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Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.
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BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×10 3 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group ( n =179 patients) and the normalization group ( n =73 patients) had better OS and RFS than the non-normalization group ( n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P <0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.
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Bilirrubina , Antígeno CA-19-9 , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Estudos Retrospectivos , Bilirrubina/sangue , Feminino , Masculino , Antígeno CA-19-9/sangue , Pessoa de Meia-Idade , Idoso , Prognóstico , AdultoRESUMO
BACKGROUND: Perihilar cholangiocarcinoma (pCCA) has a poor prognosis and urgently needs a better predictive method. The predictive value of the age-adjusted Charlson comorbidity index (ACCI) for the long-term prognosis of patients with multiple malignancies was recently reported. However, pCCA is one of the most surgically difficult gastrointestinal tumors with the poorest prognosis, and the value of the ACCI for the prognosis of pCCA patients after curative resection is unclear. AIM: To evaluate the prognostic value of the ACCI and to design an online clinical model for pCCA patients. METHODS: Consecutive pCCA patients after curative resection between 2010 and 2019 were enrolled from a multicenter database. The patients were randomly assigned 3:1 to training and validation cohorts. In the training and validation cohorts, all patients were divided into low-, moderate-, and high-ACCI groups. Kaplan-Meier curves were used to determine the impact of the ACCI on overall survival (OS) for pCCA patients, and multivariate Cox regression analysis was used to determine the independent risk factors affecting OS. An online clinical model based on the ACCI was developed and validated. The concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve were used to evaluate the predictive performance and fit of this model. RESULTS: A total of 325 patients were included. There were 244 patients in the training cohort and 81 patients in the validation cohort. In the training cohort, 116, 91 and 37 patients were classified into the low-, moderate- and high-ACCI groups. The Kaplan-Meier curves showed that patients in the moderate- and high-ACCI groups had worse survival rates than those in the low-ACCI group. Multivariable analysis revealed that moderate and high ACCI scores were independently associated with OS in pCCA patients after curative resection. In addition, an online clinical model was developed that had ideal C-indexes of 0.725 and 0.675 for predicting OS in the training and validation cohorts. The calibration curve and ROC curve indicated that the model had a good fit and prediction performance. CONCLUSION: A high ACCI score may predict poor long-term survival in pCCA patients after curative resection. High-risk patients screened by the ACCI-based model should be given more clinical attention in terms of the management of comorbidities and postoperative follow-up.
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BACKGROUND: Cholecystectomy, hepatectomy, and lymphadenectomy are recommended as the curative treatment for resectable gallbladder cancer (GBC). Textbook outcomes in liver surgery (TOLS) is a novel composite measure that has been defined by expert consensus to represent the optimal postoperative course after hepatectomy. This study aimed to determine the incidence of TOLS and the independent predictors associated with TOLS after curative-intent resection in GBC patients. METHODS: All consecutive GBC patients who underwent curative-intent resection between 2014 and 2020 were enrolled from a multicenter database from 11 hospitals as the training and the internal testing cohorts, and Southwest Hospital as the external testing cohort. TOLS was defined as no intraoperative grade greater than or equal to 2 incidents, no grade B/C postoperative bile leaks, no postoperative grade B/C liver failure, no 90-day postoperative major morbidity, no 90-day readmission, no 90-day mortality after hospital discharge, and R0 resection. Independent predictors of TOLS were identified using logistic regression and were used to construct the nomogram. The predictive performance was assessed using the area under the curve and calibration curves. RESULTS: TOLS was achieved in 168 patients (54.4%) and 74 patients (57.8%) from the training and internal testing cohorts, and the external testing cohort, respectively. On multivariate analyses, age less than or equal to 70 years, absence of preoperative jaundice (total bilirubin≤3 mg/dl), T1 stage, N0 stage, wedge hepatectomy, and no neoadjuvant therapy were independently associated with TOLS. The nomogram that incorporated these predictors demonstrated excellent calibration and good performance in both the training and external testing cohorts (area under the curve: 0.741 and 0.726). CONCLUSIONS: TOLS was only achieved in approximately half of GBC patients treated with curative-intent resection, and the constructed nomogram predicted TOLS accurately.
