PurposeThe 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... Show morePurposeThe 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).MethodsIn 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.ResultsTwelve 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.ConclusionAdjuvant (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 registrationClinicaltrials.gov NCT03437382. (registered: 19-02-2018) Show less
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... Show morePurpose: 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. (c) 2023 The Author(s). Published by Elsevier Masson SAS on behalf of Societe francaise de radiologie. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Show less
Rijn, K. van; Schepers, A.; Meer, R.W. van der; Rijswijk, C.S.P. van; Schaik, J. van; Vorst, J.R. van der 2023
A 27-year-old man underwent thoracic endovascular aortic repair for blunt thoracic aortic injury. Fourteen months later, he presented with intermittent paraplegia, congestive heart failure, and a... Show moreA 27-year-old man underwent thoracic endovascular aortic repair for blunt thoracic aortic injury. Fourteen months later, he presented with intermittent paraplegia, congestive heart failure, and a decline of kidney function as a result of high-grade aortic stenosis caused by in-stent thrombosis. He had a concurrent infection with coronavirus disease 2019. The patient was successfully treated using axillofemoral bypass, followed by stent relining 2 weeks later. The possible risk factors and the optimal therapeutic approach for in-stent thrombosis remain unknown, because only a limited number of cases describing this rare complication have been reported. (J Vasc Surg Cases Innov Tech 2023;9:101297.) Show less
Tange, F.P.; Ferrari, B.R.; Hoven, P. van den; Schaik, J. van; Schepers, A.; Rijswijk, C.S.P. van; ... ; Vorst, J.R. van der 2023
Background: The angiosome concept is defined as the anatomical territory of a source artery within all tissue layers. When applying this theory in vascular surgery, direct revascularization (DR) is... Show moreBackground: The angiosome concept is defined as the anatomical territory of a source artery within all tissue layers. When applying this theory in vascular surgery, direct revascularization (DR) is preferred to achieve increased blood flow toward the targeted angiosome of the foot in patients with lower extremity arterial disease (LEAD). This study evaluates the applicability of the angiosome concept using quantified near-infrared (NIR) fluorescence imaging with indocMethods: This study included patients undergoing an endovascular- or surgical revascularization of the leg between January 2019 and December 2021. Preinterventional and postinterventional ICG NIR fluorescence imaging was performed. Three angiosomes on the dorsum of the foot were determined: the posterior tibial artery (hallux), the anterior tibial artery (dorsum of the foot) and the combined angiosome (second to fifth digit). The angiosomes were classified from the electronic patient records and the degree of collateralization was classified based on preprocedural computed tomography angiography and/or X-ray angiography. Fluorescence intensity was quantified in all angiosomes. A subgroup analysis based on endovascular or surgical revascularized angiosomes, and within critical limb threatening ischemia (CLTI) patients was performed. Results: ICG NIR fluorescence measurements were obtained in 52 patients (54 limbs) including a total of 157 angiosomes (121 DR and 36 indirect revascularizations [IR]). A significant improvement of all perfusion parameters in both the directly and indirectly revascularized angiosomes was found (P-values between <0.001e0.007). Within the indirectly revascularized angiosomes, 90.6% of the scored collaterals were classified as significant. When comparing the percentual change in perfusion parameters between the directly and indirectly revascularized angiosomes, no significant difference was seen in all perfusion parameters (P-values between 0.253 and 0.881). Similar results were shown in the CLTI patients subgroup analysis, displaying a significant improvement of perfusion parameters in both the direct and indirect angiosome groups (P-values between <0.001 and 0.007), and no significant difference when comparing the percentual parameter improvement between both angiosome groups (P-values between 0.134 and 0.359). Furthermore, no significant differences were observed when comparing Show less
Warmerdam, B.W.C.M.; Stevens, M.; Rijswijk, C.S.P. van; Eefting, D.; Meer, R.W. van der; Putter, H.; ... ; Schaik, J. van 2023
Background: When introducing new techniques, attention must be paid to learning curve. Be-sides quantitative outcomes, qualitative factors of influence should be taken into consideration. This... Show moreBackground: When introducing new techniques, attention must be paid to learning curve. Be-sides quantitative outcomes, qualitative factors of influence should be taken into consideration. This retrospective cohort study describes the quantitative learning curve of complex endovascu-lar aortic repair (EVAR) in a nonhigh-volume academic center and provides qualitative factors that were perceived as contributors to this learning curve. With these factors, we aim to aid in future implementation of new techniques. Methods: All patients undergoing complex EVAR in the Leiden University Medical Center (LUMC) between July 2013 and April 2021 were