Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy.

OBJECTIVE: To validate the feasibility of molecular imaging-monitored intratumoral radiofrequency hyperthermia (RFH) enhanced direct oncolytic virotherapy for hepatocellular carcinoma (HCC). METHODS: This study included in vitro experiments using luciferase-labeled rat HCC cells and in vivo validation experiments on rat models with orthotopic HCCs. Both cells and HCCs in four groups (n = 6/group) were treated by: (1) combination therapy of oncolytic virotherapy (T-VEC) plus RFH at 42 °C for 30 min; (2) oncolytic virotherapy alone; (3) RFH alone; and (4) saline. For in vitro confirmation, confocal microscopy and bioluminescence optical imaging were used to evaluate the cell viabilities. For in vivo validation, oncolytic viruses were directly infused into rat HCCs through a multi-functional perfusion-thermal RF electrode, followed by RFH. Ultrasound and optical imaging were used to follow up size and bioluminescence signal changes of tumors overtime, which were correlated with subsequent laboratory examinations. RESULTS: For in vitro experiments, confocal microscopy showed the lowest number of viable cells, as well as a significant decrease of bioluminescence signal intensity of cells with combination therapy group, compared to other three groups (p < .001). For in vivo experiments, ultrasound and optical imaging showed the smallest tumor volume, and significantly decreased bioluminescence signal intensity in combination therapy group compared to other three groups (p < .05), which were well correlated with pathologic analysis. CONCLUSION: It is feasible of using molecular imaging to guide RFH-enhanced intratumoral oncolytic virotherapy of HCC, which may open new avenues to prevent residual or recurrent disease of thermally ablated intermediate-to-large HCCs.

Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment for patients with hepatocellular carcinoma (HCC) was uncommon before direct-acting antiviral (DAA) medications. Real-world effectiveness of DAAs for HCV in patients with HCC is unclear. We describe rates of sustained virologic response (SVR) with DAA regimens by HCV genotype in patients with a history of HCC. METHODS: We identified patients who initiated antiviral treatment between January 1, 2014 and June 30, 2015 in the national Veterans Affairs health care system. Regimens included sofosobuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin. HCC patients were divided into those who were treated with liver transplantation after HCC diagnosis ("HCC/LT" group) and those treated with other modalities prior to antiviral therapy ("HCC" group). RESULTS: Of 17,487 HCV treatment recipients, 624 (3.6%) had prior HCC, including 142 with HCC/LT and 482 with HCC. Overall SVR was 91.1% in non-HCC, 74.4% in HCC, and 94.0% in HCC/LT. Among HCC patients, genotype 1 had the highest SVR overall (79.1% in HCC and 96.4% in HCC/LT), and genotype 3 the lowest (47.0% in HCC and 88.9% in HCC/LT). After adjustment for confounders, the presence of HCC was associated with lower likelihood of SVR overall (AOR 0.38 [95% CI 0.29, 0.48], p<0.001). CONCLUSION: HCV can be cured with DAAs in the majority of patients with prior HCC, and in virtually all HCC patients post-liver transplant. Deferral of HCV treatment until the post-transplant setting may be considered among HCC patients listed for transplantation. LAY SUMMARY: Over three-quarters of patients with hepatocellular carcinoma who have hepatitis C can achieve viral cure with direct-acting antiviral drugs. Among patients with hepatocellular carcinoma who subsequently received liver transplantation, over 90% of patients can achieve viral cure.

Segmental Yttrium-90 Radioembolization versus Segmental Chemoembolization for Localized Hepatocellular Carcinoma: Results of a Single-Center, Retrospective, Propensity Score-Matched Study.

