Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases.

PURPOSE: To investigate the effects of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with uveal melanoma (UM) with liver-only metastasis. MATERIALS AND METHODS: In this double-blind phase II clinical trial, patients were randomized to undergo immunoembolization or bland embolization (BE). Lobar treatment was performed with GM-CSF or normal saline solution mixed with ethiodized oil followed by embolization with gelatin sponge emulsified with iodinated contrast medium. Fifty-two patients (immunoembolization, n = 25; BE, n = 27) were enrolled. Response was assessed after every two treatments. The primary endpoint was overall response rate (ORR) of liver metastases. Progression-free survival (PFS), overall survival (OS), and immunologic responses were secondary endpoints. RESULTS: There were five partial responses in the immunoembolization group (ORR, 21.2%; 90% confidence interval [CI], 10.3%-30.5%) and three in the BE group (ORR, 16.7%; 90% CI, 6.3%-26.9%). Stable disease was seen in 12 patients in the immunoembolization group and 19 in the BE group. OS times were 21.5 months (95% CI, 18.5-24.8 mo) with immunoembolization and 17.2 months (95% CI, 11.9-22.4 mo) with BE. The degree of proinflammatory cytokine production was more robust after immunoembolization and correlated with time to "systemic" extrahepatic progression. In the immunoembolization group, interleukin (IL)-6 levels at 1 hour (P = .001) and IL-8 levels at 18 hours after the procedure (P < .001) were significant predictors of longer systemic PFS. Moreover, a dose-response pattern was evident between posttreatment serum cytokine concentrations and systemic PFS. CONCLUSIONS: Immunoembolization induced more robust inflammatory responses, which correlated with the delayed progression of extrahepatic systemic metastases.

Moxifloxacin prophylaxis for chemoembolization or embolization in patients with previous biliary interventions: a pilot study.

OBJECTIVE: Abscess formation is a common serious adverse event after intraarterial therapy for hepatic malignancy in patients with colonized bile ducts. The combination of antibiotic prophylaxis and bowel preparation has been used to prevent hepatic abscess. We describe our outcomes with moxifloxacin prophylaxis alone without bowel preparation. CONCLUSION: Ten patients underwent 25 procedures and were followed for a median of 250 days. No abscesses developed. Our results suggest moxifloxacin alone may suffice for prophylaxis.

Radioembolization as salvage therapy for hepatic metastasis of uveal melanoma: a single-institution experience.

OBJECTIVE: The purpose of this study was to assess the safety and efficacy of radioembolization in the management of hepatic metastasis of uveal melanoma after failure of immunoembolization or chemoembolization. MATERIALS AND METHODS: From January 2007 through April 2009, 32 patients underwent radioembolization therapy for hepatic metastasis of uveal melanoma. Pretreatment tumor burdens were divided into three categories: less than 25% (n = 25), 25-50% (n = 5), and greater than 50% (n = 2). Toxicity, extrahepatic disease, and hepatic tumor response were assessed 1 month and then every 3 months after treatment. Best radiographic response of hepatic metastasis was determined with the Response Evaluation Criteria in Solid Tumors criteria. Overall survival and progression-free survival of hepatic metastasis were estimated by Kaplan-Meier analysis. Differences in survival between subgroups were evaluated by log-rank test in univariate analysis. RESULTS: The clinical follow-up period ranged from 1.0 to 29.0 months (median, 10.0 months). The median overall survival was 10.0 months, and the progression-free survival of hepatic metastasis, 4.7 months. Twenty-two patients died 1.0-29.0 months (median, 5.8 months) after treatment owing to progression of liver disease (n = 13), extrahepatic disease (n = 4), or both (n = 5). Patients who had a pretreatment tumor burden less than 25% had longer median overall survival (10.5 vs 3.9 months, p = 0.0003) and progression-free survival (6.4 vs 3.0 months, p = 0.03) than patients who had a pretreatment tumor burden of 25% or greater. Patients who had a complete response (n = 1), partial response (n = 1), or stable disease (n = 18) had longer median overall survival (14.7 vs 4.9 months, p = 0.0006) and progression-free survival of hepatic metastasis (7.9 vs 3.1 months, p < 0.0001) than patients with tumor progression (n = 12). Self-limiting grade 1-2 systemic toxicity included tiredness (n = 9), indigestion (n = 2), and abdominal discomfort (n = 5). Grade 3-4 hepatic toxicity was attributed to tumor progression. CONCLUSION: Radioembolization is safe and effective salvage therapy for limited metastasis of uveal melanoma.

