Andrew Common

The Ontario Uterine Fibroid Embolization Trial. Part 2. Uterine fibroid reduction and symptom relief after uterine artery embolization for fibroids

OBJECTIVE To evaluate fibroid uterine volume reduction, symptom relief, and patient satisfaction with uterine artery embolization (UAE) for symptomatic fibroids. DESIGN Multicenter, prospective, single-arm clinical treatment trial. SETTING Eight Ontario university and community hospitals. Five hundred thirty-eight patients undergoing bilateral UAE. INTERVENTION(S) Bilateral UAE performed with polyvinyl alcohol particles sized 355-500 microm. MAIN OUTCOME MEASURE(S) Three-month follow-up evaluations including fibroid uterine volume reductions, patient reported symptom improvement (7-point scale), symptom life-impact (10-point scale) reduction, and treatment satisfaction (6-point scale). RESULT(S) Median uterine and dominant fibroid volume reductions were 35% and 42%, respectively. Significant improvements were reported for menorrhagia (83%), dysmenorrhea (77%), and urinary frequency/urgency (86%). Mean menstrual duration was significantly reduced after UAE (7.6 to 5.4 days). Improvements in menorrhagia were unrelated to pre-UAE uterine size or post-UAE uterine volume reduction. Amenorrhea occurring after the procedure was highly age dependent, ranging from 3% (1%-7%) in women under age 40 to 41% (26%-58%) in women age 50 or older. Median fibroid life-impact scores were significantly reduced after UAE (8.0 to 3.0). The majority (91%) expressed satisfaction with UAE treatment. CONCLUSION(S) UAE reduced fibroid uterine volume and provided significant relief of menorrhagia that was unrelated to initial fibroid uterine size or volume reduction. Patient satisfaction with short-term UAE treatment outcomes was high.

Pregnancy after uterine artery embolization for leiomyomata: the Ontario multicenter trial.

OBJECTIVE: To report on pregnancies and deliveries occurring in a large cohort of women who underwent uterine artery embolization instead of surgery for symptomatic leiomyomata. METHODS: A total of 555 women underwent uterine embolization in a multicenter clinical trial. The primary embolic agent was 355–500 μm polyvinyl alcohol particles with treatment end-point as bilateral stasis in the uterine arteries. Women desiring pregnancy were informed of the uncertain effect of embolization on fertility and pregnancy. Average age at embolization was 43 years (range 18–59 years). Thirty-one percent were younger than age 40 years. Women were followed up prospectively by telephone, and obstetric records of the women who conceived were reviewed. RESULTS: Twenty-one women of average age 34 years (range 27–42 years) conceived, (3 of these twice), and 13 women were nulliparous. Twenty-three of the 24 pregnancies were conceived spontaneously (1 woman had in vitro fertilization). There were 4 spontaneous abortions (16.7%, 95% confidence interval 5.4–41.9%) and 2 elective pregnancy terminations. Fourteen of the 18 live births were full term and 4 were preterm. There were 9 vaginal deliveries and 9 cesarean deliveries, 4 of which were elective. Abnormal placentation occurred in 3 cases, all nulliparas (12.5% 95% confidence interval 3.1–36.3%). Two cases developed placenta previa (1 had a clinical partial accreta) and the third developed a placenta membranacea with accreta resulting in cesarean hysterectomy. Three postpartum hemorrhages all secondary to placental abnormalities occurred. Four newborns were small for gestational age (≤ 5th percentile); 2 of these pregnancies were complicated by gestational hypertension. CONCLUSION: Women are able to achieve pregnancies after uterine artery embolization, and most resulted in term deliveries and appropriately grown newborns. Close monitoring of placental status, however, is recommended. LEVEL OF EVIDENCE: II-3

Pathologic features of uteri and leiomyomas following uterine artery embolization for leiomyomas.

The objectives of this study were to identify the presence/absence and location of any embolic material and to describe the morphologic appearance of the leiomyoma and adjacent tissues of cases undergoing surgical intervention following uterine artery embolization (UAE) for leiomyomas. A total of 555 women underwent UAE using polyvinyl alcohol particles (PVA) in a multicenter clinical trial. The histopathologic slides from 17 of 18 women who subsequently underwent myomectomy or hysterectomy in the follow-up period (median 8.2 months) were reviewed without knowledge of the indication for surgery or time elapsed since UAE. The presence/absence and distribution of PVA emboli, associated inflammatory response, and necrosis were noted. Necrosis of leiomyoma(s) was classified as hyaline-type, coagulative tumor cell necrosis, and/or acute suppurative necrosis. In all cases PVA emboli were identified within smooth muscle tumors of the uterine body, its periphery, cervix, uterine body, myometrium, and/or the adnexa. A florid foreign body giant cell type of chronic inflammatory reaction was seen within 1 week of UAE and persisted with visible PVA for up to 14 months post-UAE. Typically, post-UAE leiomyomas showed hyaline-type, but rarely coagulative tumor cell necrosis and acute suppurative necrosis could be seen as well. Five of eight cases coming to surgery for complications showed necrotizing endomyometritis with tissue infarction. PVA particles are recognizable in post-UAE specimens. Leiomyoma necrosis is typically of the hyaline type; coagulative tumor cell necrosis was rarely seen. In some cases with complications, uterine and/or cervical necrosis occurred. The applicability of these findings for UAE patients who have been successfully treated and not resected is uncertain.

