Roman Kozak

Tolerance, hospital stay, and recovery after uterine artery embolization for fibroids: The Ontario uterine fibroid embolization trial

PURPOSE Uterine artery embolization (UAE) is gaining popularity as an alternative to hysterectomy for the treatment of fibroids. Although minimally invasive treatments such as UAE offer the potential of fewer complications, shorter hospital stay, and quicker recovery than surgery, there have been few published data on tolerance and recovery in patients undergoing UAE. MATERIALS AND METHODS This was a multicenter prospective single-arm clinical treatment trial involving the practices of 11 interventional radiologists in eight Ontario university-affiliated and community hospitals. Between November 1998 and November 2000, 555 women underwent UAE for symptomatic uterine fibroids. Follow-up included ultrasound examinations and telephone interviews. UAE was performed under conscious sedation. Polyvinyl alcohol particles (355-500 micro m) were the primary embolic agent, and the procedural endpoint involved stasis in the uterine arteries. Pain protocols included antiinflammatory medications and narcotics and a planned overnight hospital admission. Tolerance and recovery were measured by patient-reported pain intensity (10-point numeric rating and five-point descriptor scale), hospital length of stay (LOS), and time until return to work. RESULTS Intraprocedural pain was reported by 30% of patients and postprocedural pain was reported by 92% of patients (mean pain rating +/- SD, 7.0 +/- 2.47). The mean hospital LOS was 1.3 nights. Postprocedural pain was the most common indication for an LOS greater than 1 night (18%) or 2 nights (5%). Return visits to the hospital (10%) and readmissions (3%) were primarily for pain. The overall postprocedural complication rate was 8.0% (95% CI: 5.9%-10.6%). Of the 44 complications, 32 (73%) were pain-related. The mean recovery time after UAE was 13.1 days (median, 10.0 d). CONCLUSION The majority of patients had a 1-night LOS after UAE and recovered within 2 weeks. Postprocedural pain varied considerably and was the major indication for extended hospital stay and recovery.

Technical results and effects of operator experience on uterine artery embolization for fibroids: the Ontario Uterine Fibroid Embolization Trial.

PURPOSE To document the technical results and spectrum of practice of uterine artery embolization (UAE) for fibroids in the health care setting in Canada. The effects of interventional radiologists (IRs) experience with UAE on procedure and fluoroscopy time were also investigated. MATERIALS AND METHODS The study involved a multicenter prospective single-arm clinical treatment trial and included the practices of 11 IRs at eight university-affiliated teaching and community hospitals. Vascular access with percutaneous femoral artery approach was followed by transcatheter delivery of polyvinyl alcohol (PVA) particles into uterine arteries with fluoroscopic guidance. Technical success, complications, procedural time, fluoroscopy time, and effects of operator experience were outcomes analyzed. RESULTS Between November 1998 and November 2000, 570 embolization procedures were performed in 555 patients. UAE was bilaterally successful in 97% (95% CI: 95%-98%). Variant anatomy was the most common reason for failure to embolize bilaterally. The procedural complication rate was 5.3% (95% CI: 3.6%-7.4%). Of the 30 events, three involved major complications (one seizure and two allergic reactions) that resulted in additional care or extended hospital stay. Procedure time and fluoroscopy time averaged 61 minutes (95% CI; 58-63 minutes) and 18.9 minutes (95% CI; 18-19.8) and varied significantly among IRs (P <.001; P <.001). The average 27% reduction in procedure time (20 minutes; P <.001) and 24% reduction in fluoroscopy time (5.1 minutes; P <.001) with increasing UAE experience were significant. CONCLUSIONS A high level of technical success with few complications was obtained with a variety of operators in diverse practice settings. Increased experience in UAE significantly reduced procedure and fluoroscopy time.

