Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications.

INTRODUCTION: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. METHODS: The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. CONCLUSION: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.

Quality of Life After Early Clot Removal for Acute Iliofemoral Deep Vein Thrombosis.

Objective: To evaluate patient reported outcome measures after early clot removal for acute deep vein thrombosis (DVT), using the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) and the Short Form Health Survey (SF-36). Methods: Cross sectional design. Patients who underwent early clot removal between June 2012 and November 2021 were asked to complete the two questionnaires once. Lower CIVIQ-20 and higher SF-36 scores indicate better quality of life (QoL). Primary endpoints were the median scores. The one sample Wilcoxon signed rank test was used to compare SF-36 physical and mental component summary (PCS and MCS) to the normative and CIVIQ-20 to the minimum. Secondary, non-parametric independent t test or Fisher's exact test examined how age, sex, body mass index, stent placement, re-intervention, and time of questionnaire completion related to QoL. Multivariable linear regression tested whether various variables were associated with QoL. Results: The response rate was 73.5% (n = 39). Median time of questionnaire completion was 1.8 years (interquartile range [IQR] 3.1) after clot removal. The median CIVIQ-20 of 29.0 (IQR 28.0) was slightly higher than the minimum value 20.0 (p < .001). The median PCS (50.5, IQR 16.6) and median MCS (50.2, IQR 14.2) did not differ from the normative of 50.0. However, wide IQRs indicated impairments for a subgroup of patients. None of the tested variables affected QoL except for the finding that re-interventions had a significantly negative impact on the SF-36 MCS (standardised ß coefficient of -0.4, p = .030). Conclusion: Overall patient reported outcome measures were satisfactory after early clot removal, but impaired physical and mental functioning levels were present in a subgroup of patients. Re-interventions were found to have a negative impact on mental QoL. This finding was independent of time that had passed between the procedure and questionnaire completion. This study emphasises that mental functioning deserves attention, besides the widely recognised physical consequences after invasive acute iliofemoral DVT treatment.

Covered versus bare-metal stenting of the mesenteric arteries in patients with chronic mesenteric ischaemia (CoBaGI): a multicentre, patient-blinded and investigator-blinded, randomised controlled trial.

