , Tumor de Klatskin , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tumor de Klatskin/cirugía , Tumor de Klatskin/mortalidad , Tumor de Klatskin/patología , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Anciano , Pronóstico , Estudios Retrospectivos , Hepatectomía/mortalidad , Vena Porta/cirugía , Vena Porta/patología , AdultoRESUMEN
Tumour morphology (tumour burden score (TBS)) and liver function (albumin-to-alkaline phosphatase ratio (AAPR)) have been shown to correlate with outcomes in intrahepatic cholangiocarcinoma (ICC). This study aimed to evaluate the combined predictive effect of TBS and AAPR on survival outcomes in ICC patients. We conducted a retrospective analysis using a multicentre database of ICC patients who underwent curative surgery from 2011 to 2018. The Kaplan-Meier method was employed to examine the relationship between a new index (combining TBS and AAPR) and long-term outcomes. The predictive efficacy of this index was compared to other conventional indicators. A total of 560 patients were included in the study. Based on TBS and AAPR stratification, patients were classified into three groups. Kaplan-Meier curves demonstrated that 124 patients with low TBS and high AAPR had the best overall survival (OS) and recurrence-free survival (RFS), while 170 patients with high TBS and low AAPR had the worst outcomes (log-rank p < 0.001). Multivariate analyses identified the combined index as an independent predictor of OS and RFS. Furthermore, the index showed superior accuracy in predicting OS and RFS compared to other conventional indicators. Collectively, this study demonstrated that the combination of liver function and tumour morphology provides a synergistic effect in evaluating the prognosis of ICC patients. The novel index combining TBS and AAPR effectively stratified postoperative survival outcomes in ICC patients undergoing curative resection.
Asunto(s)
Fosfatasa Alcalina , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Carga Tumoral , Humanos , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Colangiocarcinoma/sangre , Colangiocarcinoma/mortalidad , Femenino , Masculino , Fosfatasa Alcalina/sangre , Persona de Mediana Edad , Pronóstico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/sangre , Anciano , Estudios Retrospectivos , Estimación de Kaplan-Meier , Biomarcadores de Tumor/sangreRESUMEN
PURPOSE: This study aimed to define genomic differences between perihilar cholangiocarcinoma (PCA) and distal cholangiocarcinoma (DCA) and identify genomic determinants of survival. MATERIALS AND METHODS: Consecutive patients with ECA with tissue for targeted next-generation sequencing were analyzed, stratified by anatomic site (PCA/DCA), disease extent, and treatment. Associations between genomic alterations, clinicopathologic features, and outcomes were analyzed using Cox proportional hazards regression to compare survival. RESULTS: In total, 224 patients diagnosed between 2004 and 2022 (n = 127 PCA; n = 97 DCA) met inclusion criteria. The median survival was 29 months (43 after resection and 17 from diagnosis for unresectable disease). Compared with PCA, DCA was enriched in TP53alt (alterations; 69% v 33%; Q < 0.01), epigenetic pathway alterations (45% v 29%; Q = 0.041), and had more total altered pathways (median 3 v 2; Q < 0.01). KRASalt frequency was similar between PCA (36%) and DCA (37%); however, DCA was enriched in KRAS G12D (19% v 9%; P = .002). No other clinicopathologic or genomic variables distinguished subtypes. In resected patients, no genomic alterations were associated with outcome. However, in unresectable patients, CDKN2Aalt (hazard ratio [HR], 2.59 [1.48 to 4.52]) and APCalt (HR, 5.11 [1.96 to 13.3]) were associated with reduced survival. For the entire cohort, irresectability (HR, 3.13 [2.25 to 4.36]), CDKN2Aalt (HR, 1.80 [1.80 to 2.68]), and APCalt (HR, 2.00 [1.04 to 3.87]) were associated with poor survival. CONCLUSION: CDKN2Aalt and APCalt were associated with poor survival in ECA, primarily in advanced disease. As PCA and DCA were genetically similar, coanalysis of PCA and DCA in future genomic studies is reasonable.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Masculino , Femenino , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Persona de Mediana Edad , Anciano , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Genómica , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The surgical management of perihilar carcinoma (pCCA) is still subject of ongoing debate. To provide more clarity, this study was conducted to evaluate outcomes related to the side and extent of heatectomy in patients with pCAA. METHODS: A total of 32 patients with curative resection for pCCA were identified from our prospective database. Short-and long-term clinical outcome data and histopathological results were compared between right-sided (R-H) and left-sided (L-H) hepatectomy. RESULTS: Nine patients (28.13%) underwent left-sided hepatectomy while a right-sided hepatectomy was accomplished in 23 patients (71.87%). In the R-H group hepatic conditioning of the future liver remnant (FLR) prior to extended resection was necessary in 13 cases (56.52%), and simultaneous pancreaticoduodenectomy was performed in 5 patients (21.74%). The arterial and portal venous reconstruction rates were 17.39% and 11.11% (P=1.00), and 60.87% and 33.33% (P=0.243) in the R-H and L-H groups, respectively. No statistically significant differences in short-term morbidity and mortality between both groups were observed. The rate of R0 resections was comparable (R-H: 78.26% versus L-H: 66.67%; P=0.654) resulting in similar long-term overall and disease-free survival rates after right-and left hepatectomy. CONCLUSIONS: In patients with pCCA, both right- and left-sided resections appear to be safe and feasible options with similar postoperative morbidity and oncologic outcomes. Consecutively, the ideal surgical approach should be patient-tailored based on anatomical considerations and the functional future liver capacity.
