The value of interventional radiology in clinical trial teams: experience from the BATTLE lung cancer trials.

AIM: To report on the multidisciplinary approach, focusing specifically on the role of the interventional radiologist (IR), used to support the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) and BATTLE-2 trials. MATERIALS AND METHODS: Patients who underwent percutaneous image-guided biopsy for the BATTLE and BATTLE-2 trials were reviewed. A radiology-based, three-point, lesion-scoring system was developed and used by two IRs. Lesions were given a score of 3 (most likely to yield sufficient material for biomarker analysis) if they met the following criteria: size >2 cm, solid mass, demonstrated imaging evidence of viability, and were technically easy to sample. Lesions not meeting all four criteria were scored 2 with the missing criteria noted as negative factors. Lesions considered to have risks that outweighed potential benefits receive a score of 1 and were not biopsied. Univariate and multivariate analyses were performed to evaluate the score's ability to predict successful yield for biomarker adequacy. RESULTS: A total of 555 biopsies were performed. The overall yield for analysis of the required biomarkers was 86.1% (478/555), and 84% (268/319) and 88.9% (210/236) for BATTLE and BATTLE-2, respectively (p=0.09). Lesions receiving a score of 3 were adequate for biomarker analysis in 89% of cases. Lesions receiving a score of 2 with more than two negative factors were adequate for molecular analysis in 69.2% (IR1, p=0.03) and 74% (IR2, p=0.04) of cases. The two IRs scored 78.4% of the lesions the same indicating moderate agreement (kappa=0.55; 95% confidence interval [CI]: 0.48, 0.61). CONCLUSIONS: IRs add value to clinical trial teams by optimising lesions selected for biopsy and biomarker analysis.

Embryonic origin of primary colon cancer predicts survival in patients undergoing ablation for colorectal liver metastases.

BACKGROUND: In patients with primary colorectal cancer (CRC) or unresectable metastatic CRC, midgut embryonic origin is associated with worse prognosis. The impact of embryonic origin on survival after ablation of colorectal liver metastases (CLM) is unclear. METHODS: We identified 74 patients with CLM who underwent percutaneous ablation during 2004-2015. Survival and recurrence after ablation of CLM from midgut origin (n = 18) and hindgut origin (n = 56) were analyzed. Prognostic value of embryonic origin was evaluated. RESULTS: Recurrence-free survival (RFS) and overall survival (OS) after percutaneous ablation were worse in patients from midgut origin (3-year RFS: 5.6% vs. 24%, P = 0.004; 3-year OS: 25% vs. 70%, P 0.001). In multivariable analysis, factors associated with worse OS were midgut origin (hazard ratio [HR] 4.87, 95% CI 2.14-10.9, P 0.001), multiple CLM (HR 2.35, 95% CI 1.02-5.39, P = 0.044), and RAS mutation (HR 2.78, 95% CI 1.25-6.36, P = 0.013). At a median follow-up of 25 months, 56 patients (76%) had developed recurrence, 16 (89%) with midgut origin and 40 (71%) with hindgut origin (P = 0.133). Recurrent disease was treated with local therapy in 20 patients (36%), 2 (13%) with midgut origin and 18 (45%) with hindgut origin (P = 0.022). CONCLUSION: Compared to CLM from hindgut origin tumors, CLM from midgut origin tumors were associated with worse survival after ablation, which was partly attributable to the fact that patients with hindgut origin were more frequently candidates for local therapy at recurrence.

Local tumour progression after percutaneous ablation of colorectal liver metastases according to RAS mutation status.

BACKGROUND: Percutaneous ablation is a common treatment for colorectal liver metastasis (CLM). However, the effect of rat sarcoma viral oncogene homologue (RAS) mutation on outcome after ablation of CLMs is unclear. METHODS: Patients who underwent image-guided percutaneous ablation of CLMs from 2004 to 2015 and had known RAS mutation status were analysed. Patients were evaluated for local tumour progression as observed on imaging of CLMs treated with ablation. Multivariable Cox regression analysis was performed to determine factors associated with local tumour progression-free survival. RESULTS: The study included 92 patients who underwent ablation of 137 CLMs. Thirty-six patients (39 per cent) had mutant RAS. Rates of local tumour progression were 14 per cent (8 of 56) for patients with wild-type RAS and 39 per cent (14 of 36) for patients with mutant RAS (P = 0·007). The actuarial 3-year local tumour progression-free survival rate after percutaneous ablation was worse in patients with mutant RAS than in those with wild-type RAS (35 versus 71 per cent respectively; P = 0·001). In multivariable analysis, negative predictors of local tumour progression-free survival were a minimum ablation margin of less than 5 mm (hazard ratio (HR) 2·48, 95 per cent c.i. 1·31 to 4·72; P = 0·006) and mutant RAS (HR 3·01, 1·60 to 5·77; P = 0·001). CONCLUSION: Mutant RAS is associated with an earlier and higher rate of local tumour progression in patients undergoing ablation of CLMs.

