Liver Embolization Research Articles

8537 Refractory Hypoglycemia Secondary To Metastatic Insulinoma Treated With Novel Insulin Receptor Antibody - A Case Report

Abstract Disclosure: J. Lloyd: None. S. Abu Omar: None. L. Lester: None. L. Wilson: None. Introduction: Insulinoma is the most common functional pancreatic neuroendocrine tumor, characterized by hypersecretion of insulin, causing hypoglycemia. Insulinomas are mostly benign, however malignant neoplasms account for 5-10 % of cases. Surgical resection is the preferred treatment for solitary tumor, however metastatic insulinoma requires a more aggressive approach with medications to prevent hypoglycemia, resection of primary tumor, resection of metastasis, and chemoembolization. We describe a case of metastatic insulinoma with refractory hypoglycemia despite treatment with multiple medications, surgical resection of tumor, embolization of liver metastasis and successfully treated with a novel monoclonal antibody that blocks insulin receptor. Clinical Case: 43-year-old female was initially diagnosed with metastatic insulinoma in 2021. The primary tumor was pancreatic with metastasis to the liver. She was treated with surgical resection of the primary tumor and three hepatic embolizations for liver metastasis. She required a progressive number of medications to treat frequent, debilitating hypoglycemia. These medications included diazoxide, verapamil, lanreotide then changed to pasireotide, everolimus, and dexamethasone. Despite these treatments, she experienced refractory hypoglycemia and was admitted to the hospital. She required continuous dextrose infusion up to 100ml/hr of D50. Due to the large volume of fluid from dextrose infusion and other medications, she developed severe edema and AKI and required aggressive diuretic regimens and briefly intermittent CRRT. As there were no additional medications to add and prospects for future liver embolization were limited, we requested use of RZ358 through the manufacturer’s Expanded Patient Access program. This medication is a monoclonal antibody that blocks the insulin receptor to counteract the effects of insulin and thereby reduce hypoglycemia. This mechanism of action is unique from medications used to manage insulinoma induced hypoglycemia. She received her first infusion of RZ358 which she tolerated well. She had baseline elevation of ALP due to liver metastasis with further rise after liver embolizations, most recently 4 weeks prior. There was a rise in ALP levels which stabilized after 3 days. She experienced no significant side effects. For the first time in two months, five days after her first infusion of RZ358, the dextrose infusion could be stopped. She received her second infusion of RZ358 one week after first infusion. She was discharged home in a stable condition shortly after the second infusion. Conclusion: The Insulin receptor blocking monoclonal antibody, RZ358, offers a promising approach to patients with metastatic insulinoma who have refractory hypoglycemia despite maximal medical and surgical therapy. Presentation: 6/1/2024

Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment.

Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (∼2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.

Impressive Response to TANDEM Peptide Receptor Radionuclide Therapy with 177Lu/225AcDOTA-LM3 Somatostatin Receptor Antagonist in a Patient with Therapy-Refractory, Rapidly Progressive Neuroendocrine Neoplasm of the Pancreas.

The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE, Lanreotide, Everolimus, and liver embolization. Due to severe disease progression, after a liver biopsy revealing tumor grade G3, PRRT with the somatostatin receptor antagonist LM3 was initiated. [68Ga]GaDOTA-LM3 PET/CT showed intense tracer uptake in the liver, pancreatic tumor, lymph nodes, and bone metastases. Three TANDEM-PRRT cycles using [177Lu]LuDOTA-LM3 and [225Ac]AcDOTA-LM3, administered concurrently, resulted in significant improvement, notably in liver metastases, hepatomegaly reduction, the complete regression of bone and lymph node metastases, and primary tumor improvement. Partial remission was confirmed by positron emission tomography/computed tomography, chest-abdomen-pelvis contrast-enhanced computed tomography, and magnetic resonance of the abdomen, with marked clinical improvement in pain, energy levels, and quality of life, enabling full resumption of physical activity.

Carcinoid Heart Disease Management: A Multi-Disciplinary Collaboration.

