Kenneth W. Sniderman

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.

Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome

Hepatorenal syndrome (HRS) is a functional renal disorder complicating decompensated cirrhosis. Treatments to date, except liver transplantation, have been able to improve but not normalize renal function. The aim of this study was to determine the efficacy of transjugular intrahepatic portosystemic stent shunt (TIPS) as a treatment for type 1 HRS in ascitic cirrhotic patients, following improvement in systemic hemodynamics with a combination of midodrine, octreotide, and albumin (medical treatment). Fourteen ascitic cirrhotic patients with type 1 HRS received medical therapy until their serum creatinine reached below 135 μmol/L for at least 3 days, followed by a TIPS if there were no contraindications. Patients were assessed before and after medical treatment, as well as at 1 week and 1, 3, 6, and 12 months post‐TIPS with measurements of renal function, sodium handling, systemic hemodynamics, central blood volume, and hormonal markers. Medical therapy for 14 ± 3 days improved renal function (serum creatinine: 233 ± 29 μmol/L vs. 112 ± 8 μmol/L, P = .001) and renal sodium excretion (5 ± 2 mmol/d vs. 9 ± 2 mmol/d, P = .002) in 10 of the 14 patients. TIPS insertion in five of the responders further improved renal function and sodium excretion, so that by 12 months post‐TIPS, glomerular filtration rate (96 ± 20 mL/min, P < .01 vs. pre‐TIPS) and urinary sodium excretion (119 ± 15 mmol/d, P < .01 vs. pre‐TIPS) were normal, associated with normalization of plasma renin and aldosterone levels and elimination of ascites. In conclusion, TIPS is an effective treatment for type 1 HRS in suitable patients with cirrhosis and ascites, following the improvement of renal function with combination therapy of midodrine, octreotide, and albumin. (HEPATOLOGY 2004;40:55–64.)

Transjugular intrahepatic portosystemic stent shunt : effects on hemodynamics and sodium homeostasis in cirrhosis and refractory ascites

