Phase II study of Spherex (degradable starch microspheres) injected into the hepatic artery in conjunction with doxorubicin and cisplatin in the treatment of advanced-stage hepatocellular carcinoma: interim analysis.

Patients with advanced-stage unresectable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial doxorubicin 30 mg/m2 plus escalating doses of cisplatin up to 100 mg/m2 in conjunction with rapid bolus injection of Spherex (degradable starch microspheres; Kabi Pharmacia, Lund, Sweden) into the hepatic artery, until slowing or reversal of blood flow. Treatments were repeated every 4 to 6 weeks until progression, or were continued indefinitely if there was disease stability or response. Thirty-five evaluable patients have so far been accrued to the study. Objective tumor responses have occurred in 22 patients (63%), of whom 20 had partial responses and two had complete responses. Four of the patients had reversal of tumor-induced portal vein thrombus. Toxicities included death, one patient (and a death of uncertain cause in an additional patient); hepatitis, two patients; pancreatitis, one patient; dyspnea/hypotension, two patients; and hepatic artery nontransient thrombosis in four patients. Six patients have survived 2 years and an additional 10 patients have survived 1 year. The addition of Spherex to intrahepatic arterial chemotherapy for advanced-stage HCC appears to be relatively safe and is well tolerated even in patients with portal vein thrombosis, which represent the majority of patients with advanced-stage HCC.

Hepatic artery angioplasty after liver transplantation: experience in 21 allografts.

PURPOSE: To assess whether percutaneous transluminal angioplasty (PTA) can help prolong allograft survival and improve allograft function in patients with hepatic artery stenosis after liver transplantation. PATIENTS AND METHODS: Hepatic artery PTA was attempted in 19 patients with 21 allografts over 12 years. The postangioplasty clinical course was retrospectively analyzed. Liver enzyme levels were measured before and after PTA to determine if changes in liver function occurred after successful PTA. RESULTS: Technical success was achieved in 17 allografts (81%). Retransplantation was required for four of 17 allografts (24%) in which PTA was successful and four of four allografts in which PTA was unsuccessful; this difference was significant (P = .03). Two major procedure-related complications occurred: an arterial leak that required surgical repair and an extensive dissection that necessitated retransplantation 14 months after PTA. Hepatic failure necessitated repeat transplantation in seven cases from 2 weeks to 27 months (mean, 8.4 months) after PTA. Six patients died during follow-up, three of whom had undergone repeat transplantation. Markedly elevated liver enzyme levels at presentation were associated with an increased risk of retransplantation or death regardless of the outcome of PTA. CONCLUSION: PTA of hepatic artery stenosis after liver transplantation is relatively safe and may help decrease allograft loss due to thrombosis. Marked allograft dysfunction at presentation is a poor prognostic sign; thus, timely intervention is important.

Treatment of hepatic-metastatic colorectal cancer with a chemotherapeutic emulsion: interim results of a phase I trial.

BACKGROUND: Hepatic arterial infusion of 5-fluoro-2-deoxyuridine (FUdR) is associated with a 60% response rate among previously untreated patients who have hepatic-metastatic colorectal cancer. One obstacle to further dose escalation has been concomitant hepatic toxicity. We are evaluating a FUdR-containing chemotherapeutic emulsion to further dose intensify therapy without associated toxicity. METHODS: The in vitro pharmacokinetics of the emulsion were determined using high-pressure liquid chromatography (HPLC). The rate at which FUdR is released from emulsion into an overlying aqueous phase was determined in static and dynamic assays. Fifteen patients with hepatic-metastatic colorectal cancer were treated with intrahepatic arterial infusions of emulsion on a phase I dose-escalating clinical protocol. Serum collection determined systemic drug levels using HPLC. RESULTS: In vitro studies demonstrate that FUdR is slowly released from emulsion into overlying aqueous medium. The emulsion serves as a depot for FUdR. Therapy was well tolerated. Emulsion was sequestered in the liver after infusion in all treated patients. CONCLUSIONS: This Ethiodol-based, oil-in-water emulsion serves as a sustained-release preparation of FUdR. An Ethiodol-based oil-in-water emulsion is a clinically effective vehicle for delivering FUdR to hepatic-metastatic colorectal tumors.

Transhepatic balloon dilation of biliary strictures in liver transplant patients: a 10-year experience.