In vivo CT measurement of blood-brain transfer constant of iopamidol in human brain tumors

SummaryWe have developed an in vivo method of measuring the blood-brain transfer constant (K) of iopamidol and the cerebral plasma volume (Vp) in brain tumors using a clinical X-ray CT scanner. In patient studies, Isovue 300 (iopamidol) was injected at a dosage of 1 ml/kg patient body weight. Serial CT scans of the tumor site and arterial blood samples from a radial artery were taken up to 48 min after injection. The leakage of iopamidol into the brain through the blood-brain barrier was modelled as an exchange process between two compartments, the intravascular plasma space and the tissue interstitial space. Using this model and the concentration measurements in blood plasma and tissue, quantitative estimates of K and Vp in brain tumors were obtained. In addition, distribution of the estimated values of K and Vp in tumors were displayed as false colour functional images overlaid on the conventional CT scan.In a study of twelve patients with anaplastic astrocytoma (n = 3), glioblastoma multiforme (n = 4) or metastases (n = 5) the mean K and VP values in tumor were found to be 0.0273 ± 0.0060 ml/min/g and 0.068 ± 0.11 ml/g respectively. These values were significantly higher than those in grey or white matter in the contralateral ‘normal’ hemisphere (p < 0.05). The functional images showed variations in K and Vp within the tumor which were difficult to perceive in the original contrast enhanced CT scans.

Effect of steroids on iopamidol blood-brain transfer constant and plasma volume in brain tumors measured with X-ray computed tomography

SummaryTumor blood-brain transfer constant of iopamidol (K) and plasma volume (Vp) were measured in 10 patients with primary brain tumors before and after 7 days of dexamethasone treatment (4 × 4 mg per oral per day) using X-ray computed tomography. Both K and Vp decreased significantly after dexamethasone treatment with p < 0.01 and 0.09 respectively according to one-tail paired t-test. The mean percentage decrease in K and Vp was 32% and 10% respectively. Functional images of the two parameters before and after treatment were generated and showed clearly the effect of steroids on the reduction of K in brain tumors. In contrast, when before and after treatment contrast enhanced CT scans were compared, no difference was observed in the enhancement in 8 out of 10 cases. The result obtained support the conclusion that: (1) corticosteroids reduce the blood-brain permeability to small hydrophillic molecules; (2) the X-ray computed tomography method we have developed can be used to measure the K and Vp response of brain tumors to steroid therapy; and, (3) ordinary contrast enhanced CT scans at one fixed time or multiple times after contrast injection are not sensitive in detecting the reduction of K due to steroids.

Reflex-mediated reduction in human cerebral blood volume

Adrenergic nerves innervate the human cerebrovasculature, yet the functional role of neurogenic influences on cerebral hemodynamics remains speculative. In the current study, regional cerebrovascular responses to sympathoexcitatory reflexes were evaluated. In eight volunteers, contrast-enhanced computed tomography was performed at baseline, –40 mmHg lower body negative pressure (LBNP), and a cold pressor test (CPT). Cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF) were evaluated in cortical gray matter (GM), white matter (WM), and basal ganglia/thalamus (BGT) regions. Lower body negative pressure resulted in tachycardia and decreased central venous pressure while mean arterial pressure was maintained. Cold pressor test resulted in increased mean arterial pressure concomitant with tachycardia but no change in central venous pressure. Neither reflex altered end-tidal carbon dioxide. Cerebral blood volume was reduced in GM during both LBNP and CPT (P<0.05) but was unchanged in WM and BGT. Mean transit time was reduced in WM and GM during CPT (P<0.05). Cerebral blood flow was only modestly affected with either reflex (P<0.07). The combined reductions in GM CBV (˜ –25%) and MTT, both with and without any change in central venous pressure, with small CBF changes (˜ –11%), suggest that active venoconstriction contributed to the volume changes. These data demonstrate that CBV is reduced during engagement of sympathoexcitatory reflexes and that these cerebrovascular changes are heterogeneously distributed.

