Defining textbook outcome for selective internal radiation therapy of hepatocellular carcinoma: an international expert study.

BACKGROUND: A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the "ideal" intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. METHODS: This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. RESULTS: A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73%) responded, including 23 interventional radiologists (79%), three nuclear medicine physicians (10%), two hepatologists, and one oncologist, from 11 countries spanning three continents. The final TO consisted 11 parameters across six domains ("pre-intervention workup," "tumor targeting and dosimetry," "intervention," "post-90Y imaging," "length of hospital stay," and "complications"). Of these, all but one were applied in the institutions of > 80% of experts. CONCLUSIONS: This multidimensional indicator is a comprehensive standardization tool, suitable for routine care, clinical round, and research.

Computational study of a novel catheter for liver radioembolization.

Radioembolization (RE) is a medical treatment for primary and secondary liver cancer that involves the transcatheter intraarterial delivery of micron-sized and radiation-emitting microspheres, with the goal of improving microsphere deposition in the tumoral bed while sparing healthy tissue. An increasing number of in vitro and in silico studies on RE in the literature suggest that the particle injection velocity, spatial location of the catheter tip and catheter type are important parameters in particle distribution. The present in silico study assesses the performance of a novel catheter design that promotes particle dispersion near the injection point, with the goal of generating a particle distribution that mimics the flow split to facilitate tumour targeting. The design is based on two factors: the direction and the velocity at which particles are released from the catheter. A series of simulations was performed with the catheter inserted at an idealised hepatic artery tree with physiologically realistic boundary conditions. Two longitudinal microcatheter positions in the first generation of the tree were studied by analysing the performance of the catheter in terms of the outlet-to-outlet particle distribution and split flow matching. The results show that the catheter with the best performance is one with side holes on the catheter wall and a closed frontal tip. This catheter promotes a flow-split-matching particle distribution, which improves as the injection crossflow increases.

Computational Fluid Dynamics Modeling of Liver Radioembolization: A Review.

Yttrium-90 radioembolization (RE) is a widely used transcatheter intraarterial therapy for patients with unresectable liver cancer. In the last decade, computer simulations of hepatic artery hemodynamics during RE have been performed with the aim of better understanding and improving the therapy. In this review, we introduce the concept of computational fluid dynamics (CFD) modeling with a clinical perspective and we review the CFD models used to study RE from the fluid mechanics point of view. Finally, we show what CFD simulations have taught us about the hemodynamics during RE, the current capabilities of CFD simulations of RE, and we suggest some future perspectives.

In Vitro Model for Simulating Drug Delivery during Balloon-Occluded Transarterial Chemoembolization.

BACKGROUND: Balloon-occluded transarterial chemoembolization (B-TACE) has emerged as a safe and effective procedure for patients with liver cancer, which is one of the deadliest types of cancer worldwide. B-TACE consist of the transcatheter intraarterial infusion of chemotherapeutic agents, followed by embolizing particles, and it is performed with a microballoon catheter that temporarily occludes a hepatic artery. B-TACE relies on the blood flow redistribution promoted by the balloon-occlusion. However, flow redistribution phenomenon is not yet well understood. METHODS: This study aims to present a simple in vitro model (IVM) where B-TACE can be simulated. RESULTS: By visually analyzing the results of various clinically-realistic experiments, the IVM allows for the understanding of balloon-occlusion-related hemodynamic changes and the importance of the occlusion site. CONCLUSION: The IVM can be used as an educational tool to help clinicians better understand B-TACE treatments. This IVM could also serve as a base for a more sophisticated IVM to be used as a research tool.

3D voxel-based dosimetry to predict contralateral hypertrophy and an adequate future liver remnant after lobar radioembolization.

INTRODUCTION: Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. MATERIALS AND METHODS: Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2-5 (T2), and 6-12 months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. RESULTS: Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30 Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30 Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). CONCLUSION: NTL-Dmean and NTL exposed to ≥ 30 Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30 Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.

The joint use of 99mTc-MAA-SPECT/CT and cone-beam CT optimizes radioembolization planning.

