Quality of Life Analysis of Patients Treated with Percutaneous Hepatic Perfusion for Uveal Melanoma Liver Metastases.

PURPOSE: Percutaneous hepatic perfusion with melphalan (M-PHP) is a minimally invasive therapy with proven efficacy in patients with uveal melanoma (UM) liver metastases. M-PHP is associated with a short hospital admission time and limited systemic side effects. In this study, we assessed quality of life (QoL) in UM patients treated with M-PHP. MATERIALS AND METHODS: A prospective, single-center study including 24 patients treated with M-PHP for UM metastases to the liver. QoL questionnaires were collected at baseline, on day 2/3 after M-PHP, and on day 7 and day 21 after M-PHP, according to study protocol. The results were scored according to EORTC-QLQ C30 global health status (GHS), functional scales, and symptom scales. The difference in scores at baseline and subsequent time points was analyzed with the Wilcoxon signed-rank test and multiple testing Bonferroni correction. Adverse events (AE) were registered up to 30 days after M-PHP according to CTCAE v5.0. RESULTS: Twenty-four patients (14 males; median age 63.0 years) completed 96 questionnaires. Most scores on all scales declined on day 2/3 after M-PHP. On day 21 after M-PHP, 12 out of 15 scores returned to baseline, including median GHS scores. Three variables were significantly worse on day 21 compared to baseline: fatigue (6-33; p = 0.002), physical functioning (100 vs 86.7; p = 0.003), and role functioning (100 vs 66.7; p = 0.001). Grade 3/4 AEs consisted mainly of hematological complications, such as leukopenia and thrombopenia. CONCLUSION: M-PHP causes fatigue and a decline in physical and role functioning in the 1st weeks after treatment, but GHS returns to baseline levels within 21 days. LEVEL OF EVIDENCE 3: Cohort study.

Combining Melphalan Percutaneous Hepatic Perfusion with Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma: First Safety and Efficacy Data from the Phase Ib Part of the Chopin Trial.

PURPOSE: To define a safe treatment dose of ipilimumab (IPI) and nivolumab (NIVO) when applied in combination with percutaneous hepatic perfusion with melphalan (M-PHP) in metastatic uveal melanoma (mUM) patients (NCT04283890), primary objective was defining a safe treatment dose of IPI/NIVO plus M-PHP. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAEv4.03). Secondary objective was response rate, PFS and OS. MATERIALS AND METHODS: Patients between 18-75 years with confirmed measurable hepatic mUM according to RECIST 1.1 and WHO performance score 0-1 were included. Intravenous IPI was applied at 1 mg/kg while NIVO dose was increased from 1 mg/kg in cohort 1 to 3 mg/kg in cohort 2. Transarterial melphalan dose for M-PHP was 3 mg/kg (maximum of 220 mg) in both cohorts. Treatment duration was 12 weeks, consisting of four 3-weekly courses IPI/NIVO and two 6-weekly M-PHPs. RESULTS: Seven patients were included with a median age of 63.6 years (range 50-74). Both dose levels were well tolerated without dose-limiting toxicities or deaths. Grade III/IV adverse events (AE) were observed in 2/3 patients in cohort 1 and in 3/4 patients in cohort 2, including Systemic Inflammatory Response Syndrome (SIRS), febrile neutropenia and cholecystitis. Grade I/II immune-related AEs occurred in all patients, including myositis, hypothyroidism, hepatitis and dermatitis. There were no dose-limiting toxicities. The safe IPI/NIVO dose was defined as IPI 1 mg/kg and NIVO 3 mg/kg. There was 1 complete response, 5 partial responses and 1 stable disease (3 ongoing responses with a median FU of 29.1 months). CONCLUSION: Combining M-PHP with IPI/NIVO was safe in this small cohort of patients with mUM at a dose of IPI 1 mg/kg and NIVO 3 mg/kg.

Partial Right Atrial Inflow Occlusion for Transient Systemic Hypotension During Deployment of Thoracic Stentgrafts.

PURPOSE: Temporary balloon occlusion of the inferior vena cava to lower cardiac output is a relatively infrequently used technique to induce controlled systemic hypotension. In this technical note, we describe the feasibility, reliability, and safety of partial occlusion of right atrial inflow and the effect on systemic blood pressure during the deployment of a thoracic stentgraft. MATERIALS AND METHODS: Twenty consecutive patients undergoing thoracic endovascular aortic repair, with proximal landing in zone 0-3 of the thoracic aorta, were prospectively included. Right atrial inflow occlusion was performed with a compliant occlusion balloon. RESULTS: Median time to reach a mean arterial pressure of 50 mmHg was 43 s. Median recovery time of blood pressure was 42 s. CONCLUSION: Partial right atrial inflow occlusion with an occlusion balloon is feasible with reliable results and without procedure-related complications.

