MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial.

BACKGROUND: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. METHODS: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. FINDINGS: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). INTERPRETATION: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. FUNDING: The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

Adjuvant holmium-166 radioembolization after radiofrequency ablation in early-stage hepatocellular carcinoma patients: a dose-finding study (HORA EST HCC trial).

PURPOSE: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (166Ho-MS), when administered as adjuvant therapy after RFA of HCC 2-5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume). METHODS: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2-5 cm, RFA was followed by (super-)selective infusion of 166Ho-MS on day 5-10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of 166Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort. RESULTS: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3-71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1-4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127-145]). No local recurrences were found within 1-year follow-up. CONCLUSION: Adjuvant (super-)selective infusion of 166Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2-5 cm. TRIAL REGISTRATION: Clinicaltrials.gov NCT03437382 . (registered: 19-02-2018).

Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Ocular Melanoma Metastases Confined to the Liver: A Prospective Phase II Study.

BACKGROUND: Ocular melanoma is the most common primary intraocular malignancy and has a very poor prognosis once liver metastases occur. The aim of this study was to prospectively assess the efficacy and safety of percutaneous hepatic perfusion with melphalan (M-PHP) using the new second-generation (GEN 2) hemofiltration system in patients with ocular melanoma metastases confined to the liver. METHODS: Prospective, single-center, single-arm, phase II study including patients with unresectable ocular melanoma metastases confined to the liver. Treatment consisted of two M-PHP procedures at 6-8 weeks interval. Procedures were performed using the CHEMOSAT (GEN 2) system with 3 mg/kg melphalan. Primary endpoints were overall response rate (ORR) and best overall response (BOR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS: Sixty-four M-PHP procedures were performed in 35 patients between February 2014 and June 2017. The ORR was 72%. BOR was as follows: complete response in 3%, partial response in 69%, stable disease in 13%, and progressive disease in 16%. There was no treatment-related mortality. Fourteen serious adverse events occurred. At a median follow-up of 19.1 months (range 5.6-69.5), median OS was 19.1 months and was significantly longer in responders than in nonresponders (27.5 vs. 11.9 months, p < 0.001). The 1- and 2-year OS was 77% and 43%, respectively. PFS and hPFS were 7.6 and 11.2 months, respectively. CONCLUSIONS: M-PHP using the GEN 2 filter can achieve a high ORR and prolonged survival in patients with liver-only ocular melanoma metastases.

Luminescence-based Imaging Approaches in the Field of Interventional Molecular Imaging.

Luminescence imaging-based guidance technologies are increasingly gaining interest within surgical and radiologic disciplines. Their promise to help visualize molecular features of disease in real time and with microscopic detail is considered desirable. Integrating luminescence imaging with three-dimensional radiologic- and/or nuclear medicine-based preinterventional imaging may overcome limitations such as the limited tissue penetration of luminescence signals. At the same time, the beneficial features of luminescence imaging may be used to complement the routinely used radiologic- and nuclear medicine-based modalities. To fully exploit this integrated concept, and to relate the largely experimental luminesce-based guidance approaches into perspective with routine imaging approaches, it is essential to understand the advantages and limitations of this relatively new modality. By providing an overview of the available luminescence technologies and the various clinically evaluated exogenous luminescent tracers (fluorescent, hybrid, and theranostic tracers), this review attempts to place luminescence-based interventional molecular imaging technologies into perspective to the available radiologic- and/or nuclear medicine-based imaging technologies. At the same time, the transition from anatomic to physiologic and even molecular interventional luminescence imaging is illustrated.

Intraprocedural assessment of ablation margins using computed tomography co-registration in hepatocellular carcinoma treatment with percutaneous ablation: IAMCOMPLETE study.