PURPOSE: The authors report their initial and long-term results using transhepatic balloon dilation to treat biliary strictures in liver transplant patients. PATIENTS AND METHODS: Over a 10-year period, 72 liver transplant patients with biliary strictures underwent 81 balloon dilation treatments. Anastomotic strictures were present in 56 patients; nonanastomotic strictures were present in 16. RESULTS: Initial technical success was achieved in 64 of 72 patients (89%). Balloon dilation failed in eight patients (11%), and they were treated surgically. Complications occurred in nine (12%) patients, and all were successfully treated. Within the first 6 months, five patients (6.9%) required surgical revision. Three patients (4.2%) underwent repeated liver transplantation; and five patients (6.9%) died. Fifty-one patients in whom balloon dilation was initially successful were available for at least a 6-month follow-up. Life-table analysis showed an overall 81% +/- 4.8 success rate at 6 months; it dropped to 70% +/- 6.2 at 6 years. For anastomotic strictures, it was 77% +/- 5.8 at 6 months and 66% +/- 7.3 at 6 years. For nonanastomotic strictures, it was 94% +/- 6.2 at 6 months, which dropped to 84% +/- 10 at 5 years. CONCLUSION: Transhepatic balloon dilation represents an effective and relatively safe treatment for biliary stricture in liver transplant recipients.

Double-blind study of the safety, tolerance, and diagnostic efficacy of iopromide as compared with iopamidol and iohexol in patients requiring aortography and visceral angiography.

RATIONALE AND OBJECTIVES: Nonionic contrast media have been shown to be more effective, better tolerated, and safer than standard high-osmolality contrast media when given intravascularly. The aim of this study was to assess the diagnostic efficacy, tolerance, and safety of a new nonionic contrast agent, iopromide (370 mg I/mL), in comparison with two available similar agents, iopamidol (370 mg I/mL) and iohexol (350 mg I/mL), in two randomized, double-blind clinical studies of patients undergoing abdominal aortography and visceral angiography. METHODS: The iopromide group included 80 patients, and the comparator group consisted of 36 iopamidol and 45 iohexol patients. The quality and diagnostic efficacy of all three contrast agents was rated equally as either good or excellent. RESULTS: On a scale of 0 (none) to 3 (severe) for heat and pain, respectively, the mean scores were 1.08 and 0.43 for iopromide in comparison with 1.15 and 0.35 for the comparator media. Minor adverse clinical experiences were noted in 23% of the iopromide group versus 20% of the comparator group. Nausea and vomiting were more common in the comparator group (7% versus 3%), and headache was noted only in the iopromide group (4%). There were no clinically significant changes in laboratory values in any group. Three severe adverse experiences occurred, but all were deemed unrelated to the contrast agents. CONCLUSION: Based on the results of this study, iopromide appears to be efficacious, safe, well tolerated, and comparable with iohexol and iopamidol for use in abdominal aortography and visceral angiography.

Intervention in the critically ill patient.

In summary, interventional techniques are well-established and offer safe and effective alternatives for management of patients in the intensive care unit or other setting. It is likely that the radiologist will become more involved in the management of ill children and adults. It is hoped that this will reduce the need for opened surgical procedures, reduce the complexity of surgery, and provide treatment options for complications.

Percutaneous transluminal angioplasty of venous anastomotic stenoses complicating liver transplantation: intermediate-term results.

PURPOSE: The authors evaluated the safety and efficacy of percutaneous transluminal angioplasty (PTA) for the treatment of venous stenoses in liver transplant recipients. PATIENTS AND METHODS: Over a 5-year period, 15 venous stenoses were treated with PTA in 12 patients with liver transplants (seven children and five adults). PTA was performed for portal vein stenoses in five patients, inferior vena cava (IVC) stenoses (n = 6) in five patients, combined superior mesenteric vein-portal vein graft anastomosis and hepatic vein-IVC anastomosis in one patient, and combined IVC and hepatic vein-IVC anastomosis in one patient. PTA was repeated in three patients (five procedures) for recurrent IVC stenoses. RESULTS: Initial technical and clinical success of PTA was achieved in 11 patients (92%); failure occurred in one patient (8%) with a portal vein anastomotic stenosis. No complications occurred in the immediate post-procedure period (up to 7 days). Nine patients (75%) are clinically well, with follow-up ranging from 7 to 33 months (mean, 18 months). Two of them required one or more repeated PTA procedures to maintain vessel patency. One patient required retransplantation for chronic rejection at 3 months, and another died of gastrointestinal tract bleeding from a gastric ulcer at 2 months after initially successful IVC PTA. CONCLUSIONS: PTA is a safe procedure for the treatment of venous anastomotic stenoses in liver transplant recipients. PTA of portal vein anastomotic stenosis has favorable intermediate-term results. Repeat PTA may be necessary in some cases of IVC anastomotic stenoses to maintain vessel patency and avoid surgical revision or retransplantation.