Asunto(s)
Neoplasias de los Conductos Biliares , Hepatectomía , Tumor de Klatskin , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Tumor de Klatskin/cirugía , Tumor de Klatskin/patología , Tumor de Klatskin/mortalidad , Resultado del Tratamiento , Anciano , Factores de Tiempo , Adulto , PancreaticoduodenectomíaRESUMEN
BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) has two main histological subtypes: large and small duct-type iCCA, which are characterized by different clinicopathological features. This study was conducted with the purpose of expanding our understanding of their differences in molecular features and immune microenvironment. METHODS: We selected 132 patients who underwent radical surgery at our department between 2015 and 2021 for clinical and survival analyses. Whole-exome sequencing was performed to analyse mutational landscapes. Bulk RNA sequencing and single-cell RNA sequencing data were used for pathway enrichment and immune infiltration analyses based on differentially expressed genes. The function of PPP1R1B was analysed both in vitro and in vivo and the gene mechanism was further investigated. RESULTS: We found that large duct-type iCCA had worse overall survival and recurrence-free survival rates than small duct-type iCCA. Mutations in ARID1A, DOT1L and ELF3 usually occur in large duct-type iCCA, whereas mutations in IDH1 and BAP1 occur in small duct-type iCCA. Among the differentially expressed genes, we found that PPP1R1B was highly expressed in large duct-type iCCA tumour tissues. Expression of PPP1R1B promoted cell proliferation, migration and invasion and indicated a worse prognosis. A combination of USF2 with the promoter of PPP1R1B can enhance gene expression in iCCA, which may further affect the expression of genes such as AHNAK, C4BPA and activating the PI3K/AKT pathway. CONCLUSIONS: Our findings extend our understanding of large and small duct-type iCCA. In addition, PPP1R1B may serve as a potential marker and therapeutic target for large duct-type iCCA.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/cirugía , Masculino , Femenino , Persona de Mediana Edad , Mutación , Microambiente Tumoral/genética , Anciano , Proliferación Celular/genética , Línea Celular Tumoral , Secuenciación del Exoma , Regulación Neoplásica de la Expresión Génica , Animales , Análisis de Supervivencia , Pronóstico , Biomarcadores de Tumor/genética , Movimiento Celular/genética , RatonesRESUMEN
INTRODUCTION: Perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma (IHCC), and gall bladder cancer are difficult malignancies to treat and are characterized by a tendency for local recurrence and a generally unfavorable prognosis. Surgical resection offers the only potential cure, conventionally performed via the open approach. Although minimally invasive approaches show promise, data remain limited. METHODS: With the institutional review board's approval, we prospectively followed 100 patients between 2013 and 2023 who underwent robotic surgical resection for perihilar, IHCC, and gallbladder cholangiocarcinoma. Data are presented as median (mean ± SD). Significance was accepted at P ≤ .05. RESULTS: The median patient age was 70 years, and the median operative duration was 333 min, with an estimated blood loss of 200 mL. Importantly, no unplanned conversions occurred, and only 1 intraoperative complication occurred within the IHCC cohort. The median length of stay was 4 days. There were a total of 19 postoperative complications and 19 readmissions within 30 days. Additionally, there were 3 in-hospital mortalities and 5 90-day mortalities. R0 resection was achieved in 87% of patients and R1 resection in 13%. At a median follow-up of 36 months, 62% of patients demonstrated disease-free survival, whereas 6% continued to live with the disease, and 32% did not survive. CONCLUSION: Our experience demonstrates the feasibility and safety of robotic resection for these complex malignancies, yielding promising short-term outcomes. Further investigation is required to ascertain the long-term oncologic outcomes.
