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1.
Eur Radiol ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235653

RESUMO

OBJECTIVES: To develop an MRI-based score that enables individualized predictions of the survival benefit of wide over narrow resection margins. MATERIALS AND METHODS: This single-center retrospective study (December 2011 to May 2022) included consecutive patients who underwent curative-intent resection for single Barcelona Clinic Liver Cancer (BCLC) 0/A HCC and preoperative contrast-enhanced MRI. In patients with narrow resection margins, preoperative demographic, laboratory, and MRI variables independently associated with early recurrence-free survival (RFS) were identified using Cox regression analyses, which were employed to develop a predictive score (named "MARGIN"). Survival outcomes were compared between wide and narrow resection margins in a propensity-score matched cohort for the score-stratified low- and high-risk groups, respectively. RESULTS: Four hundred nineteen patients (median age, 54 years; 361 men) were included, 282 (67.3%) undergoing narrow resection margins. In patients with narrow resection margins, age, alpha-fetoprotein (AFP) > 400 ng/mL, protein induced by vitamin K absence or antagonist-II (PIVKA-II) > 200 mAU/mL, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS (p values, 0.002-0.04) and formed the MARGIN score with a testing dataset C-index of 0.75 (95% CI: 0.65-0.84). In the matched cohort, wide resection margin was associated with improved early RFS rate for the high-risk group (MARGIN score ≥ - 1.3; 71.1% vs 41.0%; p = 0.02), but not for the low-risk group (MARGIN score < - 1.3; 79.7% vs 76.1%; p = 0.36). CONCLUSION: In patients with single BCLC 0/A HCC, the MARGIN score may serve as promising decision-making to indicate the need for wide resection margins. CLINICAL RELEVANCE STATEMENT: The MARGIN score has the potential to identify patients who would benefit more from wide resection margins than narrow resection margins, improving the postoperative survival of patients with single BCLC 0/A hepatocellular carcinoma (HCC). KEY POINTS: Age, AFP, PIVKA-II, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS and formed the MARGIN score. The MARGIN score achieved a testing dataset C-index of 0.75. Wide resection margins were associated with improved early RFS for the high-risk group, but not for the low-risk group.

2.
Insights Imaging ; 15(1): 31, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302787

RESUMO

BACKGROUND: Late recurrence of hepatocellular carcinoma (HCC) after liver resection is regarded as a de novo tumor primarily related to the severity of underlying liver disease. We aimed to investigate risk factors, especially spleen volume, associated with late recurrence in patients with HCC and cirrhosis. METHODS: We retrospectively analyzed 301 patients with HCC and cirrhosis who received curative resection and preoperative MRI. Patients were followed for late recurrence for at least 2 years. Spleen volume was automatically measured on MRI with artificial intelligence techniques, and qualitative MRI imaging features reflecting tumor aggressiveness were evaluated. Uni- and multivariable Cox regression analyses were performed to identify independent predictors and a risk score was developed to predict late recurrence. RESULTS: Eighty-four (27.9%) patients developed late recurrence during follow-up. Preoperative spleen volume was independently associated with late recurrence, and patients with a volume > 370 cm3 had significantly higher recurrence risk (hazard ratio 2.02, 95%CI 1.31-3.12, p = 0.002). Meanwhile, no qualitative imaging features were associated with late recurrence. A risk score was developed based on the APRI score, spleen volume, and tumor number, which had time-dependent area under the curve ranging from 0.700 to 0.751. The risk score at a cutoff of 0.42 allowed for the identification of two risk categories with distinct risk of late recurrence. CONCLUSIONS: Preoperative spleen volume on MRI was independently associated with late recurrence after curative-intent resection in patients with HCC and cirrhosis. A risk score was proposed for individualized risk prediction and tailoring of postoperative surveillance strategies. CRITICAL RELEVANCE STATEMENT: Spleen volume measured on MRI with the aid of AI techniques was independently predictive of late HCC recurrence after liver resection. A risk score based on spleen volume, APRI score, and tumor number was developed for accurate prediction of late recurrence. KEY POINTS: • Preoperative spleen volume measured on MRI was independently associated with late recurrence after curative-intent resection in patients with HCC and cirrhosis. • Qualitative MRI features reflecting tumor aggressiveness were not associated with late recurrence. • A risk score based on spleen volume was developed for accurate prediction of late recurrence and risk stratification.

