Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT. METHODS: Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected. RESULTS: Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3-4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8-5.1 years] after radioembolization for the entire study population was found. CONCLUSION: Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare. LEVEL OF EVIDENCE: 4, case series.

Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases: International Multicenter Study on Efficacy and Toxicity.

PURPOSE: Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large international, multicentre retrospective study was designed to address several shortcomings of the current literature. MATERIALS: 244 NEN patients with different NEN grades were included. METHODS: Primary outcome parameters were radiologic response 3 and 6 months after treatment according to RECIST 1.1 and mRECIST. Secondary outcome parameters included clinical response, clinical and biochemical toxicities. RESULTS: Radioembolization resulted in CR in 2%, PR in 14%, SD in 75% and PD 9% according to RECIST 1.1 and in CR in 8%, PR in 35%, SD in 48% and PD in 9% according to mRECIST. Objective response rates improved over time in 20% and 26% according to RECIST 1.1. and mRECIST, respectively. Most common new grade 3-4 biochemical toxicity was lymphocytopenia (6.7%). No unexpected clinical toxicities occurred. Radioembolization-specific complications occurred in < 4%. In symptomatic patients, improvement and resolution of symptoms occurred in 44% and 34%, respectively. Median overall survival from first radioembolization was 3.7, 2.7 and 0.7 years for G1, G2 and G3, respectively. Objective response is independent of NEN grade or primary tumour origin. Significant prognostic factors for survival were NEN grade/Ki67 index, ≥ 75% intrahepatic tumour load, the presence of extrahepatic disease and disease control rate according to RECIST 1.1. CONCLUSION: Safety and efficacy of radioembolization in NEN patients was confirmed with a high disease control rate of 91% in progressive patients and alleviation of NEN-related symptoms in 79% of symptomatic patients. LEVEL OF EVIDENCE: 4.

Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation.

Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.

Long-term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusion.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5-16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects. AIM: To examine the clinical outcomes of TACI. METHODS: We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates. RESULTS: Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour-node-metastasis (TNM) IV compared to those with TNM I-III and also for patients with Child's class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child's class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014). CONCLUSIONS: TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I-III; randomized controlled trials are needed to compare TACI to TACE.

Use of curved needles to perform biopsies and drainages of inaccessible targets.

Percutaneous image-guided biopsies and fluid drainages are usually feasible with use of standard, mass-produced, straight needles. Occasionally, target lesions are completely surrounded by interposed structures, such as bone, bowel, colon, pancreas, bladder, or blood vessels, so percutaneous access appears impossible. Although the commercial availability of curved needles is very limited, custom bending of needles may allow unconventional access to these well-protected targets. This technique has been used to reach biopsy and drainage targets that would have otherwise required either high-risk transgression of interposed structures or more invasive surgical procedures.

Impact of multidetector CT hepatic arteriography on the planning of chemoembolization treatment of hepatocellular carcinoma.

OBJECTIVES: We examined the impact of the increased sensitivity for hypervascular masses of multidetector CT hepatic arteriography on treatment decisions involving selective chemoembolization of hepatocellular carcinomas. SUBJECTS AND METHODS: Thirty patients were referred for chemoembolization of unresectable hepatocellular carcinoma. Initial selective chemoembolization plans were formulated on the basis of diagnostic biphasic CT or MR imaging. Ultrafast CT hepatic arteriography was performed using a multidetector CT scanner and selective contrast material injection into the hepatic artery. The entire liver was scanned in a single breath-hold of approximately 20 sec with a slice thickness of 1 mm. Lesions and their arterial supplies were identified, and these data were immediately used to formulate a final plan for chemoembolization. RESULTS: Hypervascular masses were detected in 29 patients. In 16 (53%) of the patients, preprocedural CT or MR imaging underestimated the number of lesions. In nine (30%) of these 16 patients, the additional lesions were detected only on CT hepatic arteriography, not on conventional angiography. CT hepatic arteriography findings had a major impact on planning the way in which chemoembolization treatment was performed. In three of the nine patients, the previously undetected lesions were treated with additional superselective chemoembolization. In the other six patients, chemoembolization was performed less selectively than originally planned. CONCLUSION: Primarily because of the high sensitivity of multidetector CT hepatic arteriography in revealing small and multifocal hepatomas, findings of this modality frequently alter treatment plans involving selective administration of chemoembolic material.

Delayed complications after esophageal stent placement for treatment of malignant esophageal obstructions and esophagorespiratory fistulas.

