ABSTRACT
This retrospective case series assessed the early effectiveness of combined spontaneous portosystemic shunt (SPSS) embolization and preemptive transjugular intrahepatic portosystemic shunt (TIPS) creation for alleviation of medically refractory hepatic encephalopathy (HE) and prevention of portal hypertension complications in patients with liver cirrhosis. Eight patients with liver cirrhosis (5 men and 3 women; mean age, 61 years [SD ± 10]) and HE (overt [West-Haven Grade 2-4], n = 7; covert [West-Haven Grade 1], n = 1) refractory to lactulose and rifaximin therapy who underwent concurrent or staged SPSS embolization and TIPS creation between 2018 and 2022 were included in this study. The primary outcomes were 3-month improvement in HE and postprocedural HE-related hospitalizations. HE improvement was achieved in 7 (87.5%) of 8 cases. Among all patients, there was 1 HE-related hospitalization within 90 days that responded to repeat embolization with no further admissions. No patients developed new ascites, variceal hemorrhage, or other portal hypertension complications within 3 months.
Subject(s)
Embolization, Therapeutic , Hepatic Encephalopathy , Liver Cirrhosis , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/therapy , Middle Aged , Male , Embolization, Therapeutic/adverse effects , Female , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Retrospective Studies , Treatment Outcome , Aged , Liver Cirrhosis/complications , Time Factors , Hypertension, Portal/physiopathology , Hypertension, Portal/etiology , Hypertension, Portal/therapy , Portal PressureABSTRACT
PURPOSE: To correlate epigenetic patterns with ethnoracial status and locoregional therapy (LRT) response in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: DNA and RNA were extracted from 47 distinct formalin-fixed paraffin-embedded tumor samples from 42 patients with HCC (n = 14 Black, n = 19 White, n = 9 Hispanic). LRT response was determined using computed tomography (CT) or magnetic resonance (MR) imaging 3 months posttreatment of 35 tumors (n = 22 complete response, n = 13 retreatment candidates). RNA expression and DNA methylation were used to stratify patients by ethnoracial status and treatment response using partial least-squares discriminant analysis (PLS-DA). Results were validated using hierarchical clustering. Ingenuity pathway analysis was performed to identify upstream regulators and pathways. RESULTS: PLS-DA identified 100 genes and 12 methylated regions that differentiated tumors from Black from White/Hispanic patients. Hierarchical clustering clustered samples with the top 16 genes or the top 5 methylation regions. Dysregulated pathways included adrenomedullin pathway (P = .030), EIF2 signaling (P = .007), and several metabolic pathways. AGTR1 (log2fold = 1.59) and GSTM3 (log2fold = 2.53) represented potential differentially expressed therapeutic targets. PLS-DA identified 100 genes and 150 methylation regions that differentiated between complete responders and retreatment candidates. Hierarchical clustering clustered samples with the top 30 genes or the top 13 methylation regions. Dysregulated pathways included metabolic and DNA repair-related pathways. ASAP2 (log2fold = 0.29) and RAD50 (log2fold = 0.22) represented potential differentially expressed therapeutic targets. CONCLUSIONS: Variation in gene expression and DNA methylation patterns in patients with HCC corresponded to ethnoracial status and LRT response. These initial results suggest tumor profiling has the potential to close ethnoracial disparities and improve treatment stratification.
Subject(s)
Carcinoma, Hepatocellular , DNA Methylation , Epigenesis, Genetic , Liver Neoplasms , Adult , Aged , Female , Humans , Male , Middle Aged , Biomarkers, Tumor/genetics , Black or African American/genetics , Carcinoma, Hepatocellular/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Magnetic Resonance Imaging , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , White , Hispanic or LatinoABSTRACT
Traditionally, rodent cancer models have driven preclinical oncology research. However, they do not fully recapitulate characteristics of human cancers, and their size poses challenges when evaluating tools in the interventional oncologists' armamentarium. Pig models, however, have been the gold standard for validating surgical procedures. Their size enables the study of image-guided interventions using human ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging platforms. Furthermore, pigs have immunologic features that are similar to those of humans, which can potentially be leveraged for studying immunotherapy. Novel pig models of cancer are being developed, but additional research is required to better understand both the pig immune system and malignancy to enhance the potential for pig models in interventional oncology research. This review aims to address the main advantages and disadvantages of using a pig model for interventional oncology and outline the specific characteristics of pig models that make them more suitable for investigation of locoregional therapies.