Carcinoid heart disease (CaHD) is an important complication among patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS). CS patients (25%-65%) eventually develop CaHD; these patients face a significantly increased risk of morbidity and mortality. Guidance papers (eg, clinical practice guidelines, consensus guidelines, and expert statements) have been established by major organizations across the disciplines of cardiology and oncology; however, these recommendations are not routinely implemented. The aim of this article is to encourage the integration of current recommendations from national societies into clinical practice. Early screening upon recognition of CS and prior to the development of CaHD symptoms is paramount, as no existing therapies are approved to reverse the fibrotic damage to the heart once it occurs. Valvular replacement is the only definitive treatment for CaHD once it has developed. When patients are noted to have urinary 5-hydroxyindoleacetic acid (5-HIAA) levels ≥300 µmol/24 h and/or serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels >260 pg/mL, echocardiography is recommended. Systemic approaches to control tumor growth and hormonal secretion include somatostatin analogs (SSAs), followed by options including peptide receptor radiotherapy (PRRT), everolimus and liver embolization. Telotristat is the primary choice for control of diarrhea refractory to SSA. Diuretics are the mainstay of heart failure symptom management for patients who develop CaHD. Considerations for future research are discussed, including the ongoing TELEHEART (TELotristat Ethyl in a HEART biomarker study) trial involving telotristat and not yet activated CHARRT (Carcinoid Heart disease And peptide Receptor Radiotargetted Therapy) study involving PRRT with lutetium 177 (177Lu) dotatate.

Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma—A Prospective Feasibility Study

PurposeTo evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). Materials and MethodsThis prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. ResultsTwenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9–7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0–33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8–31.0 months) versus 10.7 months (95% CI, 8.0–13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7–20.7 months) versus 37.3 months (95% CI, 16.5–58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. ConclusionsFirst-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.

Liver-directed therapy of neuroendocrine liver metastases.

647 Background: While there have been major advances in the care of neuroendocrine tumors (NETs), there is still no widely adopted therapeutic sequencing in metastatic NETs. The roles and benefits of locoregional treatments need reassessment, in order to define a modern therapeutic algorithm. We examined contemporary short-term outcomes of liver-directed therapy for metastatic NETs. Methods: We conducted a population-based retrospective cohort study of patients with metastatic NETs (2000-2019) undergoing liver embolization (LE) or liver resection (LR). Outcomes were 30-day major morbidity (Clavien-Dindo grade 3-5) and/or re-admission (composite) and length of hospital stay. Modified Poisson regression accounting for clustering at the hospital level examined factors associated with outcomes in both treatment groups. Results: Overall, 1,224 LEs and 502 LRs were performed for 5,159 patients with metastatic NETs. Median length of hospital stay was 1 day (IQR 1-4) for liver embolization and 7 days (IQR 5-9) for liver resection. 30-day major morbidity and re-admission occurred after 213 LEs (17.4%) including 40 (3.3%) deaths, and 138 LRs (27.5%) including 11 (2.2%) deaths. There were 25 (2%) LEs followed by infectious complications. Factors independently associated with increased risk after LE were prior LE treatment (adjusted relative risk- aRR 0.62; 95%CI 0.44-0.88), rural residence (aRR 0.43; 95%CI 0.20-0.91) and high comorbidity burden (aRR 1.85; 95%CI 1.34-2.54). The only factor independently associated with increased risk after LR was metachronous metastases (RR 0.60; 95%CI 0.37-0.98). Conclusions: In this contemporary cohort, LE was associated with mortality similar to that of LR. Prior LE, rural residence, comorbidities, and metachronous metastatic diagnosis were associated with higher risk of major morbidity and re-admission. This information is important when discussing the use of and choice of liver-directed therapies in the multi-disciplinary management of metastatic NETs. Further characterization of long-term outcomes and patient-reported outcomes will further support decision-making, counselling, and patient preparation.

Hypertensive disorders in pregnancy complicated by liver rupture or hematoma: a systematic review of 391 reported cases