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Carcinoma in Situ , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Fígado , Colecistectomia/efeitos adversos , Hepatectomia/efeitos adversos , Nomogramas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos RetrospectivosRESUMO
Ischemia-reperfusion (I/R) injury is a crucial factor causing liver injury in the clinic. Recent research has confirmed that human adipose-derived stem cells (ADSCs) can differentiate into functional hepatocytes. However, the mechanism of the effects of ADSCs in the treatment of liver injury remains unclear. The characteristics of ADSCs were first identified, and exosome-derived ADSCs were isolated and characterized. The function and mechanism of action of miR-183 and arachidonate 5-lipoxygenase (ALOX5) were investigated by functional experiments in HL-7702 cells with I/R injury and in I/R rats. Our data disclosed that exosome release from ADSCs induced proliferation and inhibited apoptosis in HL-7702 cells with I/R injury. The effect of miR-183 was similar to that of exosomes derived from ADSCs. In addition, ALOX5, as a target gene of miR-183, was involved in the related functions of miR-183. Moreover, in vivo experiments confirmed that miR-183 and exosomes from ADSCs could improve liver injury in rats and inhibit the MAPK and NF-κB pathways. All of these findings demonstrate that exosomes derived from ADSCs have a significant protective effect on hepatic I/R injury by regulating the miR-183/ALOX5 axis, which might provide a therapeutic strategy for liver injury.
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Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Linhagem Celular , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/metabolismo , Araquidonato 5-Lipoxigenase/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fígado/metabolismo , Reperfusão , Traumatismo por Reperfusão/metabolismoRESUMO
Background & aim: The association of perioperative blood transfusion (PBT) with long-term survival in perihilar cholangiocarcinoma (pCCA) patients after surgical resection with curative intent is controversial and may differ among different stages of the disease. This study aimed to investigate the impact of PBT on long-term survival of patients with different stages of pCCA. Methods: Consecutive pCCA patients from three hospitals treated with curative resection from 2012 to 2019 were enrolled and divided into the PBT and non-PBT groups. Propensity score matching (PSM) was used to balance differences in baseline characteristics between the PBT and non-PBT groups. Kaplan-Meier curves and log-rank test were used to compare overall survival (OS) and recurrence-free survival (RFS) between patients with all tumor stages, early stage (8th AJCC stage I), and non-early stage (8th AJCC stage II-IV) pCCA in the PBT and non-PBT groups. Cox regression analysis was used to determine the impact of PBT on OS and RFS of these patients. Results: 302 pCCA patients treated with curative resection were enrolled into this study. Before PSM, 68 patients (22 patients in the PBT group) were in the early stage and 234 patients (108 patients in the PBT group) were in the non-early stage. Patients with early stage pCCA in the PBT group had significantly lower OS and RFS rates than those in the non-PBT group. However, there were with no significant differences between the 2 groups with all tumor stages and non-early stage pCCA. After PSM, there were 18 matched pairs of patients with early stage and 72 matched pairs of patients with non-early stage. Similar results were obtained in the pre- and post-PSM cohorts: patients with early stage pCCA in the PBT group showed significantly lower OS and RFS rates than those in the non-PBT group, but there were no significant differences between the 2 groups for patients with all tumor stages and non-early stage pCCA. Cox regression analysis demonstrated that PBT was independently associated with worse OS and RFS for patients with early stage pCCA. Conclusions: PBT had a negative impact on long-term survival in patients with early stage pCCA after curative resection, but not in patients with non-early stage pCCA.