Plasma acrolein levels and their association with delayed ischemic neurological deficits following aneurysmal subarachnoid haemorrhage: a pilot study.

BACKGROUND: The molecular mechanisms of cerebral vasospasm following aneurysmal subarachnoid haemorrhage (aSAH) remain unclear. Acrolein, a reactive metabolite produced in many models of mechanical and ischemic injury, has been shown to cause vasospasm in coronary artery and aorta models. These traits suggest it may play a role in post-aSAH cerebral vasospasm. This pilot study was designed as a preliminary investigation to determine if acrolein levels could be used as a clinical tool to predict the presence of vasospasm. METHODS: Eleven patients with aSAH and Hunt and Hess admission grades of III-V were prospectively enrolled. Patients were stratified according to the presence or absence of vasospasm, defined as a delayed ischaemic neurological deficit in which all other possible causes have been excluded. Soluble acrolein levels were determined at two times points: early (day 1-3 post-SAH) and late (day 8-12 post-SAH) and the change in acrolein levels over this period was computed using a Mann-Whitney test. RESULTS: The change in acrolein levels over this period between the vasospasm and non-vasospasm group trended toward but did not achieve statistical significance (means: 5.68 versus -5.54; medians: 5.27 versus -3.99; range: -8.067 to 22.904 versus -13.83 to 5.199 p=0.13). Five out of six vasospasm patients showed an increase in acrolein levels over the vasospasm period. Three out of four non-vasospasm patients showed a decrease over the vasospasm period. CONCLUSIONS: The results of this pilot study suggest that acrolein levels increase in patients undergoing vasospasm during the vasospasm window. This suggests that acrolein may play a role in the pathways leading up to or following vasospasm. There is a need for larger more definitive studies.

Differential effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on in vitro rat t lymphocyte and macrophage functions.

Opioid receptors have been reported on immune cells of several species and shown to subserve effector functions of these cell types. Mu-selective opioid agonists such as morphine are immunosuppressive, whereas certain delta-opioid receptor-selective agonists have been associated with immunopotentiation. We have previously shown that intracerebroventricular administration of the non-peptidic delta-opioid receptor agonists did not alter certain parameters of immunocompetence. In this study, we evaluated the in vitro effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on lymphocyte and macrophage functions. We demonstrated that CGPM-9 enhanced rat thymic lymphocyte proliferative response to concanavalin A (2.85- to 5.5-fold increases), and suppressed LPS-induced nitric oxide (67 to 72 percent reduction) and TNF-alpha production (46 percent reduction) by peritoneal macrophages, compared with untreated control. The mu-opioid receptor selective antagonist CTOP used at equimolar doses, significantly suppressed the effect of CGPM-9 on lymphocyte and macrophage functions (CTOP alone did not show any effect on lymphocyte or macrophage functions). In summary, CGPM-9 activated thymic lymphocyte proliferation and suppressed macrophage functions by acting at mu-opioid receptors. This suggests that opioid receptors on immunocytes may be coupled to different signaling pathways depending on the cell type and effector function being analyzed. The mechanism (s) associated with the differential effect of CGPM-9 on these immune cells remains to be elucidated. The pharmacotherapeutic potential for compounds such as CGPM-9 which potentiate T lymphocyte proliferation and suppress production of macrophage-derived inflammatory cytokines is substantial in research and clinical medicine.

Portal vein embolization: rationale, technique and future prospects.

BACKGROUND: Advances in surgery have reduced the mortality rate after major liver resection, but complications resulting from inadequate postresection hepatic size and function remain. Portal vein embolization (PVE) was proposed to induce hypertrophy of the anticipated liver remnant in order to reduce such complications. The techniques, measurement methods and indications for this treatment remain controversial. METHODS: A Medline search was performed to identify papers reporting the use of PVE before hepatic resection. Techniques, complications and results are reviewed. RESULTS: Complications of PVE typically occur in less than 5 per cent of patients. No specific substance (cyanoacrylate, thrombin, coils or absolute alcohol) emerged as superior. The increase in remnant liver volume averages 12 per cent of the total liver. The morbidity rate of resection after treatment is less than 15 per cent and the mortality rate is 6-7 per cent with cirrhosis and 0-6.5 per cent without cirrhosis. Embolization is currently used for patients with a normal liver when the anticipated liver remnant volume is 25 per cent or less of the total liver volume, and for patients with compromised liver function when the liver remnant volume is 40 per cent or less. CONCLUSION: This treatment does not increase the risks associated with major liver resection. It may be indicated in selected patients before major resection. Future prospective studies are needed to define more clearly the indications for this evolving technique.