BackgroundSpontaneous liver rupture in pregnancy is often unrecognized, highly lethal, and not completely understood. The goal was to summarize and define the etiology, risk factors, clinical presentation, appropriate diagnostic methods, and therapeutic options for spontaneous hepatic rupture during pregnancy/puerperium (SHRP) complicated by the hypertensive disorder.MethodsLiterature search of all full-text articles included PubMed (1946–2021), PubMed Central (1900–2021), and Google Scholar. Case reports of a spontaneous hepatic rupture or liver hematoma during pregnancy or puerperium as a complication of hypertensive disorders (preeclampsia, eclampsia, HELLP syndrome) were searched. There was no restriction of language to collect the cases. Additional cases were identified by reviewing references of retrieved studies. PRISMA guidelines for the data extraction and quality assessment were applied.ResultsThree hundred and ninety-one cases were collected. The median maternal age was 31 (range 17–48) years; 36.6% were nulliparous. Most (83.4%) occurred in the third trimester. Maternal and fetal mortality was 22.1% and 37.2%, respectively. Maternal and fetal mortality was significantly higher 1) before the year 1990, 2) with maternal hemodynamic instability, and 3) eclampsia. The most important risk factors for SHRP were preeclampsia and HELLP syndrome. Most women had right lobe affected (70.9%), followed by both lobes in 22.1% and left lobe in 6.9%. The most common surgical procedure was liver packing. Liver transplantation was performed in 4.7% with 100% survival. Maternal mortality with liver embolization was 3.0%. Higher gestational age increases fetal survival.ConclusionThe diagnosis and treatment of SHRP are often delayed, leading to high maternal and fetal mortality. SHRP should be excluded in hemodynamically unstable patients with preeclampsia/eclampsia or HELLP syndrome and right upper abdominal pain. Liver embolization and liver transplantation contribute to maternal survival. Maternal and fetal mortality was significantly higher before the year 1990. Hemodynamic instability, preeclampsia, and eclampsia have a significant negative influence on maternal survival.Level of evidenceLevel V

Preparation and investigation of a novel iodine-based visible polyvinyl alcohol embolization material

Polyvinyl alcohol (PVA) embolization particles, currently used in clinical practice, have good expansibility and are capable of permanent embolization. However, the lack of adhesion of embolization particles contributes to facilitated recanalization after embolization, while the lack of visualization facilitates misembolization. At present, embolization materials with good expansion, adhesion, and visualization potential are urgently required in clinical practice. Here, we report the development of PVA/gelatin/iohexol (I) fiber blocks as a novel embolization material for liver embolization in rats. In our work, electrospun PVA/gelatin/I nanofibrous mats were first prepared, homogenized, centrifuged in a gradient manner, and freeze-dried to obtain fiber blocks (fiber diameter ​= ​296.2 ​± ​74.23 ​nm, length 99.6 ​± ​17.0 ​μm ​× ​width 46.9 ​± ​13.3 ​μm). The fiber blocks exhibited excellent cytocompatibility and hemocompatibility. Fiber blocks with a PVA/gelatin/I mass ratio of 8:2:10 were selected due to their excellent expansibility and adhesive properties. The PVA/gelatin/I fiber blocks display excellent liver embolic effects and computed tomography (CT) imaging potential due to a combination of the following characteristics: expansibility of PVA and gelatin, adhesive property of gelatin, and CT imaging potential of I. The developed fiber block material is an embolic material that may potentially be used in interventional medicine.

Simultaneous ipsilateral dual (DSM-TACE and portal vein (PVE)) liver embolization (“SIDE” Technique) as a new method of preoperative augmentation of future liver remnant (FLR) in patients with solid liver malignancies

Simultaneous ipsilateral dual (DSM-TACE and portal vein (PVE)) liver embolization (“SIDE” Technique) as a new method of preoperative augmentation of future liver remnant (FLR) in patients with solid liver malignancies

Shape‐Anisotropic Microembolics Generated by Microfluidic Synthesis for Transarterial Embolization Treatment

Particulate embolic agents with calibrated sizes, which employ interventional procedures to achieve endovascular embolization, have recently attracted tremendous interest in therapeutic embolotherapies for a wide plethora of diseases. However, the particulate shape effect, which may play a critical role in embolization performances, has been rarely investigated. Here, polyvinyl alcohol (PVA)-based shape-anisotropic microembolics are developed using a facile droplet-based microfluidic fabrication method via heat-accelerated PVA-glutaraldehyde crosslinking reaction at a mild temperature of 38° C. Precise geometrical controls of the microembolics are achieved with a nearly capsule shape through regulating surfactant concentration and flow rate ratio between dispersed phase and continuous phase in the microfluidics. Two specific models are employed, i.e., in vitro decellularized rabbit liver embolization model and in vivo rabbit ear embolization model, to systematically evaluate the embolization behaviors of the nonspherical microembolics. Compared to microspheres of the same volume, the elongated microembolics demonstrated advantageous endovascular navigation capability, penetration depth and embolization stability due to their comparatively smaller radial diameter and their central cylindrical part providing larger contact area with distal vessels. Such nonspherical microembolics present a promising platform to apply shape anisotropy to achieve distinctive therapeutic effects for endovascular treatments.

