Biliary strictures in liver transplant recipients: treatment with metal stents.

PURPOSE: To determine initial and long-term results of metal stent placement in biliary strictures that failed to respond to balloon dilation. MATERIALS AND METHODS: Sixty-one metal stents were placed in 36 liver transplant recipients (age range, 3 months to 71 years) with biliary strictures that failed to respond to balloon dilation. Patients were followed up for up to 5 years. RESULTS: Initial stent placement was successful in all patients. Primary patency was 44% at 3 years and was 0% at 5 years; secondary patency was maintained at 88% at those intervals. Patency associated with the Gianturco Z stent was superior to that with the Palmaz stent. Stents located at anastomotic sites had higher patency rates than those at nonanastomotic sites. Major stent-related complications occurred in eight patients and included two pediatric deaths. CONCLUSION: Metal stents can be useful in the short term but have limited patency, often require repeat intervention, and have substantial complications. Long-term success depends heavily on repeat interventions or stent removal.

Radiolabeled iododeoxyuridine: safety evaluation.

UNLABELLED: The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration. METHODS: Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained. RESULTS: To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation. CONCLUSION: When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.

On the safety of 5-[125I]iodo-2'-deoxyuridine--Preclinical evaluation in swine.

To increase tumor incorporation and minimize hepatic degradation of radio-IUdR, compartmental administration routes are being considered as an alternative to intravenous (i.v.) injections. Although there are significant data on the biodistribution and some reports on radiotoxicity of i.v.-administered 125IUdR, similar results for other routes of delivery are not available. We have undertaken a series of experiments intended to examine radiation effects of 125IUdR after intravesical (3 swine; eight 3 mCi doses at 4-day intervals), intracarotid (3 swine; two 10 mCi doses at 2-week intervals), and intra-aortic (5 swine, single dose of 10 mCi) administration in a swine model. Liver, renal functions, and complete blood counts were monitored throughout the duration of the experiment. Pharmacokinetics, systemic distribution of radioactivity and metabolites were measured. The normal tissue 125IUdR uptake and histology were determined after necropsy. No adverse systemic effects were identified. Clinical observations, laboratory data, and necropsy results were within normal range.

An unopened titanium Greenfield IVC filter: intravascular ultrasound to reveal associated thrombus and aid in filter opening.

A titanium Greenfield filter did not open following placement in the infrarenal inferior vena cava (IVC). Abdominal radiograph and cavogram showed no definite reason for filter malfunction. Intravascular ultrasound (IVUS) demonstrated the unopened filter in the IVC with thrombus binding the legs. The thrombus was disrupted with a catheter, and the filter completely expanded with a balloon. IVUS documented full-filter opening in addition to residual thrombus in the filter following manipulation.

Chronic catheterization of the inferior vena cava in Yucatan miniature swine.

Long-term venous access for leukapheresis, repeated blood sampling, and administration of drugs and fluids can be accomplished nonsurgically in Yucatan miniature swine. The catheter is placed under fluoroscopic guidance into the inferior vena cava using a needle and guidewire. This procedure has the advantage that it avoids a surgical incision, allows high flow rates, exists conveniently on the lower back, and can be replaced easily in the event of mechanical failure or thrombosis. Actuarial analysis of the duration of patency disclosed that of 41 catheters placed in 30 animals, the probability of function at 28, 42, and 54 days was 75%, 50%, and 25%, respectively. Eleven nonfunctioning catheters were replaced and nine of these continued to function until the completion of the experiment. No catheters were removed due to infection. Chronic catheterization of the inferior vena cava is a convenient method for long-term venous access in swine.

Thrombosed central venous catheters: restoring function with 6-hour urokinase infusion after failure of bolus urokinase.

Nineteen central venous catheters with radiographically proven thrombotic occlusion failed to have function restored with a mean of 1.6 5000-unit boluses of urokinase per catheter. Catheters then underwent a 6-hour infusion of urokinase at 40,000 units per hour followed by repeat contrast injection and evaluation of function. Reduction in thrombus size occurred in all but one patient. Catheter function was restored in 15 patients. In two patients, thrombus dissolved but catheters remained occluded because of tip malposition. In the remaining two patients, catheter function was restored with an additional 6-hour infusion. No adverse reactions to the infusion were seen. After infusion catheters continued to function normally for a mean of 36.2 days. Five catheters rethrombosed, two of which responded to urokinase bolus instillation. Thrombosed catheters failing standard intracatheter bolus urokinase are generally salvaged with a 6-hour infusion of low-dose urokinase.