Transjugular intrahepatic portosystemic shunt (TIPS) was recently introduced as an alternative treatment for massive refractory ascites associated with cirrhosis. Preliminary studies from several centers [1-4] have shown encouraging results. Patients have either been reported to improve clinically and to have decreased ascites [1-3] or have been documented as having increased creatinine clearance and urinary sodium excretion [4]. The pathophysiology of sodium retention in cirrhosis is still a controversial topic. The peripheral arterial vasodilatation hypothesis proposes that patients with cirrhosis have systemic arterial vasodilatation, which leads to a reduction in effective arterial blood volume. This reduction, in turn, activates various neurohumoral pressor systems to promote the renal retention of sodium and water [5]. However, the mechanism linking the reduction of sinusoidal portal pressure with natriuresis and diuresis is still unclear. A significant inverse relation between the indices of portal pressure and sodium excretion has been shown [6], and a critical level of sinusoidal portal pressure (8 mm Hg) has been found, below which ascites does not occur [6, 7]. Increased systemic vasodilatation after TIPS insertion [8-10] may lead to changes in renal hemodynamics and renal sodium handling. Changes in neurohumoral profile after the reduction of sinusoidal portal pressure may also be implicated in the mediation of the natriuresis, because positive correlations have been found between portal pressure and circulating antinatriuretic substances, namely, plasma renin activity and norepinephrine [11]. Therefore, our aim was to better define the pathophysiology of sodium retention by determining the following in patients with refractory ascites treated with TIPS: 1) changes in systemic and renal hemodynamics, renal sodium homeostasis, neurohumoral profile, and central blood volume; and 2) the relation among these variables. Methods Approval for the study was granted by the Human Experimentation Committee of the University of Toronto, and all patients gave informed consent. Patients Seven patients (5 men and 2 women) 38 to 75 years of age (mean age, 60 4 years) with biopsy-proven cirrhosis and refractory ascites were studied prospectively from November 1993 to June 1994. Ten patients were referred during that period for assessment of suitability for TIPS insertion, and 3 were rejected (1 was diagnosed with inoperable carcinoma of the rectum, 1 was diagnosed with hairy-cell leukemia, and one had a thrombosed portal vein on Doppler ultrasonography). The cause of cirrhosis was alcohol use in 3 patients and viral hepatitis B virus in 2 patients; cirrhosis was cryptogenic in 2 patients. Baseline clinical and biochemical data and severity of liver disease according to the Pugh classification [12] (Appendix Table 1) are shown in Tables 1 and 2. Five patients were Pugh class B (score, 7 to 9) and 2 were Pugh class C (score, 10). Patients with cirrhosis caused by alcohol use had abstained from alcohol for at least 6 months before being entered into the study. All patients had had ascites for more than 6 months before study entry. Refractoriness was defined as a prolonged history of ascites unresponsive to 400 mg of spironolactone or 30 mg of amiloride plus up to 120 mg of furosemide daily for 2 weeks. Table 1. Changes in Clinical Hematologic Measurements and Liver Function in Patients with Ascites after Insertion of Transjugular Intrahepatic Portosystemic Stent Shunts* Table 2. Changes in Renal Function and Sodium Excretion in Patients with Ascites after Insertion of Transjugular Intrahepatic Portosystemic Stent Shunts* Appendix Table 1. Assessment of Severity of Liver Disease: Pughs Modification of the Child-Turcotte Classification System* Study Protocol After discontinuing therapy with diuretics, all patients were admitted to the Clinical Investigation Unit of Toronto Hospital on a 22 mmol/d sodium, 1 L/d fluid, caffeine-free diet; this diet was maintained before and after TIPS insertion. During a 1-week stabilization period, patients were monitored daily for weight, serum electrolyte concentrations, and 24-hour urinary sodium excretion. None of the patients chosen for the study had renal disease, cardiovascular disease, or sepsis; all had a patent portal vein. Cardiologic assessment included chest radiography, electrocardiography, two-dimensional echocardiography, and examination by a cardiologist. Patients were excluded if they had primary renal disease that was ruled out by a normal serum creatinine level, normal urine on microscopy, and normal kidney size on ultrasonography; they were also excluded if they had spontaneous bacterial peritonitis that was ruled out by at least two negative ascitic-fluid cultures. Patients with other sources of sepsis, including dental sepsis, were excluded. Doppler ultrasonography was done to ascertain the patency of the portal vein. On the morning before TIPS insertion, all patients had blood drawn for the measurement of baseline plasma norepinephrine levels, plasma renin activity, and aldosterone concentrations and for renal hemodynamic and sodium handling studies. Glomerular filtration rate and renal plasma flow were measured using inulin and para-aminohippurate clearances, respectively, and renal vascular resistance was calculated. Lithium clearance was used as an indicator of proximal tubular reabsorption of sodium [13]. On the afternoon before TIPS insertion, central blood volume was measured using radionuclide angiography [14]. Insertion was done on study day 8 while patients were under intravenous sedation in the angiography suite. Cardiac output, as measured by thermodilution, portal vein pressure, and free and wedged hepatic venous pressures, was measured before and 30 minutes after insertion, and the hepatic venous pressure gradient or the corrected sinusoidal pressure was calculated. On the morning after TIPS insertion, Doppler ultrasonography was done to assess the patency of the TIPS; a shunt flow velocity of more than 100 cm/s indicated a widely patent shunt. Ultrasonography was followed by repeated renal hemodynamic studies and measurements of urinary sodium concentrations, hormonal levels, and central blood volume. In patients with a shunt flow velocity of no more than 100 cm/s, an urgent angiographic study of the TIPS was done. Acute thrombosis was lysed with urokinase, and Doppler ultrasonography was repeated. The patients were observed in the Clinical Investigation Unit for an additional 5 days after TIPS insertion; prophylactic lactulose was begun after TIPS insertion. All patients were reviewed in an outpatient clinic 2 weeks after TIPS insertion. One month after insertion, they were rehospitalized for 1 week for repeated measurements of hormonal levels and central blood volume, for Doppler ultrasonography to assess shunt patency, and for renal hemodynamic studies. These tests were done after 5 days of stabilization in the hospital. Techniques Inulin, Para-aminohippurate, and Lithium Clearances The techniques used to measure inulin and para-aminohippurate clearances [15] and lithium clearances [16] have been described previously. We used these clearances as indices of glomerular filtration rate, renal plasma flow, and proximal tubular sodium reabsorption, respectively. Central Blood Volume Measurements The use of radionuclide angiography to measure central blood volume has been described [14]. Quality assurance studies done in our Nuclear Cardiology Laboratory have established the standard error of the estimate of left ventricular ejection fraction calculation to be less than 2% using semi-automated techniques. The standard error of the estimate of ventricular volume calculation is less than 5 mL [17]. Insertion of TIPS Under sterile technique and after the patient had received local anesthesia and moderate intravenous sedation, the left branch of the portal vein was punctured from the anterior abdominal approach using a 22-G needle and ultrasonographic guidance. A Mandril guidewire (Cook, Inc., Bloomington, Indiana) was advanced through the needle into the portal vein and positioned across the confluence of the left and right portal veins. Next, the right internal jugular vein was punctured at the mid-neck under local anesthesia. Using the Seldinger technique, a 10-F sheath was inserted. A double-lumen Swan-Ganz catheter was then introduced through the sheath; right heart pressures were measured and cardiac output was measured by thermodilution. A 9-F Colapinto catheter (Cook, Inc.) was then inserted, and pressure measurements were obtained from the inferior vena cava and from the free and wedged hepatic veins. A transjugular liver biopsy needle (Cook, Inc.) was then inserted through the catheter, and the hepatic parenchyma was punctured under fluoroscopic guidance; the puncture was directed toward the Mandril wire. When blood was aspirated, a small injection of radiographic contrast medium was used to confirm cannulation of the portal vein. The Colapinto catheter was advanced over the needle into the portal vein, and then portal venography was done and portal pressure was measured. A 5-F angioplasty balloon (Cook, Inc.) was used to dilate the intrahepatic tract to 8 mm. A 68-mm Wallstent (Schneider, Inc., Richmond Hill, Ontario, Canada) was then advanced and deployed to lie in the parenchymal tract, extending at least 2 cm into the portal vein. If the stent did not completely traverse the tract to the hepatic vein, a second, overlapping stent was placed. The stent or stents were dilated to between 8 and 9 mm using a high-pressure angioplasty balloon. Portal venography and pressure measurements were repeated. If the portosystemic gradient exceeded 8 mm Hg, the stent or stents were re-dilated to 10 mm. After a resting period of 30 minutes, right heart pressures and cardiac output measurements were repeated. All catheters were then withdrawn and hemostasis w