PURPOSE: To determine which imaging method used during radioembolization (RE) work-up: contrast-enhanced computed tomography (CECT), 99mTc-MAA-SPECT/CT or cone beam-CT (CBCT), more accurately predicts the final target volume (TgV) as well as the influence that each modality has in the dosimetric calculation. METHODS: TgVs from 99mTc-MAA-SPECT/CT, CECT and CBCT were consecutively obtained in 24 patients treated with RE and compared with 90Y PET/CT TgV. Using the TgVs estimated by each imaging modality and a fictitious activity of 1 GBq, the corresponding absorbed doses by tumor and non-tumoral parenchyma were calculated for each patient. The absorbed doses for each modality were compared with the ones obtained using 90Y PET/CT TgV. RESULTS: 99mTc-MAA-SPECT/CT predicted 90Y PET/CT TgV better than CBCT or CECT, even for selective or superselective administrations. Likewise, 99mTc-MAA-SPECT/CT showed dosimetric values more similar to those obtained with 90Y PET/CT. Nevertheless, CBCT provided essential information for RE planning, such as ensuring the total coverage of the tumor and, in cases with more than one feeding artery, splitting the activity according to the volume of tumor perfused by each artery. CONCLUSION: The joint use of 99mTc-MAA-SPECT/CT and CBCT optimizes dosimetric planning for RE procedures, enabling a more accurate personalized approach.

A proof-of-concept study of the in-vivo validation of a computational fluid dynamics model of personalized radioembolization.

Radioembolization (RE) with yttrium-90 (90Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six 90Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by 90Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual 90Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict 90Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.

Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. / Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, AEC, SEOM, SERAM, SERVEI y SETH.

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.

Clinical Application of Trans-Arterial Radioembolization in Hepatic Malignancies in Europe: First Results from the Prospective Multicentre Observational Study CIRSE Registry for SIR-Spheres Therapy (CIRT).

PURPOSE: To address the lack of prospective data on the real-life clinical application of trans-arterial radioembolization (TARE) in Europe, the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) initiated the prospective observational study CIRSE Registry for SIR-Spheres® Therapy (CIRT). MATERIALS AND METHODS: Patients were enrolled from 1 January 2015 till 31 December 2017. Eligible patients were adult patients treated with TARE with Y90 resin microspheres for primary or metastatic liver tumours. Patients were followed up for 24 months after treatment, whereas data on the clinical context of TARE, overall survival (OS) and safety were collected. RESULTS: Totally, 1027 patients were analysed. 68.2% of the intention of treatment was palliative. Up to half of the patients received systemic therapy and/or locoregional treatments prior to TARE (53.1%; 38.3%). Median overall survival (OS) was reported per cohort and was 16.5 months (95% confidence interval (CI) 14.2-19.3) for hepatocellular carcinoma, 14.6 months (95% CI 10.9-17.9) for intrahepatic cholangiocarcinoma. For liver metastases, median OS for colorectal cancer was 9.8 months (95% CI 8.3-12.9), 5.6 months for pancreatic cancer (95% CI 4.1-6.6), 10.6 months (95% CI 7.3-14.4) for breast cancer, 14.6 months (95% CI 7.3-21.4) for melanoma and 33.1 months (95% CI 22.1-nr) for neuroendocrine tumours. Statistically significant prognostic factors in terms of OS include the presence of ascites, cirrhosis, extra-hepatic disease, patient performance status (Eastern Cooperative Oncology Group), number of chemotherapy lines prior to TARE and tumour burden. Thirty-day mortality rate was 1.0%. 2.5% experienced adverse events grade 3 or 4 within 30 days after TARE. CONCLUSION: In the real-life clinical setting, TARE is largely considered to be a part of a palliative treatment strategy across indications and provides an excellent safety profile. LEVEL OF EVIDENCE: Level 3. TRIAL REGISTRATION: ClinicalTrials.gov NCT02305459.

Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France.

PURPOSE: Radioembolization has emerged as a treatment modality for patients with primary and secondary liver tumours. This observational study CIRT-FR (CIRSE Registry for SIR-Spheres Therapy in France) aims to evaluate real-life clinical practice on all patients treated with transarterial radioembolization (TARE) using SIR-Spheres yttrium-90 resin microspheres in France. In this interim analysis, safety and quality of life data are presented. Final results of the study, including secondary effectiveness outcomes, will be published later. Overall, CIRT-FR is aiming to support French authorities in the decision making on reimbursement considerations for this treatment. METHODS: Data on patients enrolled in CIRT-FR from August 2017 to October 2019 were analysed. The interim analysis describes clinical practice, baseline characteristics, safety (adverse events according to CTCTAE 4.03) and quality of life (according to EORTC QLQ C30 and HCC module) aspects after TARE. RESULTS: This cohort included 200 patients with hepatocellular carcinoma (114), metastatic colorectal cancer (mCRC; 38) and intrahepatic cholangiocarcinoma (33) amongst others (15). TARE was predominantly assigned as a palliative treatment (79%). 12% of patients experienced at least one adverse event in the 30 days following treatment; 30-day mortality was 1%. Overall, global health score remained stable between baseline (66.7%), treatment (62.5%) and the first follow-up (66.7%). CONCLUSION: This interim analysis demonstrates that data regarding safety and quality of life generated by randomised-controlled trials is reflected when assessing the real-world application of TARE. TRIAL REGISTRATION: Clinical Trials.gov NCT03256994.

