Guy E. Johnson

Cloning of a Phosphatidic Acid-preferring Phospholipase A1 from Bovine Testis

We report the molecular cloning and expression of a phosphatidic acid-preferring phospholipase A1 from bovine testis. The open reading frame encoded an 875-amino acid protein with a calculated molecular mass of 97,576 daltons and a pI of 5.61. The sequence included a region similar to a lipase consensus sequence containing the putative active site serine and also included a potential, coiled-coil-forming region. Expression of the open reading frame in COS1 cells resulted in a 20–44-fold increase in phosphatidic acid phospholipase A1 activity over that of control cells. Mutation of the putative active site serine (amino acid 540) demonstrated that it was essential for this increase in enzyme activity. Northern blot analysis revealed at least five different messages with the highest overall message levels in mature testis, but detectable message in all tissues examined. Two possible alternately spliced regions in the open reading frame also were identified. Finally, a search of the data base identified six related proteins: a potential counterpart of the phospholipase A1 inCaenorhabditis elegans, two putative lipases in yeast, and three proteins separately encoded by the Drosophila retinal degeneration B gene and its mouse and human homologues.

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.

Nontarget Embolization Complicating Transarterial Chemoembolization in a Patient with Hepatocellular Carcinoma

Nontarget embolization during transarterial chemoembolization, although infrequent, can be a serious complication. The authors describe a case of nontarget gastric embolization to the stomach after transarterial chemoembolization and describe the published incidence of nontarget embolization to various organs, its diagnosis, treatment, and possible outcomes.

Yttrium-90 Radioembolization as a Salvage Treatment following Chemoembolization for Hepatocellular Carcinoma

PURPOSE To determine safety and efficacy of yttrium-90 ((90)Y) transarterial radioembolization (TARE) in patients who have undergone chemoembolization for hepatocellular carcinoma. MATERIALS AND METHODS A retrospective study identified 40 patients (median age 61 y; range, 44-84 y) who underwent (90)Y mapping angiography and had undergone ≥ one prior chemoembolizations. There were 4 (10%) patients in Barcelona Clinic Liver Cancer stage A, 7 (17.5%) in stage B, and 29 (72.5%) in stage C; 28 (70%) were Child-Pugh class A and 12 (30%) were class B. Median tumor diameter was 4.2 cm (range, 1-11.6 cm). The most common indications for changing to TARE were tumor progression (35/40; 86%) and development of portal vein thrombus (15/40; 37.5%). RESULTS Of 40 patients, 29 (72.5%) underwent TARE; the most common reasons for not undergoing TARE were attenuated hepatic arteries (5/11), high pulmonary shunt (4/11), and poor arterial flow (2/11). Patients who underwent ≤ 4 chemoembolizations to the TARE target tended to be more likely to undergo TARE after mapping than patients who had > 4 chemoembolizations (P = .056). Most common grade ≥ 3 toxicities were fatigue (9/29; 31%) and biochemical alterations (bilirubin [3/29; 10.3%], albumin [4/29; 13.8%], aspartate aminotransferase [5/29; 17.2%]). Of 27 patients treated with TARE with follow-up, responses were 11 (41%) complete response, 5 (19%) partial response, 2 (7%) stable disease, and 9 (33%) progressive disease. Median progression-free survival and overall survival were 90 days and 257 days. CONCLUSIONS TARE is safe and effective salvage therapy in patients after chemoembolization. In patients who have undergone > 4 chemoembolizations to the (90)Y target, feasibility of TARE tends to be decreased.

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.

Hepatic abscess complicating transarterial chemoembolization in a patient with liver metastases

Hepatic abscess following transarterial chemoembolization is an uncommon complication. The authors describe a case of liver abscess after transarterial chemoembolization for neuroendocrine liver metastases, including risk factors, prophylaxis, treatment, and outcomes.