3.
Radiology ; 309(2): e230527, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37934100

RESUMO

Background Identifying patients at high risk for advanced-stage hepatocellular carcinoma (HCC) recurrence after liver resection may improve patient survival. Purpose To develop a model including MRI features for predicting postoperative advanced-stage HCC recurrence. Materials and Methods This single-center, retrospective study includes consecutive adult patients who underwent preoperative contrast-enhanced MRI and curative-intent resection for early- to intermediate-stage HCC (from December 2011 to April 2021). Three radiologists evaluated 52 qualitative features on MRI scans. In the training set, Fine-Gray proportional subdistribution hazard analysis was performed to identify clinical, laboratory, imaging, pathologic, and surgical variables to include in the predictive model. In the test set, the concordance index (C-index) was computed to compare the developed model with current staging systems. The Kaplan-Meier survival curves were compared using the log-rank test. Results The study included 532 patients (median age, 54 years; IQR, 46-62 years; 465 male patients), 302 patients from the training set (median age, 54 years; IQR, 46-63 years; 265 male patients), and 128 patients from the test set (median age, 53 years; IQR, 46-63 years; 108 male patients). Advanced-stage recurrence was observed in 38 of 302 (12.6%) and 15 of 128 (11.7%) of patients from the training and test sets, respectively. Serum neutrophil count (109/L), tumor size (in centimeters), and arterial phase hyperenhancement proportion on MRI scans were associated with advanced-stage recurrence (subdistribution hazard ratio range, 1.16-3.83; 95% CI: 1.02, 7.52; P value range, <.001 to .02) and included in the predictive model. The model showed better test set prediction for advanced-stage recurrence than four staging systems (2-year C-indexes, 0.82 [95% CI: 0.74, 0.91] vs 0.63-0.68 [95% CI: 0.52, 0.82]; P value range, .001-.03). Patients at high risk for HCC recurrence (model score, ≥15 points) showed increased advanced-stage recurrence and worse all-stage recurrence-free survival (RFS), advanced-stage RFS, and overall survival than patients at low risk for HCC recurrence (P value range, <.001 to .02). Conclusion A model combining serum neutrophil count, tumor size, and arterial phase hyperenhancement proportion predicted advanced-stage HCC recurrence better than current staging systems and may identify patients at high risk. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Tsai and Mellnick in this issue.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imageamento por Ressonância Magnética
4.
Insights Imaging ; 14(1): 190, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37962669

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) expressing cytokeratin (CK) 7 or CK19 has a cholangiocyte phenotype that stimulates HCC proliferation, metastasis, and sorafenib therapy resistance This study aims to noninvasively predict cholangiocyte phenotype-positive HCC and assess its prognosis after hepatectomy. METHODS: Between January 2010 and May 2022, preoperative contrast-enhanced MRI was performed on consecutive patients who underwent hepatectomy and had pathologically confirmed solitary HCC. Two abdominal radiologists separately assessed the MRI features. A predictive model for cholangiocyte phenotype HCC was created using logistic regression analysis and five-fold cross-validation. A receiver operating characteristic curve was used to calculate the model performance. Kaplan-Meier and log-rank methods were used to evaluate survival outcomes. RESULTS: In total, 334 patients were included in this retrospective study. Four contrast-enhanced MRI features, including "rim arterial phase hyperenhancement" (OR = 5.9, 95% confidence interval [CI]: 2.9-12.0, 10 points), "nodule in nodule architecture" (OR = 3.5, 95% CI: 2.1-5.9, 7 points), "non-smooth tumor margin" (OR = 1.6, 95% CI: 0.8-2.9, 3 points), and "non-peripheral washout" (OR = 0.6, 95% CI: 0.3-1.0, - 3 points), were assigned to the cholangiocyte phenotype HCC prediction model. The area under the curves for the training and independent validation set were 0.76 and 0.73, respectively. Patients with model-predicted cholangiocyte phenotype HCC demonstrated lower rates of recurrence-free survival (RFS) and overall survival (OS) after hepatectomy, with an estimated median RFS and OS of 926 vs. 1565 days (p < 0.001) and 1504 vs. 2960 days (p < 0.001), respectively. CONCLUSIONS: Contrast-enhanced MRI features can be used to predict cholangiocyte phenotype-positive HCC. Patients with pathologically confirmed or MRI model-predicted cholangiocyte phenotype HCC have a worse prognosis after hepatectomy. CRITICAL RELEVANCE STATEMENT: Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC and a worse prognosis following hepatectomy; these features may assist in predicting prognosis after surgery and improve personalized treatment decision-making. KEY POINTS: • Four contrast-enhanced MRI features were significantly associated with cholangiocyte phenotype HCC. • A noninvasive cholangiocyte phenotype HCC predictive model was established based on MRI features. • Patients with cholangiocyte phenotype HCC demonstrated a worse prognosis following hepatic resection.