Efficacy of treatments for VIPoma: A GTE multicentric series

BackgroundVasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma. ObjectiveDescribe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma. MethodsWe retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received. ResultsTwenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025). ConclusionsSurgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.

Abstract No. 544 Evaluation of software predicting selective liver perfusion for embolization planning

To evaluate the accuracy of a liver embolization planning software (Liver ASSIST V.I. with Virtual Parenchymography prototype, GE Healthcare, Chicago, IL) to automatically predict perfused liver volume from any virtual selective injection point on a proximally enhanced planning cone-beam CT (CBCT). Planning CBCTs acquired proximally and associated selective CBCT couples from patients undergoing liver embolization in two centers were included in this retrospective study. Inclusion criteria were as follows: perfused liver parenchyma volume on the selective CBCT > 100cc and with adequate enhancement to allow for manual contouring. Perfused liver parenchyma was contoured manually on all selective CBCTs, defining the ground truth volume. The Virtual Perfused Volume (VPV) was obtained with the software by selecting the virtual injection point on the proximal CBCT matching the actual injection point of the associated selective CBCT. Software accuracy was evaluated by comparing the VPV to the ground truth volume after registering the proximal and selective CBCTs based on liver borders. Software accuracy is reported as relative volumetric error (%) and Dice spatial overlap coefficient (%). Results are expressed as mean [interquartile range]. 32 CBCT couples were included in 18 patients. Proximal CBCTs were acquired from the common (52%), right (18%), left (9%) or segmental (21%) hepatic arteries. Selective CBCTs were acquired from the right (12%), left (19%), and third or greater order right (65%) or left (4%) hepatic artery, with an average perfused liver parenchyma volume of 512cc [192, 699]. Software was successful in automatically computing VPV in all cases. Relative volumetric error and Dice coefficient were 15% [5%-20%] and 77% [73%-84%] in the entire cohort. In the sub-analysis on the 27 couples with proximal CBCTs acquired from the common, right or left hepatic artery, relative volumetric error and Dice coefficient were 12% [4%-18%] and 78% [74%-84%], with no significant difference between centers (P = .31 and .13). Preliminary evaluation of selective perfused liver volume prediction from proximal CBCTs showed acceptable accuracy. This software could help identify optimal embolization strategy based on a single proximal CBCT, avoiding multiple selective acquisitions for liver embolization planning. Further studies are warranted to demonstrate its benefits for radioembolization CBCT-based volumetry, reducing the need for distal vessel catheterization during mapping, and streamlining dosimetry workflow.

Advanced small-bowel well-differentiated neuroendocrine tumours: An international survey of practice on 3rd-line treatment.

BACKGROUNDSomatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours (Wd-SBNETs), while and peptide receptor radionuclide therapy (PRRT) is frequently used as a second-line therapy. Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence. AIMTo understand current practice and rationale for decision-making by physicians in the 3rd-line setting by building an online survey. METHODSWeighted average (WA) of likelihood of usage between responders (1 very unlikely; 4 very likely) was used to reflect the relevance of factors explored.RESULTSReplies from representatives of 28 centers were received (5/8/2020-21/9/2020); medical oncologist (53.6%), gastroenterologist (17.9%); United Kingdom (21.4%), Spain (17.9%), Italy (14.3%). Majority from European Neuroendocrine Tumor Society (ENETS) Centres of Excellence (57.1%), who followed ENETS guidelines (82.1%). Generally speaking, 3rd-line treatment for Wd-SBNETs was: everolimus (EVE) (66.7%), PRRT (18.5%), liver embolization (LE) (7.4%) and interferon-alpha (IFN) (3.7%); chemotherapy (0%); decision was based on clinical trial data (59.3%), or personal experience (22.2%). EVE was most likely used if Ki-67 < 10% (WA 3.27/4) or age < 70 years (WA 3.23/4), in the 3rd-line setting (WA 3.23/4); regardless of presence/absence of carcinoid syndrome (CS), rate of progression or extent of disease. Chemotherapy was mainly utilised only if rapid progression (within 6 mo) (WA 3.35/4), Ki-67 10%-20% (WA 2.77/4), negative somatostatin receptor imaging (WA 2.65/4) or high tumour burden (WA 2.77/4); temozolomide or streptozocin was used with capecitabine or 5-fluorouracil (5-FU) (57.7%), FOLFOX (5-FU combined with oxaliplatin) (23.1%). LE was selected if presence of CS (WA 3.24/4) or Ki-67 < 10% (WA 2.8/4), after progression to other treatments (WA 2.8/4). IFN was rarely used (WA 1.3/4).CONCLUSIONEverolimus was the most frequently used therapeutic option in the third-line setting. The most important factors for decision-making included Ki-67, rate of progression, functionality and tumour burden; since this decision is based on multiple factors, it highlights the need for a multidisciplinary assessment.