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Background: Recurrence is the main cause of death in perihilar cholangiocarcinoma (pCCA) patients after surgery. Identifying patients with a high risk of recurrence is important for decision-making regarding neoadjuvant therapy to improve long-term outcomes. Aim: The objective of this study was to develop and validate a prognostic model to predict recurrence-free survival (RFS) after curative resection of pCCA. Methods: Patients following curative resection for pCCA from January 2008 to January 2016 were identified from a multicenter database. Using random assignment, 70% of patients were assigned to the training cohort, and the remaining 30% were assigned to the validation cohort. Independent predictors of RFS after curative resection for pCCA were identified and used to construct a prognostic model. The predictive performance of the model was assessed using calibration curves and the C-index. Results: A total of 341 patients were included. The median overall survival (OS) was 22 months, and the median RFS was 14 months. Independent predictors associated with RFS included lymph node involvement, macrovascular invasion, microvascular invasion, maximum tumor size, tumor differentiation, and carbohydrate antigen 19-9. The model incorporating these factors to predict 1-year RFS demonstrated better calibration and better performance than the 8th American Joint Committee on Cancer (AJCC) staging system in both the training and validation cohorts (C-indexes: 0.723 vs. 0.641; 0.743 vs. 0.607). Conclusions: The prognostic model could identify patients at high risk of recurrence for pCCA to inform patients and surgeons, help guide decision-making for postoperative adjuvant therapy, and improve survival.
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INTRODUCTION: Surgical exploration is widely performed in hilar cholangiocarcinoma (HCCA), but the intraoperative resectability rate is only 60%-80%. Exploration substantially increases pain and mental stress, and the costs and length of hospital stay are considerably increased. Identifying preoperative risk factors associated with unresectability could decrease unnecessary exploration. MATERIALS AND METHODS: In total, 440 HCCA patients from multiple centers were enrolled. Those receiving surgical exploration were divided into the resected and unresected groups. Morphological variables including Bismuth classification, lymph node metastasis and vessel invasion were obtained from radiological exams. Logistic regression for the training cohort was used to identify risk factors for unresectability, and a nomogram was constructed to calculate the unresectability rate. A calibration curve assessed the power of the nomogram. RESULTS: Among 311 patients receiving surgical exploration, 45 (14.7%) were unresectable by intraoperative judgment. Compared with the resected group, unresected patients had similar costs (p = 0.359) and lengths of hospital stay (p = 0.439). Multivariable logistic regression of the training cohort (235 patients) revealed that CA125, Bismuth-Corlette type IV, lymph node metastasis and hepatic artery invasion were risk factors for unresectability. Liver atrophy (p = 0.374) and portal vein invasion (p = 0.114) were not risk factors. The nomogram was constructed based on the risk factors. The concordance index (C-index) values of the calibration curve for predicting the unresectability rate of the training and validation (76 patients) cohorts were 0.900 (95% CI, 0.835-0.966) and 0.829 (95% CI, 0.546-0.902), respectively. CONCLUSION: Analysis of preoperative factors could reveal intraoperative unresectability and reduce futile surgical explorations, ultimately benefiting HCCA patients.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Bismuto , Colangiocarcinoma/patologia , Humanos , Tumor de Klatskin/patologia , Tumor de Klatskin/cirurgia , Metástase Linfática , Estudos RetrospectivosRESUMO
BACKGROUND: Postoperative morbidity after curative resection for hilar cholangiocarcinoma (HCCA) is common; however, whether it has an impact on oncological prognosis is unknown. AIM: To evaluate the influence of postoperative morbidity on tumor recurrence and mortality after curative resection for HCCA. METHODS: Patients with recently diagnosed HCCA who had undergone curative resection between January 2010 and December 2017 at The First Affiliated Hospital of Army Medical University in China were enrolled. The independent risk factors for morbidity in the 30 d after surgery were investigated, and links between postoperative morbidity and patient characteristics and outcomes were assessed. Postoperative morbidities were divided into five grades based on the Clavien-Dindo classification, and major morbidities were defined as Clavien-Dindo ≥ 3. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Postoperative morbidity occurred in 146 out of 239 patients (61.1%). Multivariate logistic regression revealed that cirrhosis, intraoperative blood loss > 500 mL, diabetes mellitus, and obesity were independent risk factors. Postoperative morbidity was associated with decreased OS and RFS (OS: 18.0 mo vs 31.0 mo, respectively, P = 0.003; RFS: 16.0 mo vs 26.0 mo, respectively, P = 0.002). Multivariate Cox regression analysis indicated that postoperative morbidity was independently associated with decreased OS [hazard ratios (HR): 1.557, 95% confidence interval (CI): 1.119-2.167, P = 0.009] and RFS (HR: 1.535, 95%CI: 1.117-2.108, P = 0.008). Moreover, major morbidity was independently associated with decreased OS (HR: 2.175; 95%CI: 1.470-3.216, P < 0.001) and RFS (HR: 2.054; 95%CI: 1.400-3.014, P < 0.001) after curative resection for HCCA. CONCLUSION: Postoperative morbidity (especially major morbidity) may be an independent risk factor for unfavorable prognosis in HCCA patients following curative resection.