PURPOSE: To compare segmental radioembolization with segmental chemoembolization for localized, unresectable hepatocellular carcinoma (HCC) not amenable to ablation. MATERIALS AND METHODS: In a single-center, retrospective study (2010-2015), 101 patients with 132 tumors underwent segmental radioembolization, and 77 patients with 103 tumors underwent segmental doxorubicin-based drug-eluting embolic or conventional chemoembolization. Patients receiving chemoembolization had worse performance status (Eastern Cooperative Oncology Group 0, 76% vs 56%; P = .003) and Child-Pugh class (class A, 65% vs 52%; P = .053); patients receiving radioembolization had larger tumors (32 mm vs 26 mm; P < .001), more infiltrative tumors (23% vs 9%; P = .01), and more vascular invasion (18% vs 1%; P < .001). Toxicity, tumor response, tumor progression, and survival were compared. Analyses were weighted using a propensity score (PS). RESULTS: Toxicity rates were low, without significant differences. Index and overall complete response rates were 92% and 84% for radioembolization and 74% and 58% for chemoembolization (P = .001 and P < .001). Index tumor progression at 1 and 2 years was 8% and 15% in the radioembolization group and 30% and 42% in the chemoembolization group (P < .001). Median progression-free and overall survival were 564 days and 1,198 days in the radioembolization group and 271 days and 1,043 days in the chemoembolization group (PS-adjusted P = .002 and P = .35; censored by transplant PS-adjusted P < .001 and P = .064). CONCLUSIONS: Segmental radioembolization demonstrates higher complete response rates and local tumor control compared with segmental chemoembolization for HCC, with similar toxicity profiles. Superior progression-free survival was achieved.

Irreversible Electroporation in Patients with Hepatocellular Carcinoma: Immediate versus Delayed Findings at MR Imaging.

PURPOSE: To assess the postprocedure findings of irreversible electroporation (IRE) in patients with hepatocellular carcinoma (HCC) at magnetic resonance (MR) imaging. MATERIALS AND METHODS: This retrospective study was Institutional Review Board approved, and informed consent was waived. Twenty patients with HCC were treated with IRE over a 2.5-year period. The median patient age was 62 years, and 75% of patients had cirrhosis with a Child-Pugh score of A. The median tumor diameter was 2.0 cm (range, 1.0-3.3 cm). Contrast material-enhanced multiphase MR imaging was performed on postprocedure days 1 and 30 and every 90 days thereafter. Ablation zone sizes and signal intensities were compared between each time point for both T1- and T2-weighted images. Trends in signal intensity and tumor dimensions over time were quantified by using generalized linear models. RESULTS: MR imaging appearances of treated tumors include a zone of peripheral enhancement with centripetal filling on delayed contrast-enhanced images. Compared with postprocedure day 1, every 90 days there is a decrease of 28.9% (mean, axis) in the size of the enhancing ablation zone. Over time, there is a trend toward decreasing signal intensity in the peripheral ablation zone on both T2-weighted (P = .01) and contrast-enhanced T1-weighted (P < .08) images. Conversely, the tumor itself typically has increased signal intensity on the same sequences. CONCLUSION: IRE of HCC results in a large region of enhancement on immediate postprocedure MR images that, over time, involutes and is associated with decreasing signal intensity of the peripheral ablation zone. This phenomenon may represent resolution of the reversible penumbra.

Cone-Beam CT with Fluoroscopic Overlay Versus Conventional CT Guidance for Percutaneous Abdominopelvic Abscess Drain Placement.

PURPOSE: To compare technical success and procedure time for percutaneous abscess drain placement with fluoroscopic cone-beam computed tomography (CT) and two-axis needle guidance versus conventional CT guidance. MATERIALS AND METHODS: A total of 85 consecutive patients undergoing abdominopelvic abscess drain placement guided by fluoroscopic cone-beam CT or conventional CT were retrospectively reviewed over a 2-year period. Forty-three patients underwent drain placement with cone-beam CT using XperGuide navigation and 42 underwent placement with conventional 64-slice CT. Patient characteristics, median abscess size (6.8 cm vs 7.8 cm; P = .14), and depth to abscess (7.2 cm vs 7.7 cm; P = .88) were similar between groups. RESULTS: Technical success rates were 98% (42 of 43) in the cone-beam CT group and 100% (42 of 42) in the conventional CT group (P = .32), with a 10-F pigtail drainage catheter inserted in the majority of cases. There were no complications in either group. There was no significant difference in effective dose between groups (9.6 mSv vs 10.7 mSv; P = .30). Procedure times were significantly shorter in the cone-beam CT group (43 min vs 62 min; P = .02). In addition, during the study period, there was a gradual improvement in procedure time in the cone-beam CT group (50% reduction), whereas procedure time did not change for the conventional CT group. CONCLUSIONS: Cone-beam CT guidance appears to be equivalent to conventional CT guidance for drain placement into medium-sized abdominopelvic collections, yielding similar technical success rates and radiation doses, with the additional benefit of reduced procedure times.

Intra-Arterial Thrombolysis for Hepatic Artery Thrombosis following Liver Transplantation.

