Hepatopulmonary shunting after surgical, interventional and systemic therapy in patients with liver malignancies scheduled for radioembolization.

BACKGROUND: Hepatopulmonary shunts (HPS) lead to radiation exposure of the lungs in patients undergoing radioembolization (RE) of malignant liver tumors. PURPOSE: To retrospectively analyze how HPS is affected by prior systemic or local therapy of the liver. MATERIAL AND METHODS: The percentage HPS was calculated from SPECT/CT scans obtained after technetium-99 m macroaggregated albumin administration into hepatic arteries in 316 patients evaluated for RE. RESULTS: Patients with partial liver resection (n = 80) did not differ in HPS from the remaining patient population (n = 236) (HPS (median [range]) = 10.2 [2.1-48.3]resection% vs. 8.9 [2.3-32.9]no resection%; P = 0.527). In patients undergoing sequential RE, HPS was significantly higher in the liver lobe treated second (n = 10; HPS = 6.4 [2.1-10.2]firstlobe/session% vs. 12.0 [2.0-24.6]second lobe/session%; P = 0.019). (Chemo-)embolization (n = 19; HPS = 11.0 [2.8-48.3]%) or transcutaneous ablation (n = 63; HPS = 8.8 [3.0-32.9]%) had no effect on HPS compared to patients without prior interventions (no (chemo-)embolization: n = 297; HPS = 9.3 [2.1-47.3]%; P = 0.489; no ablation: n = 253; HPS = 9.5 [2.1-48.3]%; P = 0.382). Pretreatment with sorafenib (HPS = 9.5 [2.3-35.9]yes% vs. 10.2 [2.8-42.0]no%; P = 0.777) orbevacizumab (HPS = 10.7 [2.1-30.6]yes% vs. 9.0 [3.9-23.3]no%; P = 0.870) had no effect on HPS. CONCLUSION: Sequential RE results in an increase in the HPS in the contralateral liver lobe at the time of the second RE session. Other investigated therapy do not affect HPS.

CD133+CD34+ stem cells are mobilized after musculoskeletal surgery and target endothelium activated by surgical wound fluid.

PURPOSE: CD133+CD34+ hematopoietic stem cells (HSCs) have been shown to differentiate into cell types of nonhematopoietic lineage. It is unclear whether HSCs target and repair damaged musculoskeletal tissue. We aimed to analyze if HSCs are mobilized after musculoskeletal surgery to circulation, home to surgical wound fluid (SWF)-activated endothelium, and are chemoattracted by SWF under in vitro conditions. METHODS: Circulating HSC levels were measured at t = 3, 8, 24, 48 h postoperatively using fluorescence-activated cell sorting (FACS) and compared with preoperative levels (t = 0) and normal volunteers. For adhesion experiments, HSCs were incubated on SWF-activated human umbilical vein endothelial cells (HUVECs) and HSC/HUVEC ratios determined by FACS. Adhesion receptor expression on HSC (L-selectin, lymphocyte function-associated antigen 1 (LFA-1), very late antigen-4) and SWF-activated HUVECs (P-selectin, E-selectin, V-cell adhesion molecules (CAM), I-CAM) was determined and HSC adhesion measured again after blocking upregulated receptors. Using a modified Boyden chamber, HSC chemotaxis was analyzed for an SWF and cytokine-neutralized SWF (vascular endothelial growth factor (VEGF), stromal-derived factor-1, interleukin-8) gradient. RESULTS: Circulating HSCs were significantly increased 8 h after surgery. Increasing HSC adhesion to HUVECs was shown for SWF isolated at any postoperative time point, and chemoattraction was significantly induced in an SWF gradient with SWF isolated 8 and 24 h postoperatively. Receptor and cytokine blockade experiments with monoclonal antibodies revealed decreased HSC adhesion to SWF-activated endothelium and showed lower chemotaxis after blocking the LFA-1-I-CAM-1 receptor axis (adhesion) and neutralizing VEGF-165 (chemotaxis). CONCLUSIONS: Our data demonstrate that HSCs are mobilized after trauma, target to wound-associated endothelium via the LFA-1-I-CAM-1 axis, and are chemoattracted by VEGF-165 under in vitro conditions.

Hepatopulmonary shunting in patients with primary and secondary liver tumors scheduled for radioembolization.

