Chang Won Kim

Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer

Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n = 30). Radiologists infused low- or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes. Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses. JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity. In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14.1 months compared to 6.7 months on the high and low dose, respectively; hazard ratio 0.39; P = 0.020). JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.

Sequential Therapy With JX-594, A Targeted Oncolytic Poxvirus, Followed by Sorafenib in Hepatocellular Carcinoma: Preclinical and Clinical Demonstration of Combination Efficacy

JX-594 is a targeted and granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. In a phase 1 trial, JX-594 injection into hepatocellular carcinoma (HCC) was well-tolerated and associated with viral replication, decreased tumor perfusion, and tumor necrosis. We hypothesized that JX-594 and sorafenib, a small molecule inhibitor of B-raf and vascular endothelial growth factor receptor (VEGFR) approved for HCC, would have clinical benefit in combination given their demonstrated efficacy in HCC patients and their complementary mechanisms-of-action. HCC cell lines were uniformly sensitive to JX-594. Anti-raf kinase effects of concurrent sorafenib inhibited JX-594 replication in vitro, whereas sequential therapy was superior to either agent alone in murine tumor models. We therefore explored pilot safety and efficacy of JX-594 followed by sorafenib in three HCC patients. In all three patients, sequential treatment was (i) well-tolerated, (ii) associated with significantly decreased tumor perfusion, and (iii) associated with objective tumor responses (Choi criteria; up to 100% necrosis). HCC historical control patients on sorafenib alone at the same institutions had no objective tumor responses (0 of 15). Treatment of HCC with JX-594 followed by sorafenib has antitumoral activity, and JX-594 may sensitize tumors to subsequent therapy with VEGF/VEGFR inhibitors.

Evaluation of unusual causes of pancreatitis: role of cross-sectional imaging.

There are widely diverse causes of pancreatitis. Gallstone and alcohol have been recognized as the most common causes of pancreatitis accounting for 90% of cases. However, acute and chronic pancreatitis may also result from a variety of uncommon causes. The determination of the etiology is important for patient management and prevention of recurrence. Sludge is the most common cause of idiopathic or recurrent acute pancreatitis. Endoscopic ultrasonography is considered as the most accurate diagnostic test for this abnormality. Computed tomography (CT) and magnetic resonance imaging (MRI) have only a limited role in the diagnosis of sludge. However, papillitis observed on the contrast-enhanced CT and MR may provide clues to the detection of pancreatitis secondary to sludge, a small stone or a recently passed stone. Radiological studies, clinical presentation and laboratory data can be helpful in determining the etiology of unusual causes of pancreatitis such as anatomic anomalies, autoimmune pancreatitis, groove pancreatitis, and traumatic pancreatitis.

Discrimination of suppurative cholangitis from nonsuppurative cholangitis with computed tomography (CT).

PURPOSEnSuppurative cholangitis is characterized by obstruction, inflammation, and pyogenic infection of the biliary tract. This disease represents a true emergency. The purpose of this study was to compare the computed tomography (CT) findings between acute calculous suppurative and nonsuppurative cholangitis and to determine if there are findings that assist in the differential diagnosis.nnnMATERIALS AND METHODSnFifteen patients with acute suppurative cholangitis were enrolled in this study. Findings at endoscopic retrograde cholangiopancreaticography (ERCP) were the standard of reference for suppurative cholangitis. To compare the findings of suppurative cholangitis with those of nonsuppurative cholangitis, 35 patients with nonsuppurative cholangitis were randomly selected. The following findings were evaluated: the presence of papillitis, the presence of stones in the ampulla, the presence of intrahepatic stones, the presence of early inhomogeneous enhancement of the liver, the degree of bile duct dilatation, the degree of bile duct wall thickening and presence of cholecystitis. Sensitivity and specificity for each of the individual findings were calculated. Statistical analyses were performed the Pearson chi(2) test, Fishers exact test and the Mann-Whitney U test.nnnRESULTSnPapillitis showed the highest specificity 86% with 60% sensitivity. Marked inhomogeneous enhancement of the liver during the arterial phase showed 80% specificity with 60% sensitivity. In multivariate logistic analysis, papillitis and marked early inhomogeneous enhancement of the liver were the most significant predictors of acute suppurative cholangitis. The combination of these two CT findings improved specificity (97% specificity) for the diagnosis of suppurative cholangitis.nnnCONCLUSIONnPapillitis and marked early inhomogeneous enhancement of the liver were found to be the most discriminative CT findings for the diagnosis of acute suppurative cholangitis and the differentiation between suppurative and nonsuppurative cholangitis.