Embolization of portal vein branches induces hepatocyte replication in swine: a potential step in hepatic gene therapy.

PURPOSE: To determine whether embolization of portal vein branches would stimulate hepatocyte replication in pigs. MATERIALS AND METHODS: The portal vein branches supplying 50%-70% of the liver were embolized in eight pigs by using a combination of coils and polyvinyl alcohol particles. The extent of embolization was assessed at portography in all animals and at computed tomography in one animal. Hepatocyte replication was determined by calculating the percentage of cells that incorporated bromodeoxyuridine into their nuclei. Animals survived up to 35 days after the procedure. RESULTS: Embolization of the portal vein branches supplying the left and median lobes caused transient increases of less than 70% in portal vein pressures and of less than 100% in liver enzyme levels. Indocyanine green clearance was measured in two animals and decreased less than 50%. The percentage of replicating hepatocytes in the nonembolized lobe was 0% on day 0, 7% on day 2, 14% on day 7, and 2% on day 12. CONCLUSION: Substantial hepatocyte replication occurred 2-7 days after embolization of portal vein branches. Further research will help determine if this procedure can facilitate retroviral transduction in large animals. If successful, the low morbidity of this method may allow its use in humans for gene therapy.

Recurrent gastrointestinal bleeding: use of thrombolysis with anticoagulation in diagnosis.

PURPOSE: To determine the safety and diagnostic accuracy of a provocative protocol with heparin and urokinase to induce bleeding and determine the source in patients with chronic gastrointestinal hemorrhage. MATERIALS AND METHODS: Nine patients had gastrointestinal bleeding from an indeterminate source and had negative results from esophagogastroduodenoscopy, colonoscopy, small-bowel examination, and angiography. Ten provocative bleeding studies were performed prospectively. Patients had no clinical evidence of bleeding within 2 days before the study. Intravenous administration of heparin and urokinase was performed systemically during a 4-hour period while scintigraphy was performed continuously. Mesenteric angiography was performed immediately in patients in whom substantial gastrointestinal bleeding was detected at scintigraphy. RESULTS: The provocative protocol was successful in inducing scintigraphically detectable hemorrhage in four (40%) studies within 4 hours. In two of these four studies, the source of hemorrhage was determined and treated with embolization or surgery. Three (30%) studies demonstrated scintigraphic evidence of hemorrhage only at delayed imaging (8-24 hours after initiation of the study). The remaining three (30%) studies did not show active bleeding. No complications occurred, including hemodynamic instability or uncontrollable decreases in hematocrit. CONCLUSION: Since this protocol with heparin and urokinase enabled determination of the bleeding source in only two of 10 studies, protocol modifications are necessary before this intervention is used widely.

Rheolytic thrombectomy with use of the AngioJet-F105 catheter: preclinical evaluation of safety.

PURPOSE: A preclinical evaluation of the safety of the AngioJet-F105 rheolytic thrombectomy catheter. MATERIALS AND METHODS: The AngioJet-F105 catheter uses multiple retrograde high-speed fluid jets impinging on a primary aspiration lumen to create a hydrodynamic recirculation vortex that traps and fragments adjacent thrombus, with simultaneous evacuation of the resulting debris through the aspiration lumen. The effect of the AngioJet on treated vessels was evaluated in 10 canines. Vascular integrity on histopathologic examination and endothelial coverage on scanning electron microscopic study were examined in 15 vessel segments treated with the AngioJet-F105 catheter, compared with four vessel segments subjected to the Fogarty balloon maneuver, and 10 untreated vessel segments. The size distribution of particulate debris, upstream and downstream, after thrombectomy was determined in a flow-circuit model simulating the superficial femoral artery. Aliquots from the downstream effluent were then injected into the renal arteries of two healthy canines. RESULTS: The device caused only minimal focal endothelial denudation and no significant deep injury. No significant difference in endothelial coverage occurred in AngioJet-treated vessel segments compared to untreated control vessels (mean +/- standard deviation: 88.0% +/- 7.9% vs 89.7% +/- 11.6%, P = .77). Vessels treated with the Fogarty balloon pullback maneuver had significantly less residual endothelial coverage (58.0% +/- 8.0%, P < .03). Particulate microemboli in the effluent of the flow model accounted for 12% of the initial thrombus volume (0% > 100 microm, 99.83% < or = 10 microm). Histopathologic evaluation of the four renal beds injected with the resulting debris demonstrated no signs of necrosis. A moderate transient increase in plasma-free hemoglobin occurred, with a mild corresponding decrease in hematocrit. CONCLUSIONS: The AngioJet-F105 catheter resulted in only mild and focal injury to the treated vessels. The vast majority of resulting particulate debris consist of microscopic particles, without significant ischemic effect.