PURPOSE: Hepatic artery thrombosis (HAT) is a major cause of morbidity and death following liver transplantation. The purpose of this study was to evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) in liver transplant recipients with HAT. MATERIALS AND METHODS: Adult liver transplant recipients who underwent attempted IAT for HAT were identified. This included patients with early and late HAT (occurring less than or greater than 30 d after transplantation). Records were reviewed to determine the rates of technical success, complications, surgical revascularization, repeat liver transplantation, and ischemic cholangiopathy. RESULTS: Twenty-six patients underwent attempted thrombolysis, 13 of whom had early HAT. IAT was successfully initiated in 23 patients (88%), with a median IAT duration of 28 hours (range, 12-90 h). Recanalization was achieved in 12 patients (46%). Major complications were observed in 11 patients (42%). The early HAT group showed a trend toward increased major bleeding compared with the late HAT group (50% vs 9%; P = .07). Among 12 patients who had technically successful thrombolysis, five (42%) required surgical revascularization or repeat transplantation within 2 months. At 6 months after thrombolysis, 45% with unsuccessful recanalization avoided surgery or development of ischemic cholangiopathy, similar to the proportion in those who had successful recanalization (42%; P = .88). CONCLUSIONS: Posttransplantation hepatic artery thrombolysis yields suboptimal results with a high complication rate, especially in early HAT. Even with successful restoration of flow, clinical outcomes are poor. Although thrombolysis may still be considered in view of the limited treatment options for HAT, awareness of potential complications and suboptimal success rate is essential.

Utilization of angiography and embolization for abdominopelvic trauma: 14 years' experience at a level I trauma center.

OBJECTIVE: The objective of our study was to evaluate the long-term trends in the use of angiography and embolization for abdominopelvic injuries. MATERIALS AND METHODS: Utilization rates for pelvic and abdominal angiography, arterial embolization, and CT were analyzed for trauma patients with pelvic fractures and liver and kidney injuries admitted to a level 1 trauma center from 1996 to 2010. Multivariable linear regression was used to evaluate trends in the use of angioembolization. RESULTS: A total of 9145 patients were admitted for abdominopelvic injuries during the study period. Pelvic angiography decreased annually by 5.0% (95% CI, -6.4% to -3.7%) from 1996 to 2002 and by 1.8% (-2.4% to -1.2%) from 2003 to 2010. Embolization rates for these patients varied from 49% in 1997 to 100% in 2010. Utilization of pelvic CT on the day of admission increased significantly during this period. Abdominal angiography for liver and kidney injuries decreased annually by 3.3% (95% CI, -4.8% to -1.8%) and 2.0% (-4.3% to 0.3%) between 1996 and 2002 and by 0.8% (95% CI, -1.4% to -0.1%) and 0.9% (-2.0% to 0.1%) from 2003 to 2010, respectively. Embolization rates ranged from 25% in 1999 to 100% in 2010 for liver injuries and from 0% in 1997 to 80% in 2002 for kidney injuries. Abdominal CT for liver and kidney injuries on the day of admission also increased. CONCLUSION: A significant decrease in angiography use for trauma patients with pelvic fractures, liver injuries, and kidney injuries from 1996 to 2010 and a trend toward increasing embolization rates among patients who underwent angiography were found. These findings reflect a declining role of angiography for diagnostic purposes and emphasize the importance of angiography as a means to embolization for management.

Postembolization syndrome after hepatic transarterial chemoembolization: effect of prophylactic steroids on postprocedure medication requirements.

PURPOSE: To evaluate the impact of prophylactic use of dexamethasone and scopolamine on analgesic and antiemetic agent requirements after transarterial chemoembolization. MATERIALS AND METHODS: A total of 148 patients underwent 316 rounds of chemoembolization for hepatocellular carcinoma at a single institution over a 17-month period. Patient charts were retrospectively reviewed for demographic data, procedural technique, and use of analgesic and antiemetic medications. Patients were grouped into three categories: group A received steroid prophylaxis before and after the procedure, group B received steroid prophylaxis before the procedure only, and group C received no steroid prophylaxis. RESULTS: Analysis was performed on 125 patients undergoing 252 procedures. Demographics were similar among groups. Overall, 86 (68.8%) were male, and mean age was 62 years (range, 39-82 y). Ninety-one patients (75%) had Child-Pugh class A cirrhosis and 25% had Child-Pugh class B cirrhosis. Dexamethasone was not significantly associated with decreased analgesic agent use (P = .6). Group A patients used significantly fewer antiemetic agents (Δ = 0.89; P = .007) compared with group C. A transdermal scopolamine patch was not associated with reduced use of antiemetic agents (P = .3). Age was inversely associated with analgesic (P <.001) and antiemetic agent use (P = .004). Men received significantly fewer antiemetic agents than women (P = .002), whereas there was no significant difference in analgesic agent use (P = .7). CONCLUSIONS: The use of steroids did not affect analgesic agent use and had a minor effect on antiemetic requirements. The use of a scopolamine patch was not associated with reduced antiemetic agent use.