Subject(s)
Disease Models, Animal , Immunotherapy , Neoplasms , Animals , Immunotherapy/methods , Neoplasms/therapy , Neoplasms/diagnostic imaging , Neoplasms/immunology , Humans , Swine , Radiography, Interventional , Sus scrofa , Medical OncologyABSTRACT
PURPOSE: To estimate the risk of hepatobiliary infection, including endoTIPSitis, liver abscesses, and cholangitis, after transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with prior biliary intervention. MATERIALS AND METHODS: This multi-institution, retrospective study identified 76 patients (n = 48 males; mean age, 54.9 years; mean Model for End-stage Liver Disease [MELD] score, 13.2; n = 45 for ascites and n = 23 for varices; n = 31 with prior liver transplantation) among 2,130 (3.6%) undergoing TIPS creation who had prior biliary intervention (n = 19 bilioenteric anastomoses, n = 35 sphincterotomies, n = 28 internal plastic stent placements, n = 4 internal metal stent placements, and n = 6 percutaneous biliary drain placements). The baseline risk of post-TIPS creation hepatobiliary infection was estimated from a control group of 1,202 TIPS creation procedures in patients without prior biliary intervention. RESULTS: Eleven (14.5%) of 76 patients developed hepatobiliary infection after TIPS creation, including 7 with endoTIPSitis, 4 with hepatic abscesses, and 2 with cholangitis. The 30-day risk of infection was 10.9% (95% confidence interval [CI], 3.5%-17.8%), significantly higher than the 0.4% risk (95% CI, 0.1%-0.8%) observed in patients without prior biliary intervention (hazard ratio [HR], 25.56; 95% CI, 8.36-78.13; P < .001). All types of biliary intervention were associated with increased risk of infection, with bilioenteric anastomoses conferring the highest risk. Paradoxically, among patients with prior biliary intervention, use of postprocedural antibiotic prophylaxis was associated with an increased infection risk (HR, 19.85; 95% CI, 2.44-161.50; P = .005). Microbial culture data showed high rates of Enterococcus, Klebsiella, and Candida species. CONCLUSIONS: Prior biliary intervention was associated with a 10.9% risk of hepatobiliary infection, including endoTIPSitis, liver abscess, and cholangitis, within 30 days after TIPS creation.
Subject(s)
Cholangitis , Liver Abscess , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Male , Female , Retrospective Studies , Middle Aged , Risk Factors , Cholangitis/etiology , Aged , Liver Abscess/etiology , Liver Abscess/microbiology , Treatment Outcome , Adult , Time Factors , Risk Assessment , United States , StentsABSTRACT
Genicular artery embolization (GAE) is an emerging, minimally invasive therapy to address the global burden of knee osteoarthritis (OA) and the unmet needs for medically refractory disease. Although total knee arthroplasty has been a standard intervention for severe cases, GAE is developing into a promising alternative, particularly for patients ineligible for or unwilling to undergo surgery. GAE targets the inflammatory cascade underlying OA pathophysiology by arresting neoangiogenesis and preventing pathological neoinnervation, offering potential pain relief. Although early studies have established safety and short-term effectiveness, ensuing studies are needed to validate long-term safety, durability, and comparative effectiveness and to optimize patient selection, embolic agent selection, and administration techniques. Standardized reporting guidelines are therefore essential to enhance transparency and reproducibility across clinical trials, facilitating data aggregation and comparison. This Society of Interventional Radiology (SIR)-endorsed reporting standards consensus document provides a framework to harmonize future research efforts and to improve the interpretation of outcomes.