5.
Cancers (Basel) ; 15(19)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37835371

RESUMO

In recent years, significant advancements in immunotherapy for hepatocellular carcinoma (HCC) have shown the potential to further improve the prognosis of patients with advanced HCC. However, in clinical practice, there is still a lack of effective biomarkers for identifying the patient who would benefit from immunotherapy and predicting the tumor response to immunotherapy. The immune microenvironment of HCC plays a crucial role in tumor development and drug responses. However, due to the complexity of immune microenvironment, currently, no single pathological or molecular biomarker can effectively predict tumor responses to immunotherapy. Magnetic resonance imaging (MRI) images provide rich biological information; existing studies suggest the feasibility of using MRI to assess the immune microenvironment of HCC and predict tumor responses to immunotherapy. Nevertheless, there are limitations, such as the suboptimal performance of conventional MRI sequences, incomplete feature extraction in previous deep learning methods, and limited interpretability. Further study needs to combine qualitative features, quantitative parameters, multi-omics characteristics related to the HCC immune microenvironment, and various deep learning techniques in multi-center research cohorts. Subsequently, efforts should also be undertaken to construct and validate a visual predictive tool of tumor response, and assess its predictive value for patient survival benefits. Additionally, future research endeavors must aim to provide an accurate, efficient, non-invasive, and highly interpretable method for predicting the effectiveness of immune therapy.

6.
Quant Imaging Med Surg ; 13(5): 3029-3039, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37179928

RESUMO

Background: Liver volume is an important measure of liver reserve and helps to determine the course of liver disease. This study aimed to observe the dynamic changes of liver volume after transjugular intrahepatic portosystemic shunt (TIPS) and analyze the related factors. Methods: Clinical data of 168 patients who underwent TIPS procedures between February 2016 and December 2021 were collected and analyzed retrospectively. The changes in liver volume after TIPS in the patients were observed, and the independent predictors affecting increases in liver volume were analyzed using a multivariable logistic regression model. Results: The mean liver volume was decreased by 12.9% at 2±1 months post TIPS and rebounded at 9±3 months post TIPS, but did not recover to its pre-TIPS level completely. Most patients (78.6%) had decreased liver volume at 2±1 months post TIPS, and in multivariable logistic regression, a lower albumin (ALB) level, a lower subcutaneous fat area at L3 (L3-SFA), and a higher degree of ascites were identified as independent factors predicting increased liver volume. The risk score model for predicting increased liver volume was Logit(P)=1.683-0.078 (ALB) -0.01 (pre TIPS L3-SFA) +0.996 (grade 3 ascites =1; non-grade 3 ascites =0). The area under the curve of the receiver operating characteristic curve was 0.729, and the cut-off value was 0.375. The rate of liver volume change at 2±1 months post TIPS was significantly correlated with that of spleen volume change (R2=0.378, P<0.001). The rate of subcutaneous fat change at 9±3 months post TIPS was significantly correlated with that of liver volume change (R2=0.782, P<0.001). In patients with a liver volume increase, the mean computed tomography value (Hounsfield units) decreased significantly after TIPS placement (65.9±17.7 vs. 57.8±18.2, P=0.009). Conclusions: Liver volume was decreased at 2±1 months post TIPS and slightly increased at 9±3 months post TIPS; however, it did not recover to its pre-TIPS level completely. A lower ALB level, a lower L3-SFA, and a higher degree of ascites were all predictors for increased liver volume post TIPS.