Duplex scans before subclavian vein catheterization predict unsuccessful catheter placement.

Subclavian catheterization in patients with cancer is associated with up to a 38% incidence of subclavian vein thrombosis. These thrombi seldom recanalize. The persistent occlusion of the subclavian vein may hinder subsequent catheter placement. To determine the frequency of this occurrence and to determine if preoperative duplex scanning could identify these individuals, we performed preoperative duplex scanning in 22 patients who had previously had an indwelling subclavian catheter for chemotherapy. Subsequent subclavian vein catheterization was attempted without knowledge of the results of the duplex scan. Nineteen scans were normal. Of these, 18 patients underwent successful catheter placement. In one patient, catheterization was unsuccessful and an intraoperative venogram showed a focal obstruction of the proximal portion of the subclavian vein. Three scans showed noncompressibility of the vein, and catheter placement was unsuccessful in these three veins. In patients who have had previous subclavian catheters, persistent obstruction of the vein prevents subsequent catheter placement in 14%. Duplex scanning before subsequent catheter placement generally identifies these individuals.

Collection of blood mononuclear cells by leukapheresis for transplantation in a Yucatan miniature swine model.

A large animal model is needed to evaluate new apheresis technologies. These technologies include novel methods of harvesting the blood mononuclear cell population which contains the hematopoietic stem cells needed to restore hematopoiesis in recipients of hematopoietically lethal therapy and the use of cytokines to provide a safe and predictable method of manipulating these circulating hematopoietic stem cells. We describe the methods used to collect mononuclear cells by leukapheresis from Yucatan miniature swine. These animals are of sufficient size to tolerate the procedures and have many physiologic and hematologic similarities to man. They are of good temperament and are easily trained. Long-term venous access was obtained using single lumen silicone rubber catheters placed in the inferior vena cava. The animals were apheresed while fully awake using a Haemonetics Model V50 machine and a modified lymphocyte collection protocol. The procedure was highly efficient for the collection of mononuclear cells and a 10 pass procedure yielded a product which contained 19.7 x 10(9) mononuclear cells, 10.7 x 10(9) granulocytes, and 17 ml of erythrocytes in a volume of approximately 100 ml. This product can be cryopreserved and used for subsequent transplantation. The content of four apheresis procedures provides hematopoietic reconstitution of lethally irradiated swine on a time scale equivalent to transplantation of optimal numbers of bone marrow cells.

Utility of duplex ultrasound in the diagnosis of asymptomatic catheter-induced subclavian vein thrombosis.

Asymptomatic thrombosis of the subclavian vein is common after placement of indwelling catheters. The sequelae of these thrombi are not known. Investigation is hampered by the requirement for venography for diagnosis; consequently, a noninvasive method of diagnosis would be welcome in this context. We have studied prospectively 32 subclavian catheters to determine the usefulness of duplex ultrasound in diagnosing asymptomatic thrombosis. Sixteen arm venograms were normal and all gave normal duplex scans. No false-positive scans were obtained. Eleven venograms demonstrated nonocclusive mural thrombi. Only three of these were seen with duplex ultrasound. Five totally occlusive thrombi were seen on venography, of which only two were detected with duplex sonography. The three thrombi not found with duplex ultrasound were short proximal venous occlusions. The insensitivity of this technique to asymptomatic subclavian thrombi limits its usefulness as a screening tool.

Translumbar inferior vena cava catheters.

Translumbar inferior vena cava catheters are a safe method of providing venous access for the collection of peripheral blood stem cells for transplantation. One of the most frequent and consistent problems with these catheters is thrombotic obstruction, occurring in one-fourth of the cases. Aspirin at a dose of 325 mg daily beginning after catheter placement and continuing until completion of stem cell collection has been associated with a reduction in the frequency of catheter thrombosis from 12/60 (20%) to 1/31 (3.2%) (p = 0.007) and an increase in the number of thrombus-free apheresis procedures (p = 0.024) compared to historical controls. No adverse effects of aspirin during stem cell collection have been noted. Daily aspirin ingestion should be considered in patients undergoing peripheral stem cell collection via translumbar inferior vena cava catheters.

Successful liver transplantation in a patient with a thrombosed portomesenteric system after multiple failed shunts.