"Primum Non Nocere" in Interventional Oncology for Liver Cancer: How to Reduce the Risk for Complications?

Interventional oncology represents a relatively new clinical discipline based upon minimally invasive therapies applicable to almost every human organ and disease. Over the last several decades, rapidly evolving research developments have introduced a newer generation of treatment devices, reagents, and image-guidance systems to expand the armamentarium of interventional oncology across a wide spectrum of disease sites, offering potential cure, control, or palliative care for many types of cancer patients. Due to the widespread use of locoregional procedures, a comprehensive review of the methodologic and technical considerations to optimize patient selection with the aim of performing a safe procedure is mandatory. This article summarizes the expert discussion and report from the Mediterranean Interventional Oncology Live Congress (MIOLive 2020) held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions as a means for providing guidance on prudent ways to reduce complications. The aim of the paper is to provide an updated guiding tool not only to residents and fellows but also to colleagues approaching locoregional treatments.

Follow-up after radiological intervention in oncology: ECIO-ESOI evidence and consensus-based recommendations for clinical practice.

Interventional radiology plays an important and increasing role in cancer treatment. Follow-up is important to be able to assess treatment success and detect locoregional and distant recurrence and recommendations for follow-up are needed. At ECIO 2018, a joint ECIO-ESOI session was organized to establish follow-up recommendations for oncologic intervention in liver, renal, and lung cancer. Treatments included thermal ablation, TACE, and TARE. In total five topics were evaluated: ablation in colorectal liver metastases (CRLM), TARE in CRLM, TACE and TARE in HCC, ablation in renal cancer, and ablation in lung cancer. Evaluated modalities were FDG-PET-CT, CT, MRI, and (contrast-enhanced) ultrasound. Prior to the session, five experts were selected and performed a systematic review and presented statements, which were voted on in a telephone conference prior to the meeting by all panelists. These statements were presented and discussed at the ECIO-ESOI session at ECIO 2018. This paper presents the recommendations that followed from these initiatives. Based on expert opinions and the available evidence, follow-up schedules were proposed for liver cancer, renal cancer, and lung cancer. FDG-PET-CT, CT, and MRI are the recommended modalities, but one should beware of false-positive signs of residual tumor or recurrence due to inflammation early after the intervention. There is a need for prospective preferably multicenter studies to validate new techniques and new response criteria. This paper presents recommendations that can be used in clinical practice to perform the follow-up of patients with liver, lung, and renal cancer who were treated with interventional locoregional therapies.

The Pattern of Progression Defines Post-progression Survival in Patients with Hepatocellular Carcinoma Treated with SIRT.

PURPOSE: In patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib, post-progression survival (PPS) is marked by the pattern of progression. Our aim was to assess the influence of the pattern of progression to selective internal radiotherapy (SIRT) in PPS among patients with HCC. METHODS: A retrospective analysis of patients treated with SIRT between 2003 and 2015 was conducted, excluding those with a single nodule < 5 cm or with metastases. Four patterns of progression to SIRT were defined: target tumour growth, non-target tumour growth, new intrahepatic disease, and new extrahepatic disease. PPS was calculated from the time of progression based on RECIST 1.1 criteria. RESULTS: Out of the 102 patients who met the selection criteria, 76 progressed after a median follow-up of 15 months. Median PPS was 6.5 months (95% CI 3.8-9.3 months). Patients who progressed at pre-existing lesions had a better PPS (median 12.5 months) than those who progressed with new lesions inside or outside the liver (median 4.2 months) (p = 0.02). In a Cox model adjusted by liver function and systemic inflammation, the pattern of progression had a hazard ratio of 1.64 (95% CI 0.92-2.93; p = 0.093). CONCLUSION: In a cohort of HCC patients treated with SIRT, the pattern of progression associated with worst survival was the development of new intrahepatic lesions or extrahepatic metastases.

Therapeutic Effect of Irreversible Electroporation in Combination with Poly-ICLC Adjuvant in Preclinical Models of Hepatocellular Carcinoma.