PURPOSE: To evaluate delayed complications after esophageal expandable metallic stent placement. MATERIALS AND METHODS: From April 1993 to December 1997, 90 expandable metallic stents were placed in 82 consecutive patients with inoperable malignant esophageal obstruction (n = 49) or malignant esophagorespiratory fistula (n = 33). Stents used included covered Gianturco-Rosch Z stents (n = 20), Wallstents (covered, n = 31; uncovered, n = 13), and Ultraflex stents (covered, n = 8; uncovered, n = 10). Patients were followed prospectively and monitored for delayed complications, defined as major (hemorrhage, tracheal compression, stent migration, perforation or fistula formation, granulomatous obstruction, tumor ingrowth and overgrowth, funnel phenomenon, and stent covering disruption) or minor (reflux, chest pain, and food impaction). RESULTS: Mean survival was 4.5 months after stent placement (range, 3 weeks to 26 months). The overall incidence of delayed complications was 64.6%, with 17 patients (20.7%) experiencing more than one complication. The rates of delayed complications in patients with Z stents, Wallstents, and Ultraflex stents were 75.0%, 68.1%, and 44.4%, respectively (P <.05). Most complications were life-threatening and occurred more frequently when stents were placed in the proximal third of the esophagus, compared with more distally (P <.05). Thirteen patients (15.9%) died from complications directly related to stent placement. CONCLUSION: Esophageal stent placement for malignant obstruction or fistula is associated with a substantial incidence of delayed complications.

Truly hybrid interventional MR/X-ray system: investigation of in vivo applications.

RATIONALE AND OBJECTIVES: The purpose of this study was to provide in vivo demonstrations of the functionality of a truly hybrid interventional x-ray/magnetic resonance (MR) system. MATERIALS AND METHODS: A digital flat-panel x-ray system (1,024(2) array of 200 microm pixels, 30 frames per second) was integrated into an interventional 0.5-T magnet. The hybrid system is capable of MR and x-ray imaging of the same field of view without patient movement. Two intravascular procedures were performed in a 22-kg porcine model: placement of a transjugular intrahepatic portosystemic shunt (TIPS) (x-ray-guided catheterization of the hepatic vein, MR fluoroscopy-guided portal puncture, and x-ray-guided stent placement) and mock chemoembolization (x-ray-guided subselective catheterization of a renal artery branch and MR evaluation of perfused volume). RESULTS: The resolution and frame rate of the x-ray fluoroscopy images were sufficient to visualize and place devices, including nitinol guidewires (0.016-0.035-inch diameter) and stents and a 2.3-F catheter. Fifth-order branches of the renal artery could be seen. The quality of both real-time (3.5 frames per second) and standard MR images was not affected by the x-ray system. During MR-guided TIPS placement, the trocar and the portal vein could be easily visualized, allowing successful puncture from hepatic to portal vein. CONCLUSION: Switching back and forth between x-ray and MR imaging modalities without requiring movement of the patient was demonstrated. The integrated nature of the system could be especially beneficial when x-ray and MR image guidance are used iteratively.

Endovascular management of iliac vein compression (May-Thurner) syndrome.

PURPOSE: To evaluate the feasibility of endovascular techniques in treating venous outflow obstruction resulting from compression of the iliac vein by the iliac artery of the left lower extremity (May-Thurner syndrome). MATERIALS AND METHODS: A retrospective analysis of 39 patients (29 women, 10 men; median age, 46 years) with iliac vein compression syndrome (IVCS) was performed. Nineteen patients presented with acute deep vein thrombosis (DVT) and 20 patients presented with chronic symptoms. All patients presented with leg edema or pain. In the acute group, patients were treated with catheter-directed thrombolysis (120,000-180,000 IU urokinase/h) and angioplasty followed by stent placement. In the chronic group, patients were treated with use of angioplasty and stent placement alone (n = 8), or in combination with thrombolysis (n = 12). Patients were then followed-up with duplex ultrasound and a quality-of-life assessment. RESULTS: Initial technical success was achieved in 34 of 39 patients (87%). The overall patency rate at 1 year was 79%. Symptomatically, 85% of patients were completely or partially improved compared with findings before treatment. Thirty-five of 39 patients received stents. The 1-year patency rate for patients with acute symptoms who received stents was 91.6%; for patients with chronic symptoms who received stents, the 1-year patency rate was 93.9%. Five technical failures occurred. Major complications included acute iliac vein rethrombosis (< 24 hours) requiring reintervention (n = 2). Minor complications included perisheath hematomas (n = 4) and minor bleeding (n = 1). There were no deaths, pulmonary embolus, cerebral hemorrhage, or major bleeding complications. CONCLUSION: Endovascular reconstruction of occluded iliac veins secondary to IVCS (May-Thurner) appears to be safe and effective.

Stent-graft therapy for subclavian artery aneurysms and fistulas: single-center mid-term results.