PURPOSE: The primary objective of this study was to determine the feasibility of ablation margin quantification using a standardized scanning protocol during thermal ablation (TA) of hepatocellular carcinoma (HCC), and a rigid registration algorithm. Secondary objectives were to determine the inter- and intra-observer variability of tumor segmentation and quantification of the minimal ablation margin (MAM). MATERIALS AND METHODS: Twenty patients who underwent thermal ablation for HCC were included. There were thirteen men and seven women with a mean age of 67.1 ± 10.8 (standard deviation [SD]) years (age range: 49.1-81.1 years). All patients underwent contrast-enhanced computed tomography examination under general anesthesia directly before and after TA, with preoxygenated breath hold. Contrast-enhanced computed tomography examinations were analyzed by radiologists using rigid registration software. Registration was deemed feasible when accurate rigid co-registration could be obtained. Inter- and intra-observer rates of tumor segmentation and MAM quantification were calculated. MAM values were correlated with local tumor progression (LTP) after one year of follow-up. RESULTS: Co-registration of pre- and post-ablation images was feasible in 16 out of 20 patients (80%) and 26 out of 31 tumors (84%). Mean Dice similarity coefficient for inter- and intra-observer variability of tumor segmentation were 0.815 and 0.830, respectively. Mean MAM was 0.63 ± 3.589 (SD) mm (range: -6.26-6.65 mm). LTP occurred in four out of 20 patients (20%). The mean MAM value for patients who developed LTP was -4.00 mm, as compared to 0.727 mm for patients who did not develop LTP. CONCLUSION: Ablation margin quantification is feasible using a standardized contrast-enhanced computed tomography protocol. Interpretation of MAM was hampered by the occurrence of tissue shrinkage during TA. Further validation in a larger cohort should lead to meaningful cut-off values for technical success of TA.

New vertebral fractures after percutaneous vertebroplasty for painful osteoporotic vertebral compression fractures: a clustered analysis and the relevance of intradiskal cement leakage.

PURPOSE: To perform clustered analysis of fracture-free probabilities of intact nontreated vertebrae after percutaneous vertebroplasty (PVP) in painful long-standing osteoporotic vertebral compression fractures (OVCFs) to determine risk factors for new vertebral fractures and estimate fracture-free probabilities of multiple intact nontreated vertebrae given their patient- and vertebra-specific covariate status. MATERIALS AND METHODS: Informed consent and institutional review board approval were obtained. A total of 115 patients who underwent PVP for 216 painful long-standing OVCFs were prospectively followed up to detect new OVCFs during the 1st postoperative year. A total of 1031 intact vertebrae were available for clustered analysis of fracture-free probabilities by using a Cox proportional hazard frailty model. A clustered analysis takes clustering or correlation of fracture-free survival probabilities of individual intact vertebrae within one patient into account to improve estimates of fracture-free probabilities and risk factors. Relevant patient- and vertebra-specific covariates were included. Volumetric analysis of intradiskal cement leakage was performed by using a receiver operating characteristic curve (ROC). RESULTS: Three- and 12-month vertebral fracture-free probability was 97.0% and 94.5%, respectively. Strong patient-level risk factors included low bone mineral density (hazard ratio [HR], 0.53 per unit increase), high spinal deformity index (HR, 2.23 per five units increase), and low fracture age (HR, 0.52 per 2 months increase). Strong vertebra-specific risk factors were thoracolumbar localization (HR, 2.33), vicinity to the treated level (adjacent level HR, 3.53), and presence of intradiskal cement leakage (HR, 8.21). Fracture-free probabilities of individual vertebrae were clustered within a patient (ie, not independent) (P = .009). The predicted 1-year fracture-free probability of an individual vertebra could be as high as 99.8% or as low as 19.9% based on absence or presence of risk factors, respectively. Larger intradiskal cement leakage volumes were associated with a higher likelihood of occurrence of new adjacent OVCFs (area under the ROC curve, 0.70). CONCLUSION: New vertebral fractures after PVP were clustered within patients and depended heavily on the presence or absence of both patient- and vertebra-specific risk factors. Intradiskal cement leakage was a pronounced augmentation-related risk factor, for which a volumetric association was found.