7.
J Interv Med ; 6(1): 29-34, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37180364

RESUMO

Purpose: This study aimed to report our 10-year experience with the management of iatrogenic (penetrating trauma) and traumatic (blunt or penetrating trauma) peripheral artery pseudoaneurysms, based on data from a tertiary referral center. Methods: From January 2012 to December 2021, the medical records of consecutive patients with iatrogenic and traumatic peripheral artery pseudoaneurysms were retrospectively reviewed. Patient demographics, clinical features, imaging data, treatment details, and follow-up results were analyzed. Results: Sixty-one consecutive patients were included in this study; 48 (79%) were men and 13 (21%) women, with a mean age of 49.4 â€‹± â€‹13.4 years (range 24-73 years). There were 42 patients (69%) who underwent open surgery, 18 (29%) undergoing endovascular embolization or stent implantation, and one (2%) undergoing ultrasound-guided thrombin injection. All patients successfully underwent open or interventional treatment. The median follow-up was 46.8 months (2.5-117.9 months), and the overall reintervention rate was 10%. Of these, one (5%) patient in the interventional treatment group and five (12%) patients in the open surgery group underwent reintervention. The overall complication rate was 8%, with complications occurring only in the open surgery group. No deaths occurred in the peri-operative period. No late complications, such as thrombosis or pseudoaneurysm recurrence, were observed. Conclusion: Peripheral artery pseudoaneurysms arising from iatrogenic or traumatic causes can be effectively treated by both open surgery and interventional procedures in selected patients with acceptable mid- and long-term outcomes.

8.
Biomedicines ; 12(1)2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38255165

RESUMO

In the realm of managing malignant liver tumors, the convergence of radiomics and machine learning has redefined the landscape of medical practice. The field of radiomics employs advanced algorithms to extract thousands of quantitative features (including intensity, texture, and structure) from medical images. Machine learning, including its subset deep learning, aids in the comprehensive analysis and integration of these features from diverse image sources. This potent synergy enables the prediction of responses of malignant liver tumors to various treatments and outcomes. In this comprehensive review, we examine the evolution of the field of radiomics and its procedural framework. Furthermore, the applications of radiomics combined with machine learning in the context of personalized treatment for malignant liver tumors are outlined in aspects of surgical therapy and non-surgical treatments such as ablation, transarterial chemoembolization, radiotherapy, and systemic therapies. Finally, we discuss the current challenges in the amalgamation of radiomics and machine learning in the study of malignant liver tumors and explore future opportunities.

9.
Cell Death Discov ; 8(1): 411, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36202781

RESUMO

Transcatheter arterial chemoembolization (TACE) has become the preferred therapy for unresectable advanced hepatocellular carcinoma (HCC). However, the embolization of tumor-feeding arteries by TACE always leads to hypoxia-related tumor angiogenesis, which limited the therapeutic effect for HCC. In this paper, we used a VEGFR targeting peptide VEGF125 - 136 (QKRKRKKSRYKS) to conjugate with a lytic peptide (KLUKLUKKLUKLUK) to form a peptide-drug conjugate (PDC). We used cell affinity assay to detect the peptide binding ability to VEGFR highly expressed cell lines, and CCK8, cell apoptosis to confirm the cellular toxicity for different cell lines. Meanwhile, we created a VX2 tumor-bearing rabbit model to assess the in vivo anti-tumor effect of the peptide conjugate in combination with TAE. HE staining was used to verify the in vivo safety of the peptide conjugate. IHC was used to assess the anti-angiogenesis and cell toxicity of the peptide conjugate in tumor tissues. The peptide conjugate could not only target VEGFR in cell surface and inhibit VEGFR function, but also have potent anti-cancer effect. We luckily found the peptide conjugate showed potent cytotoxicity for liver cancer cell Huh7 (IC50 7.3 ± 0.74 µM) and endothelial cell HUVEC (IC50 10.7 ± 0.292 µM) and induced cell apoptosis of these two cell lines. We also found the peptide conjugate inhibited cell migration of HUVEC through wound healing assay. Besides, these peptides also showed better in vivo anti-tumor effect than traditional drug DOX through TACE in VX2 rabbit tumor model, and efficiently inhibit angiogenesis in tumor tissues with good safety. In conclusion, our work may provide an alternative option for clinical HCC therapy via TACE combination.