Quantitative Volumetric Assessment of Ablative Margins in Hepatocellular Carcinoma: Predicting Local Tumor Progression Using Nonrigid Registration Software.

PURPOSE: After radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), pre- and postinterventional contrast-enhanced CT (CECT) images are usually qualitatively interpreted to determine technical success, by eyeballing. The objective of this study was to evaluate the feasibility of quantitative assessment, using a nonrigid CT-CT coregistration algorithm. MATERIALS AND METHODS: 25 patients treated with RFA for HCC between 2009 and 2014 were retrospectively included. Semiautomated coregistration of pre- and posttreatment CECT was performed independently by two radiologists. In scans with a reliable registration, the tumor and ablation area were delineated to identify the side and size of narrowest RFA margin. In addition, qualitative assessment was performed independently by two other radiologists to determine technical success and the anatomical side and size of narrowest margin. Interobserver agreement rates were determined for both methods, and the outcomes were compared with occurrence of local tumor progression (LTP). RESULTS: CT-CT coregistration was technically feasible in 18/25 patients with almost perfect interobserver agreement for quantitative analysis (κ = 0.88). The interobserver agreement for qualitative RFA margin analysis was κ = 0.64. Using quantitative assessment, negative ablative margins were found in 12/18 patients, with LTP occurring in 8 of these patients. In the remaining 6 patients, quantitative analysis demonstrated complete tumor ablation and no LTP occurred. CONCLUSION: Feasibility of quantitative RFA margin assessment using nonrigid coregistration of pre- and postablation CT is limited, but appears to be a valuable tool in predicting LTP in HCC patients (p=0.013).

Quantitative margin assessment of radiofrequency ablation of a solitary colorectal hepatic metastasis using MIRADA RTx on CT scans: a feasibility study.

BACKGROUND: Compared to surgery, radiofrequency ablation(RFA) for colorectal liver metastasis(CRLM) is associated with higher local recurrence(LR) rates. A wide margin (at least 5 mm) is generally recommended to prevent LR, but the optimal method to assess ablation margins is yet to be established. The aim of our study was to evaluate the feasibility and reproducibility of CT-CT co-registration, using MIRADA software, in order to assess ablation margins of patients with CRLM. METHODS: In this retrospective study, pre- and post-ablation contrast-enhanced CT scans of 29 patients, treated with percutaneous RFA for a solitary CRLM, were co-registered. Co-registration was performed by two independent radiologist, based on venous structures in proximity to the tumor. Feasibility of CT-CT co-registration and inter-observer agreement for reproducibility and ablation margins was determined. Furthermore, the minimal ablation margin was compared with the occurrence of LR during follow-up. RESULTS: Co-registration was considered feasible in 18 patients (61% male, 63.1(±10.9) year), with a perfect inter-observer agreement for completeness of ablation: κ = 1.0(p < 0.001). And substantial inter-observer agreement for measurement of the minimal margin (≤ 0 mm, 1-5 mm, ≥ 5 mm): κ = 0.723(p-value < 0.001). LR occurred in eight of nine(88.9%) incompletely ablated CRLM and in one of the nine completely ablated CRLM(11.1%). CONCLUSION: Co-registration using MIRADA is reproducible and potentially a valuable tool in defining technical success. Feasibility of co-registration of pre- and post-ablation CT scans is suboptimal if scans are not acquired concordantly. Co-registration may potentially aid in the prediction of LR after percutaneous ablation.

Evaluation of CT Angiography Image Quality Acquired with Single-Energy Metal Artifact Reduction (SEMAR) Algorithm in Patients After Complex Endovascular Aortic Repair.

PURPOSE: To evaluate the value of single-energy metal artifact reduction (SEMAR) algorithm on image quality in patients after complex endovascular aortic repair (EVAR) with fenestrated and branched devices. METHODS: Routine follow-up computed tomography angiography (CTA) examinations were performed between February 2016 and May 2017 in 18 patients who underwent a complex EVAR procedure at our institution. Objective analysis was performed by measuring the standard deviation (SD) of attenuation (Hounsfield Units), and the contrast-to-noise ratio (CNR) in regions of interests in the stented visceral arteries. Subjective analysis of the degree of artifacts and stent visualization was performed independently by two interventional radiologists, blinded to the image reconstruction. RESULTS: The SD of attenuation was significantly lower in all target visceral arteries (p < .001), the celiac artery (p = .002), the superior mesenteric artery (SMA; p = .043), and renal arteries (p < .001) in the CT images with SEMAR reconstruction. The CNR significantly increased in all SEMAR-reconstructed target visceral arteries (overall: p < .001, celiac artery: p = .009; SMA: p = .003; renal arteries: p < .001). The reviewers rated a significantly lower artifact degree in all target vessels (overall: p < .001, celiac artery: p = .001; SMA: p = .008; renal arteries: p < .001) and a significantly improved visualization of the stent patency in all target vessels (overall: p < .001, celiac artery: p = .031; SMA: p = .047; renal arteries: p < .001) in the SEMAR images. Overall preference of both reviewers was in favor of the SEMAR reconstruction in 15/18 cases (83%). CONCLUSION: Reconstruction with SEMAR algorithm significantly improves CTA image quality in patients after complex EVAR. LEVEL OF EVIDENCE: Level 4, Case series.