BACKGROUND: Mesenteric artery stenting with a bare-metal stent is the current treatment for atherosclerotic chronic mesenteric ischaemia. Long-term patency of bare-metal stents is unsatisfactory due to in-stent intimal hyperplasia. Use of covered stents might improve long-term patency. We aimed to compare the patency of covered stents and bare-metal stents in patients with chronic mesenteric ischaemia. METHODS: We conducted a multicentre, patient-blinded and investigator-blinded, randomised controlled trial including patients with chronic mesenteric ischaemia undergoing mesenteric artery stenting. Six centres in the Netherlands participated in this study, including two national chronic mesenteric ischaemia expert centres. Patients aged 18 years or older were eligible for inclusion when an endovascular mesenteric artery revascularisation was scheduled and a consensus diagnosis of chronic mesenteric ischaemia was made by a multidisciplinary team of gastroenterologists, interventional radiologists, and vascular surgeons. Exclusion criteria were stenosis length of 25 mm or greater, stenosis caused by median arcuate ligament syndrome or vasculitis, contraindication for CT angiography, or previous target vessel revascularisation. Digital 1:1 block randomisation with block sizes of four or six and stratification by inclusion centre was used to allocate patients to undergo stenting with bare-metal stents or covered stents at the start of the procedure. Patients, physicians performing follow-up, investigators, and radiologists were masked to treatment allocation. Interventionalists performing the procedure were not masked. The primary study outcome was the primary patency of covered stents and bare-metal stents at 24 months of follow-up, evaluated in the modified intention-to-treat population, in which stents with missing data for the outcome were excluded. Loss of primary patency was defined as the performance of a re-intervention to preserve patency, or 75% or greater luminal surface area reduction of the target vessel. CT angiography was performed at 6 months, 12 months, and 24 months post intervention to assess patency. The study is registered with ClinicalTrials.gov (NCT02428582) and is complete. FINDINGS: Between April 6, 2015, and March 11, 2019, 158 eligible patients underwent mesenteric artery stenting procedures, of whom 94 patients (with 128 stents) provided consent and were included in the study. 47 patients (62 stents) were assigned to the covered stents group (median age 69·0 years [IQR 63·0-76·5], 28 [60%] female) and 47 patients (66 stents) were assigned to the bare-metal stents group (median age 70·0 years [63·5-76·5], 33 [70%] female). At 24 months, the primary patency of covered stents (42 [81%] of 52 stents) was superior to that of bare-metal stents (26 [49%] of 53; odds ratio [OR] 4·4 [95% CI 1·8-10·5]; p<0·0001). A procedure-related adverse event occurred in 17 (36%) of 47 patients in the covered stents group versus nine (19%) of 47 in the bare-metal stent group (OR 2·4 [95% CI 0·9-6·3]; p=0·065). Most adverse events were related to the access site, including haematoma (five [11%] in the covered stents group vs six [13%] in the bare-metal stents group), pseudoaneurysm (five [11%] vs two [4%]), radial artery thrombosis (one [2%] vs none), and intravascular closure device (none vs one [2%]). Six (13%) patients in the covered stent group versus one (2%) in the bare-metal stent group had procedure-related adverse events not related to the access site, including stent luxation (three [6%] vs none), major bleeding (two (4%) vs none), mesenteric artery perforation (one [2%] vs one [2%]), mesenteric artery dissection (one [2%] vs one [2%]), and death (one [2%] vs none). INTERPRETATION: The findings of this trial support the use of covered stents for mesenteric artery stenting in patients with chronic mesenteric ischaemia. FUNDING: Atrium Maquet Getinge Group.

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.

Quality of Life after Venous Stenting for Post-thrombotic Syndrome and the Effect of Inflow Disease.

OBJECTIVE: Patients with PTS experience an impaired quality of life (QoL). We aimed to study QoL in patients stented for post thrombotic syndrome (PTS) and analyze the influence of different parameters. METHODS: Patients stented for PTS after iliofemoral deep vein thrombosis were asked to complete the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) and the Short Form Health Survey (SF-36) in this cross-sectional study. All other data were collected retrospectively. Primary endpoints were median CIVIQ-20 and physical (PCS) and mental (MCS) component summary SF-36 scores. The influence of age, sex, and years between the procedure and completion of questionnaire were investigated using a multivariate linear regression model. Wilcoxon signed rank test compared the PCS and MCS with the normative. Effects of inflow from the deep femoral vein (DFV) and/or the femoral vein (FV) on QoL was analyzed in patients with patent stents. RESULTS: The response rate was 70.3% (n = 45/64). Time period (median) from stenting to questionnaire completion was 6.6 years (IQR: 8.0). Most stents were placed unilateral left-sided (73.3%). For patients with patent stents (n = 42) median CIVIQ-20 was 35.5 (IQR: 17.3), higher than the minimum of 20.0 (P < .001). Median PCS of 44.7 (IQR: 14.2) was lower (P < .001), and MCS of 55.9 (IQR: 7.1) higher (P = .001) than the normative (50.0). Time since stenting and sex were not associated with QoL. Age was a significant predictor [standardized coefficient ß = .36, P = .04] for QoL using the CIVIQ-20, but not for the SF-36. Inflow disease did not impact QoL, but patients with occluded stents (n = 3) had poor functioning levels. CONCLUSION: Quality of life is impaired after venous stenting for PTS, particularly physical functioning, among patients with an open stent, but was similar between patients with good and impaired inflow. Patients with a permanent stent occlusion had the lowest QoL.