Frequency of external iliac artery branch injury in blunt trauma: improved detection with selective external iliac angiography.

PURPOSE: To assess the utility of selective external iliac artery (EIA) angiography and the frequency of injury to branches of the EIA in cases of blunt pelvic trauma. MATERIALS AND METHODS: A retrospective review of pelvic angiograms in 66 patients with blunt pelvic trauma was conducted over a 12-month period. Pelvic and femur fracture patterns were correlated to the presence of EIA injury. Pelvic arteriography was compared versus selective EIA angiography for the detection of arterial injury. RESULTS: Fifty-four of 66 patients (82%) exhibited pelvic arterial injury or elicited enough suspicion for injury to warrant embolization. Internal iliac artery embolization was performed in 50 of 66 (76%). EIA branch injury was identified in 11 of 66 patients (17%), and 10 were successfully embolized. EIA branch vessel injury was identified more frequently when there was ipsilateral intertrochanteric fracture (P = .07) or ipsilateral ilium fracture (P = .07). The sensitivity of nonselective pelvic angiography in the detection of EIA branch vessel injury was 45%. CONCLUSIONS: EIA branch injury occurs in a substantial fraction of patients with blunt pelvic trauma who undergo pelvic angiography. Selective EIA angiography should be considered in all patients undergoing pelvic angiography in this situation.

Safety and efficacy of drug-eluting bead chemoembolization for hepatocellular carcinoma: comparison of small-versus medium-size particles.

PURPOSE: To compare safety and imaging response with 100-300 µm and 300-500 µm doxorubicin drug-eluting bead (DEBs) to determine optimal particle size for chemoembolization of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: DEB chemoembolization using 100-300 µm (n = 39) or 300-500 µm (n = 22) LC beads loaded with 50 mg of doxorubicin was performed in 61 patients with HCC. Patient age, sex, etiology of liver disease, degree of underlying liver disease, tumor burden, and performance status were similar between the groups. All treatments were performed in a single session and represented the patient's first treatment. Toxicities and imaging response in a single index tumor were analyzed using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. RESULTS: There was a significantly lower incidence of postembolization syndrome and fatigue after treatment in the 100-300 µm group (8% and 36%) versus the 300-500 µm group (40% and 70%) (100-300 µm group, P = .011; 300-500 µm group, P = .025). Mean change in tumor size was similar between the two groups based on WHO and EASL criteria and similar rates of objective response, but there was a trend toward a higher incidence of EASL complete response with 100-300 µm beads versus 300-500 µm beads (59% vs 36%; P = .114). CONCLUSIONS: In DEB chemoembolization for treatment of HCC, 100-300 µm doxorubicin DEBs are favored over 300-500 µm doxorubicin DEBs because of lower rates of toxicity after treatment and a trend toward more complete imaging response at initial follow-up.

Characteristics and outcomes of transjugular intrahepatic portosystemic shunt recipients in the VA Healthcare System.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) placement is an effective treatment for complications of portal hypertension. We aimed to describe post-TIPS mortality and its predictors in the modern era of covered stents. PATIENTS AND METHODS: We identified patients with cirrhosis who underwent TIPS insertion at Veterans Affairs Healthcare facilities nationally from 2004 to 2014 (n=703), most of which (95%) were performed as elective procedures. We followed patients until the date of death, transplantation, or the end of the observation period. RESULTS: TIPS recipients had a mean age of 59.3 years (SD 8) and 97% were men. The mean Model for End Stage Liver Disease (MELD) score was 13 (SD 4.8); 47% had hepatitis C virus (HCV) infection, 48% had variceal hemorrhage, and 40% had ascites. During a mean follow-up of 1.72 years (SD 1.9), 57.5% of TIPS recipients died (n=404) and only 5.3% underwent liver transplantation (n=37). The median survival after TIPS was 1.74 years (interquartile range 0.3-4.7). Thirty-day mortality after TIPS was 11.6% [95% confidence interval (CI) 9.4-14.2], 1-year mortality was 40.3% (95% CI 36.7-44.2), and 3-year mortality was 61.9% (95% CI 57.9-66.0). Independent predictors of post-TIPS mortality included medical comorbidity burden, low albumin, HCV infection, and high MELD score (or high international normalized ratio and bilirubin when the components of the MELD score were analyzed individually). TIPS revision was performed at least once in 27.3% of TIPS recipients. CONCLUSION: TIPS should not be considered simply as a bridge to transplantation. Burden of extra-hepatic comorbidities, HCV infection, and low serum albumin strongly predict post-TIPS mortality in addition to the MELD score.

