End-hole Versus Microvalve Infusion Catheters in Patients Undergoing Drug-Eluting Microspheres-TACE for Solitary Hepatocellular Carcinoma Tumors: A Retrospective Analysis.
ABSTRACT: INTRODUCTION:Pre-transplant locoregional therapy for hepatocellular carcinoma (HCC) during bridge-to-transplant impacts recurrence and survival rates following liver transplantation. Optimizing the effectiveness of transarterial chemoembolization (TACE) in this population is imperative, and microvalve infusion catheters offer a means of such improvement. METHODS:All treatment-naive patients with solitary HCC tumors?
Project description:BACKGROUND:The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma (HCC) patients with solitary tumor and microvascular invasion (MVI) is controversial. This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization (TACE) after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor???5 cm and MVI. METHODS:In this randomized, open-labeled, phase III trial, HCC patients with a solitary tumor???5 cm and MVI were randomly assigned (1:1) to receive either 1-2 cycles of adjuvant TACE after hepatectomy (Hepatectomy-TACE) or hepatectomy alone (Hepatectomy Alone). The primary endpoint was disease-free survival (DFS); the secondary endpoints included overall survival (OS) and adverse events. RESULTS:Between June 1, 2009, and December 31, 2012, 250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group (n?=?125) or the Hepatectomy Alone group (n?=?125). Clinicopathological characteristics were balanced between the two groups. The median follow-up time from randomization was 37.5 months [interquartile range 18.3-48.2 months]. The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [17.45 months (95% confidence interval [CI] 11.99-29.14) vs. 9.27 months (95% CI 6.05-13.70), hazard ratio [HR]?=?0.70 (95% CI 0.52-0.95), P?=?0.020], respectively. The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [44.29 months (95% CI 25.99-62.58) vs. 22.37 months (95% CI 10.84-33.91), HR?=?0.68 (95% CI 0.48-0.97), P?=?0.029]. Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group, although these were generally mild and manageable. The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction. CONCLUSION:Hepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor???5 cm and MVI, with acceptable toxicity.
Project description:BackgroundProphylactic transarterial chemoembolization (p-TACE) is strongly recommended for hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI), but the potential beneficiaries remain controversial.MethodsData of HCC patients with MVI who underwent R0 resection between December 2013 and December 2015 were identified through the primary liver cancer big data. Disease-free survival (DFS) and overall survival (OS) were compared between patients who received p-TACE or not using Kaplan?–Meier survival curves before and after propensity scoring match (PSM).ResultsA total of 695 patients were eligible for this study, including 199 patients (28.6%) receiving p-TACE and 496 patients (71.4%) receiving resection alone. In the crude cohort, median DFS and OS were longer in the p-TACE group than those in the non-TACE group without significant differences (25.0 months vs 24.2 months, P=0.100; 48.0 months vs 46.5 months, P=0.150; respectively), but significant differences were observed both in DFS and OS (both P<0.05) after 1:1 PSM. p-TACE was identified as one of the independent risk factors of both DFS and OS using multivariate analysis in the matched cohort (HR=0.69, 95% CI=0.54–0.88; HR=0.66, 95% CI=0.50–0.88; respectively). Subgroup analysis showed that p-TACE could beneficiate patients if they were male, aged ?50 years old, had HBV infection, preoperative AFP level ?400 ng/mL, Child-Pugh grading A, no transfusion, single tumor, tumor diameter ?5cm, Edmondson–Steiner grading I/II, capsule, or BCLC stage A, CNLC stage Ib, AJCC stage II both in DFS and OS (all P<0.05).ConclusionWith the current data, we concluded that not all HCC patients with MVI would be benefited from p-TACE, and p-TACE could benefit patients with “middle risk” according to the current staging systems.