Subject(s)
Consensus , Embolization, Therapeutic , Osteoarthritis, Knee , Humans , Embolization, Therapeutic/standards , Embolization, Therapeutic/adverse effects , Treatment Outcome , Osteoarthritis, Knee/therapy , Osteoarthritis, Knee/diagnostic imaging , Research Design/standards , Radiography, Interventional/standardsABSTRACT
The hepatic venous pressure gradient (HVPG) is currently considered the gold standard to assess portal hypertension (PH) in patients with cirrhosis. A meticulous technique is important to achieve accurate and reproducible results, and values obtained during measurement are applied in risk stratification of patients with PH, allocating treatment options, monitoring follow-up, and deciding management options in surgical patients. The use of portosystemic pressure gradients in patients undergoing placement of transjugular intrahepatic portosystemic shunts has been studied extensively and has great influence on decisions on shunt diameter. The purpose of this study was to describe the recommended technique to measure HVPG and portosystemic pressure gradient and to review the existing literature describing the importance of these hemodynamic measurements in clinical practice.
Subject(s)
Hypertension, Portal , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Liver Cirrhosis/complications , Hemodynamics , Portal Pressure , Portasystemic Shunt, Transjugular Intrahepatic/adverse effectsABSTRACT
PURPOSE: To assess clinical outcomes and patency after transjugular intrahepatic portosystemic shunt (TIPS) reduction for overshunting adverse events. MATERIALS AND METHODS: This multicenter, retrospective observational study included 33 patients (male-to-female ratio, 20:13; mean age, 59 years; mean Model for End-Stage Liver Disease [MELD] score, 15) who underwent TIPS reduction between 2007 and 2020. Procedure indications included medically refractory hepatic encephalopathy (HE) (85%), post-TIPS hepatic insufficiency (HI) (12%), and heart failure (3%). The measured outcomes included improvement in HE (classified using the West Haven system) and HI, patency of reduced TIPS, and transplant-free survival (TFS). RESULTS: TIPS reductions were successfully performed using parallel stent (94%) or other (6%) techniques at a median of 120 days after TIPS creation (HE, median, 164 days; HI, median, 5 days). The portosystemic pressure gradient increased from a mean of 10 to 17 mm Hg (P < .001). The overall HE rate after TIPS reduction was 54%; HE was persistent, improved, and resolved in 21%, 32%, and 46% cases, respectively. In patients with HI, the MELD score increased from a mean of 22 before TIPS to 34 after TIPS (P = .061), but without improvement (0%) in HI after TIPS reduction (mean MELD score, 30; P = .266). Recurrent ascites occurred in 14% of the patients. The median shunt patency was 961 days (95% confidence interval, 476-1,447). The 30-day, 6-month, 1-year, and 3-year shunt patency rates were 92%, 81%, 74%, and 37%, respectively. The median TFS was not reached. The 30-day, 6-month, 1-year, and 3-year survival rates were 97%, 90%, 81%, and 60%, respectively. CONCLUSIONS: Although TIPS reduction may be an effective and durable approach to treat post-TIPS medically refractory HE, shunt reduction may not achieve meaningful benefit for HI.