High-dose immunoembolization: survival benefit in patients with hepatic metastases from uveal melanoma.

PURPOSE: To retrospectively evaluate prognostic factors for survival in patients with uveal melanoma who received chemoembolization (CE) with 1,3-bis (2-chloroethyl)-1-nitrosourea or immunoembolization (IE) with granulocyte-macrophage colony-stimulating factor (GM-CSF) for hepatic metastases. MATERIALS AND METHODS: Fifty-three consecutive patients with uveal melanoma were treated by using CE or IE in clinical trials approved by the Institutional Review Board. Prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in the liver and extrahepatic (systemic) organs were retrospectively evaluated. Covariates of age, sex, preexisting extrahepatic metastases, liver enzyme levels, tumor volume, radiologic response in hepatic metastases, and treatment type were analyzed. RESULTS: Compared with CE, high-dose (>or=1500 microg of GM-CSF) IE resulted in significantly better OS (20.4 vs 9.8 months, P = .005) and systemic PFS (12.4 vs 4.8 months, P = .001) at univariate analysis. Overall, women outlived men (14.4 vs 9.8 months, P = .01). Patients who achieved regression of hepatic metastases after embolization lived much longer than did those who did not achieve regression (27.2 vs 9.9 months, P < .001). At multivariate analysis, prolonged OS was confirmed for women, patients who underwent high-dose IE, younger patients (age < 60 years), and patients with regression of hepatic metastases. Independent predictors of longer systemic PFS included high-dose IE, younger age, and regression of hepatic metastases. No covariate predicted liver PFS except for hepatic response. CONCLUSION: Treatment with high-dose IE prolonged survival of patients with uveal melanoma who received embolization of hepatic metastases and possibly delayed progression of extrahepatic metastases.

Hepatic artery chemoembolization.

Chemoembolization is a technique that can deliver high concentrations of therapeutic agents directly to the liver for prolonged periods. Considerable experience has been gained in the treatment of hepatocellular carcinoma, where it appears to be a safe procedure that provides survival advantage over conservative therapy. There is much less experience in the treatment of hepatic metastases. Patients with carcinoid, pancreatic islet cell tumor, and sarcoma metastatic to the liver do appear to benefit from chemoembolization. Efficacy in other groups, such as patients with colorectal cancer metastatic to the liver, is less well established, but a recently initiated multicenter trial may resolve this issue.

Ventilator-associated pneumonia and oral care: a successful quality improvement project.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a nosocomial pneumonia that develops in patients on mechanical ventilation for >or=48 hours. VAP develops at an estimated rate of 1% to 3% per day of mechanical ventilation. METHODS: Quality improvement project. Mechanically ventilated patients received the following oral care every 4 hours: the teeth were brushed with cetylpyridinium chloride (changed to 0.12% chlorhexidine gluconate in 2007) using a suction toothbrush, the oral cavity was cleansed with suction swabs treated with hydrogen peroxide, a mouth moisturizer was applied, deep oropharyngeal suctioning was performed, and suction catheters were used to control secretions. The primary efficacy variable was a diagnosis of VAP in patients mechanically ventilated for >or=48 hours. RESULTS: The historical average rate of VAP in 2004 was 12.6 cases/1000 ventilator-days. After the inception of the quality improvement project, VAP rates decreased to 4.12 (VAP cases/days of ventilation x 1000) for May to December 2005, to 3.57 for 2006, and to 1.3 for 2007. CONCLUSION: The use of an oral care protocol intervention and ventilator bundle led to an 89.7% reduction in the VAP rate in mechanically ventilated patients from 2004 to 2007.

Immunoembolization of malignant liver tumors, including uveal melanoma, using granulocyte-macrophage colony-stimulating factor.

PURPOSE: We conducted a phase I study to investigate the feasibility and safety of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) for malignant liver tumors, predominantly hepatic metastases from patients with primary uveal melanoma. PATIENTS AND METHODS: Thirty-nine patients with surgically unresectable malignant liver tumors, including 34 patients with primary uveal melanoma, were enrolled. Hepatic artery embolization accompanied an infusion of dose-escalated GM-CSF (25 to 2,000 microg) given every 4 weeks. Primary end points included dose-limiting toxicity and maximum tolerated dose (MTD). Patients who completed two cycles of treatments were monitored for hepatic antitumor response. Survival rates of patients were also monitored. RESULTS: MTD was not reached up to the dose level of 2,000 microg, and there were no treatment-related deaths. Thirty-one assessable patients with uveal melanoma demonstrated two complete responses, eight partial responses, and 10 occurrences of stable disease in their hepatic metastases. The median overall survival of intent-to-treat patients who had metastatic uveal melanoma was 14.4 months. Multivariate analyses indicated that female sex, high doses of GM-CSF (> or = 1,500 microg), and regression of hepatic metastases (complete and partial responses) were correlated to longer overall survival. Moreover, high doses of GM-CSF were associated with prolonged progression-free survival in extrahepatic sites. CONCLUSION: Immunoembolization with GM-CSF is safe and feasible in patients with hepatic metastasis from primary uveal melanoma. Encouraging preliminary efficacy and safety results warrant additional clinical study in metastatic uveal melanoma.