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Neoplasias dos Ductos Biliares , Tumor de Klatskin , Neoplasias dos Ductos Biliares/patologia , Humanos , Tumor de Klatskin/cirurgia , Morbidade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: An important prognostic indicator of hilar cholangiocarcinoma (HCCA) in patients after surgery is metastasis of lymph nodes (LN). However, there are many types of LN staging systems to the issue of a better determination of the prognosis of patients through the lymphatic staging system which needs research. Based on the above, we tried to re-evaluate the staging system of HCCA LNs. We compared the American Joint Committee on Cancer (AJCC), number of metastatic LNs (MLN), ratio of LN (LNR), and log odds of MLNs (LODDS) in individuals undergoing curative resection to determine the best LN staging system. METHODS: In the current study, we retrospectively analyzed 229 patients undergoing curative resection. We evaluated the impact of the stage of AJCC pN, LNR, LODDS, and MLN on OS (overall survival) and RFS (recurrence-free survival). According to the curve of receiver operating characteristic (ROC), we compared the predictive capacity of different staging systems of LN for survival and recurrence. RESULTS: Multivariate analysis results revealed that LODDS > - 0.45 (95% CI = 1.115-2.709, P = 0.015; 95% CI = 1.187-2.780, P = 0.006) are independent risk factors affecting OS and RFS, respectively. Compared with LN status, AJCC pN stage, MLN, and LNR, the variable having the highest area under the ROC curve (AUC) was LODDS when predicting 1-year, 3-year, and 5-year OS and RFS. CONCLUSION: This study shows that metastasis of LNs is a key indicator for predicting patient death and recurrence. Among them, LODDS is the best LN staging system for the prognostic evaluation of HCCA patients after surgery. Clinicians can incorporate LODDS into HCCA patient lymphatic staging system for a more accurate prognosis of HCCA patients post-surgery.
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Neoplasias dos Ductos Biliares , Tumor de Klatskin , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Humanos , Tumor de Klatskin/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Background & Aims: Tumor-associated chronic inflammation has been determined to play a crucial role in tumor progression, angiogenesis and immunosuppression. The objective of this study was to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in perihilar cholangiocarcinoma (pCCA) patients following curative resection. Methods: Consecutive pCCA patients following curative resection at 3 Chinese hospitals between 2014 and 2018 were included. The NLR was defined as the ratio of neutrophil count to lymphocyte count. PLR was defined as the ratio of platelet count to lymphocyte count. The optimal cutoff values of preoperative NLR and PLR were determined according to receiver operating characteristic (ROC) curves for the prediction of 1-year overall survival (OS), and all patients were divided into high- and low-risk groups. Kaplan-Meier curves and Cox regression models were used to investigate the relationship between values of NLR and PLR and values of OS and recurrence-free survival (RFS) in pCCA patients. The usefulness of NLR and PLR in predicting OS and RFS was evaluated by time-dependent ROC curves. Results: A total of 333 patients were included. According to the ROC curve for the prediction of 1-year OS, the optimal cutoff values of preoperative NLR and PLR were 1.68 and 113.1, respectively, and all patients were divided into high- and low-risk groups. The 5-year survival rates in the low-NLR (<1.68) and low-PLR groups (<113.1) were 30.1% and 29.4%, respectively, which were significantly higher than the rates of 14.9% and 3.3% in the high-NLR group (≥1.68) and high-PLR group (≥113.1), respectively. In multivariate analysis, high NLR and high PLR were independently associated with poor OS and RFS for pCCA patients. The time-dependent ROC curve revealed that both NLR and PLR were ideally useful in predicting OS and RFS for pCCA patients. Conclusions: This study found that both NLR and PLR could be used to effectively predict long-term survival in patients with pCCA who underwent curative resection.