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.

Intraabdominal hemorrhage as a result of segmental mediolytic arteritis of an omental artery: Case report *

This article describes the fifth reported case of segmental mediolytic arteritis and the second in a survivor. The patient had intraabdominal bleeding as a result of a ruptured omental artery. The pathologic and arteriographic findings are described. The pathology is characterized by segmental disruption of the medial smooth muscle cells and the initiation of mediolysis. Mediolysis is associated with marked segmental thinning of the vessel wall, often with only the adventitia intact. Fibrin is deposited at the adventitial and medial surfaces, and hemorrhage into the media may occur. As in this reported case, lysis of the adventitia leads to sudden, often catastrophic intraabdominal hemorrhage. Little associated adventitial inflammation occurred. Segmental mediolytic arteritis seems to involve the intra-abdominal muscular arteries in elderly patients with nonspecific abdominal symptoms. An angiogram showed patchy areas of narrowing involving ileal, gastroduodenal, and renal arteries that correlated with the pathologic findings observed in the excised omental arteries.

Percutaneous Transluminal Angioplasty of Abdominal Aortic Stenoses

Percutaneous transluminal angioplasty (PTA) was performed on 25 patients with localized distal abdominal aortic stenoses. All patients were smokers and all complained of bilateral lower limb claudication. Eleven patients had small distal aortas and iliac vessels. Technically successful dilatation was achieved in all patients. Long-term follow-up was available on 17 of the patients. The mean follow-up period was 38 months. Cumulative patency at 5 years was 70%. Thirteen patients remain asymptomatic 15–83 months following PTA. Late failure occurred in 4 patients, 1–38 months following PTA. No complications related to PTA were experienced. PTA of localized aortic stenoses is a safe alternative to surgery and should be the treatment of choice in this condition.

The renal sympathetic and renin-angiotensin response to lower body negative pressure in well-compensated cirrhosis

BACKGROUND & AIMS Certain antinatriuretic hormonal systems may be involved in the subclinical sodium handling abnormality in preascitic cirrhosis. The aims of this study were to determine the following in preascitic cirrhosis: (1) basal activity of the renal sympathetic and renin-angiotensin systems and (2) the relationship between the response of these systems to lower body negative pressure and sodium excretion. METHODS Seven preascitic cirrhotic patients and 9 age- and sex-matched controls were studied on a 150 mmol sodium per day diet. Systemic and renal hemodynamics, renal neurohormonal secretion rates, and sodium excretion were assessed before, during increasing levels of, and after lower body negative pressure, each for 30 minutes. RESULTS Both groups responded with a significant decrease in central venous pressure (P < 0.01) that remained higher in the cirrhotics than in the controls throughout the study. Cirrhotics showed significant increases compared with controls in renal renin and angiotensin II secretion rates at -20 mm Hg of lower body negative pressure, which was associated with significant renal sodium retention (96 +/- 17 micromol/min vs. 218 +/- 21 micromol/min at baseline, P < 0.05), but there was no change in renal sympathetic activity. CONCLUSIONS In preascitic cirrhosis, sodium retention occurs in response to lower body negative pressure, which was associated with increased renal renin-angiotensin activity. Stimulation of the intrarenal renin-angiotensin system may be the initial renal pathophysiological change causing sodium retention in cirrhosis.

Long‐term clinical outcome of patients with cirrhosis and refractory ascites treated with transjugular intrahepatic portosystemic shunt insertion

Transjugular intrahepatic portosystemic shunt (TIPS) is indicated for the treatment of refractory ascites in cirrhosis. The long‐term outcome of TIPS for refractory ascites is unknown. The aim of this study is to describe the natural history of patients with refractory ascites post‐TIPS, and compare between polytetrafluoroethylene (PTFE)‐covered versus bare stents.

Salvage of in situ femoropopliteal and femorotibial saphenous vein bypass with interventional radiology.

Arteriovenous fistulas and late graft stenoses are well-known potential causes of in situ saphenous vein bypass failure. Three patients are described who had one or both of these complications postoperatively (early and late). Two techniques are described that can be performed at the time of arteriography to save a functioning bypass.