10.
Sci Rep ; 12(1): 11445, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794140

RESUMO

To explore the applicability of multi-arterial phase imaging technique in gadoxetate disodium-enhanced MRI. We studied 140 consecutive patients with suspected liver lesions who underwent gadoxetate disodium-enhanced MRI before surgery. All patients were randomized into three groups: group A (n = 50) was examined with VIBE-based single-artery phase imaging, group B (n = 44) with StarVIBE, and group C (n = 46) with CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE)-based multi-artery phase imaging. We evaluated the display rate of late arterial images and image quality in arterial phase images. We performed a study of 140 consecutive patients suspected with liver lesions who received gadoxetate disodium-enhanced MRI examination before surgery. All patients were randomly divided into three groups: group A (n = 50) was examined with single arterial phase imaging based on VIBE, group B (n = 44) was based on StarVIBE and group C (n = 46) was analyzed with multi-arterial phase imaging based on CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE). We evaluated the display rate of late arterial images and the image quality of dynamically enhanced images. Both radiologists had an almost perfect agreement (Kappa value > 0.8) in the assessment of late arterial and image quality. For late arterial acquisition, group C was superior to groups A and B (x2 = 18.940, P < 0.05); The image of phase 4 had the highest display rate in the late artery phase. For arterial phase image quality, there was no difference between groups A, B and C at five phases (H = 10.481, P = 0.106); and the best image quality score was lower in group C than in groups A and B (H = 8.573, P = 0.014).For the quality of the late arterial images, there was a statistical difference between the best images in groups A, B and C (H = 6.619, P = 0.037), and the images in group C were significantly better than those in group A (P.adj < 0.05). By applying multi-arterial phase acquisition based on CDT-VIBE, gadoxetate disodium-enhanced MRI scanning can obtain a better late arterial phase and provide high-quality images with fewer motion artifacts.


Assuntos
Meios de Contraste , Neoplasias Hepáticas , Artérias , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagem
11.
Clin Res Hepatol Gastroenterol ; 46(5): 101893, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247625

RESUMO

PURPOSE: To evaluate clinical outcomes of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres and conventional TACE (cTACE) as the initial treatment in patients with unresectable hepatocellular carcinoma (HCC) beyond up-to-seven criteria. METHODS: The study retrospectively assessed the medical records of HCC patients beyond up-to-seven criteria who received the initial treatment of DEB-TACE or cTACE from June 2016 to December 2019 in our institution. To reduce the patient selection bias, propensity score matching (PSM) analysis was used. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were compared between the two groups. In addition, prognostic factors affecting PFS and OS were analyzed by univariate and multivariate methods. RESULTS: A total of 312 eligible HCC patients were included in the study, including 140 patients in the DEB-TACE group and 172 patients in the cTACE group. 110 patients were chosen in each group after PSM analysis and there were no significant differences in baseline characteristics (P > 0.05). Before PSM analysis, DEB-TACE had better ORR and DCR compared to cTACE group (P < 0.05). After PSM analysis, the ORR for DEB-TACE group was still higher than that for cTACE group, while no significant difference in the DCR between the two groups. In addition, DEB-TACE group had better survival benefits than cTACE group before PSM analysis (mPFS: 11.5 months vs 9.0 months, P < 0.001; mOS: 24.0 months vs 19.2 months, P = 0.045). Similarly, after PSM analysis, the median PFS and OS in the DEB-TACE group were still higher than that in the cTACE group (mPFS: 11.1 months vs 9.0 months, P = 0.015; mOS: 25.0 months vs 19.0 months, P = 0.030). Further, the univariate and multivariate analysis indicated that DEB-TACE treatment was a positive prognostic factor for PFS and OS. CONCLUSION: DEB-TACE with CalliSpheres microspheres might be an effective and safe treatment for patients with unresectable HCC beyond up-to-seven criteria.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Humanos , Neoplasias Hepáticas/patologia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
12.
BMC Cancer ; 22(1): 335, 2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35346114

RESUMO

OBJECTIVE: The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it. METHODS: In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS. RESULTS: A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8-30.5 months) and the median PFS was 15.7 months (95% CI: 14.7-16.6 months). The ORR was 58.8% (95% CI: 47.2-69.6) and DCR reached 81.2% (95% CI: 71.0-89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060-0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184-0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed. CONCLUSION: TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Piridinas , Estudos Retrospectivos
13.
Int J Hyperthermia ; 39(1): 278-286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35129044