Accelerated 3D image reconstruction with a morphological pyramid and noise-power convergence criterion

Model-based iterative reconstruction (MBIR) for cone-beam CT (CBCT) offers better noise-resolution tradeoff and image quality than analytical methods for acquisition protocols with low x-ray dose or limited data, but with increased computational burden that poses a drawback to routine application in clinical scenarios. This work develops a comprehensive framework for acceleration of MBIR in the form of penalized weighted least squares optimized with ordered subsets separable quadratic surrogates. The optimization was scheduled on a set of stages forming a morphological pyramid varying in voxel size. Transition between stages was controlled with a convergence criterion based on the deviation between the mid-band noise power spectrum (NPS) measured on a homogeneous region of the evolving reconstruction and that expected for the converged image, computed with an analytical model that used projection data and the reconstruction parameters. A stochastic backprojector was developed by introducing a random perturbation to the sampling position of each voxel for each ray in the reconstruction within a voxel-based backprojector, breaking the deterministic pattern of sampling artifacts when combined with an unmatched Siddon forward projector. This fast, forward and backprojector pair were included into a multi-resolution reconstruction strategy to provide support for objects partially outside of the field of view. Acceleration from ordered subsets was combined with momentum accumulation stabilized with an adaptive technique that automatically resets the accumulated momentum when it diverges noticeably from the current iteration update. The framework was evaluated with CBCT data of a realistic abdomen phantom acquired on an imaging x-ray bench and with clinical CBCT data from an angiography robotic C-arm (Artis Zeego, Siemens Healthineers, Forchheim, Germany) acquired during a liver embolization procedure. Image fidelity was assessed with the structural similarity index (SSIM) computed with a converged reconstruction. The accelerated framework provided accurate reconstructions in 60 s (SSIM = 0.97) and as little as 27 s (SSIM = 0.94) for soft-tissue evaluation. The use of simple forward and backprojectors resulted in 9.3× acceleration. Accumulation of momentum provided extra ∼3.5× acceleration with stable convergence for 6–30 subsets. The NPS-driven morphological pyramid resulted in initial faster convergence, achieving similar SSIM with 1.5× lower runtime than the single-stage optimization. Acceleration of MBIR to provide reconstruction time compatible with clinical applications is feasible via architectures that integrate algorithmic acceleration with approaches to provide stable convergence, and optimization schedules that maximize convergence speed.

Abstract 1853: Lipiodol-based emulsion to disrupt oxygenation and lipid homeostasis of liver tumors

