Paul J. Rochon

The Inhibition of Apoptosis in Myositis and in Normal Muscle Cells

The mechanism of injury and death of muscle cells in the inflammatory myopathies (dermatomyositis, polymyositis, and inclusion body myositis) remains obscure. We and others have not detected apoptosis in the muscle biopsies from patients with myositis despite clear evidence of cell damage and loss. We provide evidence in this study that Fas ligand (FasL) as well as Fas is present on muscle cells and inflammatory cells in myositis biopsies: Fas is present on most muscle cells and lymphocytes, and FasL is present on degenerating muscle cells and many infiltrating mononuclear cells. The expression of both Fas and FasL in the inflamed tissue makes the absence of apoptosis more striking. To address the mechanisms of this resistance to classical apoptosis in muscle cells, we have investigated the expression of the antiapoptotic molecule FLICE (Fas-associated death domain-like IL-1-converting enzyme)-inhibitory protein (FLIP) in muscle biopsies of myositis patients and in cultured human skeletal muscle cells. Using laser capture microscopy, we have shown that FLIP is expressed in the muscle fibers and on infiltrating lymphocytes of myositis biopsies. Furthermore, we have shown that FLIP, but not Bcl-2, is expressed in cultured human skeletal muscle cells stimulated with proinflammatory cytokines, and inhibition of FLIP with antisense oligonucleotides promotes significant cleavage of poly(ADP-ribose) polymerase autoantigen, a sensitive indicator of apoptosis. These studies strongly suggest that the resistance of muscle to Fas-mediated apoptosis is due to the expression of FLIP in muscle cells in the inflammatory environment in myositis.

Endovascular Treatment of Visceral and Renal Artery Aneurysms

PURPOSE To analyze early and midterm results of endovascular treatment of visceral aneurysms regarding technical considerations, technical success rate, aneurysm rupture, and end-organ ischemia. MATERIALS AND METHODS Endovascular treatment of 41 visceral and renal artery aneurysms (VAAs) in 40 consecutive patients (25 women; mean age, 59.4 y ± 16.2) was retrospectively reviewed. The series included 30 true aneurysms and 11 pseudoaneurysms in renal (n = 17), splenic (n = 13), hepatic (n = 4), celiac (n = 4), gastroduodenal (n = 2), and middle colic (n = 1) arteries. Demographic, clinical, procedural, and follow-up data were analyzed. RESULTS Forty-one aneurysms underwent endovascular treatment. Hypertension (73%) and hyperlipidemia (32%) were the most common associated comorbidities. Nineteen patients presented with symptoms of pain (15%) or rupture (32%) in 10 pseudoaneurysms (91%) and nine true aneurysms (30%; P = .0007). The most commonly used technique (93%) was coil embolization with (15%) or without (78%) other endovascular agents. The rate of technical success (cessation of hemorrhage or blood flow into aneurysm sac) was 98%. There was no periprocedural mortality. Mean hospital stays were 1 and 2 days for asymptomatic and symptomatic patients, respectively. Mean clinical follow-up was 44.5 months; mean imaging follow-up was 11.7 months. The only complication was an intraprocedural thromboembolic event in one case (3%). Follow-up imaging evidence of end-organ partial infarct was detected in six patients (21%), with no clinical evidence of organ insufficiency. CONCLUSIONS Endovascular treatment of VAAs is a safe and highly successful procedure. Associated side effects such as distal embolization and end-organ infarcts were not found to be clinically significant.

Metaanalysis of survival, complications, and imaging response following chemotherapy-based transarterial therapy in patients with unresectable intrahepatic cholangiocarcinoma.

PURPOSE Unresectable intrahepatic cholangiocarcinoma represents a devastating illness with poor outcomes when treated with standard systemic therapies. Several smaller nonrandomized outcomes studies have been reported for such patients undergoing transarterial therapies. A metaanalysis was performed to assess primary clinical and imaging outcomes, as well as complication rates, following transarterial interventions in this patient population. MATERIALS AND METHODS By using standard search techniques and metaanalysis methodology, published reports (published in 2012 and before) evaluating survival, complications, and imaging response following transarterial treatments for patients with unresectable intrahepatic cholangiocarcinoma were identified and evaluated. RESULTS A total of 16 articles (N = 542 subjects) met the inclusion criteria and are included. Overall survival times were 15.7 months ± 5.8 and 13.4 months ± 6.7 from the time of diagnosis and time of first treatment, respectively. The overall weighted 1-year survival rate was 58.0% ± 14.5. More than three fourths of all subjects (76.8%) exhibited a response or stable disease on postprocedure imaging; 18.9% of all subjects experienced severe toxicities (National Cancer Institute/World Health Organization grade ≥ 3), and most experienced some form of postembolization syndrome. Overall 30-day mortality rate was 0.7%. CONCLUSIONS As demonstrated by this metaanalysis, transarterial chemotherapy-based treatments for cholangiocarcinoma appears to confer a survival benefit of 2-7 months compared with systemic therapies, demonstrate a favorable response by imaging criteria, and have an acceptable postprocedural complication profile. Such therapies should be strongly considered in the treatment of patients with this devastating illness.