Asunto(s)
Tiempo de Internación , Tempo Operativo , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Colangiocarcinoma/cirugía , Colangiocarcinoma/mortalidad , Resultado del Tratamiento , Tumor de Klatskin/cirugía , Tumor de Klatskin/mortalidad , Tumor de Klatskin/patología , Anciano de 80 o más Años , Estudios Prospectivos , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Mortalidad Hospitalaria , Tasa de Supervivencia , Neoplasias del Sistema Biliar/cirugía , Neoplasias del Sistema Biliar/mortalidad , Complicaciones Intraoperatorias/epidemiología , AdultoRESUMEN
BACKGROUND: Pancreatoduodenectomy is the only cure for cancers of the pancreas and the periampullary region but has considerable operative complications and uncertain prognosis. Our goal was to analyse temporal improvements and provide contemporary population-based benchmarks for outcomes following pancreatoduodenectomy. METHODS: We empanelled a cohort comprising all patients in Sweden with pancreatic or periampullary cancer treated with pancreatoduodenectomy from 1964 to 2016 and achieved complete follow-up through 2016. We analysed postoperative deaths and disease-specific net survival. RESULTS: We analysed 5923 patients with cancer of the pancreas (3876), duodenum (444), bile duct (504), or duodenal papilla (963) who underwent classic (3332) or modified (1652) Whipple's procedure or total pancreatectomy (803). Postoperative deaths declined from 17.2% in the 1960s to 1.6% in the contemporary time period (2010-2016). For all four cancer types, median, 1-year and 5-year survival improved substantially over time. Among patients operated between 2010 and 2016, 5-year survival was 29.0% (95% confidence interval (CI): 25.5, 33.0) for pancreatic cancer, 71.2% (95% CI: 62.9, 80.5) for duodenal cancer, 30.8% (95% CI: 23.0, 41.3) for bile duct cancer, and 62.7% (95% CI: 55.5, 70.8) for duodenal papilla cancer. CONCLUSION: There is a continuous and substantial improvement in the benefit-harm ratio after pancreatoduodenectomy for cancer.
Asunto(s)
Ampolla Hepatopancreática , Neoplasias Duodenales , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Humanos , Pancreaticoduodenectomía/métodos , Pancreaticoduodenectomía/mortalidad , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Suecia/epidemiología , Ampolla Hepatopancreática/cirugía , Ampolla Hepatopancreática/patología , Neoplasias Duodenales/cirugía , Neoplasias Duodenales/mortalidad , Neoplasias Duodenales/patología , Resultado del Tratamiento , Neoplasias del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Anciano de 80 o más Años , Adulto , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/mortalidadRESUMEN
PURPOSE: Intrahepatic cholangiocarcinoma (IHC) is a heterogeneous tumor. The hidden-genome classifier, a supervised machine learning-based algorithm, was used to quantify tumor heterogeneity and improve classification. EXPERIMENTAL DESIGN: A retrospective review of 1,370 patients with IHC, extrahepatic cholangiocarcinoma (EHC), gallbladder cancer (GBC), hepatocellular carcinoma (HCC), or biphenotypic tumors was conducted. A hidden-genome model classified 527 IHC based on genetic similarity to EHC/GBC or HCC. Genetic, histologic, and clinical data were correlated. RESULTS: In this study, 410 IHC (78%) had >50% genetic homology with EHC/GBC; 122 (23%) had >90% homology ("biliary class"), characterized by alterations of KRAS, SMAD4, and CDKN2A loss; 117 IHC (22%) had >50% genetic homology with HCC; and 30 (5.7%) had >90% homology ("HCC class"), characterized by TERT alterations. Patients with biliary- versus non-biliary-class IHC had median overall survival (OS) of 1 year (95% CI, 0.77, 1.5) versus 1.8 years (95% CI, 1.6, 2.0) for unresectable disease and 2.4 years (95% CI, 2.1, NR) versus 5.1 years (95% CI, 4.8, 6.9) for resectable disease. Large-duct IHC (n = 28) was more common in the biliary class (n = 27); the HCC class was composed mostly of small-duct IHC (64%, P = 0.02). The hidden genomic classifier predicted OS independent of FGFR2 and IDH1 alterations. By contrast, the histology subtype did not predict OS. CONCLUSIONS: IHC genetics form a spectrum with worse OS for tumors genetically aligned with EHC/GBC. The classifier proved superior to histologic subtypes for predicting OS independent of FGFR2 and IDH1 alterations. These results may explain the differential treatment responses seen in IHC and may direct therapy by helping stratify patients in future clinical trials.