PURPOSE: To evaluate the potential of covered stents to replace surgery in the treatment of subclavian artery aneurysms and traumatic injuries. MATERIALS AND METHODS: Nine patients (five men, four women; age range, 20-83 years; mean, 54 years) with subclavian artery aneurysms (n = 5) or fistulas (n = 4) were treated with stent-grafts. All devices used were custom-made, consisting of polytetrafluoroethylene (PTFE)-covered Palmaz (n = 5), Wallstent (n = 2), Z stents (n = 8), or a polyester-covered Z stent (n = 1). One patient was lost to follow-up after 2 months. All others were followed up with clinical evaluation, computed tomography (CT), and/or ultrasound. RESULTS: All devices were deployed successfully with exclusion of the aneurysms and fistulas. There were two procedure-related complications (22%), consisting of groin pseudoaneurysms requiring surgical repair 3 and 9 days after the procedure. One of those patients required additional oral antibiotic therapy for a postsurgical groin wound infection. One patient developed a stenosis at 12 months, which required angioplasty. The stent-graft thrombosed in one patient because of a kink 2 months after placement, which was successfully treated by thrombolysis and placement of a Wallstent. The primary and secondary patencies are 89% and 100%, respectively, after a mean follow-up of 29 months (2-66 mo). CONCLUSION: Mid-term results of stent-graft therapy of subclavian artery aneurysms and fistulas are encouraging, with low morbidity and excellent clinical outcome.

Chronically occluded inferior venae cavae: endovascular treatment.

PURPOSE: To report the results of endoluminal recanalization and stent placement in patients with chronic occlusions of the inferior vena cava (IVC). MATERIALS AND METHODS: Seventeen consecutive patients (12 male, five female patients; mean age, 40.6 years; age range, 15-77 years) with chronic IVC occlusions were treated during a 6-year period. The mean duration of symptoms was 32 months. Underlying active malignancy was the cause of occlusion in four patients. Five patients with superimposed acute thrombus underwent catheter-directed thrombolysis prior to IVC recanalization. Clinical patency was defined as absence or improvement of symptoms. Clinical follow-up was supplemented with ultrasonography, vena cavography, or both in 10 patients. RESULTS: Technical success was achieved in 15 (88%) patients. Additional thrombolytic therapy and stent placement was needed in two patients to maintain patency at 4 and 6 months after the procedure. Twelve patients had IVCs that remained patent after a mean follow-up of 19 months for a primary patency rate of 80%. The primary assisted patency rate was 87% (13 of 15). There were four deaths owing to underlying disease 6-21 months after the procedures. There were no procedure-related complications. CONCLUSION: Endoluminal recanalization and stent placement in chronically occluded IVCs has a good intermediate-term outcome and should be considered in patients who have symptoms and who often do not have adequate alternative therapy.

Diagnostic yield of MR-guided liver biopsies compared with CT- and US-guided liver biopsies.

PURPOSE: To compare diagnostic yield and complication rates of magnetic resonance (MR)-guided versus computed tomography (CT)- and ultrasound (US)-guided liver biopsies. MATERIALS AND METHODS: MR-, CT-, and US-guided liver biopsies performed between 9/96 and 9/98 were compared. Sixty patients (21 men and 39 women, mean age 60 years) underwent MR-guided biopsy of liver lesions. Thirty patients (16 men and 14 women, mean age 59 years) underwent CT-guided biopsy. Eighteen patients (seven men and 11 women, mean age 50 years) underwent US-guided biopsy. MR procedures were performed in an open-configuration 0.5-T Signa SP MR unit. Lesion localization used standard T1 and T2 sequences, whereas biopsies were performed with multiplanar spoiled gradient recalled echo and fast gradient recalled echo sequences. A coaxial system with an MR-compatible 18-gauge stabilizing needle and a 21-gauge aspiration needle was used to obtain all samples. In CT and US procedures, a 19-gauge stabilizing needle and a 21-gauge aspiration or a 20-gauge core biopsy needle were used. A cytotechnologist was present to determine the adequacy of samples. RESULTS: MR had a diagnostic yield of 61%. CT and US had diagnostic yields of 67% and 61%, respectively. No serious complications were reported for MR and US procedures. Two CT biopsies resulted in postprocedural hemorrhage. One patient required surgical exploration and died. CONCLUSIONS: MR-guided biopsy of liver lesions with use of a 0.5-T open-configuration magnet is safe and accurate when compared with CT and US. No statistical difference was observed between the diagnostic yield of biopsies performed with MR, CT, and US guidance. MR enabled biopsy of a number of lesions in the hepatic dome and lesions with low contrast, which would normally be difficult to sample safely with use of CT or US.

Endovascular treatment of hepatic venous outflow obstruction after piggyback technique liver transplantation.