Combined portal and mesenteric vein thrombosis preventing restoration of adequate portal venous flow has been considered a contraindication to liver transplantation. We report a patient with failed splenorenal (SR), portocaval (PC), and mesocaval (MC) shunts, who despite the absence of any obvious means for supplying portal venous inflow to a hepatic graft, successfully underwent orthotopic liver transplantation. A method of reconstruction of the portal vein with the use of vein grafts anastomosed to a large splanchnic venous collateral is described. This technique can be used in selected patients in whom orthotopic liver transplantation might otherwise be considered technically impossible.

Limitations of magnetic resonance imaging and ultrasound-directed (duplex) scanning in the diagnosis of subclavian vein thrombosis.

To investigate the potential role of magnetic resonance imaging and duplex scanning in the diagnosis of catheter-induced subclavian vein thrombosis, we correlated the results of 43 arm phlebograms with duplex scans; 28 of these phlebograms were also correlated with magnetic resonance imaging scans of the thoracic veins. Eighteen of the 43 phlebograms were normal, and all had normal magnetic resonance imaging and duplex studies. Eleven subclavian veins were totally occluded on phlebography; all had duplex scans, and five were also scanned with magnetic resonance imaging. Duplex scans detected 6 of 11 occlusions, whereas magnetic resonance imaging detected 4 of the 5 occlusions scanned. The five occlusions that were not detected by either magnetic resonance imaging or duplex scans were short segmental occlusions of the medial one third of the left subclavian vein. Of 14 nonocclusive thrombi seen on phlebography, duplex scans correctly identified 8. Magnetic resonance imaging was done on eight nonocclusive thrombi but identified only two. All abnormal findings on duplex scanning and magnetic resonance imaging were confirmed by phlebography. Short occlusions of the proximal portion of the left subclavian vein were often undetected by duplex scanning but occasionally seen with magnetic resonance imaging. Neither modality was sensitive to the presence of nonocclusive mural thrombi. Magnetic resonance imaging is highly reliable in ruling out the presence of a thrombotic process in the subclavian vein, but it may on occasion fail to detect the presence of subclavian thrombi. For this reason, in cases with suspected subclavian vein thrombosis magnetic resonance imaging cannot be used as the only diagnostic modality.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheter-related thrombosis in patients with refractory lymphoma undergoing autologous stem cell transplantation.

Long-term indwelling central venous catheters have eased the administration of drugs, blood products, and hyperalimentation to patients with cancer. However, their use is associated with thrombotic complications. We report here on the thrombotic complications prospectively observed in 46 patients with refractory lymphoma (22 Hodgkin's disease, 24 non-Hodgkin's lymphoma) who had placement of one or more catheters in preparation for autologous stem cell transplantation (ASCT). Thrombosis of 26 catheters in 19 patients was observed. Specific abnormalities of hemostasis were equally common in patients who developed thrombosis and in those who did not. Thrombotic complications were more common in patients with Hodgkin's disease (13/22) than in patients with non-Hodgkin's lymphoma (6/24, p = 0.04). Although more patients with Hodgkin's disease had received prior splenectomy and/or irradiation to the area involved by thrombosis than patients with non-Hodgkin's lymphoma, the incidence of splenectomy and irradiation was similar for patients with Hodgkin's disease who developed thrombosis and those who did not. Therefore, although the etiology remains unexplained, patients with Hodgkin's disease undergoing intensive chemotherapy and ASCT appear to have a higher incidence of catheter-related thrombosis than patients with non-Hodgkin's lymphoma undergoing similar therapy.

Thrombotic complications of silicone rubber catheters during autologous marrow and peripheral stem cell transplantation: prospective comparison of Hickman and Groshong catheters.

Thrombosis is common after placement of silicone rubber subclavian vein catheters in patients with malignancy receiving conventional doses of chemotherapy. To determine the incidence of this complication in marrow transplant patients and the effect of different catheter designs on thrombosis rates, patients were randomized to receive either open-ended Hickman catheters or valve-ended Groshong catheters for venous access during the transplantation procedure. A total of 35 catheters were placed, of which 23 were double-lumen (11 Groshong and 12 Hickman) and 12 were single-lumen (six Groshong and six Hickman). Arm venograms were performed on all patients at the time of hematopoietic recovery or occurrence of symptoms of subclavian vein thrombosis. There were 10 cases of total subclavian vein thrombosis (three were symptomatic) and 12 cases of asymptomatic non-occlusive mural thrombi. Only 13 normal veins were found. There was no difference in thrombosis rate between the Hickman and Groshong catheters. Double lumen catheters tended to be more likely to cause total venous occlusion (nine of 23) than single lumen catheters (one of 12) (p = 0.06, Fisher's exact test). We conclude that subclavian vein thrombosis is a common occurrence after placement of silicone rubber catheters for venous access during marrow transplantation. Most cases are asymptomatic. Groshong catheters are just as likely to cause this complication as Hickman catheters.