Survival Outcomes in Patients With Advanced Hepatocellular Carcinoma Treated With Drug-Eluting Bead Chemoembolization

OBJECTIVE. The purpose of this study was to determine the overall survival rates in patients with advanced hepatocellular carcinoma (HCC) who undergo treatment with drug-eluting bead (DEB) therapy. MATERIALS AND METHODS. A retrospective review of the clinical HCC database of a single institution was undertaken for patients treated between September 2008 and December 2011. Demographic information, laboratory and imaging findings, procedural details, and outcomes after treatment were obtained. The primary outcome was overall survival, which was stratified by Barcelona Clinic Liver Cancer (BCLC) stage, Child-Pugh class, Eastern Cooperative Oncology Group (ECOG) score, serum bilirubin level, and ethnicity. Multiple secondary independent variables were also measured. RESULTS. Of 239 consecutive patients treated during the prescribed time frame, 43 patients met the inclusion criteria. Thirty patients met the criteria for BCLC stage C, and 13 met the criteria for BCLC stage D based largely on ECOG score. Eight patients had venous invasion or portal venous thrombosis, and four had limited extrahepatic metastases. Eight patients had Child-Pugh class C liver disease but remained candidates for liver transplant based on the Milan criteria. The median overall survival was 596 days; 23 patients are still alive, 12 of whom underwent liver transplant. The only independent variables affecting survival were serum bilirubin value of 2.0 mg/dL or greater (hazard ratio [HR] = 3.96; 95% CI, 1.46-10.7; p = 0.007) and Child-Pugh class B or C disease (HR = 3.33; 95% CI, 1.07-10.34; p = 0.037). CONCLUSION. The use of DEBs for TACE therapy is safe and effective in carefully selected patients with advanced HCC.

Intravascular US–Guided Portal Vein Access: Improved Procedural Metrics during TIPS Creation

PURPOSE To evaluate transjugular intrahepatic portosystemic shunt (TIPS) outcomes and procedure metrics with the use of three different image guidance techniques for portal vein (PV) access during TIPS creation. MATERIALS AND METHODS A retrospective review of consecutive patients who underwent TIPS procedures for a range of indications during a 28-month study period identified a population of 68 patients. This was stratified by PV access techniques: fluoroscopic guidance with or without portography (n = 26), PV marker wire guidance (n = 18), or intravascular ultrasound (US) guidance (n = 24). Procedural outcomes and procedural metrics, including radiation exposure, contrast agent volume used, procedure duration, and PV access time, were analyzed. RESULTS No differences in demographic or procedural characteristics were found among the three groups. Technical success, technical success of the primary planned approach, hemodynamic success, portosystemic gradient, and procedure-related complications were not significantly different among groups. Fluoroscopy time (P = .003), air kerma (P = .01), contrast agent volume (P = .003), and total procedural time (P = .02) were reduced with intravascular US guidance compared with fluoroscopic guidance. Fluoroscopy time (P = .01) and contrast agent volume (P = .02) were reduced with intravascular US guidance compared with marker wire guidance. CONCLUSIONS Intravascular US guidance of PV access during TIPS creation not only facilitates successful TIPS creation in patients with challenging anatomy, as suggested by previous investigations, but also reduces important procedure metrics including radiation exposure, contrast agent volume, and overall procedure duration compared with fluoroscopically guided TIPS creation.

ACR appropriateness criteria radiologic management of benign and malignant biliary obstruction

The optimal treatment for patients with biliary obstruction varies depending on the underlying cause of the obstruction, the clinical condition of the patient, and anticipated long-term effects of the procedure performed. Endoscopic and image-guided procedures are usually the initial procedures performed for biliary obstructions. Various options are available for both the radiologist and endoscopist, and each should be considered for any individual patient with biliary obstruction. This article provides an overview of the current status of radiologic procedures performed in the setting of biliary obstruction and describes multiple clinical scenarios that may be treated by radiologic or other methods. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria® Radiologic Management of Mesenteric Ischemia

Mesenteric vascular insufficiency is a serious medical condition that may lead to bowel infarction, morbidity, and mortality that may approach 50%. Recommended therapy for acute mesenteric ischemia includes aspiration embolectomy, transcatheter thrombolysis, and angioplasty with or without stenting for the treatment of underlying arterial stenosis. Nonocclusive mesenteric ischemia may respond to transarterial infusion of vasodilators such as nitroglycerin, papaverine, glucagon, and prostaglandin E1. Recommended therapy for chronic mesenteric ischemia includes angioplasty with or without stent placement and, if an endovascular approach is not possible, surgical bypass or endarterectomy. The diagnosis of median arcuate ligament syndrome is controversial, but surgical release may be appropriate depending on the clinical situation. Venous mesenteric ischemia may respond to systemic anticoagulation alone. Transhepatic or transjugular superior mesenteric vein catheterization and thrombolytic infusion can be offered depending on the severity of symptoms, condition of the patient, and response to systemic anticoagulation. Adjunct transjugular intrahepatic portosystemic shunt creation can be considered for outflow improvement. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Role of Interventional Radiologists in the Management of Lower Extremity Venous Insufficiency