Value-assessment of computer-assisted navigation strategies during percutaneous needle placement.

PURPOSE: Navigational strategies create a scenario whereby percutaneous needle-based interventions of the liver can be guided using both pre-interventional 3D imaging datasets and dynamic interventional ultrasound (US). To score how such technologies impact the needle placement process, we performed kinematic analysis on different user groups. METHODS: Using a custom biopsy phantom, three consecutive exercises were performed by both novices and experts (n = 26). The exercise came in three options: (1) US-guidance, (2) US-guidance with pre-interventional image-registration (US + Reg) and (3) US-guidance with pre-interventional image-registration and needle-navigation (US + Reg + Nav). The traveled paths of the needle were digitized in 3D. Using custom software algorithms, kinematic metrics were extracted and related to dexterity, decision making indices to obtain overall performance scores (PS). RESULTS: Kinematic analysis helped quantifying the visual assessment of the needle trajectories. Compared to US-guidance, novices yielded most improvements using Reg (PSavg(US) = 0.43 vs. PSavg(US+Reg) = 0.57 vs. PSavg(US+Reg+Nav) = 0.51). Interestingly, the expert group yielded a reversed trend (PSavg(US) = 0.71 vs PSavg(US+Reg) = 0.58 vs PSavg(US+Reg+Nav) = 0.59). CONCLUSION: Digitizing the movement trajectory allowed us to objectively assess the impact of needle-navigation strategies on percutaneous procedures. In particular, our findings suggest that these advanced technologies have a positive impact on the kinematics derived performance of novices.

Prospective evaluation of percutaneous hepatic perfusion with melphalan as a treatment for unresectable liver metastases from colorectal cancer.

PURPOSE: Percutaneous hepatic perfusion with melphalan (M-PHP) is increasingly used in patients with liver metastases from various primary tumors, yet data on colorectal liver metastases (CRLM) are limited. The aim of this study was to prospectively evaluate the efficacy and safety of M-PHP in patients with CRLM. MATERIALS AND METHODS: Prospective, single-center, single-arm phase II study of M-PHP with hemofiltration in patients with unresectable CRLM. Proven, extrahepatic metastatic disease was one of the exclusion criteria. Primary outcomes were overall response rate (ORR) and best overall response (BOR). Secondary outcomes were overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS: A total of 14 M-PHP procedures were performed in eight patients between March 2014 and December 2015. All patients (median age 56 years, ranging from 46 to 68) had received (extensive) systemic chemotherapy before entering the study. The ORR was 25.0%, with two out of eight patients showing partial response as BOR. Median OS was 17.3 months (ranging from 2.6 to 30.9) with a one-year OS of 50.0%. Median PFS and hPFS were 4.4 and 4.5 months, respectively. No serious adverse events occurred. Grade 3/4 hematologic adverse events were observed in the majority of patients, though all were transient and well-manageable. CONCLUSION: M-PHP is a safe procedure with only limited efficacy in patients with unresectable CRLM who already showed progression of disease after receiving one or more systemic treatment regimens.

Study Protocol: Adjuvant Holmium-166 Radioembolization After Radiofrequency Ablation in Early-Stage Hepatocellular Carcinoma Patients-A Dose-Finding Study (HORA EST HCC Trial).

PURPOSE: To investigate the biodistribution of holmium-166 microspheres (166Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume). MATERIALS AND METHODS: This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2-5 cm, or a maximum of 3 lesions of ≤ 3 cm each. The day after RFA patients undergo angiography and cone-beam CT (CBCT) with (super)selective infusion of technetium-99 m labelled microalbumin aggregates (99mTc-MAA). The perfused liver volume is segmented from the CBCT and 166Ho-MS is administered to this treatment volume 5-10 days later. The dose of holmium-166 is escalated in a maximum of 3 patient cohorts (60 Gy, 90 Gy and 120 Gy) until the endpoint is reached. SPECT/CT is used to determine the biodistribution of holmium-166. The endpoint is met when a dose of ≥ 120 Gy has been reached on the target volume in 9/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival. DISCUSSION: This study aims to find the optimal administration dose of adjuvant radioembolization with 166Ho-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for early-stage HCC patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03437382.