Project description:Background: Previous studies reported that stress-induced phosphoprotein 1 (STIP1) can be secreted by hepatocellular carcinoma (HCC) cells and is increased in the serum of HCC patients. However, the therapy-monitoring and prognostic value of serum STIP1 in HCC remains unclear. Here, we aimed to systemically explore the prognostic significance of serum STIP1 in HCC. Methods: A total of 340 HCC patients were recruited to this study; 161 underwent curative resection and 179 underwent transcatheter arterial chemoembolization (TACE). Serum STIP1 was detected by enzyme-linked immunosorbent assay (ELISA). Optimal cutoff values for serum STIP1 in resection and TACE groups were determined by receiver operating characteristic (ROC) analysis. Prognostic value was assessed by Kaplan-Meier, log-rank, and Cox regression analyses. Predictive values of STIP1 for objective response (OR) to TACE and MVI were evaluated by ROC curves and logistic regression. Results: Serum STIP1 was significantly increased in HCC patients when compared with chronic hepatitis B patients or health donors (both P < 0.05). Optimal cutoff values for STIP1 in resection and TACE groups were 83.43 and 112.06 ng/ml, respectively. High pretreatment STIP1 was identified as an independent prognosticator. Dynamic changes in high STIP1 status were significantly associated with long-term prognosis, regardless of treatment approaches. Moreover, post-TACE STIP1 was identified as an independent predictor for OR, with a higher area under ROC curve (AUC-ROC) than other clinicopathological features. Specifically, pretreatment STIP1 was significantly increased in patients with microvascular invasion (MVI), and was confirmed as a novel, powerful predictor for MVI. Conclusions: Serum STIP1 is a promising biomarker for outcome evaluation, therapeutic response assessment, and MVI prediction in HCC. Integration serum STIP1 detection into HCC management might facilitate early clinical decision making to improve the prognosis of HCC.
Project description:The MIRACLE I pilot study was designed as a preliminary investigation of safety and efficacy of Embozene TANDEM microspheres loaded with doxorubicin for treatment of locally untreatable (i.e., unresectable and not suitable for local thermal ablation) hepatocellular carcinoma (HCC).Patients with locally untreatable HCC (mono- or bilobar disease, ECOG performance status 0-2, Child-Pugh score < 11) were eligible for this single-arm multicenter study. DEB-TACE was performed with 75 µm Embozene TANDEM loaded with 150 mg of doxorubicin.Twenty-five subjects with 41 tumors were treated (mean age 65 years); 16, 52, and 32% had BCLC A, B, and C status, respectively. Child-Pugh status was A for 64%, B for 32%, and C for 4%; 40% had ascites. About 92% had disease localized to one liver lobe. Most (72%) underwent ≤ 2 DEB-TACE procedures. Average doxorubicin dose was 124.5 ± 36.1 mg (median 150 mg) per procedure. Two patients had procedure-related SAE (liver necrosis, worsening of liver insufficiency) within 30 days of the first DEB-TACE procedure. Six-month freedom from procedure-related SAE or death was 68% (one hepatic encephalopathy, five deaths). Tumor response or stable disease was achieved in 95% (20/21) of subjects. Freedom from tumor progression or death at 6 months was 76%. The one-year survival rate was 56% overall and 73% among patients without ascites at baseline.MIRACLE I results suggest that Embozene TANDEM microspheres loaded with doxorubicin can provide good local tumor control in a heterogeneous group of patients with locally untreatable HCC.Level 2b, Individual cohort study.