Subject(s)
End Stage Liver Disease , Hepatic Encephalopathy , Hypertension, Portal , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Male , Female , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/methods , Hypertension, Portal/etiology , End Stage Liver Disease/diagnosis , End Stage Liver Disease/surgery , End Stage Liver Disease/etiology , Treatment Outcome , Severity of Illness Index , Hepatic Encephalopathy/etiology , Retrospective StudiesABSTRACT
PURPOSE: To investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: VX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry. RESULTS: The median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 µg/mL (interquartile range [IQR], 7.42-33.5 µg/mL), and its maximal plasma concentration (Cmax) was 0.164 µg/mL (IQR, 0.0798-0.528 µg/mL). The intratumoral concentration and Cmax of doxorubicin were similar between the groups: 4.08 µg/mL (IQR, 3.18-4.79 µg/mL) and 0.677 µg/mL (IQR, 0.315-1.23 µg/mL), respectively, in the DOX-TACE group and 1.68 µg/mL (IQR, 0.795-4.08 µg/mL) and 0.298 µg/mL (IQR, 0.241-0.64 µg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups. CONCLUSIONS: The addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Animals , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Doxorubicin , Emulsions , Ethiodized Oil , Hypoxia/therapy , Liver Neoplasms/therapy , Necrosis/therapy , Rabbits , Sorafenib , Vascular Endothelial Growth Factor AABSTRACT
Refractory ascites is a costly and debilitating condition that occurs most frequently in the setting of substantial cirrhotic portal hypertension, where it portends a poor prognosis. Many treatment options are available, among them medical management, serial large volume paracenteses, transjugular intrahepatic portosystemic shunts, and implanted drainage devices. Although the availability of multiple therapies ensures that most patients will achieve satisfactory results, it can be challenging for the provider to select the appropriate treatment for each specific patient. This article reviews the available therapeutic options for refractory ascites and incorporates available data and clinical experience to suggest a linear stepwise management approach to enhance patient outcomes.
Subject(s)
Ascites/etiology , Ascites/therapy , Hypertension, Portal/complications , Ascites/diagnostic imaging , Ascites/physiopathology , Combined Modality Therapy , Humans , Hypertension, Portal/diagnostic imaging , Hypertension, Portal/physiopathology , PrognosisABSTRACT
PURPOSE: To compare the safety and clinical outcomes of combined transjugular intrahepatic portosystemic shunt (TIPS) plus variceal obliteration to those of TIPS alone for the treatment of gastric varices (GVs). MATERIALS AND METHODS: A single-center, retrospective study of 40 patients with bleeding or high-risk GVs between 2008 and 2019 was performed. The patients were treated with combined therapy (n = 18) or TIPS alone (n = 22). There were no significant differences in age, sex, model for end-stage liver disease score, or GV type between the groups. The primary outcomes were the rates of GV eradication and rebleeding. The secondary outcomes included portal hypertensive complications and hepatic encephalopathy. RESULTS: The mean follow-up period was 15.4 months for the combined therapy group and 22.9 months for the TIPS group (P = .32). After combined therapy, there was a higher rate of GV eradication (92% vs 47%, P = .01) and a trend toward a lower rate of GV rebleeding (0% vs 23%, P = .056). The estimated rebleeding rates were 0% versus 5% at 3 months, 0% versus 11% at 6 months, 0% versus 18% at 1 year, and 0% versus 38% at 2 years after combined therapy and TIPS, respectively (P = .077). There was no difference in ascites (13% vs 11%, P = .63), hepatic encephalopathy (47% vs 55%, P = .44), or esophageal variceal bleeding (0% vs 0%, P > .999) after the procedure between the groups. CONCLUSIONS: The GV eradication rate is significantly higher after combined therapy, with no associated increase in portal hypertensive complications. This translates to a clinically meaningful trend toward a reduction in GV rebleeding. The value of a combined treatment strategy should be prospectively studied in a larger cohort to determine the optimal management of GVs.
Subject(s)
Embolization, Therapeutic , Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/therapy , Portasystemic Shunt, Transjugular Intrahepatic , Sclerotherapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Embolization, Therapeutic/adverse effects , Esophageal and Gastric Varices/diagnostic imaging , Esophageal and Gastric Varices/etiology , Female , Gastrointestinal Hemorrhage/diagnostic imaging , Gastrointestinal Hemorrhage/etiology , Humans , Male , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Recurrence , Retrospective Studies , Sclerotherapy/adverse effects , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: To develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies. MATERIALS AND METHODS: Liver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53R167H and KRASG12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40-120 µm (4 pigs) or 100-300 µm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy. RESULTS: Liver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3-4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40-120 µm or 100-300 µm Embosphere microspheres, while untreated tumors showed continued growth. CONCLUSIONS: Liver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.