An absorptiometry method for the determination of arterial blood concentration of injected iodinated contrast agent

A single photon absorptiometry method to measure the arterial concentration of injected iodinated contrast agent was developed. A prototype absorptiometry unit was built which consists of either a square or circular cross section acrylic (polymethylmethacrylate) cuvette connected to an arterial catheter at one end and a paristaltic pump at the other via PE60 surgical tubing. At opposing ends of the length of the cuvette were a 0.4 GBq 125I source and a scintillation crystal/photomultiplier tube assembly. This assembly was connected to a single-channel analyser (SCA)/scaler unit to count the transmitted photons through the cuvette. The scaler was interfaced to an IBM PC and counts accumulated in preset time intervals were transmitted to the computer via a serial interface. Experiments were performed to calibrate the unit for measurement of blood concentration of contrast agent (Isovue 300) and to determine the dispersion characteristics of the unit. Deconvolution was used to correct the measured concentration waveform for the dispersion introduced by passage through the lead-in tubing and the cuvette. The precision of concentration measurements was determined to be between 5 and 10% using computer simulations and theoretical calculations. The method was used successfully in a number of patient and animal studies to measure the contrast concentration in blood following intravenous injection of contrast agent.

Prediction and reduction of motion artifacts in free-breathing dynamic contrast enhanced CT perfusion imaging of primary and metastatic intrahepatic tumors.

RATIONALE AND OBJECTIVE To develop and evaluate a method for predicting and reducing motion artifacts in free-breathing liver perfusion computed tomography (CT) scanning with couch shuttling and to compare tumor and liver parenchyma perfusion values. MATERIALS AND METHODS Thirty patients (23 males, 7 females, median age of 74 years) with primary or metastatic intrahepatic tumors underwent dynamic contrast enhanced CT scans with axial shuttling. A semiautomatic respiratory motion correction algorithm was applied to align the acquired images along the z-axis. Perfusion maps were generated using the dual-input Johnson-Wilson model. Root mean squared deviation (RMSD) maps of the model fit to the pixel time-density curves were calculated. RESULTS Precorrection RMSD correlated positively with magnitude of change in functional values resulting from motion. Blood flow, arterial blood flow, and permeability surface product were significantly increased in tumor compared to normal tissue (P < .05), blood volume was significantly reduced in tumor compared to normal tissue (P < .05). In a subgroup of patients with high-amplitude motion significant difference was observed between uncorrected and motion correction blood flow maps. CONCLUSIONS Patients can breathe freely during hepatic perfusion imaging if retrospective motion correction is applied to reduce motion artifacts. RMSD provides a regional assessment of motion induced artifacts in liver perfusion maps.

Dynamic contrast enhanced CT aiding gross tumor volume delineation of liver tumors: An interobserver variability study

PURPOSE To evaluate the application of perfusion CT for gross tumor volume (GTV) delineation for radiotherapy of intrahepatic tumors. MATERIALS AND METHODS 15 radiotherapy patients with confirmed liver tumors underwent contrast enhanced 4D-CT (Philips Brilliance Big-bore) as well as dynamic contrast enhanced (DCE) CT (GE 750HD). Perfusion maps were generated with CT perfusion v5 from GE. Five observers delineated GTVs of all intrahepatic foci on the 4D-CT, time-averaged DCE-CT and perfusion CT for every patient. STAPLE consensus contours were generated. Dices coefficients were compared between GTVs generated by observers on each image set and the corresponding consensus GTVs. Comparisons were also performed with patients stratified by hepatocellular carcinoma (HCC) metastatic tumors, and by tumor volume. RESULTS Overall, mean Dices coefficients were 0.81±0.14, 0.84±0.10, and 0.81±0.14 for 4D-CT, DCECT and perfusion. DCE-CT performed significantly better than 4D-CT and perfusion (p=0.005 and p=0.01 respectively). For patients with HCC, DCE-CT reduced interobserver variability significantly compared to 4D-CT (Dices coefficients 0.87 vs. 0.84, p<0.05). For patients with metastatic disease time-averaged DCE-CT images decreased variability compared to 4D-CT (Dices coefficient 0.81 vs. 0.76, p<0.05), especially true for tumors<100cc. The smaller tumors results are important to be included here. CONCLUSIONS DCE-CT imaging of liver perfusion reduced interobserver variability in GTV delineation for both HCC and metastatic liver tumors.