included (n = 90). Quantitative outcomes were as follows: operating time, blood loss, volume of contrast, hospital stay, major adverse events (MAE), 30-day mortality, and complexity. Patients were divided into 3 temporal groups (n = 30) for dichotomous outcomes. Regression plots were used for continuous outcomes. In 2017, the treatment team was interviewed by an external researcher. These interviews were reanalyzed for factors that contributed to successful implementation. Results: Length of hospital stay (P = 0.008) and operating time (P = 0.010) decreased signif-icantly over time. Fewer cardiac complications occurred in the third group (3: 0% vs. 2: 17% vs. 1: 17%, P = 0.042). There was a trend of increasing complexity (P = 0.076) and number of fen-estrations (P = 0.060). No significant changes occurred in MAE and 30-day mortality. Qualitative factors that, according to the interviewees, positively influenced the learning curve were as fol-lows: communication, mutual trust, a shared sense of responsibility and collective goals, clear authoritative structures, mutual learning, and team capabilities. Conclusions: In addition to factors previously identified in the literature, new learning curve factors were found (mutual learning and shared goals in the operating room (OR)) that should be taken into account when implementing new techniques. Show less
Reeder, A. de; Hendriks, P.; Plas, H. van der; Zweers, D.; Overbeeke, P.S.M. van; Gravendeel, J.; ... ; Burgmans, M.C. 2023
BackgroundHealthcare is a highly polluting industry and attention to the need for making this sector more sustainable is growing. The interventional radiology (IR) department is a relatively unique... Show moreBackgroundHealthcare is a highly polluting industry and attention to the need for making this sector more sustainable is growing. The interventional radiology (IR) department is a relatively unique department in the hospital because of its synergetic use of both imaging equipment and medical instruments. As a result, the interventional radiology department causes a significant environmental burden in terms of energy usage, waste and water pollution. The aim of this study was to explore the current state of sustainability within IR by conducting a survey and interviews among IR specialists in the Netherlands.ResultsThe main findings of this study were that there is a high awareness for the need of sustainability within IR, but that there is still limited action. Previous studies point towards the various opportunities in the field of energy, waste and water pollution, yet our study unveils these opportunities are often not implemented because of (1) sustainability not being a priority, (2) a dependency on employees, and (3) factors that simply cannot be changed by an individual IR department or hospital. Generally, our study indicates that there is a willingness to become more sustainable, but that the current system involves a wide range barriers that hinder true change. Furthermore, it seems that no one is currently taking the lead and a leading role from higher management, government, healthcare authorities or professional societies is lacking.ConclusionsDespite the hurdles found in our study, IR departments can implement several improvements. An important factor is that sustainability should not lead to lower convenience for employees, which can be ensured by a sufficiently designed waste infrastructure and behavioral nudges. Furthermore, there lies an opportunity in more collaboration between IR departments in knowledge sharing and open innovation. Show less
Garsen, M.; Buijsers, B.; Sol, M.; Gockeln, L.; Sonneveld, R.; Kuppevelt, T.H. van; ... ; Vlag, J. van der 2023
Background Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the... Show moreBackground Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the development of proteinuria, whereas peroxisome proliferator-activated receptor y (PPARy) agonists can ameliorate proteinuria. Since a recent study showed that PPARy regulates HPSE expression in liver cancer cells, we hypothesized that PPARy agonists exert their reno-protective effect by inhibiting glomerular HPSE expression.Methods Regulation of HPSE by PPARy was assessed in the adriamycin nephropathy rat model, and cultured glomerular endothelial cells and podocytes. Analyses included immunofluorescence staining, real-time PCR, heparanase activity assay and transendothelial albumin passage assay. Direct binding of PPARy to the HPSE promoter was evaluated by the luciferase reporter assay and chromatin immunoprecipitation assay. Furthermore, HPSE activity was assessed in 38 type 2 diabetes mellitus (T2DM) patients before and after 16/24 weeks treatment with the PPARy agonist pioglitazone.Findings Adriamycin-exposed rats developed proteinuria, an increased cortical HPSE and decreased heparan sulfate (HS) expression, which was ameliorated by treatment with pioglitazone. In line, the PPARy antagonist GW9662 increased cortical HPSE and decreased HS expression, accompanied with proteinuria in healthy rats, as previously shown. In vitro, GW9662 induced HPSE expression in both endothelial cells and podocytes, and increased trans -endothelial albumin passage in a HPSE-dependent manner. Pioglitazone normalized HPSE expression in adriamycin-injured human endothelial cells and mouse podocytes, and adriamycin-induced transendothelial albumin passage was reduced as well. Importantly, we demonstrated a regulatory effect of PPARy on HPSE promoter activity and direct PPARy binding to the HPSE promoter region. Plasma HPSE activity of T2DM patients treated with pioglitazone for 16/24 weeks was related to their hemoglobin A1c and showed a moderate, near significant correlation with plasma creatinine levels.Interpretation PPARy-mediated regulation of HPSE expression appears an additional mechanism explaining the anti-proteinuric and renoprotective effects of thiazolidinediones in clinical practice.Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