Hepatic parenchymal perfusion defects detected with CTAP: imaging-pathologic correlation.

To determine whether characteristics of focal hepatic parenchymal perfusion defects detected with computed tomographic arterial portography (CTAP) correlate with underlying pathologic processes, 245 perfusion defects detected with CTAP in 60 patients who subsequently underwent definitive hepatic surgery were characterized by shape, location within the liver, and relative attenuation value and were prospectively correlated with sectioned pathologic specimens. Of 177 round perfusion defects, 102 (58%) were malignant and 75 (42%) were benign. Only one (2%) of 53 peripheral wedge-shaped defects was malignant. All 15 peripheral flat defects were benign. Defects in characteristic locations anterior to the porta hepatis (n = 15) and adjacent to the intersegmental fissure (n = 7) were uniformly benign. While 83 (56%) of 147 soft-tissue attenuation defects were malignant, only four (6%) of 68 intermediate-attenuation defects were malignant. Although these characteristics of parenchymal perfusion defects aid in differentiation of benign from malignant processes, all other types of perfusion defects are nonspecific and may require biopsy.

Hemobilia complicating transhepatic catheter drainage in liver transplant recipients: management with selective embolization.

Two liver transplantation patients are reported who experienced severe hemobilia following percutaneous placement of a transhepatic biliary drainage catheter. In both, hepatic angiography demonstrated the source of bleeding from a traumatic pseudoaneurysm of a right hepatic artery branch. Hemobilia in both patients was successfully treated using selective embolization techniques. Follow-up computed tomography of the liver showed no evidence of allograft necrosis or abscess formation. One patient developed an intrahepatic biliary stricture adjacent to the embolized branch artery nine months following the procedure. Hepatic artery embolization techniques are effective in the treatment of life-threatening hemobilia posttransplantation.

Diagnostic value of brush cytology in the diagnosis of bile duct carcinoma: a study in 65 patients with bile duct strictures.

Malignant strictures of the extrahepatic bile ducts are difficult to distinguish from benign strictures, particularly in patients with primary sclerosing cholangitis. Because attempts at diagnosing small cancers with fine-needle aspiration biopsy are not possible in the absence of an associated mass lesion and because the sensitivity of exfoliative biliary cytology is controversial, brush cytology has been used as a potential means of establishing a specific diagnosis of bile duct carcinoma. Herein we report our experience with this technique when performed on 65 patients over a 5-yr period. Each had at least one brushing. Thirty-seven were found to have bile duct carcinoma and 28 were found to have benign strictures. Of these 37, the first brushing was positive for malignancy in 15 (40%), whereas four (11%) had cells suspected but not diagnostic of malignancy. Thirteen patients with bile duct carcinoma whose initial brushings were negative for malignancy had second brushings. Of these, five (38%) had malignant cells, whereas three (24%) yielded suspicious cells. Three of the eight whose first two brushings were negative for malignancy were found to have malignant cells on the third brushing. In contrast, of the 28 patients with benign strictures, malignant cells were never found. However, in two patients, suspicious cells were reported with the first but not the second brushing. A single negative or suspicious cytological finding decreased the probability of bile duct carcinoma to 43%. Two and three sequential negative tests reduced the probability to 32% and 0%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent cholangiocarcinoma in the biliary tree after liver transplantation.

Four liver transplant recipients with recurrent cholangiocarcinoma (CCA) within the allograft biliary tree are described. One patient received a transplant for known CCA and three received transplants for end-stage primary sclerosing cholangitis, in which CCA was found within the hepatectomy specimen. All four developed biliary obstruction due to malignant stricture at the bile duct anastomosis 9-15 months after transplantation. Diagnosis of recurrent CCA was made by means of transhepatic brush biopsy in two patients. Recognition that the biliary tract, especially the anastomosis, is a site of recurrence of CCA should facilitate prompt diagnosis by means of transhepatic brush biopsy in patients with biliary obstruction due to stricture. In addition, because of an association between CCA and primary sclerosing cholangitis, preoperative bile duct biopsy should be considered for liver transplantation candidates with the latter condition. Positive biopsy findings may preclude transplantation.