PURPOSE: To evaluate the therapeutic efficacy of irreversible electroporation (IRE) combined with the intratumoral injection of the immunogenic adjuvant poly-ICLC (polyinosinic-polycytidylic acid and poly-L-lysine, a dsRNA analog mimicking viral RNA) inmediately before IRE. MATERIALS AND METHODS: Mice and rabbits bearing hepatocellular carcinoma tumors (Hepa.129 and VX2 tumor models, respectively) were treated with IRE (2 pulses of 2500V), with poly-ICLC, or with IRE + poly-ICLC combination therapy. Tumor growth in mice was monitored using a digital caliper and by computed tomography in rabbits. RESULTS: Intratumoral administration of poly-ICLC immediately before IRE elicited shrinkage of Hepa.129 cell-derived tumors in 70% of mice, compared to 30% and 26% by poly-ICLC or IRE alone, respectively (P = .0004). This combined therapy induced the shrinkage of VX-2-based hepatocellular carcinoma tumors in 40% of rabbits, whereas no response was achieved by either individual treatment (P = .045). The combined therapy activated a systemic antitumor response able to inhibit the growth of other untreated tumors. CONCLUSIONS: IRE treatment, immediately preceded by the intratumoral administration of an immunogenic adjuvant such as poly-ICLC, might enhance the antitumor effect of the IRE procedure. This combination might facilitate the induction of a long-term systemic response to prevent tumor relapses and the appearance of metastases.

A methodology for numerically analysing the hepatic artery haemodynamics during B-TACE: a proof of concept.

Balloon-occluded transarterial chemoembolisation (B-TACE) is an intraarterial transcatheter treatment for liver cancer. In B-TACE, an artery-occluding microballoon catheter occludes an artery and promotes collateral circulation for drug delivery to tumours. This paper presents a methodology for analysing the haemodynamics during B-TACE, by combining zero-dimensional and three-dimensional modelling tools. As a proof of concept, we apply the methodology to a patient-specific hepatic artery geometry and analyse two catheter locations. Results show that the blood flow redistribution can be predicted in this proof-of-concept study, suggesting that this approach could potentially be used to optimise catheter location.

Radioembolisation in patients with hepatocellular carcinoma that have previously received liver-directed therapies.

PURPOSE: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation. METHODS: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records. RESULTS: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1-45.9) versus 30.9 months (19.6-46.8); p = 0.243); stage B: 18.4 months (11.2-19.4) versus 22.8 months (10.9-34.2); p = 0.815; and stage C: 8.8 months (7.1-10.8) versus 10.8 months (7.7-12.6); p = 0.976. CONCLUSIONS: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

Numerical zero-dimensional hepatic artery hemodynamics model for balloon-occluded transarterial chemoembolization.

Balloon-occluded transarterial chemoembolization (B-TACE) is a valuable treatment option for patients with inoperable malignant tumors in the liver. Balloon-occluded transarterial chemoembolization consists of the transcatheter infusion of an anticancer drug mixture and embolic agents. Contrary to conventional TACE, B-TACE is performed via an artery-occluding microballoon catheter, which makes the blood flow to redistribute due to the intra- and extrahepatic arterial collateral circulation. Several recent studies have stressed the importance of the redistribution of blood flow in enhancing the treatment outcome. In the present study, the geometries of a representative hepatic artery and the communicating arcades (CAs) are modeled. An in silico zero-dimensional hemodynamic model is created by characterizing the geometry and the boundary conditions and then is validated in vitro. The role of CAs is assessed by combining 2 cancer scenarios and 2 catheter locations. The importance of the diameter of the CAs is also studied. Results show that occluding a main artery leads to collateral circulation and CAs start to play a role in blood-flow redistribution. In summary, numerical zero-dimensional simulations permit a fast and reliable approach for exploring the blood-flow redistribution caused by the occlusion of a main artery, and this approach could be used during B-TACE planning.

Laparoscopic Treatment of Median Arcuate Ligament Syndrome: Analysis of Long-Term Outcomes and Predictive Factors.