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 ... Show morePurpose 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. Show less
Aarts, B.M.; Gomez, F.M.; Lopez-Yurda, M.; Bevers, R.F.M.; Herndriks, J.; Beets-Tan, R.G.H.; ... ; Meer, R.W. van der 2022
Objectives Percutaneous radiofrequency ablation (RFA) is stated as a treatment option for renal cell carcinoma (RCC) smaller than 4 cm (T1a). Microwave ablation (MWA) is a newer technique and is... Show moreObjectives Percutaneous radiofrequency ablation (RFA) is stated as a treatment option for renal cell carcinoma (RCC) smaller than 4 cm (T1a). Microwave ablation (MWA) is a newer technique and is still considered experimental in some guidelines. The objective of this study was to compare the safety and efficacy of RFA and MWA for the treatment of RCC. Methods Patients with T1a RCC treated by RFA or MWA in two referral centers were retrospectively analyzed. Patient records were evaluated to generate mRENAL nephrometry scores. Local tumor progression (LTP) was considered when new (recurrence) or residual tumor enhancement within/adjacent to the ablation zone was objectified. Differences in LTP-free interval (residual + recurrence) between ablation techniques were assessed with Cox proportional hazards models and propensity score (PS) methods. Results In 164 patients, 87 RFAs and 101 MWAs were performed for 188 RCCs. The primary efficacy rate was 92% (80/87) for RFA and 91% (92/101) for MWA. Sixteen patients had residual disease (RFA (n = 7), MWA (n = 9)) and 9 patients developed recurrence (RFA (n = 7), MWA (n = 2)). LTP-free interval was significantly worse for higher mRENAL nephrometry scores. No difference in LTP-free interval was found between RFA and MWA in a model with inverse probability weighting using PS (HR = 0.99, 95% CI 0.35-2.81, p = 0.98) and in a PS-matched dataset with 110 observations (HR = 0.82, 95% CI 0.16-4.31, p = 0.82). Twenty-eight (14.9%) complications (Clavien-Dindo grade I-IVa) occurred (RFA n = 14, MWA n = 14). Conclusion Primary efficacy for ablation of RCC is high for both RFA and MWA. No differences in efficacy and safety were observed between RFA and MWA. Show less
Purpose To investigate the biodistribution of holmium-166 microspheres (Ho-166-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to... Show morePurpose To investigate the biodistribution of holmium-166 microspheres (Ho-166-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 (Tc-99m-MAA). The perfused liver volume is segmented from the CBCT and Ho-166-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 Ho-166-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. Show less
Purpose To investigate the biodistribution of holmium166 microspheres (166Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to... Show morePurpose To investigate the biodistribution of holmium166 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 B 3 cm each. The day after RFA patients undergo angiography and conebeam CT (CBCT) with (super)selective infusion of technetium-99 m labelled microalbumin aggregates (99mTcMAA). 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 C 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 earlystage HCC patients. Show less
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... Show morePurpose 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 (similar to 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. Show less
PurposeThe 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.... Show morePurposeThe 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 MethodsThis 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.DiscussionIt 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. Show less
Tong, T.M.L.; Kooij, M.K. van der; Speetjens, F.M.; Erkel, A.R. van; Meer, R.W. van der; Lutjeboer, J.; ... ; Kapiteijn, E. 2022
Background: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal... Show moreBackground: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response. We hypothesize that combining M-PHP with ICI will lead to enhanced antigen presentation and increased immunomodulatory effect, improving control of both hepatic and extrahepatic disease.Methods: Open-label, single-center, phase Ib/randomized phase II trial, evaluating the safety and efficacy of the combination of M-PHP with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) in patients with unresectable hepatic metastases of UM in first-line treatment, with or without the limited extrahepatic disease. The primary objective is to determine the safety, toxicity, and efficacy of the combination regimen, defined by maximum tolerated dose (MTD) and progression-free survival (PFS) at 1 year. Secondary objectives include overall survival (OS) and overall response rate (ORR). A maximum of 88 patients will be treated in phase I and phase II combined. Baseline characteristics will be described with descriptive statistics (t-test, chi-square test). To study the association between risk factors and toxicity, a logistic regression model will be applied. PFS and OS will be summarized using Kaplan-Meier curves.Discussion: This is the first trial to evaluate this treatment combination by establishing the maximum tolerated dose and evaluating the efficacy of the combination treatment. M-PHP has shown to be a safe and effective treatment for UM patients with liver metastases and became the standard treatment option in our center. The combination of ICI with M-PHP is investigated in the currently described trial which might lead to a better treatment response both in and outside the liver. Show less