Study Protocol PROMETHEUS: Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma.

PURPOSE: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of < 10% in patients with hepatocellular carcinoma undergoing thermal ablation. Secondary objectives are to analyze the correlation between ablation margins and local recurrence and to assess efficacy. MATERIALS AND METHODS: This study is a prospective, multicenter, non-experimental, non-comparative, open-label study. Patients > 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan-Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. DISCUSSION: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713 .

Viable tumor tissue adherent to needle applicators after local ablation: a risk factor for local tumor progression.

BACKGROUND: Local tumor progression (LTP) is a serious complication after local ablation of malignant liver tumors, negatively influencing patient survival. LTP may be the result of incomplete ablation of the treated tumor. In this study, we determined whether viable tumor cells attached to the needle applicator after ablation was associated with LTP and disease-free survival. METHODS: In this prospective study, tissue was collected of 96 consecutive patients who underwent local liver ablations for 130 liver malignancies. Cells and tissue attached to the needle applicators were analyzed for viability using glucose-6-phosphate-dehydrogenase staining and autofluorescence intensity levels of H&E stained sections. Patients were followed-up until disease progression. RESULTS: Viable tumor cells were found on the needle applicators after local ablation in 26.7% of patients. The type of needle applicator used, an open approach, and the omission of track ablation were significantly correlated with viable tumor tissue adherent to the needle applicator. The presence of viable cells was an independent predictor of LTP. The attachment of viable cells to the needle applicators was associated with a shorter time to LTP. CONCLUSIONS: Viable tumor cells adherent to the needle applicators were found after ablation of 26.7% of patients. An independent risk factor for viable cells adherent to the needle applicators is the omission of track ablation. We recommend using only RFA devices that have track ablation functionality. Adherence of viable tumor cells to the needle applicator after local ablation was an independent risk factor for LTP.

Percutaneous vertebroplasty in very severe osteoporotic vertebral compression fractures: feasible and beneficial.

PURPOSE: To assess clinical outcome and technical feasibility of percutaneous vertebroplasty (PVP) in 34 patients with 37 osteoporotic vertebral compression fractures (OVCFs) with vertebral body collapse to less than one-third of the original height, termed very severe osteoporotic vertebral compression fractures (vsOVCFs). MATERIALS AND METHODS: A prospective follow-up study was conducted using a 0-10 pain intensity numerical rating scale and the Short Form-36 General Health Survey (SF-36) quality-of-life questionnaire, completed before PVP and 7 days (pain only), 1 month, 3 months, and 12 months after PVP. Cement leakage was analyzed on postoperative computed tomography (CT) scanning. The presence of new fractures was assessed at 6 weeks and 52 weeks and when suspected clinically. RESULTS: Decrease in average and worst back pain was 2.5 points and 3.0 points after 7 days, and 2.5 points and 2.9 points after 12 months. The physical and mental SF-36 summary scores were significantly increased. Incidence of cement leakage in vsOVCFs was 91.9%, which was substantially higher compared with non-vsOVCFs (n = 40) treated in the same patients (64.1%; odds ratio [OR] 6.4, 95% confidence interval [CI] 1.7-24.5, P = .004). Mean leakage volume per treated vertebra was more than twice as high (0.80 mL vs 0.32 mL; P < .001). Seventeen new OVCFs in 11 patients (32.4%) were identified. Only one (2.9%) minor complication occurred, confirming the feasibility of PVP in vsOVCFs. CONCLUSIONS: Patients with painful vsOVCFs can be treated with, and benefit from, PVP. Although technically more demanding and with a higher procedural risk (ie, more frequent necessity of placement of a second needle, higher leakage incidence, and greater leakage volumes), PVP is technically feasible and should not be withheld from these patients.