BACKGROUND: The piggyback technique of orthotopic liver transplantation is an attractive alternative that preserves the recipient inferior vena cava and allows uninterrupted venous blood return during the anhepatic phase. As with other transplantation techniques, the vascular anastomoses required by the piggyback technique can develop strictures. METHODS: Review of records of 264 piggyback transplantations revealed two cases of delayed-onset hepatic venous obstruction from anastomotic strictures. Both patients also had symptoms of inferior vena cava obstruction, with azotemia and lower extremity edema. Both patients were treated percutaneously with balloon-expandable stents. RESULTS: Rapid, dramatic resolution of symptoms was achieved in both patients. Patients remain completely asymptomatic at 39 and 3 months of follow-up. CONCLUSIONS: Hepatic venous anastomotic strictures in recipients of piggyback technique transplants are a very uncommon complication. They may be easily and effectively treated by minimally invasive endovascular intervention.

Descending thoracic aortic aneurysm: thoracic CT findings after endovascular stent-graft placement.

PURPOSE: To evaluate the usefulness of thoracic computed tomography (CT) after placement of an endovascular stent-graft for the treatment of descending thoracic aortic aneurysm. MATERIALS AND METHODS: From 1992 to 1996, 85 patients with thoracic aortic aneurysm underwent stent-graft placement. In 63 patients, thoracic CT scans were obtained both before and within 10 days after placement. The CT findings were retrospectively studied, and their clinical effect analyzed. In 20 of 63 patients, long-term follow-up CT findings were also evaluated. RESULTS: After stent-graft placement in the 63 patients, CT demonstrated an increase in pleural effusion in 46 (73%), periaortic changes in 21 (33%), perigraft leak in 13 (21%), atelectasis in six (10%), mural thrombus within the stent-graft in two (3%), and new aortic dissection in one (2%). The mean maximum diameter of the aneurysm was 58.8 mm before and 60.0 mm after stent-graft insertion. Sixty-two (98%) patients were successfully treated until discharge. Interventional procedures were performed to eliminate the leakage into the aneurysm sac in 10 patients with perigraft flow depicted at CT. Other complications were managed conservatively. CONCLUSION: Thoracic CT is useful in the treatment of patients after stent-graft insertion for the management of descending thoracic aortic aneurysm.

Recurrent TIPS failure associated with biliary fistulae: treatment with PTFE-covered stents.

PURPOSE: To evaluate the efficacy of covered stents for the treatment of transjugular intrahepatic portosystemic shunt (TIPS) obstruction in human subjects with identified or suspected biliary fistulae. METHODS: Five patients were treated for early failure of TIPS revisions. All had mid-shunt thrombus, and four of these had demonstrable biliary fistulae. Three patients also propagated thrombus into the native portal venous system and required thrombolysis. TIPS were revised in four patients using a custom-made polytetrafluoroethylene (PTFE)-covered Wallstent, and in one patient using a custom-made PTFE-covered Gianturco Z-stent. RESULTS: All identified biliary fistulae were successfully sealed. All five patients maintained patency and function of the TIPS during follow-up ranging from 2 days to 21 months (mean 8.4 months). No patient has required additional revision. Thrombosis of the native portal venous system was treated with partial success by mechanical thrombolysis. CONCLUSION: Early and recurrent failure of TIPS with mid-shunt thrombosis, which may be associated with biliary fistulae, can be successfully treated using covered stents. Stent-graft revision appears to be safe, effective, and potentially durable.

1999 Gary J. Becker Young Investigator Award. MR-guided transjugular portosystemic shunt placement in a swine model.

PURPOSE: To evaluate the performance of portal venous puncture with use of magnetic resonance (MR) guidance, and to place a transjugular intrahepatic portosystemic shunt (TIPS) in a swine model. MATERIALS AND METHODS: A study of 12 swine was performed to evaluate the ability of interventional MR imaging to guide portal vein puncture and TIPS placement. Six swine had catheters placed in the right hepatic vein under C-arm fluoroscopy. A nitinol guide wire was left in the vein and the animals were then moved into an open configuration MR imaging unit. A TIPS needle set was used to puncture the portal vein using MR fluoroscopy. The animals were transferred to the C-arm, and venography confirmed portal vein puncture. A follow-up study was performed in six additional swine to place a TIPS using only MR imaging guidance. MR tracking was used to advance a catheter from the right atrium into the inferior vena cava. Puncture of the portal vein was performed and a nitinol stent was placed, bridging the hepatic parenchyma. MR venogram confirmed placement. RESULTS: Successful portal vein puncture was achieved in all animals. The number of punctures required decreased from 12 in the first animal to a single puncture in the last eight swine. A stent was successfully placed across the hepatic tract in all six swine. CONCLUSIONS: Real-time MR imaging proved to be a feasible method to guide portal vein puncture and TIPS placement in pigs.