Postpartum hemorrhage: Clinical and radiologic aspects

Postpartum hemorrhage (PPH) is a potentially life threatening condition, and it remains the leading cause of maternal morbidity. Uterine atony, lower genital tract lacerations, uterine rupture or inversion, retained products of conception and underlying coagulopathy are some of the common causes of PPH. Most conditions can be diagnosed based on clinical and laboratory evaluation supplemented by ultrasound information. Computed tomography (CT) or magnetic resonance (MR) imaging can provide information for the detection, localization and characterization of PPH in some difficult cases. CT can accurately demonstrate the anatomic location of significant arterial hemorrhage as sites of intravenous contrast material extravasation, which can be as a guide for angiographic intervention. The presence of focal or diffuse intravenous contrast extravasation or a hematoma within the enlarged postpartum uterine cavity on CT can help the diagnosis of uterine atony when the clinical diagnosis of uterine atony is unclear. CT can also provide the information of other alternative conditions such as a puerperal genital hematoma, uterine rupture and concealed hematoma in other sites. MR imaging may be considered as a valuable complement to ultrasound where the ultrasound findings are inconclusive in the diagnosis and differential diagnosis of retained products of conception. Knowledge of the various radiologic appearances of PPH and the correlation with clinical information can ensure correct diagnosis and appropriate and prompt treatment planning in the patients with PPH.

Reconstructive treatment using a stent graft for a dural arteriovenous fistula of the transverse sinus in the case of hypoplasia of the contralateral venous sinuses: technical case report.

OBJECTIVETransvenous coil embolization for transverse sinus (TS) and sigmoid sinus dural arteriovenous fistulae (DAVFs) is now recognized as one of the most effective treatment modalities. However, in the case of hypoplasia of the contralateral venous sinuses and internal jugular vein, complete occlusion of the ipsilateral sinus may cause fatal consequences. We describe a case of combined intravenous graft stent placement and transarterial coil embolization for DAVFs that involved the dominant right TS in a patient with hypoplasia of the contralateral venous sinuses. CLINICAL PRESENTATIONA 50-year-old man presented with headache, left hand tremor, and pulsatile right tinnitus. A cerebral angiogram demonstrated a right TS DAVF that was supplied by tentorial branches of both internal carotid arteries, multiple branches of the right external carotid artery, and branches of the left occipital artery. Unfortunately, left TS and sigmoid sinus hypoplasia were observed. INTERVENTIONA right TS balloon occlusion test revealed contrast stagnation of the cortical veins and of the right TS and superior sagittal sinus. In this case, the use of transvenous stent graft placement with or without transarterial embolization is safer and more effective than sacrifice of the right TS. We therefore performed balloon-expandable stent graft deployment at the right TS, and the remnant DAVF flow between the stent graft and venous sinus was treated with transarterial coil embolization. Postprocedural angiograms showed patent right TS outflow with disappearance of retrograde cortical venous drainage as well as complete eradication of the fistulous connections. CONCLUSIONIn a DAVF involving the dominant TS or sigmoid sinus in a patient with hypoplasia of the contralateral venous sinuses and an intolerable balloon occlusion test for the ipsilateral venous sinuses, the complete occlusion of the diseased venous sinus may cause hazardous consequences. In this situation, the use of a stent graft with or without transarterial embolization to preserve venous sinus flow can be an effective treatment.

Endovascular Graft-Stent Placement for Treatment of Traumatic Carotid Cavernous Fistulas

Detachable balloon-based endovascular fistula occlusion is a widely accepted treatment for traumatic carotid cavernous fistulas (CCF). However, more recently coils have been used to obliterate the lesion, especially in case detachable balloon is not available. We failed balloon-assisted coil embolization for CCF because of large fistulas and herniation of coil loops into the parent artery. The authors describe our experiences of balloonexpandable graft-stents to treat CCF, and place emphasis on arterial wall reconstruction. Three traumatic CCF patients were treated using a graft-stent with/without coils, and underwent angiographic follow-up to evaluate the patency of the internal carotid artery (ICA). In all cases, symptoms related to CCF regressed after stent deployment and did not recur during follow-up. Follow-up angiography revealed good patency of the ICA in all patients. Graft-stents should be considered as an alternative means of treating CCF and preserving the parent artery by arterial wall reconstruction especially in patients with a fistula that cannot be successfully occluded with detachable balloons or coils.