The role of sonography and transhepatic cholangiography in the diagnosis of biliary complications after liver transplantation.

We retrospectively reviewed the results of real-time sonography in 41 patients in whom biliary complications after liver transplantation were documented by percutaneous transhepatic cholangiography. Abnormalities included bile duct stricture (26 cases), occluded internal biliary stent (six cases), common duct redundancy with resultant functional biliary obstruction (three cases), bile leak (three cases), choledocholithiasis (two cases), and an abscess in a cystic duct remnant (one case). Sonography was abnormal in 22 of the 41 cases (sensitivity, 54%). Bile duct dilatation was the positive sonographic finding in 19 (86%) of the 22 abnormal examinations. In the remaining 19 patients, sonography was normal. Sonography is not a reliable test for the early detection of biliary abnormalities after liver transplantation. Percutaneous transhepatic cholangiography should be performed in patients with suspected biliary complications after liver transplantation.

Pseudoaneurysms complicating organ transplantation: roles of CT, duplex sonography, and angiography.

In a retrospective study of proved pseudoaneurysms (PAs) in 15 patients with transplanted organs (11 liver, three kidney, one pancreas), the results of computed tomography (CT), duplex sonography, and angiography were reviewed. Of the 15 cases of PA, eight occurred at the arterial anastomosis and seven were nonanastomotic. Three of the eight anastomotic PAs were caused by infection. Of the seven nonanastomotic PAs, four were caused by percutaneous biopsy, two were caused by infection, and one was of undetermined cause. In nine (60%) of the 15 patients the PAs were incidentally detected at imaging studies performed for other reasons. Diagnosis requires a high degree of suspicion. CT was performed in nine cases and duplex sonography in ten. The diagnosis of PA was made with CT in six (67%) patients and with duplex sonography in five (50%). CT and duplex sonography could not enable diagnosis when the PA was small, when the arterial anastomosis was not included in the field of study, or when enhancement with intravenously administered contract material was suboptimal. Angiography depicted the PAs in all 15 patients. In three liver transplant recipients with gastrointestinal tract bleeding, the causative PAs were detected only with angiography.

Diagnostic and interventional radiology in liver transplantation.

Diagnostic and interventional radiology play major roles in the evaluation and management of liver transplant patients. This article begins with a discussion of imaging techniques used in the preoperative evaluation of transplant candidates. Surgical approaches and normal posttransplant anatomy are presented. An in-depth discussion of the radiologic evaluation of posttransplantation complications follows, with numerous illustrative cases. Finally, the role of interventional radiology in the nonoperative management of certain complications, especially biliary problems, is discussed.

Percutaneous transhepatic balloon dilatation of benign biliary strictures.

Between February 1981 and June 1984, 15 patients with benign biliary strictures were treated with percutaneous transhepatic balloon dilatation. Three of these patients had received liver transplants. The treatment began with a course of balloon dilatation therapy, after which a stent catheter was left across the stricture. Six weeks later, after duct patency had been shown by cholangiography, the stent catheter was removed from all but two patients, both of whom had intrahepatic sclerosing cholangitis. After this procedure, six patients (40%), including two liver-transplant patients, were stricture-free after one treatment for periods ranging from 27 to 56 months, and were considered to be treatment successes. Nine patients (60%) suffered stricture recurrences. In eight of these patients, the stricture was heralded by symptoms of either cholangitis or jaundice; in one patient, who was on permanent catheter drainage, the stricture was discovered only on follow-up cholangiography. All successfully treated patients had only one stricture, while all patients with more than one stricture suffered recurrences. Our data also suggest a greater responsiveness for anastomotic strictures than for non-anastomotic strictures. Of the patients with recurrences, five had symptom-free intervals of 23 months or more (up to 31 months). The fact that strictures recurred after such long periods of time underscores the importance of long-term follow-up. In view of the number of patients helped, the favorable experience with post-liver-transplantation strictures, and the lack of any major complications in our series, percutaneous biliary balloon dilatation offers a viable alternative to surgical management of benign biliary strictures.