Portal Embolisation as Treatment of Severe Portal Hypertension Due to Idiopathic Intrahepatic Arterioportal Fistula: A Case Report.

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension. Treatment is usually aimed at restoring the normal portal hemodynamics by obliterating the shunt. This report describes a case of idiopathic IAPF with severe portal hypertension complicated by portal enteropathy with vomiting, gastrointestinal hemorrhage and sepsis. The patient was successfully treated with portal embolization.

Independent validation of CT radiomics models in colorectal liver metastases: predicting local tumour progression after ablation.

OBJECTIVES: Independent internal and external validation of three previously published CT-based radiomics models to predict local tumor progression (LTP) after thermal ablation of colorectal liver metastases (CRLM). MATERIALS AND METHODS: Patients with CRLM treated with thermal ablation were collected from two institutions to collect a new independent internal and external validation cohort. Ablation zones (AZ) were delineated on portal venous phase CT 2-8 weeks post-ablation. Radiomics features were extracted from the AZ and a 10 mm peri-ablational rim (PAR) of liver parenchyma around the AZ. Three previously published prediction models (clinical, radiomics, combined) were tested without retraining. LTP was defined as new tumor foci appearing next to the AZ up to 24 months post-ablation. RESULTS: The internal cohort included 39 patients with 68 CRLM and the external cohort 52 patients with 78 CRLM. 34/146 CRLM developed LTP after a median follow-up of 24 months (range 5-139). The median time to LTP was 8 months (range 2-22). The combined clinical-radiomics model yielded a c-statistic of 0.47 (95%CI 0.30-0.64) in the internal cohort and 0.50 (95%CI 0.38-0.62) in the external cohort, compared to 0.78 (95%CI 0.65-0.87) in the previously published original cohort. The radiomics model yielded c-statistics of 0.46 (95%CI 0.29-0.63) and 0.39 (95%CI 0.28-0.52), and the clinical model 0.51 (95%CI 0.34-0.68) and 0.51 (95%CI 0.39-0.63) in the internal and external cohort, respectively. CONCLUSION: The previously published results for prediction of LTP after thermal ablation of CRLM using clinical and radiomics models were not reproducible in independent internal and external validation. CLINICAL RELEVANCE STATEMENT: Local tumour progression after thermal ablation of CRLM cannot yet be predicted with the use of CT radiomics of the ablation zone and peri-ablational rim. These results underline the importance of validation of radiomics results to test for reproducibility in independent cohorts. KEY POINTS: • Previous research suggests CT radiomics models have the potential to predict local tumour progression after thermal ablation in colorectal liver metastases, but independent validation is lacking. • In internal and external validation, the previously published models were not able to predict local tumour progression after ablation. • Radiomics prediction models should be investigated in independent validation cohorts to check for reproducibility.

Outflow obstruction after living donor liver transplantation managed with a temporary vena cava filter: A case report.

INTRODUCTION: Outflow obstruction is a rare but critical vascular complication in liver transplantation, which may lead to graft loss and mortality. We report a case of caval vein outflow obstruction due to retrohepatic compression after living donor liver transplantation (LDLT), which was managed by temporary implantation of a vena cava filter. PRESENTATION OF CASE: A 63-year-old male with end stage liver disease presented with caval vein outflow obstruction and massive ascites 12 days after right lobe LDLT. We opted for a minimally invasive approach and implanted a vena cava filter at the compressed site through transjugular route. The patient's ascites drainage significantly decreased and graft function maintained stable after the intervention. On day 50 posttransplant, the filter was successfully removed and the patient was discharged without complications. DISCUSSION: Outflow obstruction after liver transplantation can result from anastomotic stenosis, graft size mismatch, thrombosis or compression of the outflow tract. Various management strategies have been employed both peri- and posttransplant, ranging from surgical interventions to minimally-invasive techniques. The treatment strategy should be tailored to the individual case, considering the timing of presentation and the specific cause for the obstruction. CONCLUSION: We successfully managed a case of compressive outflow obstruction by temporary implantation of a vena cava filter after LDLT. The vena cava filter was safely removed under angiography.

Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol.

BACKGROUND: High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. METHODS: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. DISCUSSION: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NL8902 , registered on 2020-09-15.

Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm.

BACKGROUND: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. METHODS: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. RESULTS: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of -0.092 (-0.148, -0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: -0.128 (-0.212, -0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). CONCLUSION: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD.ClinicalTrials.gov Identifier: NCT03703947.

Long Term Follow Up, Causes for Re-intervention, and Consequences for Surveillance After Stenting for Proximal Deep Vein Obstruction.

OBJECTIVE: Venous stenting is performed increasingly for acute deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS) with good short term patency results, but long term data are scarce. The purpose of this study was to evaluate long term outcome of stenting for acute DVT and PTS and to study causes of re-intervention. METHODS: All patients stented for acute DVT and PTS between May 2006 and November 2021 were included retrospectively in this single centre cohort study. Patency was studied by duplex ultrasound (DUS) or computed tomography. The primary endpoint was stent patency. Re-intervention free survival was calculated using Kaplan-Meier methods. Secondary endpoints were causes of re-intervention, using the Pouncey classification system (2022). Binary logistic regression was used to calculate odds ratios for predictors of re-intervention. RESULTS: A total of 114 patients were included, with 129 limbs involved (acute DVT n = 53; 41%), PTS n = 76; 59%). Median follow up was 2.3 years (interquartile range [IQR] 2.3) for acute DVT and 5.2 years (IQR 7.1) for PTS. Primary patency, secondary patency, and permanent occlusion were 73.5%, 98.1%, and 1.9% for acute DVT, and 63.2%, 92.1%, and 7.9% for PTS limbs. Overall, 41 limbs underwent at least one re-intervention: 14 in the acute DVT group and 27 for PTS. Most re-interventions (82.9%) were performed within the first year after stenting. Missed inflow, insufficient flow, and thrombosis despite anticoagulation were the most common causes of re-intervention. The strongest predictor for re-intervention for PTS was inflow disease (odds ratio 3.57, 95% confidence interval 1.26 - 10.13, p= .017). CONCLUSION: Long term patency of deep venous stenting is good. Re-interventions are typically performed in the first year and are potentially preventable by improving the procedure and patient selection. Since secondary patency rates are excellent, selected patients may be considered for discharge from long term surveillance.

Long-term efficacy of metal versus plastic stents in inoperable perihilar cholangiocarcinoma; a multicenter retrospective propensity score matched comparison.

BACKGROUND: For palliative drainage of inoperable perihilar cholangiocarcinoma (pCCA) uncovered metal stents are preferred over plastic stents. However, there is a lack of data on re-interventions at the long-term. The aim is to evaluate the potential difference in the number of re-interventions in patients surviving at least 6 months. METHODS: Retrospective study including patients with pCCA who underwent plastic stent placement(s) or had metal stent(s) in situ for at least 6 months. The primary outcome was the number of re-interventions per patient-year. A propensity score matching (1:1) analysis was performed using age, Bismuth classification, reason for inoperability, pathological confirmation, systemic therapy and initial approach (endoscopic vs percutaneous). RESULTS: Patients in the metal stent group (n = 87) underwent fewer re-interventions compared with the plastic stent group (n = 40) (3.0 vs. 4.7 per patient-year; IRR, 0.64; 95% CI, 0.47 to 0.88). When only non-elective re-interventions were included, there was no significant difference (2.1 vs. 2.7; IRR, 0.76; 95% CI, 0.55 to 1.08). Results were similar in the propensity score-matched dataset. CONCLUSIONS: This study shows that, also in patients with inoperable pCCA who survive at least 6 months, placement of metal stent(s) leads to fewer re-interventions in comparison with plastic stents.