PurposePercutaneous 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... Show morePurposePercutaneous 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 methodsProspective, 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.ResultsA 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.ConclusionM-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. Show less
Warmerdam, B.W.C.M.; Holstein, Y. van; Eefting, D.; Rijswijk, C.S.P. van; Meer, R.W. van der; Mooijaart, S.P.; ... ; Schaik, J. van 2021
Purpose Complex endovascular aortic repair (EVAR) procedures provide a treatment option for patients with aortic aneurysms involving visceral branches. Good technical results and short-term... Show morePurpose Complex endovascular aortic repair (EVAR) procedures provide a treatment option for patients with aortic aneurysms involving visceral branches. Good technical results and short-term outcomes have been reported. Whether complex EVAR provides acceptable functional outcomes is not clear. The current study aims to describe postoperative functional outcomes in complex EVAR patients-an older and relatively frail patient group. Materials and Methods A single-center retrospective cohort study was performed, using data from a computerized database of consecutive patients who underwent complex EVAR in the Leiden University Medical Center (LUMC, The Netherlands) between July 2013 and September 2020. As of May 2017, patients scheduled for complex EVAR were referred to a geriatric care pathway to determine (Instrumental) Activities of Daily Living ((I)ADL) scores at baseline and, if informed consent was given, after 12 months. For the total patient group, adverse functional performance outcomes were: discharge to a nursing home and 12-month mortality. For the patients included in geriatric follow-up, the additional outcome was the incidence of functional decline (defined by a >= 2 point increase in (I)ADL-score) at 12-month follow-up Results Eighty-two patients underwent complex EVAR, of which 68 (82.9%) were male. Mean age was 73.3 years (SD=6.3). Within 30 days postsurgery, 6 patients (7.3%) died. Mortality within 12 months for the total patient group was 14.6% (n=12). After surgery, no patients had to be discharged to a nursing home. Fifteen patients (18.3%) were discharged to a rehabilitation center. Twenty-three patients gave informed consent and were included in geriatric follow-up. Five patients (21.7%) presented functional decline 12 months postsurgery and 4 patients had died (17.4%) by that time. This means that 39.1% of the patients in the care pathway suffered an adverse outcome. Conclusion To our knowledge, this is the only study that examined functional performance after complex EVAR, using a prospectively maintained database. No patients were newly discharged to a nursing home and functional performance results at 12 months are promising. Future multidisciplinary research should focus on determining which patients are most prone to deterioration of function, so that efforts can be directed toward preventing postoperative functional decline. Show less
Pietersen, L.C.; Meer, R.W. van der; Alders, D.J.C.; Schaik, J. van; Eefting, D.; Rijswijk, C.S.P. van 2021
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,... Show morePurpose 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. Show less
Meershoek, P.; Berg, N.S. van den; Lutjeboer, J.; Burgmans, M.C.; Meer, R.W. van der; Rijswijk, C.S.P. van; ... ; Leeuwen, F.W.B. van 2021
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... Show morePurpose: 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 (alpha VNav) 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 alpha VNav 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, alpha VNav 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. Show less
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... Show moreBackground 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. Show less
Baetens, T.R.; Rotmans, J.I.; Meer, R.W. van der; Rijswijk, C.S.P. van 2020
Exhausted central venous access is a potentially life-threatening situation for patients dependent on haemodialysis. If standard guidewire recanalisation fails, unconventional venous access or... Show moreExhausted central venous access is a potentially life-threatening situation for patients dependent on haemodialysis. If standard guidewire recanalisation fails, unconventional venous access or central venous needle recanalisation can be considered but are often associated with higher rates of complications and/or dysfunction. Here, we report about two patients treated successfully with the Surfacer(R) Inside-Out(R) Access Catheter System (Bluegrass Vascular Technologies, San Antonio, TX, USA) to achieve transmediastinal central venous access. Show less