RESUMO

BACKGROUND: To evaluate the changes of immune environment of distant tumors after combined microwave ablation (MWA) and anti- programmed death receptor - 1 (anti-PD-1) therapy, and assess the changes of systemic immune response. METHODS: Bilateral hepatocellular carcinoma model was established in mice, which were then subsequently treated with MWA, or anti-PD-1, or no treatment, or MWA + anti-PD-1. The contralateral tumor volume and mice survival time were recorded. Flow cytometry and immunohistochemistry were used for evaluation of the immune cells subgroup change of contralateral tumor. In addition, tumor rechallenge tests were conducted on unilateral tumor-bearing mice to examine the systemic immune effects of the combination therapy. RESULTS: We found that MWA treatment alone failed to produce a significant abscopal effect. In contrast, the combination group had longer survival than the MWA or anti-PD-1 group alone, with slower distant tumor growth. Moreover, the tumor-specific immune responses induced by combination therapy are stronger than anti-PD-1 or MWA alone. Combination therapy also elevated the levels of Th1-type cytokines in peripheral blood. In addition, after tumor rechallenge, the combination group showed more rejection to the reimplanted tumors (6 out of 10 mice). CONCLUSIONS: The combination of MWA and anti-PD-1 therapy resulted in the inhibition of distant tumor growth and the construction of a systemic anti-tumor immune environment that can reduce recurrence.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Imunoterapia , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Micro-Ondas/uso terapêutico
14.
Langenbecks Arch Surg ; 407(3): 1217-1224, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34994827

RESUMO

PURPOSE: To investigate the clinical course and optimal management for spontaneous isolated intramural hematoma of the superior mesenteric artery (SIHSMA). METHODS: From January 2015 to October 2020, a total of 31 consecutive patients with SIHSMA were included in this study. The demographics, clinical features, treatment details, imaging information, and outcomes were reviewed. RESULTS: There were 24 males and 7 females, with a mean age of 54.9 years (SD 6.9 years). Seven patients (7/31, 23%) were associated with ulcer-like projection (ULP), one patient (1/31, 3%) with intramural blood pool (IBP), and the remaining twenty-three patients (23/31, 74%) had no ULP or IBP. All patients were initially managed conservatively and underwent a median follow-up of 25.5 months (IQR 14.5, 39.9), which showed 3 patients (3/31, 10%) subsequently underwent stenting (2 within 7 days and 1 after 1.5 months), 1 patient (1/31, 3%) progressed to a localized dissection 7 months later but remained stable and asymptomatic until the time of writing, and the remaining patients (27/31, 87%) had no progression. In the present cohort, the overall survival was 100% (31/31). The free-from progression and stenting rate under conservative treatment was 87% (27/31). The invasive intervention rate was 10% (3/31). The natural complete regression rate of IMH in patients without ULP was higher than those with ULP (91% [21/23] vs. 29% [2/7], p = .003). CONCLUSION: The majority of patients with SIHSMA can be managed conservatively. Patients with ULP seemed to have a lower IMH regression rate than those without ULP.


Assuntos
Hematoma , Artéria Mesentérica Superior , Feminino , Hematoma/diagnóstico por imagem , Hematoma/cirurgia , Humanos , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Resultado do Tratamento , Úlcera/complicações
15.
Scand J Gastroenterol ; 57(3): 364-370, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34842020

RESUMO

BACKGROUND AND AIMS: Endoscopic stent placement is a palliative therapy for malignant digestive tract obstruction. However, its use for malignant afferent loop obstruction (mALO) has not been adequately investigated. METHODS: From March 2009 to December 2020, 137 patients with mALO who underwent endoscopic stent placement at three tertiary care centers were retrospectively enrolled. The primary aim of this study was to compare stent dysfunction (SD) between the covered self-expandable metal stent (CSEMS) and uncovered self-expandable metal stent (UCSEMS) groups, with subgroup analysis among patients with extrinsic and intrinsic tumors separately. RESULTS: Twenty-three patients developed SD in the CSEMS group and 29 patients in the UCSEMS group (log-rank p = .974). The primary contributors to SD included a higher risk of stent migration in the CSEMS group and stent ingrowth in the UCSEMS group (p = .003; p < .001). Among patients with extrinsic tumors, the CSEMS group showed a significantly higher probability of overall SD (p = .008) and stent migration (p = .001) with a shorter time to SD (log-rank p = .006) than the UCSEMS group. Among patients with intrinsic tumors, the CSEMS group showed a significantly lower incidence of overall SD (p < .001) and stent ingrowth (p < .001) with a longer time to SD (log-rank p = .011) than the UCSEMS group. CONCLUSIONS: Our results showed no significant difference in SD between the CSEMS and UCSEMS groups for palliation of mALO. Furthermore, subgroup analysis suggested using CSEMSs for patients with intrinsic tumors, and UCSEMSs for those with extrinsic tumors.