Assessing the value of volume navigation during ultrasound-guided radiofrequency- and microwave-ablations of liver lesions.

PURPOSE: The goal of our study was to determine the influence of ultrasound (US)-coupled volume navigation on the use of computed tomography (CT) during minimally-invasive radiofrequency and microwave ablation procedures of liver lesions. METHOD: Twenty-five patients with 40 liver lesions of different histological origin were retrospectively analysed. Lesions were ablated following standard protocol, using 1) conventional US-guidance, 2) manual registered volume navigation (mVNav), 3) automatic registered (aVNav) or 4) CT-guidance. In case of ultrasonographically inconspicuous lesions, conventional US-guidance was abandoned and mVNav was used. If mVNav was also unsuccessful, the procedure was either continued with aVNav or CT-guidance. The number, size and location of the lesions targeted using the different approaches were documented. RESULTS: Of the 40 lesions, sixteen (40.0 %) could be targeted with conventional US-guidance only, sixteen (40.0 %) with mVNav, three (7.5 %) with aVNav and five (12.5 %) only through the use of CT-guidance. Of the three alternatives (mVNav, aVNav and CT only) the mean size of the lesions targeted using mVNav (9.1 ± 4.6 mm) was significantly smaller from those targeted using US-guidance only (20.4 ± 9.4 mm; p < 0.001). The location of the lesions did not influence the selection of the modality used to guide the ablation. CONCLUSIONS: In our cohort, mVNav allowed the ablation procedure to become less dependent on the use of CT. mVNav supported the ablation of lesions smaller than those that could be ablated with US only and doubled the application of minimally-invasive US-guided ablations.

Localized development of knee osteoarthritis can be predicted from MR imaging findings a decade earlier.

PURPOSE: To define localized development of knee osteoarthritis (OA) that arises from anterior cruciate ligament (ACL) and meniscal injuries identified at magnetic resonance (MR) imaging performed a decade ago and the subsequent management of those findings in patients with subacute knee symptoms. MATERIALS AND METHODS: The present study was approved by local medical ethics review boards, and written informed consent was obtained. Three hundred twenty-six patients (mean age, 42 years; 108 female) from a previously reported series of 855 patients were followed up with regard to the effect of MR imaging-guided treatment for subacute knee problems. The mean follow-up period was 10 years. Initial findings and treatment were compared with the follow-up radiograph and 3.0-T MR image findings. Odds ratios (ORs), with corresponding 95% confidence intervals, were used to identify the effects between variables. RESULTS: Patients with ACL ruptures had an increased risk of developing joint space narrowing (JSN), cartilaginous defects, osteophytes, bone marrow lesions, and subchondral cysts medially or laterally (OR, 2.4-9.8). Patients with medial meniscal tears had an increased risk of developing JSN, cartilaginous defects, osteophytes, and bone marrow lesions medially (OR, 2.0-15.3). Patients with lateral meniscal tears had an increased risk of developing JSN, cartilaginous defects, osteophytes, bone marrow lesions, and subchondral cysts laterally (OR, 2.1-10.5). Meniscectomy had no effect on the risk of developing OA. CONCLUSION: Localized knee OA developed from risk factors identified from the findings of MR imaging performed a decade ago in patients with subacute knee symptoms and did not depend on the surgical treatment of those findings.

Only MR can safely exclude patients from arthroscopy.