Lower extremity venous insufficiency affects over half of all women. Interventional radiologists should be aware of the clinical evaluation of women with venous insufficiency and classification of disease. Endovascular therapies available for treatment of lower extremity venous insufficiency include: endovenous laser ablation, radiofrequency endovascular ablation, and sclerotherapy. The interventional radiologist should be versed on which therapy to select in each clinical presentation and the procedural techniques. The authors review the role of the interventional radiologist in managing this lower extremity venous disorder.

Preservation of Internal Iliac Arterial Flow during Endovascular Aortic Aneurysm Repair Using the “Sandwich” Technique

Conventional endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm (AAA) requires adequate graft seal proximally in the infrarenal aorta and distally in the common or external iliac arteries. When possible, sealing in the common iliac artery is performed to maintain perfusion to the internal iliac artery. Approximately 40% of AAAs have associated common iliac artery aneurysms that would require an external iliac seal zone and ipsilateral internal iliac artery embolization to prevent a type II endoleak. Concurrent or staged internal iliac artery occlusion may result in pelvic ischemia, which commonly manifests as buttock claudication or, in men, impotence. Uncommon but more serious consequences include colonic and spinal artery ischemia. Coverage or embolization of a single internal iliac artery is generally well tolerated. There is a varied incidence (20 to 50%) of clinically significant buttock claudication that tends to improve over time resulting in ∼10% incidence of buttock claudication at 1 year with single hypogastric artery embolization. Published case series and individual reports of bilateral internal iliac artery embolization demonstrate that bilateral hypogastric occlusion appears safe, although there is an increased risk of serious complications that may be life threatening. Most physicians attempt to preserve flow to a single internal iliac artery whenever possible. Various methods have been described to preserve internal iliac artery flow during EVAR. Investigational iliac branched devices (not currently approved by the Food and Drug Administration [FDA]), hybrid surgical revascularization of the internal iliac artery, physician modification of existing endografts, and, more recently, parallel endografting with the “sandwich” technique are some of the ways flow can be preserved to the hypogastric artery. The sandwich endograft technique involves placing two endografts side by side into an existing iliac limb to create an off-the-shelf bifurcated component to preserve flow to both the internal iliac and external iliac arteries. This technique has been gaining acceptance as a viable method for preservation of flow to at least a single internal iliac artery allowing for expansion of anatomy suitable for EVAR with the use of commercially available endograft components, albeit in an off-label manner. The sandwich technique is applicable to a variety of endograft designs, although the steep bifurcation of most endografts requires axillary or brachial artery access to deliver a stent into the preserved internal iliac artery. The bifurcation-sparing nature of the Endologix AFX (Endologix, Irvine, CA) endograft allows for this technique to be performed from an entirely femoral approach and has become our preferred approach for internal iliac preservation during EVAR when the anatomy is appropriate.

National Trends and Outcomes of Transjugular Intrahepatic Portosystemic Shunt Creation Using the Nationwide Inpatient Sample

PURPOSE To elucidate trends in transjugular intrahepatic portosystemic shunt (TIPS) use and outcomes over the course of a decade, including predictors of inpatient mortality and extended length of hospital stay. MATERIALS AND METHODS The Nationwide Inpatient Sample was interrogated for the most recent 10 years available: 2003-2012. TIPS procedures and associated diagnoses were identified via International Classification of Diseases (version 9) codes, with the latter categorized into primary diagnoses in a hierarchy of disease severity. Linear regression analysis was used to determine trends of TIPS use and outcomes over time. Independent predictors of mortality and extended length of stay were determined by logistic regression. RESULTS A total of 55,145 TIPS procedures were captured during the study period. Annual procedural volume did not change significantly (5,979 in 2003, 5,880 in 2012). The majority of TIPSs were created for ascites and/or varices (84%). Inpatient mortality (12.5% in 2003, 10.6% in 2012; P < .05) decreased but varied considerably by diagnosis (from 3.7% to 59.3%), with a disparity between bleeding and nonbleeding varices (18.7% vs 3.8%; P < .01). Multivariate predictors of mortality (P < .001 for all) included primary diagnoses (bleeding varices, hepatorenal and abdominal compartment syndromes), patient characteristics (age > 80 y, black race), and sequelae of advanced cirrhosis (comorbid hepatocellular carcinoma, spontaneous bacterial peritonitis, encephalopathy, and coagulopathy). CONCLUSIONS National TIPS inpatient mortality has decreased since 2003 while procedural volume has not changed. Postprocedural outcome is a function of patient demographic and socioeconomic factors and associated diagnoses. Independent predictors of poor outcome identified in this large national population study may aid clinicians in better assessing preprocedural risk.