Transarterial Chemoembolization With Drug-Eluting Beads Versus Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Outcomes From a Multicenter, Randomized, Phase 2 Trial (the TRENDY Trial).

PURPOSE: To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial. METHODS AND MATERIALS: Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients. RESULTS: Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACEDEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACEDEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms. CONCLUSIONS: In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed.

Quantification of liver-Lung shunt fraction on 3D SPECT/CT images for selective internal radiation therapy of liver cancer using CNN-based segmentations and non-rigid registration.

PURPOSE: Selective internal radiation therapy (SIRT) has been proven to be an effective treatment for hepatocellular carcinoma (HCC) patients. In clinical practice, the treatment planning for SIRT using 90Y microspheres requires estimation of the liver-lung shunt fraction (LSF) to avoid radiation pneumonitis. Currently, the manual segmentation method to draw a region of interest (ROI) of the liver and lung in 2D planar imaging of 99mTc-MAA and 3D SPECT/CT images is inconvenient, time-consuming and observer-dependent. In this study, we propose and evaluate a nearly automatic method for LSF quantification using 3D SPECT/CT images, offering improved performance compared with the current manual segmentation method. METHODS: We retrospectively acquired 3D SPECT with non-contrast-enhanced CT images (nCECT) of 60 HCC patients from a SPECT/CT scanning machine, along with the corresponding diagnostic contrast-enhanced CT images (CECT). Our approach for LSF quantification is to use CNN-based methods for liver and lung segmentations in the nCECT image. We first apply 3D ResUnet to coarsely segment the liver. If the liver segmentation contains a large error, we dilate the coarse liver segmentation into the liver mask as a ROI in the nCECT image. Subsequently, non-rigid registration is applied to deform the liver in the CECT image to fit that obtained in the nCECT image. The final liver segmentation is obtained by segmenting the liver in the deformed CECT image using nnU-Net. In addition, the lung segmentations are obtained using 2D ResUnet. Finally, LSF quantitation is performed based on the number of counts in the SPECT image inside the segmentations. Evaluations and Results: To evaluate the liver segmentation accuracy, we used Dice similarity coefficient (DSC), asymmetric surface distance (ASSD), and max surface distance (MSD) and compared the proposed method to five well-known CNN-based methods for liver segmentation. Furthermore, the LSF error obtained by the proposed method was compared to a state-of-the-art method, modified Deepmedic, and the LSF quantifications obtained by manual segmentation. The results show that the proposed method achieved a DSC score for the liver segmentation that is comparable to other state-of-the-art methods, with an average of 0.93, and the highest consistency in segmentation accuracy, yielding a standard deviation of the DSC score of 0.01. The proposed method also obtains the lowest ASSD and MSD scores on average (2.6 mm and 31.5 mm, respectively). Moreover, for the proposed method, a median LSF error of 0.14% is obtained, which is a statically significant improvement to the state-of-the-art-method (p=0.004), and is much smaller than the median error in LSF manual determination by the medical experts using 2D planar image (1.74% and p<0.001). CONCLUSIONS: A method for LSF quantification using 3D SPECT/CT images based on CNNs and non-rigid registration was proposed, evaluated and compared to state-of-the-art techniques. The proposed method can quantitatively determine the LSF with high accuracy and has the potential to be applied in clinical practice.

Efficacy of endovascular treatment of pelvic varicose veins: A single-center retrospective observational study.