OBJECTIVE: The aim of this study was to determine in patients with subacute knee complaints and normal standardized physical examination the fraction of magnetic resonance imaging (MRI) studies showing arthroscopically treatable intra-articular pathology. MATERIAL AND METHODS: There were 290 consecutive patients (between 16 and 45 years) with at least 4 weeks of knee complaints and low clinical suspicion of intra-articular pathology based on physical exam. Two hundred seventy-four patients were included. Sixteen patients with prior knee surgery, rheumatic arthritis, or severe osteoarthritis were excluded. MRI was used to assign patients to group 1 (treatable abnormalities) or group 2 (normal or no treatable findings), depending on whether MR demonstrated treatable pathology. Arthroscopy was performed in group 1 patients. If symptoms persisted for 3 months in group 2 patients, cross over to arthroscopy was allowed. RESULTS: MR showed treatable pathology in 73 patients (26.6%). Arthroscopy was performed in 64 patients of 73 patients (group 1). In 52 patients (81.3%, 95% confidence interval (CI) 71.4-91.1%), arthroscopy was therapeutic. Of the 13 arthroscopies (6.5%) in group 2, four were therapeutic (30.8%, 95% CI 1.7-59.8). The highest fraction of MR studies showing treatable pathology was found in males, aged over 30 years, with a history of effusion (54.5%, six of 11 patients). CONCLUSION: Authors believe that the negative predictive value of clinical assessment in patients with subacute knee complaints is too low to exclude these patients from MR. MR should at least be considered in male patients aged 30 years and over with a history of effusion.

Antegrade Ureteral Stenting is a Good Alternative for the Retrograde Approach.

BACKGROUND/AIMS: Double J (JJ) stents for treating obstructive ureteral pathology are generally inserted through a retrograde route with cystoscopic guidance. Antegrade percutaneous insertion using fluoroscopy can be performed alternatively but is less known. Indications, success rate and complications of antegrade ureteral stenting were evaluated. METHODS: Data of consecutive patients in which antegrade ureteral stenting was performed were retrospectively analysed using the radiology information system and patient records. Patient characteristics, details of the antegrade JJ stent insertion procedure and registered complications were collected. Furthermore, it was investigated if prior to the antegrade procedure a retrograde attempt for JJ stent insertion was performed. RESULTS: Total 130 attempts for antegrade JJ stent insertion were performed in 100 patients. A percutaneous nephrostomy catheter had already been placed in the majority of kidneys (n = 109) for initial treatment of hydronephrosis. Most prevelant indication for a JJ stent was obstructive ureteral pathology due to malignancy (n = 63). A JJ stent was successfully inserted in 125 of 130 procedures. In 21 cases, previous retrograde ureteral stenting had failed but, subsequent antegrade ureteral stenting was successful. There were 8 procedure related complications; 6 infections, 1 false tract and 1 malposition. CONCLUSION: Antegrade percutaneous insertion of a JJ stent is a good alternative for retrograde insertion.

Phantom Study Investigating the Accuracy of Manual and Automatic Image Fusion with the GE Logiq E9: Implications for use in Percutaneous Liver Interventions.

PURPOSE: To determine the accuracy of automatic and manual co-registration methods for image fusion of three-dimensional computed tomography (CT) with real-time ultrasonography (US) for image-guided liver interventions. MATERIALS AND METHODS: CT images of a skills phantom with liver lesions were acquired and co-registered to US using GE Logiq E9 navigation software. Manual co-registration was compared to automatic and semiautomatic co-registration using an active tracker. Also, manual point registration was compared to plane registration with and without an additional translation point. Finally, comparison was made between manual and automatic selection of reference points. In each experiment, accuracy of the co-registration method was determined by measurement of the residual displacement in phantom lesions by two independent observers. RESULTS: Mean displacements for a superficial and deep liver lesion were comparable after manual and semiautomatic co-registration: 2.4 and 2.0 mm versus 2.0 and 2.5 mm, respectively. Both methods were significantly better than automatic co-registration: 5.9 and 5.2 mm residual displacement (p < 0.001; p < 0.01). The accuracy of manual point registration was higher than that of plane registration, the latter being heavily dependent on accurate matching of axial CT and US images by the operator. Automatic reference point selection resulted in significantly lower registration accuracy compared to manual point selection despite lower root-mean-square deviation (RMSD) values. CONCLUSION: The accuracy of manual and semiautomatic co-registration is better than that of automatic co-registration. For manual co-registration using a plane, choosing the correct plane orientation is an essential first step in the registration process. Automatic reference point selection based on RMSD values is error-prone.