Digital subtraction versus film-screen angiography for detecting acute pulmonary emboli: evaluation in a porcine model.

PURPOSE: To compare the diagnostic performance of digital subtraction angiography (DSA) to that of film-screen angiography (FSA) for detecting acute pulmonary embolism (PE) in a porcine model. MATERIALS AND METHODS: DSA and FSA were performed in 13 pigs before and after central venous administration of autologous emboli. Results were compared to findings at necropsy with use of ex vivo pulmonary angiography to guide pathologic sectioning. The sensitivity and predictive value of a positive case for detecting each embolus were computed for each pulmonary artery branch order and compared with use of 95% confidence intervals. Interobserver variability among three readers for individual PE detection was calculated. RESULTS: Pathologic examination of the lungs revealed 100 total PEs (location by vessel order: 1st = 1, 2nd = 0, 3rd = 15, 4th = 32, > 5th = 52). On average, FSA review identified 72 (72%) emboli and DSA review, 65 (65%). There was no significant difference in sensitivity or predictive value of a positive case between DSA and FSA for detecting emboli (P > .05). There was similar agreement among readers for individual PE detection with DSA (mean, 84%) and FSA (mean, 80%). CONCLUSION: The diagnostic performance of DSA is equivalent to that of FSA for detecting emboli in porcine PA branches. Interobserver agreement for individual PE detection is similar for both imaging techniques.

A review of radiologically guided percutaneous nephrostomies in 303 patients.

PURPOSE: To determine the morbidity and mortality associated with radiologically guided percutaneous nephrostomy (PCN) and to identify possible contributory risk factors. MATERIALS AND METHODS: The authors retrospectively reviewed 454 consecutive PCNs in 303 patients performed during a 4-year period. PCNs performed specifically for nephrolithotomy were excluded. Self-retention loop catheters (8-12 F) were placed with use of a modified Seldinger technique in all patients. Preprocedural antibiotics were administered routinely. Demographic variables, technical factors related to tube placement, and risk factors were examined with respect to tube malfunction and 30-day morbidity and mortality. RESULTS: Technical success was 99%. The overall complication rate was 6.5%, including hemorrhage requiring transfusion after 13 PCNs (2.8%). A baseline platelet count of less than 100,000/mm3 was a significant risk factor for hemorrhage requiring blood transfusion. The 30-day mortality rate was 3.1%; however, none of these deaths were procedure related. CONCLUSION: Radiologically guided PCN with self-retention catheters is associated with a high technical success rate and low morbidity.

Long-term results of transrenal ureteral occlusion with use of Gianturco coils and gelatin sponge pledgets.

PURPOSE: To evaluate transrenal ureteral occlusion with Gianturco coils and gelatin sponge pledgets. MATERIALS AND METHODS: The authors reviewed 34 ureteral occlusions in 22 patients during a 4-year period. The indications for this procedure included vesicovaginal fistula in 11 patients and urinary incontinence in three patients. All patients except one had a history of pelvic malignancy and previous radiation therapy. Pre-existing percutaneous nephrostomy tubes were in place in 20 ureters to be embolized. Distal ureteral occlusion was achieved by placement of Gianturco coils alone or in combination with gelatin sponge pledgets. A percutaneous nephrostomy catheter was then placed to provide permanent external diversion. Follow-up ranged from 2 weeks to 29 months (mean, 6.2 months). RESULTS: Occlusion was technically successful in all embolized ureters. All patients experienced prompt resolution of symptoms as indicated by complete or near complete perineal dryness within 72 hours. Complications were limited to coil migration into the renal pelvis in two patients and nephrostomy catheter occlusion requiring replacement in another three patients. CONCLUSION: Ureteral occlusion with Gianturco coils and gelatin sponge is a safe and reliable method of achieving permanent supravesical urinary diversion in the management of chronic lower urinary tract fistulas.

Nonsurgical management of gastric or duodenal perforation from a Wills-Oglesby-type gastrostomy tube.