Traumatic renal vein pseudoaneurysm.

Traumatic renal injury is infrequent, occurring in ∼1% to 3% of trauma cases, with major renal vein injury an even more rare traumatic entity. Conservative, operative, and endovascular management strategies have been infrequently reported in the literature. We report a patient with traumatic renal vein injury with pseudoaneurysm formation that was successfully treated with endovascular stenting.

Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma and Transjugular Intrahepatic Portosystemic Shunts.

PURPOSE: Locoregional therapy for hepatocellular carcinoma (HCC) can be challenging in patients with a transjugular intrahepatic portosystemic shunt (TIPS). This study compares safety and imaging response of ablation, chemoembolization, radioembolization, and supportive care in patients with both TIPS and HCC. METHODS: This retrospective study included 48 patients who had both a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60%) underwent treatment for HCC, and 19/48 (40%) received best supportive care (i.e., symptomatic management only). While etiology of cirrhosis and indication for TIPS were similar between the two groups, treated patients had better baseline liver function (34 vs. 67% Child-Pugh class C). Tumor characteristics were similar between the two groups. A total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90 radioembolizations were performed on 29 patients. RESULTS: Ablation procedures resulted in low rates of hepatotoxicity and clinical toxicity. Post-embolization/ablation syndrome occurred more frequently in patients undergoing chemoembolization than ablation (47 vs. 15%). Significant hepatic dysfunction occurred more frequently in the chemoembolization group than the ablation group. Follow-up imaging response showed objective response in 100% of ablation procedures, 67% of radioembolization procedures, and 50% of chemoembolization procedures (p = 0.001). When censored for OLT, patients undergoing treatment survived longer than patients receiving supportive care (2273 v. 439 days, p = 0.001). CONCLUSIONS: Ablation appears to be safe and efficacious for HCC in patients with TIPS. Catheter-based approaches are associated with potential increased toxicity in this patient population. Chemoembolization appears to be associated with increased toxicity compared to radioembolization.

Proximal interruption of the pulmonary artery: Transcatheter embolization for emergent management of massive hemoptysis.

Transcatheter embolization is the first-line treatment for massive hemoptysis and recurrent intractable hemoptysis. Proximal interruption of the pulmonary artery is a rare congenital anomaly characterized by hypertrophy and neovasculsarity of bronchial and nonbronchial aortopulmonary collaterals; hemoptysis complicates a minority of cases. We present a case of unilateral proximal interruption of the left pulmonary artery associated with a right-sided aorta, presenting in adulthood with hemoptysis. The patient was managed emergently with bronchial, intercostal, and inferior phrenic artery embolization.

Hepatobiliary oncologic emergencies: imaging appearances and therapeutic options.

During the course of their disease, many patients with cancer may require urgent care related to hepatobiliary disease. Cross-sectional imaging of these patients is usually performed initially, and the radiologist plays a pivotal role in the initial diagnosis. In this article, we discuss the commonly seen hepatobiliary oncologic emergencies, briefly review imaging diagnosis, and discuss in detail the management options for these conditions. The radiologist's awareness and prompt diagnosis aid in formulating a management plan to decrease morbidity and mortality in these potentially lethal conditions.

Spontaneous regression of hepatocellular carcinoma in a cirrhotic patient: possible vascular hypothesis.

Spontaneous regression of hepatocellular carcinoma is extremely rare, and the exact pathogenesis leading to this remarkable phenomenon remains unclear. We describe a case of spontaneous regression of an incidentally discovered hepatocellular carcinoma in a 63-year-old man with hepatitis C cirrhosis. The regression followed a series of events, in particular, an upper gastrointestinal haemorrhage. Ischaemic insult may be a major pathway leading to tumour regression. As limited data is available in the literature, knowledge and recognition of this rare event will have implications for patient management and may alter treatment. Further, data may be useful to assess if these patients have an altered prognosis with improved survival.