BACKGROUND: Laparoscopic arcuate ligament release has been demonstrated a valid therapeutic option for arcuate ligament syndrome. Nevertheless, long-term follow-up and predictive factors have not been described for this treatment. METHODS: Clinical and surgical data and short- and long-term outcomes together with the impact of the degree of stenosis of the celiac trunk were analyzed in 13 consecutive patients who underwent laparoscopic arcuate ligament release between 2001 and 2013. RESULTS: Thirteen patients (12 F/1 M) underwent surgery. The median age was 32 years old, and their mean body mass index was 20.7 (range 14.7-25). The 13 patients presented with intense postprandial abdominal pain. Ten cases were associated with weight loss. The median duration of symptoms was 24 months (range 2-240). Three patients presented symptoms associated with superior mesenteric artery syndrome. Median operative time was 120 min (range 90-240), and there were no conversions to open surgery. Median hospital stay was 3 days (range 2-14). Over a median follow-up of 117 months (range 45-185), nine patients had excellent results although two required endovascular procedures at 70 and 24 months after surgery. Four patients (30.7%) experienced poor outcomes. When we analyzed the impact of the degree of occlusion of the celiac trunk, we observed that in patients with severe occlusion (> 70%), better results were obtained, with complete resolution of symptoms in 71% of cases. CONCLUSION: Laparoscopic arcuate ligament release constitutes an excellent treatment for arcuate ligament syndrome. The degree of occlusion of the celiac trunk may be a factor predictive of long-term outcomes.

Is a Technetium-99m Macroaggregated Albumin Scan Essential in the Workup for Selective Internal Radiation Therapy with Yttrium-90? An Analysis of 532 Patients.

PURPOSE: To determine if baseline patient, tumor, and pretreatment evaluation characteristics could help identify patients who require technetium-99m (99mTc) macroaggregated albumin (99mTc MAA) imaging before selective internal radiation therapy (SIRT). MATERIALS AND METHODS: In this retrospective analysis, 532 consecutive patients with primary (n = 248) or metastatic (n = 284) liver tumors were evaluated between 2006 and 2015. Variables were compared between patients in whom 99mTc MAA imaging results contraindicated/modified SIRT administration with yttrium-90 (90Y) resin microspheres and those who were treated as initially planned. The 99mTc MAA findings that contraindicated/modified SIRT were a lung shunt fraction (LSF) > 20%, gastrointestinal 99mTc MAA uptake, or a mismatch between 99mTc MAA uptake and intrahepatic tumor distribution. RESULTS: LSF > 20% and gastrointestinal MAA uptake were observed in 7.5% and 3.9% of patients, respectively, and 11% presented a mismatch. Presence of a single lesion (odds ratio [OR] = 2.4) and vascular invasion (OR = 5.5) predicted LSF > 20%, and GI MAA uptake was predicted by the presence of liver metastases (OR = 3.7) and 99mTc MAA injection through the common/proper hepatic artery (OR = 4.7). Vascular invasion (OR = 4.1) was the only predictor of LSF > 20% and/or GI MAA uptake (sensitivity = 49.2%, specificity = 80.3%, negative predictive value = 92.4%). Previous antiangiogenic treatment (OR = 2.4) and presence of a single lesion (OR = 2.6) predicted mismatch. CONCLUSIONS: Imaging with 99mTc MAA is essential in SIRT workup because baseline characteristics may not adequately predict 99mTc MAA results. Nevertheless, the absence of vascular invasion potentially identifies a group of patients at low risk of SIRT contraindication/modification in whom performing SIRT in a single session (ie, pretreatment evaluation and SIRT on the same day) should be explored.

Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae.

Mass administration of endectocides, drugs that kill blood-feeding arthropods, has been proposed as a complementary strategy to reduce malaria transmission. Ivermectin is one of the leading candidates given its excellent safety profile. Here we provide proof that the effect of ivermectin can be boosted at two different levels by drugs inhibiting the cytochrome or ABC transporter in the mammal host and the target mosquitoes. Using a mini-pig model, we show that drug-mediated cytochrome P450/ABC transporter inhibition results in a 3-fold increase in the time ivermectin remains above mosquito-killing concentrations. In contrast, P450/ABC transporter induction with rifampicin markedly impaired ivermectin absorption. The same ketoconazole-mediated cytochrome/ABC transporter inhibition also occurs outside the mammal host and enhances the mortality of Anopheles gambiae. This was proven by using the samples from the mini-pig experiments to conduct an ex-vivo synergistic bioassay by membrane-feeding Anopheles mosquitoes. Inhibiting the same cytochrome/xenobiotic pump complex in two different organisms to simultaneously boost the pharmacokinetic and pharmacodynamic activity of a drug is a novel concept that could be applied to other systems. Although the lack of a dose-response effect in the synergistic bioassay warrants further exploration, our study may have broad implications for the control of parasitic and vector-borne diseases.