Assuntos
Cuidados Paliativos , Stents Metálicos Autoexpansíveis , Humanos , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/efeitos adversos , Stents/efeitos adversos , Resultado do Tratamento
16.
J Hepatocell Carcinoma ; 8: 1525-1535, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34888263

RESUMO

OBJECTIVE: To investigate the efficiency and safety of callispheres beads loaded with donafenib (DCBs) for embolization in a VX2 liver tumor, as well as the improvement of tumor angiogenesis following embolization. METHODS: Forty New Zealand white rabbit VX2 liver tumors were treated with four different drugs via the hepatic artery: NS (normal saline), CB (blank callispheres beads), ACB (adriamycin-loaded callispheres beads) and DCB (DCBs). Hematoxylin-eosin staining was performed to assess tumor necrosis, while MRI was employed to detect the changes in tumor size. The safety was evaluated by the liver and kidney function parameters, and the immunofluorescence and immunohistochemical staining were performed to reflect the tumor hypoxia and tumor angiogenesis following embolization. RESULTS: The DCB group had the smallest tumor growth rate, but the tumor necrosis rate was the highest of the four groups. Compared to the CB and ACB groups, the DCB group did not aggravate the liver damage and had no influence on kidney function. The staining results showed that, although the tumor hypoxia deteriorated after DCBs embolization, the expression of VEGF (vascular endothelial growth factor) reduced, thus inhibiting tumor angiogenesis. CONCLUSION: DCB administration via hepatic artery is an effective and safe treatment for a preclinical liver cancer model, with the unique benefit of suppressing tumor angiogenesis following embolization.

17.
Sci Rep ; 11(1): 22846, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819565

RESUMO

Liver fibrosis plays a crucial role in promoting tumor immune escape and tumor aggressiveness for liver cancer. However, an interesting phenomenon is that the tumor size of liver cancer patients with liver fibrosis is smaller than that of patients without liver fibrosis. In this study, 16 SD rats were used to establish orthotopic liver tumor transplantation models with Walker-256 cell lines, respectively on the fibrotic liver (n = 8, LF group) and normal liver (n = 8, control group). MRI (magnetic resonance imaging) was used to monitor the size of the tumors. All rats were executed at the third week after modeling, and the immunohistochemical staining was used to reflect the changes in the tumor microenvironment. The results showed that, compared to the control group, the PD-L1 (programmed cell death protein receptor-L1) expression was higher, and the neutrophil infiltration increased while the effector (CD8+) T cell infiltration decreased in the LF group. Additionally, the expression of MMP-9 (matrix metalloproteinase-9) of tumor tissue in the LF group increased. Three weeks after modeling, the size of tumors in the LF group was significantly smaller than that in the control group (382.47 ± 195.06 mm3 vs. 1736.21 ± 657.25 mm3, P < 0.001). Taken together, we concluded that liver fibrosis facilitated tumor immunity escape but limited the expansion of tumor size.


Assuntos
Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Neoplasias Hepáticas Experimentais/imunologia , Neoplasias Hepáticas Experimentais/patologia , Evasão Tumoral , Microambiente Tumoral/imunologia , Animais , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/metabolismo , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Imageamento por Ressonância Magnética , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Transplante de Neoplasias , Neovascularização Patológica , Infiltração de Neutrófilos , Ratos Sprague-Dawley , Fatores de Tempo , Carga Tumoral
18.
Rev Cardiovasc Med ; 22(3): 1029-1035, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565104

RESUMO

The data on endovascular aortic repair (EVAR) for traumatic aortic dissection (TAD) are lacking. Hence, this study aimed to evaluate the efficacy of EVAR for TAD and report our experience based on patients from our medical center with a relatively long follow-up. A total of 25 consecutive patients with TAD underwent EVAR from October 2015 to October 2020. The demographics, imaging characteristics, clinical features, treatment details, and follow-up results were reviewed. Urgent EVAR was performed in 3 patients (12%), while the remaining 22 patients (88%) underwent delayed EVAR. Systematic heparinization was used in all patients during the endovascular procedure. The EVAR was technically successful in all patients, with no cases converted into open surgery. No death occurred during the perioperative period. One patient presented with a type II endoleak on postoperative 1-month CT images during a mean follow-up of 42.3 ± 17.7 months (5-67.5 months) and showed spontaneous regression of the endoleak without any intervention during the subsequent follow-up. All the patients survived until the time of writing, and none of them showed late endoleak, stent migration, paraplegia, and reintervention. The patients with left subclavian artery covered (n = 8) had no obvious ischemia of the arm and brain. The study results demonstrated that EVAR for TAD proved to be safe and effective, and most patients could undergo delayed EVAR. Systematically heparinization during EVAR under the setting of multi-trauma was safe.