OBJECTIVE: To evaluate the efficacy of endovascular embolization of pelvic varicose veins in the treatment of pelvic venous disorders (PeVD). METHODS: A single-center retrospective study was performed, including 156 women referred to the Erasmus University Medical Center between January 2011 and October 2020 for an evaluation of PeVD. Data on presenting symptoms, clinical workup, treatment, and clinical outcomes were collected. The primary end point was resolution of symptoms after treatment. Secondary outcomes were correlation between symptoms at presentation and relief of symptoms after treatment, minor or major procedural complications, recurrences, and additional treatments needed. RESULTS: Ninety patients underwent a pelvic phlebography, of which 75 received embolization of pelvic varicose veins. Median follow-up after phlebography was 13.2 months (interquartile range, 6.0-40.1 months). Of the treated patients, 53 (70.7%) had partial or complete relief of symptoms. Forty-six women (61.3%) who received embolization of pelvic varicose veins required additional treatments for leg and/or vulvar varicose veins. CONCLUSIONS: This study found that endovascular embolization of pelvic varicose veins can be an effective treatment for PeVDs. However, additional treatments are often required for leg and/or vulvar varicose veins.

Success, complication, and mortality rates of initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma.

BACKGROUND: The patients with unresectable perihilar cholangiocarcinoma require biliary drainage to relieve symptoms and allow for palliative systemic chemotherapy. The aim of this study was to establish the success, complication, and mortality rates of the initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma at presentation. METHODS: In this retrospective multicenter study, patients with unresectable perihilar cholangiocarcinoma who underwent initial endoscopic or percutaneous transhepatic biliary drainage between 2002 and 2014 were included. The success of drainage was defined as a successful biliary stent or drain placement, no unscheduled reintervention within 14 days, and serum bilirubin levels <50 µmol/L (ie, 2.9 mg/dL) or a >50% decrease in serum bilirubin after 14 days. Severe complications, and 90-day mortality were recorded. RESULTS: Included were 186 patients: 161 (87%) underwent initial endoscopic biliary drainage and 25 (13%) underwent initial percutaneous transhepatic biliary drainage. The success of initial drainage was observed in 73 patients (45%) after endoscopic biliary drainage and 6 (24%) after percutaneous transhepatic biliary drainage. The reasons for an unsuccessful initial drainage were: the failure to place a drain or stent in 39 patients (21%), an unplanned reintervention within 14 days in 52 patients (28%), and the bilirubin level >50 µmol/L (or not halved) after 14 days of initial drainage in 16 patients (9%). Severe drainage-related complications occurred in 19 patients (12%) after endoscopic biliary drainage and in 3 (12%) after percutaneous transhepatic biliary drainage. Overall, 66 patients (36%) died within 90 days after initial biliary drainage. CONCLUSION: Initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma had a success rate of 45% and a 90-day mortality rate of 36%. Future studies for patients with perihilar cholangiocarcinoma should focus on improving biliary drainage.

[Radiofrequency ablation of benign thyroid nodules; an alternative treatment option to surgery]. / Radiofrequente ablatie van benigne schildkliernodus.

Radiofrequency ablation (RFA) is a technique that uses a needle to generate local thermal energy. This minimally invasive technique is used in patients with a symptomatic benign thyroid nodule, so that surgical resection can be avoided. There is now scientific evidence that RFA can reduce the volume of the benign symptomatic thyroid nodule and contributes to a significant reduction of complaints. RFA is also included in international guidelines as an alternative treatment option for patients with a symptomatic benign thyroid nodule, in addition to surgery.

Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in the Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial.

BACKGROUND: Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection. METHODS: We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low-medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671. FINDINGS: From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 [8%] of 863 patients vs 124 [14%] of 885 patients; adjusted risk ratio [RR] 0·48, 95% CI 0·38-0·61; p<0·0001). Among patients treated according to the algorithm, compared with patients who received usual care there was a decrease in bleeding that required intervention (47 [5%] patients vs 51 [6%] patients; RR 0·65, 0·42-0·99; p=0·046), organ failure (39 [5%] patients vs 92 [10%] patients; 0·35, 0·20-0·60; p=0·0001), and 90-day mortality (23 [3%] patients vs 44 [5%] patients; 0·42, 0·19-0·92; p=0·029). INTERPRETATION: The algorithm for the early recognition and minimally invasive management of complications after pancreatic resection considerably improved clinical outcomes compared with usual care. This difference included an approximate 50% reduction in mortality at 90 days. FUNDING: The Dutch Cancer Society and UMC Utrecht.