Prospective Clinical and Pharmacological Evaluation of the Delcath System's Second-Generation (GEN2) Hemofiltration System in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan.

INTRODUCTION: Percutaneous hepatic perfusion (PHP) with melphalan is an effective treatment for patients with hepatic metastases, but associated with high rates of bone marrow depression. To reduce systemic toxicity, improvements have been made to the filtration system. In pre-clinical studies, the Delcath System's GEN2 filter was superior to the first-generation filters. In this clinical study, we analysed the pharmacokinetics and toxicity of PHP using the new GEN2 filter. METHODS AND MATERIALS: Starting February 2014, two prospective phase II studies were initiated in patients with hepatic metastases from ocular melanoma or colorectal cancer. In 10 PHP procedures performed in the first 7 enrolled patients, blood samples were obtained to determine filter efficiency and systemic drug exposure. PHP was performed with melphalan 3 mg/kg with a maximum of 220 mg. Complications were assessed according to CTCAE v4.03. Response was assessed according to RECIST 1.1. RESULTS: Pharmacokinetic analysis of blood samples showed an overall filter efficiency of 86% (range 71.1-95.5%). The mean filter efficiency decreased from 95.4% 10 min after the start of melphalan infusion to 77.5% at the end of the procedure (p = 0.051). Bone marrow depression was seen after up to 80.0% of 10 procedures, but was self-limiting and mostly asymptomatic. No hypotension-related complications or procedure-related mortality occurred. CONCLUSION: The GEN2 filter has a higher melphalan filter efficiency compared to the first-generation filters and a more consistent performance. PHP with the GEN2 filter appears to have an acceptable safety profile, but this needs further validation in larger studies.

Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies.

Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest and the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.

Differences in Patient Characteristics and Midterm Outcome Between Asian and European Patients Treated with Radiofrequency Ablation for Hepatocellular Carcinoma.

PURPOSE: The aim of this study was to compare patient characteristics and midterm outcomes after RFA for unresectable Hepatocellular carcinoma (HCC) in Asian and European cohorts. MATERIALS AND METHODS: The study was based on retrospective analysis of 279 patients (mean 64.8 ± 12.1 years; 208 males) treated with RFA for de novo HCC in tertiary referral centers in Singapore and the Netherlands, with median follow-up of 28.2 months (quartiles: 13.1-40.5 months). Cumulative incidence of recurrence and death were analyzed using a competing risk model. RESULTS: Age was higher in the Asian group: 66.5 versus 60.1 years (p < 0.0001). The most common etiology was hepatitis B in the Asian group (48.0 %) and alcohol-induced cirrhosis in Europeans (54.4 %); p < 0.001. Asian patients had less advanced disease: 35.5, 55.0, and 3.0 %, respectively, had BCLC 0, A, and B versus 21.5, 58.2, and 15.2 % in the European group (p = 0.01). The cumulative incidences of recurrence in the Asian group at 1, 2, 3, and 5 years were 37.0, 56.4, 62.3, and 67.7 %, respectively, compared to 32.6, 47.2, 49.7, and 53.4 % in the European group (p = 0.474). At 1, 2, 3, and 5 years, the cumulative incidence rates of death in the Asian group were 2.0, 3.9, 4.9, and 4.9 %, respectively, corresponding to 7.7, 9.2, 14.1, and 21.0 % in the European group (p = 0.155). CONCLUSION: Similar short-term treatment outcomes are achieved with RFA in HCC patients in the South-East Asian and Northern-European populations. Midterm recurrence and death rates differ between the groups as a result of differences in baseline patient characteristics and patient selection. Our study provides insight relevant to the design of future international studies.