Subject(s)
Acrylic Resins/administration & dosage , Embolization, Therapeutic , Gelatin/administration & dosage , Liver Neoplasms/therapy , Acrylic Resins/toxicity , Animals , Animals, Genetically Modified , Cell Line , Disease Models, Animal , Embolization, Therapeutic/adverse effects , Gelatin/toxicity , Genes, p53 , Genes, ras , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Sus scrofa/genetics , Time Factors , Tumor Burden , X-Ray MicrotomographyABSTRACT
BACKGROUND: The Viatorr Controlled Expansion (VCX) stent-graft was designed to mitigate hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation. AIMS: To determine the incidence and degree of HE after VCX TIPS. METHODS: Thirty-three patients (M:F 17:16, mean age 58 years, mean MELD score 12) who underwent VCX TIPS between 2018 and 2019 were retrospectively studied. 11/33 (33%) patients had medically controlled pre-TIPS HE. TIPS indications included variceal hemorrhage (n = 12, 30%) and ascites (n = 21, 70%). Measured outcomes were post-TIPS HE (overall, recurrent, de novo) graded using the West Haven system, time-to-HE occurrence, HE-related hospitalization rate, and TIPS reduction rate. RESULTS: VCX TIPS were 8 mm in 28/33 (85%) and 10 mm in 5/33 (15%). Mean final portosystemic pressure gradient was 6 mmHg. Cumulative HE incidence post-TIPS was 61% (20/33). 1-, 3-, 6-, and 12-month HE rates were 24%, 30%, 53%, and 61% over 247-day median follow-up. Median time-to-HE was 180 days. HE grades spanned grade 1 (n = 6), grade 2 (n = 8), and grade 3 (n = 6); 9 and 11 cases were recurrent and de novo HE, respectively. Medication non-compliance/infection was implicated in HE in 9/20 (45%) cases. Medical therapy addressed HE in 18/20 (90%) cases; however, HE still resulted in 39 hospitalizations among 13 patients, and median time to first hospitalization was 75 days. Shunt reduction was necessary in 2 (10%) cases of medically refractory HE. CONCLUSIONS: The incidence of HE after VCX TIPS is high. Though HE symptoms may be medically controlled, hospitalization rates are high, and shunt reduction may be necessary.
Subject(s)
Hepatic Encephalopathy/etiology , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Portasystemic Shunt, Transjugular Intrahepatic/instrumentation , Stents/adverse effects , Female , Humans , Incidence , Male , Middle Aged , Risk Factors , Treatment OutcomeABSTRACT
PURPOSE OF REVIEW: For three decades, portal vein embolization (PVE) has been the "gold-standard" strategy to hypertrophy the anticipated future liver remnant (FLR) in advance of major hepatectomy. During this time, CT volumetry was the most common method to preoperatively assess FLR quality and function and used to determine which patients are appropriate surgical candidates. This review provides the most up-to-date methods for preoperatively assessing the anticipated FLR and summarizes data from the currently available strategies used to induce FLR hypertrophy before surgery for hepatobiliary malignancy. RECENT FINDINGS: Functional and physiological imaging is increasingly replacing standard CT volumetry as the method of choice for preoperative FLR assessment. PVE, associating liver partition and portal vein ligation, radiation lobectomy, and liver venous deprivation are all currently available techniques to hypertrophy the FLR. Each strategy has pros and cons based on tumor type, extent of resection, presence or absence of underlying liver disease, age, performance status, complication rates, and other factors. Numerous strategies can lead to FLR hypertrophy and improve the safety of major hepatectomy. Which is best has yet to be determined.