Safety and Efficacy Outcomes of Embolization in Hepatic Sarcomas

OBJECTIVE The outcome for patients with unresectable hepatic sarcoma is poor with a median survival period of 12-16 months. The purpose of this study was to evaluate liver-directed transcatheter therapies for the treatment of hepatic sarcomas. MATERIALS AND METHODS In a retrospective study, the cases of patients with primary and metastatic hepatic sarcoma treated by transcatheter embolization, chemoembolization, and 90Y radioembolization between 2004 and 2015 were identified. Response Evaluation Criteria in Solid Tumors version 1.1 response was assessed for the target tumor. Survival was assessed by means of Kaplan-Meier analysis. RESULTS Twenty-eight patients (17 [61%] men, 11 [39%] women; median age, 47 years) were included. Eighteen patients were treated electively. Two of the electively treated patients underwent embolization; eight, chemoembolization; six, radioembolization; and two, a combination of transcatheter treatments. Treatment was well tolerated; only one patient had grade 3 hepatic toxicity. The objective response rate of the index tumor was 61%, and the median overall survival period was 26.7 months. Ten patients underwent emergency embolization to control acute hemorrhage from tumor rupture. The median overall survival periods were 611 days for the patients with ruptured gastrointestinal stromal tumors (GIST) (n = 3) and 19 days for the patients with ruptured angiosarcoma (n = 7). CONCLUSION Liver-directed transcatheter therapies are safe and may have a role in the elective management of unresectable primary and metastatic liver sarcomas. Emergency embolization for ruptured GIST may be effective for stabilizing the patients condition and allowing more definitive therapy in the future. However, emergency embolization has limited efficacy in treating patients with ruptured angiosarcoma, likely because of substantial venous bleeding at rupture and the aggressive behavior of this lesion.

An Interventionist’s Guide to Endocrine Consultations

Endocrinopathies are a heterogeneous group of disorders often resulting from pathologic sources of hormone production. When the clinical scenario, laboratory testing, and noninvasive imaging fail to aid confident identification of the source of hormone excess, endocrine venous sampling may localize obscure lesions to guide subsequent treatment. Knowledge of basic hormone signaling pathways, common pathophysiologic disruptions of these pathways, and serologic evaluation fosters informed conversations with referring physicians and effective patient selection. Success in the angiography suite requires familiarity with normal and variant anatomy of the multiple organs of the endocrine system, patient preparation, stimulation and sampling techniques, specimen handling, and results interpretation. ©RSNA, 2017.

Radiofrequency hyperthermia-enhanced herpes simplex virus-thymidine kinase/ganciclovir direct intratumoral gene therapy of hepatocellular carcinoma

Abstract Purpose: To determine the feasibility of using radiofrequency hyperthermia (RFH) and to enhance the therapeutic effect of herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) for the treatment of hepatocellular carcinoma (HCC). Materials and methods: Human HCC cells (HepG2) were first transfected with lentivirus/luciferase. For both in vitro confirmation and in vivo validation, luciferase-labeled HCC cells and HCC tumour xenografts on mice received different treatments: (i) combination therapy of intratumoral HSV-TK/GCV-mediated gene therapy plus magnetic resonance imaging heating guidewire (MRIHG)-mediated RFH; (ii) gene therapy only; (iii) RFH only; and (iv) phosphate-buffered saline (PBS) as control. Cell proliferation was quantified. Tumour changes were monitored by ultrasound imaging and bioluminescence optical imaging before and at days 7 and 14 after treatments, which were correlated with subsequent histology. Results: In vitro, the lowest cell proliferation was seen in the combination therapy group compared with control groups (29 ± 6% vs. 56 ± 9%, 93 ± 4%, and 100 ± 5%, p < .05). Ultrasound imaging of treated animal xenografts showed smaller relative tumour volume in combination therapy group than those in three control groups (0.74 ± 0.19 vs. 1.79 ± 0.24, 3.14 ± 0.49 and 3.22 ± 0.52, p < .05). Optical imaging demonstrated significant decrease of bioluminescence signals of tumours in the combination therapy group, compared to those in three control groups (1.2 ± 0.1 vs. 1.9 ± 0.2% vs. 3.3 ± 0.6% vs. 3.5 ± 0.4%, p < .05). These imaging findings were correlated well with histologic confirmation. Conclusion: RFH can enhance HSV-TK/GCV-mediated gene therapy of HepG2 cell line and mice human HCC xenografts, which may open new avenues for effective management of HCC using MR/RFH integrated interventional gene therapy.