Safety and Efficacy of 166Ho Radioembolization in Hepatocellular Carcinoma: The HEPAR Primary Study.

The safety and efficacy of 166Ho radioembolization was first determined in the HEPAR and HEPAR II studies, which, however, excluded patients with hepatocellular carcinoma (HCC). The aim of this prospective clinical early phase II study was to establish the toxicity profile of 166Ho radioembolization in patients with measurable, liver-dominant HCC; Barcelona clinic liver cancer stage B or C; a Child-Pugh score of no more than B7; and an Eastern Cooperative Oncology Group performance status of 0-1 without curative treatment options. Methods: The primary endpoint was a rate of unacceptable toxicity defined as grade 3 hyperbilirubinemia (Common Terminology Cancer Adverse Events, version 4.03) in combination with a low albumin or ascites level in the absence of disease progression or treatment-related serious adverse events. Secondary endpoints included overall toxicity, response, survival, change in α-fetoprotein, and quality of life. Thirty-one patients with Barcelona clinic liver cancer stage B (71%) or C (29%) HCC were included, mostly multifocal (87%) or bilobar (55%) disease. Results: Common grade 1 or 2 clinical toxicity included fatigue (71%), back pain (55%), ascites (32%), dyspnea (23%), nausea (23%), and abdominal pain (23%), with no more than 10% grade 3-5 toxicity. Grade 3 laboratory toxicity (>10%) included an aspartate transaminase and γ-glutamyltransferase increase (16%), hyperglycemia (19%), and lymphopenia (29%). Treatment-related unacceptable toxicity occurred in 3 of 31 patients. At 3 mo, 54% of target lesions showed a complete or partial response according to modified RECIST. Median overall survival was 14.9 mo (95% CI, 10.4-24.9 mo). No significant changes in quality of life or pain were observed. Conclusion: The safety of 166Ho radioembolization was confirmed in HCC, with less than 10% unacceptable toxicity. Efficacy data support further evaluation.

MRI-based pre- and postprandial flow in the mesenteric vasculature of patients with suspected chronic mesenteric ischemia.

PURPOSE: The physiological increase of mesenteric blood flow after a meal is impaired in patients with occlusive chronic mesenteric ischemia (CMI). This principle could be used to develop a highly desired diagnostic test assessing the sufficiency of the collateral mesenteric circulation. This study assesses the potential to identify CMI patients using two-dimensional time-resolved phase-contrast magnetic resonance imaging (2D PC-MRI) flow measurements. METHOD: This prospective cohort study included patients with suspected CMI, based on: typical history, imaging, and functional testing. Cardiac gated 2D PC-MRI flow measurements (expressed as ml/min/kg) were performed in mesenteric arteries and veins during inspiration and expiration, after six hours of fasting and 20, 30, and 40 min after a meal challenge with a high caloric drink. RESULTS: Flow measurements were obtained in 19 patients: 8 CMI and 11 non-CMI. CMI patients showed a significantly smaller increase in postprandial blood flow in the superior mesenteric artery (SMA) at 30 and 40 min (30 min CMI 1.27(0.12-2.44) vs. non-CMI 7.82(6.28-10.90); 40 min CMI 0.30(-0.26-3.16) vs. non-CMI 7.94(6.32-10.90)) and a lower total arterial flow at 40 min (CMI 3.21(-0.72-5.05) vs. non-CMI 9.31(5.58-13.83)). Repeated flow measurements showed normalization of impaired postprandial venous flow after mesenteric artery stenting in one patient. CONCLUSIONS: The significantly lower increase in postprandial mesenteric blood flow in CMI patients confirms the promise of mesenteric blood flow measurements, before and 30-40 min after a meal, as a future diagnostic test to identify CMI patients among patients with a high clinical suspicion of CMI and mesenteric artery stenosis.