PURPOSE: In patients undergoing transarterial radioembolization (RE) of malignant liver tumors, hepatopulmonary shunts (HPS) can lead to nontarget irradiation of the lungs. This study aims at analyzing the HPS fraction in relation to liver volume, tumor volume, tumor-to-liver volume ratio, tumor vascularity, type of tumor, and portal vein occlusion. MATERIALS AND METHODS: In the presented retrospective study the percentage HPS fraction was calculated from SPECT/CT after infusion of Tc-99m macroaggregated albumin (Tc-99m MAA) into the proper hepatic artery of 233 patients evaluated for RE. RESULTS: HPS fractions correlate very weakly with liver volume (r=0.303), tumor volume (r=0.345), and tumor-to-liver volume ratio (r=0.340). Tumors with strong contrast enhancement (HPSmedian(range)=11.7%(46.3%); n=73) have significantly larger shunt fractions than tumors with little enhancement (HPS=8.3%(16.4%); n=61; p<0.001). Colorectal cancer metastases (HPS=10.6%(28.6%); n=68) and hepatocellular cancers (HPS=11.7%(39.4%); n=63) have significantly larger HPS fractions than metastases from breast cancer (HPS=7.4%(16.7%); n=40; p=0.012 and p=0.001). Patients with compression (HPS=13.9%(43.7%); n=33) or tumor thrombosis (HPS=15.8% (31.2%); n=33) of a major portal vein branch have significantly higher degrees of shunting than patients with normal portal vein perfusion (HPS=8.1% (47.0%); n=167; both p<0.001). The shunt fraction is largest in patients with HCC and thrombosis or occlusion of a major portal vein branch (HPS=16.6% (31.0%); n=32). CONCLUSION: The degree of hepatopulmonary shunting depends on the type of liver tumor, tumor vascularity, and portal vein perfusion. There is little to no correlation of HPS with liver volume, tumor volume, or tumor-to-liver volume ratio.

Impaired hepatic Gd-EOB-DTPA enhancement after radioembolisation of liver malignancies.

INTRODUCTION: To evaluate the uptake of the liver-specific magnetic resonance imaging (MRI) contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by functional liver parenchyma after radioembolisation (RE) of hepatic malignancies. METHODS: Uptake of Gd-EOB-DTPA prior to RE versus 60+/-24d and 126+/-32d after RE was compared in a group of 33 patients with primary or secondary hepatic malignancies. In patients who underwent single-lobe treatment, left and right lobes were compared 59+/-24 days after RE. Gd-EOB-DTPA uptake was determined as follows: ratio of mean signal intensity in liver parenchyma to muscle in Gd-EOB-DTPA-enhanced T1-weighted MRI was subtracted from ratio of mean intensity in liver parenchyma to muscle in unenhanced T1-weighted MRI. RESULTS: Gd-EOB-DTPA uptake in liver parenchyma was 0.845+/-0.29 before RE, 0.615+/-0.38 (P = 0.0022) at day 60+/-24, and 0.739+/-0.30 at day 126+/-32 after RE. In cases of single-lobe treatment, Gd-EOB-DTPA uptake was 0.581+/-0.256 for treated and 0.828+/-0.32 (P = 0.0164) for untreated hepatic lobes. CONCLUSIONS: Uptake of Gd-EOB-DTPA by liver parenchyma is impaired after RE, indicating dysfunction of the local hepatic system. These findings suggest that Gd-EOB-DTPA-enhanced MRI has the potential to be used for monitoring liver damage after RE.

Improved hypertrophy of future remnant liver after portal vein embolization with plugs, coils and particles.

PURPOSE: To retrospectively analyze efficacy as measured by volume gain of future remnant liver (FRL) after right portal vein embolization (PVE) using particles only versus particles and additional central plug and/or coil (CP/C) embolization. METHODS: All patients who underwent PVE between July 2011 and December 2012 were retrospectively analyzed. Right PVE was performed either with particle-only (PO) embolization or additional CP/C embolization. All enrolled patients underwent computed tomography or magnetic resonance imaging before PVE and surgery. The images were used for volumetry of the FRL. RESULTS: Of 75 patients, 40 had PO and 35 CP/C embolization. Age, sex, and tumor entities did not differ significantly between the two groups. Tumor entities included cholangiocarcinoma (n = 52), metastasis from colorectal cancer (n = 14), hepatocellular carcinoma (n = 2), and others (n = 7). Time from PVE to preoperative imaging was similar in both groups. FRL volume before PVE was 329 ± 121 ml in the PO group and 333 ± 135 ml in the CP/C group, and 419 ± 135 ml and 492 ± 165 ml before operation. The average percentage volume gain was significantly higher in the CP/C group than in the PO group, with 53.3 ± 34.5 % versus 30.9 ± 28.8 % (p = 0.002). CONCLUSION: Right PVE with additional CP/C embolization leads to a significantly higher gain in FRL volume than embolization with particles alone.