Project description:BackgroundDue to heterogeneity of hepatocellular carcinoma (HCC), outcome assessment of HCC with transarterial chemoembolization (TACE) is challenging.MethodsWe built histologic-related scores to determine microvascular invasion (MVI) and Edmondson-Steiner grade by training CT radiomics features using machine learning classifiers in a cohort of 494 HCCs with hepatic resection. Meanwhile, we developed a deep learning (DL)-score for disease-specific survival by training CT imaging using DL networks in a cohort of 243 HCCs with TACE. Then, three newly built imaging hallmarks with clinicoradiologic factors were analyzed with a Cox-Proportional Hazard (Cox-PH) model.FindingsIn HCCs with hepatic resection, two imaging hallmarks resulted in areas under the curve (AUCs) of 0.79 (95% confidence interval [CI]: 0.71–0.85) and 0.72 (95% CI: 0.64–0.79) for predicting MVI and Edmondson-Steiner grade, respectively, using test data. In HCCs with TACE, higher DL-score (hazard ratio [HR]: 3.01; 95% CI: 2.02–4.50), American Joint Committee on Cancer (AJCC) stage III+IV (HR: 1.71; 95% CI: 1.12–2.61), Response Evaluation Criteria in Solid Tumors (RECIST) with stable disease?+?progressive disease (HR: 2.72; 95% CI: 1.84–4.01), and TACE-course > 3 (HR: 0.65; 95% CI: 0.45–0.76) were independent prognostic factors. Using these factors via a Cox-PH model resulted in a concordance index of 0.73 (95% CI: 0.71–0.76) for predicting overall survival and AUCs of 0.85 (95% CI: 0.81–0.89), 0.90 (95% CI: 0.86–0.94), and 0.89 (95% CI: 0.84–0.92), respectively, for predicting 3-year, 5-year, and 10-year survival.InterpretationOur study offers a DL-based, noninvasive imaging hallmark to predict outcome of HCCs with TACE.FundingThis work was supported by the key research and development program of Jiangsu Province (Grant number: BE2017756).
Project description:Intermediate-stage hepatocellular carcinoma (HCC) is usually treated with locoregional therapy using transarterial chemoembolization (TACE). Transarterial radioembolization (TARE) using ?-emitting yttrium-90 integral to the glass matrix of the microspheres is an alternative to TACE. This retrospective case-control study compared the outcomes and safety of TARE versus TACE in patients with unresectable HCC.Patients with unresectable HCC without portal vein thrombosis treated with TARE between 2005 and 2008 (n = 61) were retrospectively frequency-matched by age, sex, and liver dysfunction with TACE-treated patients (n = 55) in the Mayo Clinic Hepatobiliary Neoplasia Registry. Imaging studies were reviewed, and clinical and safety outcomes were abstracted from the medical records.Complete tumor response was more common after TARE (12 %) than after TACE (4 %) (p = 0.17). When complete response was combined with partial response and stable disease, there was no difference between TARE and TACE. Median survival did not differ between the two groups (15.0 months for TARE and 14.4 months for TACE; p = 0.47). Two-year survival rates were 30 % for TARE and 24 % for TACE. TARE patients received fewer treatments (p < 0.001). Fifty-nine (97 %) TARE patients received outpatient treatment. In contrast, 53 (98 %) TACE patients were hospitalized for ?1 day (p < 0.001). Compared with TACE, TARE was more likely to induce fatigue (p = 0.003) but less likely to cause fever (p = 0.02).There was no significant difference in efficacy between TARE and TACE. TARE patients reported more fatigue but had less fever than TACE patients. Treatment with TARE required less hospitalization than treatment with TACE. These findings require confirmation in randomized trials.
Project description:Kidney transplant recipients with biopsy-proven microvascular injury (MVI) have increased risk for allograft failure. MVI is often caused by antibody-mediated injury that is resistant to available treatments. Current diagnostic methods are also inadequate, with interobserver variability in traditional pathology reads, variable assessment of circulating donor-specific antibody between HLA laboratories, and peritubular capillary C4d staining. Molecular assessments of kidney biopsies can provide improved sensitivity for diagnosing MVI and other allograft pathology, while improving reproducibility and objectivity. Most molecular classifiers have been based on whole genome sequencing to develop diagnostic tests, but have provided limited therapeutic targets. In this study, we pursued a candidate gene approach to measure WNT pathway genes in residual clinical FFPE biopsies with and without MVI. We focused on the WNT pathway because of previous translational studies that implicated this pathway in chronic renal allograft injury as well as vascular injury in native chronic kidney disease. Overall design: Case-control study of 95 residual FFPE biopsies with MVI (g+ptc score >= 2, n=50) or Stable (g+ptc score < 2 and no other major abnormalities, n=45). Biopsies were retrieved from a biorepository of over 500 kidney transplant biopsies. We compared expression of 180 WNT pathway genes and 30 custom skipe-in targets (derived from previous studies of endothelial injury in transplantation) between MVI and Stable groups, with correction for multiple comparisons using FDR < 5%.