Assessment of the Intracranial Stents Patency and Re-Stenosis by 16-Slice CT Angiography with Optimized Sharp Kernel : Preliminary Study

OBJECTIVEnOur retrospective study aimed to determine whether 16-slice computerized tomography (CT) angiography optimized sharp kernel is suitable for the evaluation of visibility, luminal patency and re-stenosis of intracranial stents in comparison with conventional angiography.nnnMETHODSnFifteen patients with symptomatic intracranial stenotic lesions underwent balloon expandable stent deployment of these lesions (10 middle cerebral arteries, 2 intracranial vertebral arteries, and 3 intracranial internal carotid arteries). CT angiography follow-up ranged from 6 to 15 months (mean follow-up, 8 months) after implantation of intracranial stents and conventional angiography was confirmed within 2 days. Curved multiplanar reformations with maximal intensity projection (MIP) with optimal window settings for assessment of lumen of intracranial stents were evaluated for visible lumen diameter, stent patency (contrast distal to the stent as an indirect sign), and re-stenosis by two experienced radiologists who blinded to the reports from the conventional angiography.nnnRESULTSnAll of stents deployed into symptomatic stenotic lesions. All stents were classified as patent and no re-stenosis, which was correlated with results of conventional angiography. Parts of the stent lumen could be visualized in all cases. On average, 57% of the stent lumen diameter was visible using optimized sharp kernel. Significant improvement of lumen visualization (22%, p<0.01) was observed using the optimized sharp kernel compared with the standard sharp kernel. Inter-observer agreements on the measurement of lumen diameter and density were judged as good, respectively (p<0.05).nnnCONCLUSIONnSixteen-slice CT using the optimized sharp kernel may provide a useful information for evaluation of lumen diameter patency, and re-stenosis of intracranial stents.

Image quality and radiation dose of 128-slice dual-source CT venography using low kilovoltage combined with high-pitch scanning and automatic tube current modulation

To compare vascular enhancement, image quality, and radiation dose of 128-slice dual-source CT venography (CTV) between an imaging setting of 120xa0kVp with low pitch, and a setting of 100xa0kVp combined with high pitch and automatic tube current modulation. A total of 100 patients with suspected deep vein thrombosis and varicose veins were divided into two groups: Group 1 [50 patients, 120xa0kVp, low pitch (0.6), and fixed 120xa0mA) and Group 2 (50 patients, 100xa0kVp, high pitch (3.0), and automatic tube current modulation]. Two radiologists, who were blinded to the image protocol, assessed vascular enhancement and image noise in the inferior vena cava (IVC), femoral vein, and popliteal vein. They also assigned an image quality score independently using a 5-point visual scale. Effective dose was estimated using the dose-length product (DLP). Group demographics, radiation dose, vascular enhancement, image noise, and image quality in the two groups were analyzed. Mean vascular enhancement of the IVC, femoral vein, and popliteal vein was significantly higher in group 2 than in group 1, and images in group 2 had significantly higher image noise. However, there were no significant differences in subjective image quality score of the IVC, femoral vein, and popliteal vein. The mean DLP in group 2 (402.10xa0±xa094.29xa0mGyxa0cm) was significantly lower than that in group 1 (973.36xa0±xa063.20xa0mGyxa0cm) (Pxa0<xa00.001). Lower extremity CTV using 100xa0kVp, high pitch (3.0), and automatic tube current modulation improved vascular enhancement with acceptable image quality and low radiation dose.

Effect of yttrium-90 radioembolization on outcomes in Asian patients with early to advanced stage hepatocellular carcinoma.

The aim of this study was to investigate the effect of yttrium‐90 radioembolization on the outcome of Asian patients with early to advanced stage hepatocellular carcinoma (HCC).