PURPOSE: To describe the clinical and radiologic appearance of gastrointestinal perforation related to a Wills-Oglesby-type gastrostomy tube, as well as techniques for nonsurgical management. MATERIALS AND METHODS: Five patients with a previously placed 14-F modified Wills-Oglesby-type gastrostomy catheter experienced viscus perforation by the distal limb of the catheter during a 30-month period. RESULTS: The average interval between tube placement and perforation event was 4.3 months. Three patients had migration of the gastrostomy tube into the duodenum and subsequent duodenal perforation. One patient had posterior perforation of the stomach, and one patient developed a gastrocolic fistula. Generalized peritonitis was not present in any patient. All patients were treated successfully without surgery, and tube feedings were re-established in 4-14 days. CONCLUSIONS: Gastrostomy tube-related perforation is an uncommon, delayed complication of percutaneous gastrostomy with the modified Wills-Oglesby-type catheter. Nonsurgical management is feasible in select instances. Because of these gastrointestinal perforations, the gastrostomy tube has been modified (eliminating the distal tip), and no gastrostomy-associated gastrointestinal perforation has been experienced since.

Preliminary investigation of the Irie inferior vena caval filter.

PURPOSE: In vitro and in vivo investigations were performed to evaluate the Irie retrievable inferior vena caval (IVC) filter. MATERIALS AND METHODS: The clot capturing performance of the Irie and five other IVC filters were assessed in both horizontal and vertical orientations within a pulsed-flow circuit with 240 clot challenges for each filter. Subjective comparisons of the flow disturbance characteristics of the Irie and three other filters were also performed. In vivo studies consisted of 13 Irie filter insertions and eight attempted retrievals in 11 pigs. Histologic evaluation of the IVC was performed with the Irie filter in situ and following retrieval. RESULTS: In vitro testing demonstrated the clot capturing capability and flow disturbance characteristics of the Irie filter to be similar to those of other IVC filters. Filter deployment problems occurred during three of the 13 insertions. Six of the eight retrieval procedures were successful; four filters were retrieved 1 month after insertion. Follow-up cavography demonstrated two tilted filters and three caval perforations. CONCLUSION: The performance of the Irie filter is similar to that of other currently available IVC filters. The filter can be retrieved after neointimal incorporation of the struts into the IVC wall.

Percutaneous gallstone removal: long-term follow-up.

PURPOSE: To evaluate gallstone and symptom recurrence rates, long-term complications, and life expectancy after percutaneous gallstone removal. PATIENTS AND METHODS: Medical records of 87 patients (mean age, 69 years +/- 14 [standard deviation]) undergoing percutaneous gallstone removal between 1987 and 1992 were reviewed. Physicians and patients (or their families) were contacted for clinical follow-up. Thirty-one patients returned for follow-up ultrasound (US). RESULTS: The final study group consisted of 65 patients. Mean survival from the time of initial gallbladder drainage was 33 months +/- 19. Over a mean clinical follow-up period of 33 months, eight of 65 patients (12%) developed recurrent symptoms; six of these eight had recurrent gallstones shown at US. Of 30 patients with technically adequate US images (mean follow-up, 14 months +/- 12), 12 (40%) had recurrent gallstones. Six of these 12 patients had recurrent symptoms. No long-term complications were identified. CONCLUSION: The risk of gallstone recurrence after percutaneous removal is notable, but the symptom recurrence rate is much lower. Percutaneous gallstone removal is beneficial for patients at prohibitive surgical or general anesthetic risk.

Evaluation of coagulation tests as predictors of angiographic bleeding complications.

PURPOSE: To determine whether prothrombin time (PT), partial thromboplastin time (PTT), and platelet count are useful predictors of postangiographic hematoma. MATERIALS AND METHODS: The authors prospectively studied 1,000 consecutive patients who underwent femoral arterial puncture for a diagnostic or therapeutic vascular procedure. Demographic and procedural variables were recorded, including patient age and sex, history of medications and bleeding, procedure type and length, catheter size, and experience level of radiologist applying compression for hemostasis. RESULTS: Abnormal results of coagulation tests were not correlated with an increased occurrence of hemorrhagic complications, but bleeding complications did occur more often in patients with thrombocytopenia. Hematomas occurred in 8.1% (10 of 123) of patients with any abnormal coagulation test results and 9.7% (85 of 877) of patients with normal test results. A platelet count of less than 100 X 10(9)/L was correlated with a higher occurrence of hematoma (P = .002). CONCLUSION: Abnormal PT and PTTs do not correlate with an increased risk of postangiographic hematoma, but a low platelet count is associated with more bleeding complications.