Subject(s)
Biliary Tract Neoplasms/therapy , Embolization, Therapeutic/methods , Hepatectomy/methods , Liver Neoplasms/therapy , Liver Regeneration/physiology , Embolization, Therapeutic/adverse effects , Hepatectomy/adverse effects , Humans , Liver/diagnostic imaging , Liver/physiopathology , Portal Vein/surgery , Preoperative CareABSTRACT
PURPOSE: To compare outcomes of unresectable hepatocellular-cholangiocarcinoma (HCC-CC) with hepatocellular carcinoma (HCC) after locoregional therapy (LRT). MATERIALS AND METHODS: Consecutive patients with histologically confirmed HCC-CC or HCC treated with LRT between 2007 and 2017 were retrospectively reviewed. Ten patients (8 men; median age, 60 y) with 12 HCC-CCs (mean diameter, 4.2 cm ± 1.9; mean number, 3.7 ± 3.3) treated with chemoembolization (n = 6), yttrium-90 radioembolization (n = 2), RF ablation (n = 1), or chemoembolization/RF ablation (n = 1) were compared with 124 patients (92 men; median age, 59 y) with 134 HCCs (mean diameter, 4.8 cm ± 4.0; mean number, 2.6 ± 2.2) treated with chemoembolization (n = 51), yttrium-90 radioembolization (n = 17), RF ablation (n = 41), or chemoembolization/RF ablation (n = 15). Propensity score-matched analysis with conditional logistic regression adjusted for age, sex, LRT modality, tumor-specific features, and Child-Pugh class. Tumor-volume doubling time (TVDT) before LRT and objective response rates were compared by Kruskal-Wallis and Fisher exact test; progression-free survival (PFS) and transplant-free survival (TFS) were compared by Cox proportional hazards model. RESULTS: On univariate analysis, HCC-CC was associated with lower median TVDT (2.4 months vs 5.2 months, P = .03), objective response (30% vs 71%, P = .01), and median PFS (2.4 months vs 7.4 months, HR 4.3, 95% CI 2.2-8.4, P < .0001). Propensity score-matched analysis demonstrated greater distant progression (60% vs 30%, P = .003) and significantly shorter median PFS (2.4 months vs 6.0 months, HR 3.3, 95% CI 1.3-8.9, P = .017) for HCC-CC. No significant difference was observed in TFS (7.5 months vs 13.8 months, HR 1.5, 95% CI 0.4-6.1). CONCLUSIONS: HCC-CC was associated with reduced PFS and greater distant progression after LRT compared with HCC, indicating a need for adjunctive treatment strategies to improve outcomes.
Subject(s)
Bile Duct Neoplasms/therapy , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Cholangiocarcinoma/therapy , Embolization, Therapeutic/methods , Liver Neoplasms/therapy , Radiofrequency Ablation , Radiopharmaceuticals/administration & dosage , Yttrium Radioisotopes/administration & dosage , Aged , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Chemoembolization, Therapeutic/adverse effects , Chemoembolization, Therapeutic/mortality , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Combined Modality Therapy , Disease Progression , Embolization, Therapeutic/adverse effects , Embolization, Therapeutic/mortality , Female , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation , Male , Middle Aged , Progression-Free Survival , Radiofrequency Ablation/adverse effects , Radiofrequency Ablation/mortality , Radiopharmaceuticals/adverse effects , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Yttrium Radioisotopes/adverse effectsABSTRACT
Purpose To determine the frequency of hepatobiliary infections after transarterial radioembolization (TARE) with yttrium 90 (90Y) in patients with liver malignancy and a history of biliary intervention. Materials and Methods For this retrospective study, records of all consecutive patients with liver malignancy and history of biliary intervention treated with TARE at 14 centers between 2005 and 2015 were reviewed. Data regarding liver function, 90Y dosimetry, antibiotic prophylaxis, and bowel preparation prophylaxis were collected. Primary outcome was development of hepatobiliary infection. Results One hundred twenty-six patients (84 men, 42 women; mean age, 68.8 years) with primary (n = 39) or metastatic (n = 87) liver malignancy and history of biliary intervention underwent 180 procedures with glass (92 procedures) or resin (88 procedures) microspheres. Hepatobiliary infections (liver abscesses in nine patients, cholangitis in five patients) developed in 10 of the 126 patients (7.9%) after 11 of the 180 procedures (6.1%; nine of those procedures were performed with glass microspheres). All patients required hospitalization (median stay, 12 days; range, 2-113 days). Ten patients required percutaneous abscess drainage, three patients underwent endoscopic stent placement and stone removal, and one patient needed insertion of percutaneous biliary drains. Infections resolved in five patients, four patients died (two from infection and two from cancer progression while infection was being treated), and one patient continued to receive suppressive antibiotics. Use of glass microspheres (P = .02), previous liver resection or ablation (P = .02), and younger age (P = .003) were independently predictive of higher infection risk. Conclusion Infectious complications such as liver abscess and cholangitis are uncommon but serious complications of transarterial radioembolization with 90Y in patients with liver malignancy and a history of biliary intervention.
Subject(s)
Brachytherapy/adverse effects , Carcinoma, Hepatocellular/radiotherapy , Cholangitis/etiology , Liver Abscess/etiology , Liver Neoplasms/radiotherapy , Yttrium Radioisotopes/therapeutic use , Adult , Aged , Aged, 80 and over , Brachytherapy/methods , Carcinoma, Hepatocellular/complications , Female , Glass , Humans , Infections , Liver/microbiology , Liver Neoplasms/complications , Male , Microspheres , Middle Aged , Retreatment , Retrospective Studies , Treatment OutcomeSubject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Ethanol , Catheter Ablation/adverse effects , Treatment OutcomeABSTRACT
PURPOSE: To systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of ethiodized oil-based locoregional therapy (LRT) for liver cancer in preclinical models. MATERIALS AND METHODS: A MEDLINE search was performed from 1988 to 2016. Search terms included hepatocellular carcinoma (HCC), HCC, liver-cell carcinoma, liver, hepatic, hepatocarcinoma, transarterial or chemoembolization, TACE, animal, Lipiodol, Ethiodol, iodized oil, and/or poppy-seed oil. Inclusion criteria were: publication in a peer-reviewed journal, an accepted animal model, and PK/safety/efficacy data reported. Exclusion criteria were: inadequate PK, safety, or efficacy data; anticancer drug name/dose not available; and article not in English. Outcomes included intratumoral anticancer drug uptake, PKs, tolerance, tumor response, and survival. RESULTS: Of 102 identified articles, 49 (49%) met the inclusion criteria. Seventeen, 35, and 2 articles used rat, rabbit, and pig models. Mechanism of action was investigated in 11 articles. Eleven articles reported drug uptake, PK, and tolerance data, showing 0.5%-9.5% of injected chemotherapy dose in tumor. Tumor-to-liver drug distribution ratios were 2-157. Toxicology data across 6 articles showed transient liver laboratory level elevations 1 day after LRT. There was no noteworthy liver or extrahepatic histologic damage. Nine articles reported tumor response, with 0%-30% viable tumor and -10% to -38% tumor growth at 7 days after LRT. Two articles reported survival, showing significantly longer survival after LRT vs untreated controls (56/60 d vs 33/28 d). Several articles described ethiodized oil mixed with radiopharmaceutical (n = 7), antiangiogenic (n = 6), gene (n = 6), nanoembolic (n = 5), immune (n = 2), or other novel (n = 1) agents. CONCLUSIONS: Animal studies show preferential tumor uptake of anticancer agent, good hepatic/systemic tolerance, high tumor response, and enhanced survival after ethiodized oil-based LRT.