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.

Hysterectomy for Complications after Uterine Artery Embolization for Leiomyoma: Results of a Canadian Multicenter Clinical Trial

STUDY OBJECTIVE To determine the complication-related hysterectomy rate after uterine artery embolization (UAE) for symptomatic uterine leiomyomas. DESIGN Prospective, multicenter, nonrandomized, single-arm clinical trial (Canadian Task Force classification II-2). SETTING Eight Ontario University-affiliated teaching and community hospitals. PATIENTS Five hundred fifty-five women. INTERVENTION Polyvinyl alcohol particles were delivered through a catheter into uterine arteries under fluoroscopic guidance. MEASUREMENTS AND MAIN RESULTS Prospective follow-up investigations consisted of telephone interviews, ultrasound examinations, and reviews of pathology and surgery reports. Median follow-up was 8.1 months, and all but five patients had complete 3-month follow-up. At 3 months, eight women (1.5%, 95% CI 0.6-2.8) underwent complication-related hysterectomy. Half of the surgeries were performed at institutions other than where UAE had been performed. Indications for hysterectomies were infections (2), postembolization pain (4), vaginal bleeding (1), and prolapsed leiomyoma (1). CONCLUSIONS The 3-month complication rate resulting in hysterectomy after UAE in a large cohort of women was low. Hysterectomy after UAE is an important measure of safety and a key outcome measure of this new therapy.

Therapeutic failure of uterine fibroid embolization caused by underlying leiomyosarcoma

The authors describe an unusual case in which continued growth of uterine fibroids in a postmenopausal patient after polyvinyl alcohol embolization therapy prompted hysterectomy, which revealed an underlying leiomyosarcoma. The surgery was nearly fatal as a result of venous bleeding, and parasitization of blood from adjacent bowel by the tumor was noted. The difficulty of preoperative diagnosis of leiomyosarcoma and the need for diligent follow-up after uterine fibroid embolization are discussed.

Digital Subtraction Angiography of the Abdominal Aorta and Lower Extremities: Carbon Dioxide versus Iodinated Contrast Material

PURPOSE To compare the diagnostic value of carbon dioxide to that of iodinated contrast material for digital subtraction angiography of the abdominal aorta and lower extremities. MATERIALS AND METHODS Thirty-five patients underwent comparative CO2 and iodinated contrast material arteriography of the abdominal aorta and lower extremities. For each contrast study, three independent observers evaluated the degree of opacification and percentage of stenosis of each vessel, the degree of certainty of their observations, and the overall quality of the study. Data of CO2 and iodinated studies were compared using analysis of variance for repeated measures. Interobserver and intertechnique agreements were estimated with Cohens kappa and intraclass correlation coefficient. RESULTS Iodine-based vascular opacification was superior to that with CO2 in the central and distal arteries (P = .02). The degree of certainty and overall quality score were higher for iodine than for CO2-based contrast studies (P = .00001). The interobserver agreement for categorizing stenoses was higher for iodine as compared to CO2-based angiography. No significant difference was observed between the mean stenosis values obtained with CO2 and iodine-based angiography in any segment. Intraclass correlation coefficient demonstrated a high degree of convergence of the two techniques for assessing the percentage of stenosis. CONCLUSION CO2 can be used as an alternative to iodinated contrast material for obtaining arteriograms of the abdominal aorta and lower extremities for investigating atherosclerotic disease.

HIV-Specific T-Cells Accumulate in the Liver in HCV/HIV Co-Infection

Background and Aims Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses. Methods Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry. Results HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4+ T-cells compared to HCV biopsies. In co-infection, intra-hepatic HIV-specific CD8+ and CD4+ T-cells producing IFN-γ and TNF-α were detected and were comparable in frequency to those that were HCV-specific. In co-infected individuals, viral-specific CD8+ T-cells produced more of the fibrogenic cytokine, TNF-α. In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells. In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4+ T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses. Conclusion The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease.

Aggressive clinical pattern of angina at restenosis following coronary angioplasty in unstable angina

The frequency, clinical pattern, and timing of recurrent angina following successful single-lesion percutaneous transluminal coronary angioplasty (PTCA) was assessed in a consecutive group of 104 patients with stable angina and in 85 with unstable angina. In addition, the relationship between lesion morphology and angiographic features and the pattern of recurrent angina was determined. Restenosis, defined as recurrence of symptoms with > 50% stenosis at the site of PTCA, occurred in 25 (24%) of the stable group and in 23 (27%) of the unstable group (p = NS). The pattern of angina at repeat presentation was aggressive in nature in 8% of the stable group and in 48% of the unstable group (p = 0.002). The time interval between the recurrence of symptoms and repeat coronary angiogram or PTCA was longer in the nonaggressive group than in the aggressive group, 16 +/- 12.1 and 5 +/- 6.8 weeks, respectively (p < 0.003). The key factors predicting the recurrent angina pattern identified by multiple logistic regression analysis were the angina status pre-PTCA (p = 0.001) and the presence of double-vessel disease (p = 0.01). An aggressive pattern of angina at the time of restenosis is frequent in patients with unstable angina at the time of PTCA, and close post-PTCA surveillance is necessary in these patients.