Uterine artery embolization for uterine arteriovenous malformation in five women desiring fertility: pregnancy outcomes.

Uterine arteriovenous malformations (AVM) are rare and can be classified as either congenital or acquired. Acquired AVMs may result from trauma, uterine instrumentation, infection or gestational trophoblastic disease. The majority of acquired AVMs are encountered in women of reproductive age with a history of at least one pregnancy. Traditional therapies of AVMs include medical management of symptomatic bleeding, blood transfusions, uterine artery embolization (UAE) or hysterectomy. In this retrospective case series, we report our experience with AVM and UAE in five symptomatic women of reproductive age who wished to preserve fertility. Patients were 18-32 years old, and had 1-3 previous pregnancies prior to initial presentation. All patients were followed until their deliveries. All five patients delivered live births. Three of the five patients required two embolization procedures and one of these women required a subsequent hysterectomy. Two deliveries were at term and had normal weight babies and normal placenta. One woman had cerclage placed and developed chorioamnionitis at 34 weeks but had a normal placenta. Two pregnancies were induced <37 weeks for pre-eclampsia/b intrauterine growth restriction ± abnormal umbilical artery dopplers. The low birthweight were both <2000 g. Both placentas showed accelerated maturity and infarcts. All estimated blood losses were recorded as <500 cc. In conclusion, UAE may not be as effective at managing AVM as previously thought and should be questioned as an initial therapy in symptomatic women of reproductive age desiring fertility preservation.

Post-Uterine Artery Embolization Pain and Clinical Outcomes for Symptomatic Myomas Using Gelfoam Pledgets Alone Versus Embospheres Plus Gelfoam Pledgets: A Comparative Pilot Study

BACKGROUND To evaluate the efficacy and post-procedural pain associated with uterine artery embolization (UAE) using Gelfoam alone versus Embospheres plus Gelfoam in women with symptomatic uterine fibroids. METHOD We conducted a prospective, non-randomized pilot study. Fluoroscopy-guided trans-femoral artery UAE was performed using Gelfoam pledgets alone or Embospheres (500 to 700 mg) plus Gelfoam under conscious sedation and local anaesthesia. This was followed by patient-controlled analgesia (PCA) using a morphine pump overnight. Post-procedural pain was assessed by the mean amount of self-administered morphine delivered by PCA pump (mL) from 0 to 19 hours in each group. The mean volumes of the uterus and the dominant fibroid were calculated by ultrasound at baseline, three months, six months, and 12 months. RESULTS A total of 17 women participated in the study. Bilateral uterine artery occlusion was performed in eight women using Gelfoam alone, and in nine women using Embosphere + Gelfoam. One woman in the Embosphere + Gelfoam group developed a puncture-site hematoma requiring further intervention one week later. The mean (SD) amount of morphine self-administered by PCA pump at time 0, 1, and 2 hours was 3.4 mg (3.1), 2.9 mg (2.2), and 2.4 mg (3.3) in the Gelfoam-only group and 6.1 mg (3.0), 9.6 mg (7.1), and 5.3 mg (4.4) in the Embosphere + Gelfoam group, respectively. After three hours, the amount of morphine used was equal in both groups. The mean (SD) total dose of morphine used was 29.5 mg (18.6) in the Gelfoam group and 41.1 mg (19.3) in the Embosphere + Gelfoam group (P = 0.228). At 12 months, the reduction in median total uterine volume and median dominant fibroid volume in each group was equal. CONCLUSION Clinical outcomes were equivalent after uterine artery embolization using Gelfoam alone versus Gelfoam + Embospheres. Although the amount of immediate post-procedure pain may be less with Gelfoam alone, we could not demonstrate this objectively using morphine use as a measure of pain.