Postprocedural aspiration test to predict adequacy of dialysis following tunneled catheter placement.

The objective of the study was to determine if a timed aspiration technique with a 20-ml syringe can be used to predict adequacy of blood flow in tunneled dialysis catheters. Sixteen patients referred for de novo placement or manipulation of failing tunneled hemodialysis catheters had the time it takes to fill a 20-ml syringe with the plunger fully withdrawn measured to the nearest tenth of a second. These measurements were correlated with flow rates recorded in dialysis just prior to (if failed catheter) and in the following dialysis session with adequacy determined as at least 300 ml/min. Syringe-filling time (22 catheters in 16 patients) was plotted against adequacy of dialysis. The mean time to fill a 20-ml syringe was 2.2 sec, with a range of 1.0-4.7 sec. The mean time to fill syringes for catheters with adequate dialysis was 1.7 +/- 0.5 sec, and for inadequate catheters, it was 2.8 +/- 0.8 sec. These differences are statistically significant (p < 0.001). Using a filling time of greater than or equal to 2 sec as a threshold gives the highest sensitivity (100%) for predicting inadequate dialysis while maintaining high specificity (75%). To achieve a specificity of 100%, a 3-sec cutoff would be necessary, but would lead to a sensitivity of only 20%. A simple and objective aspiration technique can be performed at the time of tunneled dialysis catheter placement/manipulation to reasonably predict adequacy of subsequent dialysis.

Incidence of central vein stenosis and occlusion following upper extremity PICC and port placement.

The purpose of this study was to determine the incidence of central vein stenosis and occlusion following upper extremity placement of peripherally inserted central venous catheters (PICCs) and venous ports. One hundred fifty-four patients who underwent venography of the ipsilateral central veins prior to initial and subsequent venous access device insertion were retrospectively identified. All follow-up venograms were interpreted at the time of catheter placement by one interventional radiologist over a 5-year period and compared to the findings on initial venography. For patients with central vein abnormalities, hospital and home infusion service records and radiology reports were reviewed to determine catheter dwell time and potential alternative etiologies of central vein stenosis or occlusion. The effect of catheter caliber and dwell time on development of central vein abnormalities was evaluated. Venography performed prior to initial catheter placement showed that 150 patients had normal central veins. Three patients had central vein stenosis, and one had central vein occlusion. Subsequent venograms (n = 154) at the time of additional venous access device placement demonstrated 8 patients with occlusions and 10 with stenoses. Three of the 18 patients with abnormal follow-up venograms were found to have potential alternative causes of central vein abnormalities. Excluding these 3 patients and the 4 patients with abnormal initial venograms, a 7% incidence of central vein stenosis or occlusion was found in patients with prior indwelling catheters and normal initial venograms. Catheter caliber showed no effect on the subsequent development of central vein abnormalities. Patients who developed new or worsened central vein stenosis or occlusion had significantly (p = 0.03) longer catheter dwell times than patients without central vein abnormalities. New central vein stenosis or occlusion occurred in 7% of patients following upper arm placement of venous access devices. Patients with longer catheter dwell time were more likely to develop central vein abnormalities. In order to preserve vascular access for dialysis fistulae and grafts and adhere to Dialysis Outcomes Quality Initiative guidelines, alternative venous access sites should be considered for patients with chronic renal insufficiency and end-stage renal disease.

Complications of a percutaneous suture-mediated closure device versus manual compression for arteriotomy closure: a case-controlled study.