Establishing New Cut-Off Limits for Galactose 1-Phosphate-Uridyltransferase Deficiency for the Dutch Newborn Screening Programme.

Newborn screening for classical galactosemia in the Netherlands is performed by five laboratories and is based on the measurement of galactose 1-phosphate-uridyltransferase (GALT) activity and total galactose (TGAL) in heel prick blood spots. Unexpected problems with the GALT assay posed a challenge to switch to a new assay. The aim of this study was to make an analytical and clinical evaluation of GALT assays to replace the current assay and to establish new cut-off values (COVs).First, the manual assay from PerkinElmer (NG-1100) and the GSP assay were compared by analyzing 626 anonymous heel prick samples in parallel. Secondly, a manual GSP method was evaluated and 2,052 samples were compared with the automated GSP assay. Finally, a clinical evaluation was performed by collecting data from 93 referred newborns.No satisfactory correlation was observed between GALT activity measured with the manual NG-1100 assay and the automated GSP assay. An acceptable correlation was found between the manual and automated GSP assay. Intra- and inter-assay variation of the automated GSP were 1.8-10.0% and 3.1-13.9%, respectively. Evaluation of clinical data demonstrated that adjusting the COVs for GALT to 2.0 U/dl and TGAL to 1,100 µmol/l improved specificity of screening for classical galactosemia.An assay designed for automated processing to measure GALT activity in heel prick samples works equally well when processed manually. We therefore adopted both methods in the Dutch screening laboratories. As a result of this evaluation new COVs for GALT and TGAL have been introduced and are valid from July 2015.

MRI appearances of atypical cartilaginous tumour/grade I chondrosarcoma after treatment by curettage, phenolisation and allografting: recommendations for follow-up.

AIMS: The purpose of this retrospective study was to differentiate between the MRI features of normal post-operative change and those of residual or recurrent disease after intralesional treatment of an atypical cartilage tumour (ACT)/grade I chondrosarcoma. PATIENTS AND METHODS: We reviewed the case notes, radiology and histology of 75 patients, who had been treated for an ACT/grade I chondrosarcoma by curettage, phenolisation and bone allografting between 1994 and 2005. The first post-operative Gd-enhanced MRI scan was carried out within one year of surgery. Patients had a minimum of two scans and a mean follow-up of 72 months (13 to 169). Further surgery was undertaken in cases of suspected recurrence. RESULTS: In 14 patients (18.6%) a second procedure was undertaken after a mean period of 59 months (8 to 114). Radio frequency ablation (RFA) was used in lesions of < 10 mm and curettage, phenolisation and bone grafting for those ≥ 10 mm. Only six of these (8% of total) had a histologically-proven recurrence. No increase in tumour grade was seen at time of recurrence. CONCLUSION: Based on this study, we have been able to classify the post-operative MRI appearances into four groups. These groups differ in follow-up, and have a different risk of recurrence of the lesion. Follow-up and treatment vary for the patients in each group. We present a flow diagram for the appropriate and safe follow-up for this specific group of patients. Cite this article: Bone Joint J 2016;98-B:1674-81.

The management of diffuse-type giant cell tumour (pigmented villonodular synovitis) and giant cell tumour of tendon sheath (nodular tenosynovitis).

Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT. Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered.

Synovial sarcoma: dynamic contrast-enhanced MR imaging features.

OBJECTIVE: To determine whether previously described so-called malignant dynamic contrast-enhanced magnetic resonance (MR) imaging features--early start, peripheral enhancement and early plateau or washout phase--occur consistently in synovial sarcoma. DESIGN AND PATIENTS: Dynamic contrast-enhanced MR images of 10 patients with histologically proven synovial sarcoma were reviewed. The start, pattern and progression of tumor enhancement were assessed and correlated with histopathology. RESULTS: In all patients, the time interval between arterial and early tumor enhancement was less than 7 s (mean 4.40 s, SD 2.09 s). Six synovial sarcomas showed enhancement with a subsequent rapidly progressive linear increase in signal intensity followed by a plateau in one lesion and washout in five. Four lesions showed a late sustained increase in enhancement after the initial rapid increase in enhancement. The pattern of initial enhancement was peripheral in only two lesions, diffuse in four and heterogeneous in four lesions. CONCLUSIONS: Enhancement of tumor within 7 s after arterial enhancement is, of the three parameters described previously, the only sign that occurs consistently in synovial sarcoma.