No infectious hepatic complications following radioembolization with 90Y microspheres in patients with biliodigestive anastomosis.

AIM: To retrospectively evaluate infectious hepatic complications of transarterial radioembolization (RE) of the liver in patients with pre-existing biliodigestive anastomosis. PATIENTS AND METHODS: Patients who underwent RE were retrospectively analyzed. All patients had at least a contrast-enhanced magnetic resonance imaging or contrast-enhanced triple-phase computed tomographic scan before and 6-8 weeks after RE. RESULTS: Overall, 143 patients (67 women, 76 men; median age = 65 ± 11.2 years) were analyzed. Nine patients had a biliodigestive anastomosis. The complications were as follows: one case of cholecystitis, three of gastroduodenal ulcer with one ulcer perforation, and six of radioembolization-induced liver disease. There were no infectious complications. There were no major or minor complications in the group with previous biliodigestive anastomosis. CONCLUSION: Pre-existing bilioenteric anastomoses are not a negative predictive factor for the development of infectious hepatic complications after RE. RE with (90)Y microspheres can be safely performed following careful patient selection.

Computed-tomography-guided high-dose-rate brachytherapy (CT-HDRBT) ablation of metastases adjacent to the liver hilum.

PURPOSE: To evaluate technical feasibility and clinical outcome of computed tomography-guided high-dose-rate-brachytherapy (CT-HDRBT) ablation of metastases adjacent to the liver hilum. MATERIALS AND METHODS: Between November 2007 and May 2012, 32 consecutive patients with 34 metastases adjacent to the liver hilum (common bile duct or hepatic bifurcation ≤5 mm distance) were treated with CT-HDRBT. Treatment was performed by CT-guided applicator placement and high-dose-rate brachytherapy with an iridium-192 source. MRI follow-up was performed 6 weeks and every 3 months post intervention. The primary endpoint was local tumor control (LTC); secondary endpoints included time to progression (TTP) and overall survival (OS). RESULTS: Patients were available for MRI evaluation for a mean follow-up time of 18.75 months (range: 3-56 months). Mean tumor diameter was 4.3 cm (range: 1.3-10.7 cm). One major complication was observed. Four (11.8%) local recurrences were observed after a local tumor control of 5, 8, 9 and 10 months, respectively. Twenty-two patients (68.75%) experienced a systemic tumor progression during the follow up period. Mean TTP was 12.9 months (range: 2-56 months). Nine patients died during the follow-up period. Median OS was 20.24 months. CONCLUSION: Minimally invasive CT-HDRBT is a safe and effective option also for unresectable liver metastases adjacent to the liver hilum that would have been untreatable by thermal ablation.

Clinical practice in radioembolization of hepatic malignancies: a survey among interventional centers in Europe.

OBJECTIVES: A survey was conducted to give an overview about the practice of radioembolization in malignant liver tumors by European centers. METHODS: A questionnaire of 23 questions about the interventional center, preinterventional patient evaluation, the radioembolization procedure and aftercare were sent to 45 European centers. RESULTS: The response rate was 62.2% (28/45). The centers performed 1000 (median = 26) radioembolizations in 2009 and 1292 (median = 40) in 2010. Most centers perform preinterventional evaluation and radioembolization on an inpatient basis. An arterioportal shunt not amendable to preinterventional embolization is considered a contraindication. During preinterventional angiography, the gastroduodenal artery is embolized by 71%, the right gastric artery by 59%, and the cystic artery by 41%. In case of bilobar disease, yttrium-90 microspheres are infused into the common hepatic artery (14%) or separately into left and right hepatic artery (86%). 33% prefer a time interval between right and left liver lobe radioembolization to prevent radiation induced liver disease. 43% of the respondents do not prescribe prophylactic medication after radioembolization. In case of iatrogenic manipulation to the biliary duct system most centers perform radioembolization with prophylactic antibiotics. CONCLUSIONS: Despite standardization of the procedure, there are some differences in how radioembolization of liver tumors is performed in Europe.