Obstructed central venous catheters. Restoring function with a 12-hour infusion of low-dose urokinase.

Thrombotic obstruction frequently prohibits infusion through or withdrawal of blood from central venous catheters and can occur in conjunction with symptomatic thrombosis of the subclavian vein. Thirty catheters were radiographically proved to be obstructed by thrombus and had not responded to at least one instillation of 5000 units of urokinase. All catheters were treated with a 12-hour infusion of urokinase at the rate of 40,000 units/hour. The obstructing thrombus was either eliminated or reduced in size in all instances and full function was restored in all but one catheter. No bleeding complications were seen. Six patients with obstructed catheters also had symptoms of subclavian vein thrombosis. All patients with symptoms of subclavian vein obstruction became asymptomatic on anticoagulant therapy even though no attempt at dissolving the thrombus obstructing the subclavian vein was made. A 12-hour infusion of low doses of urokinase can safely salvage function of obstructed catheters that otherwise may require replacement. Patients with concomitant subclavian vein thrombosis become asymptomatic on anticoagulant therapy without need to dissolve the obstructing thrombus.

Hickman catheter-induced thoracic vein thrombosis. Frequency and long-term sequelae in patients receiving high-dose chemotherapy and marrow transplantation.

One hundred sixty-eight bone marrow transplant recipients and 49 patients who received high-dose chemotherapy were evaluated for symptomatic thrombosis after Hickman catheter placement. The timing of thrombotic complications was different between these two groups, with the transplant group having a significantly lower thrombus-free survival by 28 days after catheter placement. By 100 days after placement the thrombus-free survival rates of the two groups were similar. The platelet count at time of catheter placement was significantly lower in the nontransplant group, and the thrombus-free survival was longer in patients whose catheter was placed when their platelet count was less than 150,000, suggesting that thrombocytopenia delays thrombotic complications. Placement of two Hickman catheters resulted in a 12.9% thrombosis rate (21 of 162 patients) and was significantly more likely to be associated with thrombosis than placement of one catheter. Long-term follow-up evaluation of patients treated without successful fibrinolytic therapy showed no residual symptoms of venous obstruction. In those patients presenting with concomitant catheter obstruction resulting from thrombosis, low-dose fibrinolytic therapy was successful in restoring catheter function 70% of the time. Placement of two Hickman catheters is associated with an inordinate incidence of thrombosis. Thrombocytopenia at the time of catheter placement may delay this complication. Thrombotic catheter obstruction can be treated successfully with low-dose fibrinolytic therapy. Even without fibrinolytic therapy, catheter-induced subclavian vein thrombosis rarely causes long-term disability.

Translumbar inferior vena cava catheters: safety and efficacy in peripheral blood stem cell transplantation.

Most patients who need peripheral blood stem cell transplantation do not have peripheral venous access that would allow apheresis for stem cell collection. Subclavian apheresis catheters have an unacceptably high incidence of thrombosis-related access failure. A technique has been developed for translumbar placement of permanent, subcutaneously tunneled, silicone rubber apheresis catheters into the inferior vena cava, and 40 of these catheters have been placed in 36 patients for stem cell collection. Twenty-six catheters have been left in place for venous access during the transplantation procedure. These catheters had a very low rate (2.3%) of apheresis-related related complications. Access failure was attributed to thrombosis in 10 catheters (25%) and to mechanical complications in another 9 (22%), but access was regained in all but 4 of these cases. The catheters functioned well as venous access devices during transplantation, only rarely developing complications during that time. Venograms performed at the time of removal of 16 catheters showed no case of caval occlusion. A residual fibrin sheath was found around 14 catheters. There was no clinical or computed tomographic scan evidence of bleeding after placement or removal of the catheters. Percutaneously placed, translumbar inferior vena cava apheresis catheters provide a safe and effective route for the collection of peripheral blood stem cells for transplantation, and they can be left in place for venous access during transplantation.