Project description:Kidney transplant recipients with biopsy-proven microvascular injury (MVI) have increased risk for allograft failure. MVI is often caused by antibody-mediated injury that is resistant to available treatments. Current diagnostic methods are also inadequate, with interobserver variability in traditional pathology reads, variable assessment of circulating donor-specific antibody between HLA laboratories, and peritubular capillary C4d staining. Molecular assessments of kidney biopsies can provide improved sensitivity for diagnosing MVI and other allograft pathology, while improving reproducibility and objectivity. Most molecular classifiers have been based on whole genome sequencing to develop diagnostic tests, but have provided limited therapeutic targets. In this study, we pursued a candidate gene approach to measure WNT pathway genes in residual clinical FFPE biopsies with and without MVI. We focused on the WNT pathway because of previous translational studies that implicated this pathway in chronic renal allograft injury as well as vascular injury in native chronic kidney disease. Case-control study of 95 residual FFPE biopsies with MVI (g+ptc score >= 2, n=50) or Stable (g+ptc score < 2 and no other major abnormalities, n=45). Biopsies were retrieved from a biorepository of over 500 kidney transplant biopsies. We compared expression of 180 WNT pathway genes and 30 custom skipe-in targets (derived from previous studies of endothelial injury in transplantation) between MVI and Stable groups, with correction for multiple comparisons using FDR < 5%. This dataset is part of the TransQST collection.
Project description:Patients with hepatocellular carcinoma (HCC) accompanying portal vein tumor thrombosis (PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelona clinic liver cancer stage C and sorafenib is suggested as the standard therapy of care. However, overall survival (OS) gain from sorafenib is unsatisfactory and better treatment modalities are urgently required. Therefore, we critically appraised recent data for the various treatment strategies for patients with HCC accompanying PVTT. In suitable patients, even surgical resection can be considered a potentially curative strategy. Transarterial chemoembolization (TACE) can be performed effectively and safely in a carefully chosen population of patients with reserved liver function and sufficient collateral blood flow nearby the blocked portal vein. A recent meta-analysis demonstrated that TACE achieved a substantial improvement of OS in HCC patients accompanying PVTT compared with best supportive care. In addition, transarterial radioembolization (TARE) using yttrium-90 microspheres achieves quality-of-life advantages and is as effective as TACE. A large proportion of HCC patients accompanying PVTT are considered to be proper for TARE. Moreover, TACE or TARE achieved comparable outcomes to sorafenib in recent studies and it was also reported that the combination of radiotherapy with TACE achieved a survival gain compared to sorafenib in HCC patients accompanying PVTT. Surgical resection-based multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.
Project description:Transplant glomerulopathy (TGP) is frequently found in the setting of chronic antibody mediated rejection along with microvascular inflammation (MVI) (peritubular capillaritis+glomerulitis score > 1) and/or positive c4d staining. We assessed the molecular profiles of TGP in the absence of microvascular inflammation and C4d staining as compared to TGP with positive MVI and/or C4d. Gene expression profiles of TGP in the absence of microvascular inflammation and C4d lack molecular features of antibody-mediated rejection but suggest chronic cellular rejection. Overall design: 44 for-cause renal allograft biopsies were studied using Affymetrix HuGene 1.0 ST expression arrays; 12 with normal biopsy findings (G1), 17 with a diagnosis of TGP, C4d positive and/or a MVI score >1 (G2), and 10 with a diagnosis of TGP and C4d negative and MVI score <=1 which were DSA negative (G3A) and 5 TGP and C4d negative and MVI score <=1 (G3B).