PURPOSE: To evaluate the incidence and types of complications encountered with use of a percutaneous suture-mediated closure device versus manual compression for arteriotomy closure in a retrospective case-controlled study. MATERIALS AND METHODS: The authors identified 100 consecutive patients, 15 men and 85 women 21-85 years of age (mean, 50 years), between December 2000 and July 2001 in whom the Closer percutaneous suture-mediated closure device was used during 65 uterine artery embolization (UAE) procedures, 11 hepatic chemoembolization procedures, nine diagnostic angiography procedures, seven peripheral vascular interventions, six visceral arterial interventions, and two thrombolysis procedures. An age-, sex-, and procedure-matched control population was identified in which manual compression was performed. Procedure reports and clinical charts were reviewed for the presence of puncture-site complications, as categorized according to Society of Interventional Radiology reporting standards, and for risk factors and comorbid conditions (hypertension, diabetes, stroke, smoking, and coronary artery disease). Follow-up visits and imaging studies were reviewed for patients with complications. RESULTS: In the Closer group, there were seven device failures, four minor complications, and three major complications. Minor complications included two groin hematomas and two cases of persistent pain at the arteriotomy site. Three major complications consisted of two cases of external iliac artery dissection, one with distal embolization, and one case of common femoral artery (CFA) occlusion and distal embolization. All major complications occurred in women undergoing UAE. One patient required thromboendarterectomy and patch angioplasty to repair the CFA occlusion, as well as amputation of a gangrenous toe. In the manual-compression group, there was one minor complication (a groin hematoma) and no major complications. There were significantly more complications in the Closer group than in the manual compression group (P =.02). CONCLUSIONS: Significantly more complications were associated with use of a percutaneous suture-mediated closure device than with manual compression for arteriotomy-site hemostasis. Major complications and associated morbidity may be seen with use of percutaneous suture-mediated closure devices. In particular, an unexpectedly high frequency of device-related complications was demonstrated in young women undergoing UAE.

Infectious complications of implantable venous access devices in patients with sickle cell disease.

PURPOSE: To evaluate the incidence of implantable venous access device infection in patients with sickle cell disease. MATERIALS AND METHODS: The authors performed a retrospective search of their hospital's information system from January 1, 1996 to December 31, 2001 to identify hospital admissions with ICD-9 codes related to sickle cell anemia. This search yielded 2703 admissions in 293 patients. A search of the radiology information system identified 23 of these patients who had placement of an implantable venous access device. Excluding two patients who were lost to follow-up, the population of this study included eight men and 13 women aged 23 to 62 years old (mean, 37 years). A total of 30 implantable venous access devices (25 venous ports, five tunneled catheters) were placed by interventional radiologists. Cases of device infection were identified based on clinical data, microbiology, reports of device removal, and clinical follow-up. Infections were defined according to the Centers for Disease Control criteria for catheter-related bloodstream infection. The incidence of infection, organism, and time from device placement to infection was determined. RESULTS: In 21 patients with 30 devices, 18 device infections (60%) occurred in 12 patients (57%) involving 15 venous ports and three tunneled catheters. There were a total of 12389 days of catheter use and a rate of 1.5 infections per 1000 catheter days. Infections occurred from 16 to 1542 days (mean, 349 days) after device placement. Blood, wound, and catheter tip cultures yielded solitary organisms in 13 cases and mixed organisms in four cases. Staphylococcus aureus was the most common pathogen (59%). One patient was considered infected based on clinical signs and purulent discharge from the port site, despite negative cultures after partial antibiotic treatment. One patient died of sepsis resulting from an infected port. CONCLUSION: This study shows a high incidence of infection associated with placement of implantable venous access devices in patients with sickle cell disease. Therefore, the authors avoid placing these devices in this patient population.

Angiographic assessment of initial balloon angioplasty results.

PURPOSE: To determine the influence of three factors involved in the angiographic assessment of balloon angioplasty-interobserver variability, operator bias, and the definition used to determine success-on the primary (technical) results of angioplasty in the peripheral arteries. MATERIALS AND METHODS: Percent stenosis in 107 lesions in lower-extremity arteries was graded by three independent, experienced vascular radiologists ("observers") before and after balloon angioplasty and their estimates were compared with the initial interpretations reported by the physician performing the procedure ("operator") and an automated quantitative computer analysis. Observer variability was measured with use of intraclass correlation coefficients and SD. Differences among the operator, observers, and the computer were analyzed with use of the Wilcoxon signed-rank test and analysis of variance. For each evaluator, the results in this series of lesions were interpreted with three different definitions of success. RESULTS: Estimation of residual stenosis varied by an average range of 22.76% with an average SD of 8.99. The intraclass correlation coefficients averaged 0.59 for residual stenosis after angioplasty for the three observers but decreased to 0.36 when the operator was included as the fourth evaluator. There was good to very good agreement among the three independent observers and the computer, but poor correlation with the operator (P