Assuntos
Aneurisma da Aorta Abdominal , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Reoperação , Estudos Retrospectivos , Fatores de Risco , Stents , Resultado do Tratamento
19.
Cancer Manag Res ; 13: 6935-6941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522136

RESUMO

PURPOSE: In clinical practice, we found some of the patients who received transarterial chemoembolization (TACE) with molecular targeted agents (MTGs) plus immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) had obvious liquefactive necrosis formation within the tumor and some even progressed to a liver abscess, which seems more frequent than patients who received other treatments. Thus, we aim to identify this condition and analyze the potential risk factors. PATIENTS AND METHODS: Medical records of 72 consecutive patients with intermediate (BCLC B) and advanced (BCLC C) HCC who received TACE plus MTGs combined with (n=30) or without (n=42) ICIs were reviewed. Liquefactive necrosis formation was defined as the presence of obvious liquefactive necrosis within the tumor that required intervention. RESULTS: The liquefactive necrosis rate was higher in the TACE+MTGs+ICIs group than in the TACE+MTGs group (30% vs 4.8%, P=0.006). Moreover, 18.2% (2/11) of the patients with liquefactive necrosis within the tumor had a bacterial infection. We then take the binary logistic regression analysis model to identify the predictors of liquefactive necrosis formation, and which showed the tumor size (P=0.006, OR=1.355, 95% CI: 1.090-1.684), alpha-fetoprotein level (P=0.036, OR=6.745, 95% CI: 1.130-40.262) and treatment modality (P=0.015, OR=11.717, 95% CI: 1.617-84.887) were the independent risk factor for liquefactive necrosis formation within the tumor. CONCLUSION: Patients with HCC who received TACE combined with MTGs plus ICIs have increased liquefactive necrosis formation, and the larger tumor size and higher alpha-fetoprotein level were associated with more liquefactive necrosis formation within the tumor.

20.
J Gastroenterol Hepatol ; 36(10): 2893-2902, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33973270

RESUMO

BACKGROUND AND AIM: Patients indicated to transjugular intrahepatic portosystemic shunt (TIPS) placement may have splenectomy history due to thrombocytopenia. This study aimed to evaluate the effect of prior splenectomy on TIPS procedure and post-TIPS outcomes. METHODS: We conducted a longitudinal analysis based on a cohort of 284 patients with cirrhosis submitted to TIPS; 74 patients had splenectomy history (splenectomy group) and 210 did not (non-splenectomy group). Cox proportional hazards models were used to evaluate the association between splenectomy and outcomes after TIPS. The primary outcome was shunt dysfunction. Secondary outcomes included all-cause mortality, clinical recurrence of bleeding or ascites, and overt hepatic encephalopathy (OHE). RESULTS: During a median follow-up of 16.2 months, the splenectomy group had significantly lower rates of postoperative shunt patency (85.5% vs 95.6% at 1 year and 75.2% vs 86.5% at 2 years; adjusted hazard ratio [HR] 2.53; 95% confidence interval [CI] 1.21-5.12; P = 0.01) and higher risk of OHE (adjusted HR 1.82; 95% CI 1.03-3.54; P = 0.04). But the risk of mortality (adjusted HR 0.87; 95% CI 0.41-1.87; P = 0.73) and recurrent bleeding or ascites (adjusted HR 1.17; 95% CI 0.53-2.35; P = 0.77) showed no statistical difference. Multivariate analysis confirmed splenectomy history and endoscopic therapy as independent predictors of shunt dysfunction. Besides, pre-TIPS splenectomy increased the difficulty of TIPS procedure by complicating portal vein puncture. CONCLUSIONS: For patients with cirrhosis submitted to TIPS, prior splenectomy complicated TIPS procedure and increased the risk of shunt dysfunction and OHE after TIPS, but was not significantly associated with the occurrence of mortality and recurrent bleeding or ascites.


Assuntos
Encefalopatia Hepática , Derivação Portossistêmica Transjugular Intra-Hepática , Ascite/etiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Recidiva Local de Neoplasia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Estudos Retrospectivos , Esplenectomia/efeitos adversos , Resultado do Tratamento
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