Abstract Trans-arterial embolic therapies for liver tumors are used routinely in patients with hepatocellular carcinoma (HCC) and patients with liver dominant metastatic disease. Lipiodol® (Ethiodized oil; ethyl esters of iodized fatty acids of poppy seed oil) has been historically used as a vehicle for delivering chemotherapeutic agents as part of chemoembolization (cTACE) of liver tumors. Lipiodol's role in cTACE is to visualize the delivery of the mixture under fluoroscopy, emulsification and delivery of the chemotherapeutic agent, and as a microembolic agent itself. Contrary to previous studies that showed better outcome in patients with HCC treated with cTACE compared to bland embolization (TAE), more recent studies demonstrated no significant difference between drug-eluting chemoembolization and bland embolization (TAE), negating the added benefit of chemotherapy as a required agent when performing liver embolization of HCC. Therefore, we hypothesized that the added benefit of cTACE over TAE stems from the Lipiodol-based emulsion and not chemotherapy. We performed embolization of liver tumors using Lipiodol-Isovue emulsion and bland particles (TALE) but replacing chemotherapy with Isovue-300® (Iopamidol, a non-ionic iodinated contrast agent). Our preliminary data of 5 patients with non-resectable HCC (1 to 14.9 cm) treated with TALE without systemic therapy were followed for at least 5 months and response was evaluated using RECIST and mRECIST. By mRECIST, 3 patients had complete response (CR), one had a partial response (PR) and one could not be evaluated since the biopsy-proven HCC was hypovascular. Using RECIST 1.1 criteria, two patients had a stable disease (SD), and 3 had PR, including Interestingly CR of one of 2 tumors. We also treated 5 patients with metastatic renal cell carcinoma (RCC) using TALE with tumors ranging from 2.2 to 4.3 cm; using RECIST, three patients had PR, one SD, and one PD (progressive disease). Based on these results, we investigated the cytotoxic effects of Lipiodol in HCC and RCC cell lines Huh7 and A498. Lipiodol-Isovue emulsions were cytotoxic to these cells while viability of a normal/primary cell line HEK293 was not affected. Additionally, Lipiodol alone showed similar cytotoxic effects as the emulsions. Furthermore, Lipiodol was taken up by cells as seen by staining with Nile Red, a fluorescent dye that stains neutral lipids in lipid droplets using confocal microscopy. Our in vitro data indicate that RCC and HCC cells are more vulnerable to Lipiodol-induced lipotoxicity than non-cancerous primary kidney epithelial cells. There might be a synergistic effect between causing hypoxia as a result of blocking blood flow to the tumors during liver embolization and disrupting lipid homeostasis with the use of a Lipid-based emulsion. Our studies unravel a potential metabolic vulnerability that can be exploited therapeutically with liver-directed therapies. Citation Format: Smitha R. Pillai, Pravin Phadatare, Antonio Ortiz, Elie Barakat, Ghassan El-Haddad. Lipiodol-based emulsion to disrupt oxygenation and lipid homeostasis of liver tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1853.

Sarcopenia as a predictor of survival in patients undergoing bland transarterial embolization for unresectable hepatocellular carcinoma.

Sarcopenia has been associated with lower overall survival in patients with cirrhosis and hepatocellular carcinoma (HCC) undergoing surgical resection, TACE, TARE, or transplantation. This monocentric study evaluated the prognostic significance of sarcopenia in patients affected by HCC who received bland transarterial embolization (TAE) therapy, by analyzing its impact on survival and treatment-related complications. All consecutive patients who underwent the 1st TAE between March 1st 2011 and July 1st 2019 in our Institution were retrospectively studied. To evaluate sarcopenia, the skeletal muscle index (SMI) was calculated by normalizing the cross-sectional muscle area at the level of L3 on an abdominal CT scan prior to embolization (cm2) by patient height (m2). SMI cut-off values for sarcopenia were considered ≤ 39 cm2/m2 for women and ≤55 cm2/m2 for men. Data about age, gender, body mass index (BMI), underlying liver disease, liver function, MELD score, Child-Pugh score, multifocal disease, performance status, previous interventions, length of stay (LOS), complications after the procedure, readmission rate within 30 days, survival time from TAE and total number and type of TAE received following the first procedure were collected. From 2011 to 2019, 142 consecutive patients underwent 305 TAEs. Observation time ranged from 1.4 to 100.5 months (median 20.1 SD = 22). Sarcopenia at baseline was present in 121 (85%) patients. Overall 87 (61.2%) patients died during follow-up with survival rates at 1-, 2-, 3-, 4-, and 5-year of 71%, 41%, 22%, 16% and 11% respectively. After multivariate analysis sarcopenia (HR = 2.22, p = 0.046), previous ablation/resection (HR = 0.51, p = 0.005) and multifocal disease (HR = 1.84, p = 0.02) were associated with reduced survival. Sarcopenia did not influence the safety of TAE in terms of LOS (2 days vs 1.5 days, p = 0.2), early complications rate (8% vs 5%, p = 0.5) and readmission rate within 30 days (7% vs 5%, p = 0.74). Sarcopenia, estimated by the L3SMI method, is an emerging prognostic factor in patients with HCC undergoing bland TAE therapy as it is associated with increased mortality, without impairing the safety of the locoregional treatment. Measures to ameliorate the SMI, such as nutritional support and physical exercise, should be evaluated in clinical trials for HCC patients receiving liver embolization to determine their impact on overall survival.