Bone tumors.

We present an overview of the imaging modalities in bone tumors. The imaging strategies of preoperative work-up, monitoring the effect of chemotherapy and the detection of recurrences by long-term follow-up are discussed.

Cervical carcinoma: can dynamic contrast-enhanced MR imaging help predict tumor aggressiveness?

PURPOSE: To determine whether fast dynamic contrast agent-enhanced magnetic resonance (MR) imaging can demonstrate tumor aggressiveness of cervical carcinoma in patients who are eligible for surgical treatment. MATERIALS AND METHODS: Dynamic contrast-enhanced MR imaging of cervical carcinoma was performed in 82 consecutive patients with stage I or IIA disease who were referred for radical hysterectomy. The maximum slope and amplitude of dynamic first-pass contrast enhancement were quantified. These parameters were correlated with histologic measures of tumor aggressiveness (tumor invasion depth, pelvic lymph node status). RESULTS: The analysis was based on tumors in 62 patients: 30 aggressive and 32 relatively nonaggressive tumors. Twenty patients were excluded from analysis owing to insufficient surgical data, tumor too small for accurate assessment, or technical problems. There were no significant differences between aggressive and nonaggressive tumors in terms of the first-pass contrast-enhancement parameters of slope (2.0 vs 2.1 arbitrary signal intensity units per second, P > .5) or amplitude (24.8 vs 27.8 arbitrary units, P > .2). CONCLUSION: Dynamic contrast-enhanced MR imaging does not facilitate differentiation between aggressive and nonaggressive tumors and therefore has no clinical role in assisting in treatment decisions in patients who are candidates for radical hysterectomy.

Fast dynamic contrast-enhanced colour-coded MRI in uterine cervix carcinoma: useful for tumour staging?

OBJECTIVE: To quantify first-pass enhancement of cervix carcinoma using fast dynamic MRI. To assess the accuracy of dynamic contrast-enhanced colour-coded MRI for determining tumour invasion into surrounding pelvic tissues. METHODS: Gadolinium enhanced dynamic MRI at one image every 2 s was performed in 47 patients with cervical carcinoma and five controls. First-pass contrast enhancement of cervix carcinoma and surrounding pelvic tissues was quantified. Automated colour-coded images were constructed using the dynamic parameters slope, amplitude and timing of enhancement. Of 47 patients, 28 underwent surgery and colour coded images were correlated with histological findings. RESULTS: First-pass contrast enhancement imaging of cervix carcinoma required a temporal resolution of dynamic MRI of one image every 3-4 s. Cervix carcinoma first-pass was more rapid and intense than that of other pelvic tissues (P<0.001) with the exception of normal myometrium (P>0.05). Binary colour coding, however, was not reliable for tumour delineation or for accurate assessment of tumour invasion into the parametria or the bladder wall. Overestimation of the extent of tumour invasion occurred in 15, 16 and nine out of 28 patients, respectively, using amplitude, slope and timing of enhancement as parameters. CONCLUSION: Dynamic contrast-enhanced colour-coded MRI of cervix carcinoma has limited value for assessing the extent of tumour spread and tumour staging.

MR imaging of uterine cervical carcinoma: comparison between fast spin-echo MRI and GRASE.

The aim of our study was to compare the image quality of T2-weighted gradient-echo-and-spin-echo (GRASE) MRI and fast spin-echo (FSE) MRI for imaging of cervical carcinoma. In 40 patients FSE8 (TR/TE = 3400/90 ms) MRI with echo train length (ETL) of 8, GRASE (3400/90) MRI with ETL of 18, turbo factor of 6 and 3 gradient reversals, and FSE18 (2500/120) MRI with ETL of 18 were performed. Tissue contrast, subjectively rated image quality, and accuracy of tumor delineation were compared. Surgical correlation was obtained in 27 subjects. Contrast-to-noise ratios of the tumor-cervix stroma, tumor-parametrium and tumor-rectum wall interfaces were better in FSE18 than in FSE8 and GRASE (P < 0.001) but not different between FSE8 and GRASE. Subjective image quality was better in FSE18 and FSE8 than in GRASE (P < 0.02). The accuracy of tumor delineation was similar for the three different sequences. The accuracy of FSE and GRASE MRI for the delineation of cervical carcinoma is similar. Based on measurement of image quality and CNRs, however, high turbo factor FSE provides better image quality in MRI of cervical carcinoma. Whether the superior characteristics may result in better staging has to be explored in larger clinical trials.