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.

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.

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.

Subcutaneous urinary diversion utilizing a nephrovesical stent: a superior alternative to long-term external drainage?

OBJECTIVES: The use of external percutaneous nephrostomy drainage in patients with end-stage ureteral obstruction in whom ureteral stenting has failed presents significant compromises in the patient's quality of life. Toward this end, we present the initial experience in the United States with an intracorporeal nephrovesical stent. METHODS: We performed successful subcutaneous urinary diversion in 2 patients with malignant, metastatic periureteral obstruction. Both patients had previously been managed with a chronic percutaneous nephrostomy that was both painful and inconvenient. The nephrovesical stent was inserted utilizing percutaneous access to both the kidney and bladder followed by creation of a subcutaneous tunnel between the two sites. RESULTS: The nephrovesical stents are patent at 6 and 9 weeks postoperatively and both patients have had their nephrostomy tubes removed. Both patients have noted a marked improvement in their overall comfort and quality of life since the stent has been in place. CONCLUSIONS: Subcutaneous urinary diversion with a nephrovesical stent provides effective urinary drainage and may improve the quality of life of patients with malignant metastatic ureteral obstruction. Further long-term studies are needed.

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.

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.

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.

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.

Massive arterial hemorrhage from the stomach and lower esophagus: impact of embolotherapy on survival.

The authors retrospectively reviewed the clinical courses in 36 patients referred for angiographic evaluation of massive arterial hemorrhage from the stomach, gastroesophageal junction, and lower esophagus. Twenty-four patients underwent embolotherapy, and 12 were treated with nontranscatheter therapy such as surgery, Sengstaken-Blakemore tube placement, endoscopic submucosal injection of epinephrine, or supportive medical therapy. Bleeding was controlled completely in 15 (62%) and partially in three (13%) of the patients who underwent embolotherapy. In nine of the patients treated with nontranscatheter therapy (75%), bleeding control was complete. Sixteen patients died, including seven of 28 in whom bleeding was controlled. There was no significant difference in the mortality rates of patients treated with nontranscatheter therapy (46% and 42%, respectively). Survival correlated with the clinical condition at the time of intervention. All patients with multiorgan failure died, while 87% of the other patients, even those with serious cardiovascular compromise, survived. The results imply that massive gastric hemorrhage should be treated aggressively, before it results in multiorgan failure.

Multilevel infusion catheter for use with thrombolytic agents.

A new multilevel infusion catheter for administration of thrombolytic agents is described that provides near equal flow distribution through each of four infusion ports. Advantages of the catheter include fluoroscopically visible infusion length markers, small size (4.7 F), and secure positioning of the catheter within the occluded segment of graft or vessel. This catheter was used for infusion of urokinase in the treatment of 20 peripheral vascular occlusions. Complete or near complete thrombolysis was achieved in all cases.

Comparison of nonsubtracted digital angiography and conventional screen-film angiography for the evaluation of patients with peripheral vascular disease.

Recently, x-ray equipment manufacturers have produced systems capable of generating nonsubtracted digital angiograms (NSDA) of the arteries of the lower extremities with a high-resolution 1,024 x 1,024 matrix. One such system was compared with conventional screen-film angiography (CSFA) for the evaluation of peripheral vascular disease. Both NSDA and CSFA were performed prospectively in an identical fashion on 47 patients. The images were evaluated, and diagnostic adequacy (ie, information sufficient to direct subsequent therapy) and a variety of image quality attributes--vessel opacification, correct timing, complete anatomic coverage, and ease of reading--were compared. CSFA and NSDA provided similar diagnostic information. NSDA was judged superior to CSFA with regard to timing (P less than .001). CSFA was judged superior with regard to anatomic coverage (P less than .001) and ease of reading (P less than .01). NSDA is a promising method for evaluating patients with peripheral vascular disease. Further work is needed to provide more complete anatomic coverage and to improve the quality of the hard-copy images.

Prevalence of local venous thrombosis after transfemoral placement of a Bird's Nest vena caval filter.

Bird's Nest vena caval filters were placed in 63 patients over a 6-month period by means of a transfemoral (n = 62) or transjugular (n = 1) approach. To determine the prevalence of access-site thrombosis, compression color Doppler flow imaging was performed 1-11 days after the procedure in 48 patients without suspected or documented preexisting thrombus. Clinical follow-up was from 5 to 289 days (mean, 100 days). Findings at ultrasound (US) examination were normal in 38 patients, and all of these patients remained clinically asymptomatic. Nonocclusive thrombus was seen in nine patients, eight of whom remained asymptomatic. A single patient had an occlusive thrombus at US. This patient had leg swelling. Nonocclusive thrombus did not predispose patients to the development of clinically evident occlusive thrombosis. The authors conclude that the transfemoral placement of the Bird's Nest vena caval filter is associated with a low prevalence (2%) of femoral vein occlusion documented at US follow-up. This contrasts with results from a similarly designed study demonstrating a 17% prevalence after percutaneous Greenfield filter placement.

Fluoroscopically guided percutaneous gastrostomy and gastroenterostomy: analysis of 158 consecutive cases.

We reviewed our experience with 158 consecutive patients who underwent either percutaneous gastrostomy or percutaneous gastroenterostomy during a 2-year period. The catheters used included Foley catheters (36), Cope-type gastric catheters (86), or Carey-Alzate-Coons gastrojejunostomy catheters (36). Gastrojejunostomy tubes were placed in patients with gastroesophageal reflux or aspiration, gastric atony, or partial gastric obstruction. Ninety percent of the tubes were placed for feeding purposes. The technical success rate was 100%. Thirty-day follow-up was obtained in 89%. Thirty-day mortality was 26%, reflecting the substantial number of debilitated patients. No deaths were directly related to tube placement. Major morbidity was 6% and included hemorrhage, peritonitis, tube migration, and sepsis. Minor morbidity was 12%. There was no difference in 30-day mortality or feeding tolerance between the tube types (p less than .05). Patients with Foley catheters had more complications necessitating surgical intervention and an increased incidence of tube changes required within 30 days. These were the only statistically significant differences between the tubes (p less than .05). Our results show that percutaneous gastrostomy is a safe and effective means of gastroenteric feeding or decompression. Because of the fewer complications and ease of insertion, the Cope type of gastrostomy tube has become our preferred catheter for percutaneous feeding or decompression.

Peripheral vascular disease: evaluation with stepping DSA and conventional screen-film angiography.

PURPOSE: To prospectively evaluate stepping digital subtraction angiography (S-DSA), which enables peripheral digital subtraction angiography (DSA) of both lower extremities after one injection of contrast material, in comparison with conventional screen-film angiography (SFA) for evaluation of lower-extremity vascular disease. MATERIALS AND METHODS: Fifty consecutive patients were prospectively examined. Each study was performed without knowledge of the findings in the other. Additional stationary DSA images were obtained whenever necessary. All studies were individually evaluated for diagnostic adequacy and then side by side for vascular opacification, timing of contrast enhancement, ease of reading, and overall superiority. RESULTS: The diagnostic adequacy of S-DSA was not statistically different from that of SFA (P > .30). SFA was subjectively considered superior in opacification (P < .003), ease of reading (P < .003), and subjective overall superiority (P < .005). S-DSA was superior in timing of contrast enhancement (P < .001). CONCLUSION: The advantages of S-DSA can be achieved while the diagnostic adequacy of SFA is maintained. However, SFA was considered superior in three of four subjective characteristics.

Massive upper gastrointestinal hemorrhage with normal findings on arteriography: value of prophylactic embolization of the left gastric artery.

During a 5-year period, 13 patients who presented with massive upper gastrointestinal hemorrhage had normal findings on arteriography. Seven had prophylactic embolization of the left gastric artery, and six had conservative therapy. Normal angiographic findings were associated with clinical cessation of bleeding in 12 of 13 patients. Lesions not treated by embolization or other invasive therapy had a high rate of massive recurrent hemorrhage (four of six). Of lesions subsequently found to be supplied by the left gastric artery, two of four cases not treated by embolization or surgery had clinically significant recurrent hemorrhage, whereas none of six cases treated by embolization had recurrent hemorrhage. Prophylactic embolization of the left gastric artery appears warranted when (1) there is definite prior identification of a lesion in the left gastric artery territory or (2) there is no prior localization of a lesion but the patient is at risk for multiorgan failure if bleeding recurs.

Percutaneous ureteral occlusion with use of Gianturco coils and gelatin sponge. Part II. Clinical experience.

A previous report described the use of coils and gelatin sponge pledgets as a means of producing ureteral occlusion to achieve urinary diversion in patients with urinary fistulas. The authors have performed this procedure in nine ureters of six patients. Five of the patients had urinary leaks with extensive pelvic tumor, and one had severe chronic cystitis. Ureters were occluded with use of Gianturco coils and gelatin sponge pledgets placed via a sheath through a percutaneous nephrostomy tract. The procedure was successful in all patients as judged by means of antegrade nephrostogram or intravenous pyelogram and by marked improvement or complete resolution of symptoms.

Percutaneous cholecystolithotomy: preliminary experience and technical considerations.

Surgical cholecystectomy is associated with a high morbidity and mortality in elderly patients with acute calculous cholecystitis and underlying cardiac or pulmonary disease. Currently there are few alternatives for treating these patients. The authors have used percutaneous cholecystolithotomy in 11 such high-risk patients for definitive treatment of gallbladder calculi. In all 11 patients all stones were successfully removed from the gallbladder and cystic duct. The entire procedure--from initial tube placement to final tube removal--lasted 17-40 days (mean, 21 days). There were two complications: one minor--local wound infection--and one major--bile peritonitis with eventual death. Percutaneous cholecystolithotomy is an effective alternative therapy for acute calculous cholecystitis in elderly, debilitated patients.

Transcervical salpingoplasty: current techniques and results.

In the last five years angio-interventional techniques have been applied to the recanalization of proximally occluded fallopian tubes in infertile women. The reported technical success of 90% and subsequent pregnancies in up to 54% of patients has led to considerable interest in this technique. This article will discuss current methodologies and review the reported results of this procedure.