MON-908 Carcinoid Causing Catastrophic Calcemia

Intro: Carcinoid tumors are rare, slow growing, indolent neuroendocrine tumors typically originating from enterochromaffin in the gastrointestinal tract and bronchopulmonary tree1. While often found to be secreting serotonin, many different secretory products have been described2. We present the case of a patient with refractory hypercalcemia due to a carcinoid tumor producing parathyroid hormone related peptide (PTHrP). Case: A 65-year-old male was found to have hypercalcemia of 14.7 mg/dL after presenting for nausea and vomiting. He was treated with Zolendronic acid and intravenous (IV) fluids as initial work-up revealed an appropriately suppressed parathyroid hormone level, no monoclonal spike, and a PTHrP that was dramatically elevated. He refused further work-up initially but was admitted two months later for persistent severe hypercalcemia. Computed tomography imaging showed innumerable liver lesions. Histologic analysis of the largest liver lesion was consistent with carcinoid tumor. For the next two years, he was managed outpatient with Pamidronate, Denosumab, and Sandostatin, along with two liver embolizations. Control of serum calcium levels became more difficult and he had multiple hospitalizations for symptomatic hypercalcemia until chemotherapy, Sunitinib, was initiated. Calcium levels normalized for one year after starting Sunitinib prior to onset of suspected medication-induced pancreatitis. He was switched to Everolimus but did not respond to that and was readmitted mere weeks later for symptomatic hypercalcemia and a combination of Folinic acid, Fluorouracil, and Oxaliplatin (Folfox) was started. He continued to get frequent bisphosphonates and IV fluids along with Folfox but several months later he stopped responding to all medical options. His calcium level climbed to 19.9mg/dL and he underwent a technically complicated surgical procedure in which significant tumor burden was removed from his liver. Since surgery, the patient has remained normocalcemic without additional medical therapy. Discussion: Carcinoid tumors are uncommon with reported incidence of 40 per one million people2. PTHrP is most commonly produced by squamous cell lung cancer, renal cell cancer, gynecologic cancers, and lymphoma3. Carcinoid tumors producing PTHrP with resultant hypercalcemia is rare with a few cases reported in literature4. Our patient had a complex treatment course including IV fluids, anti-resorptive agents, somatostatin analogs, liver embolization, chemotherapeutic agents, and eventual surgical debulking. Surgical intervention is not commonly required for carcinoid tumors5. This patient had a rare tumor, producing an uncommon hormone, and required extensive treatment. This case shows the importance of a multidisciplinary approach in patients with hypercalcemia secondary to carcinoid tumors but refractory to traditional therapy.

SAT-LB24 Association of Expression of Somatostatin Receptor 2 Subtype in Non-Pituitary Neuroendocrine Tumors With Response to Treatment With Somatostatin Analogues

Background: The WHO classification of non-pituitary neuroendocrine tumors (NETs) includes grading (Ki67 proliferation index and mitosis index) and staging, and has been shown to be associated with outcome in this patient population. Neuroendocrine tumors show different somatostatin receptor (SSTR) subtypes expression, but their role has not been considered in tumor progression and prognosis. We hypothesize patients with non-pituitary NET, whose tumor tissues have higher specific SSTR2 expression patterns will experience better outcomes when treated with Somatostatin Analogues (SSA) compared to those with lower or absent SSTR2 expression. Methods and patients: City of Hope patients with non-pituitary NET who received SSA (Octreotide and Lanreotide) for over 1 year as treatment. The progression free survival was based on imaging studies (MRI, CAT scan of index tumor) on RECIST criteria, and expression of SSTR2 on the tumor obtained by surgery at the time of diagnosis. Immunohistochemical staining with a monoclonal antibody to SSTR2 performed at core pathology lab at City of Hope. H-scoring (intensity of immunostaining and percent of SSTR2 expression) was performed by one pathologist, and divided into four categories of 0-4. Pearson Chi-square test was used to assess the correlation between the SSTR2 score and 1-year progression. Outcome Measures: The effect of SSA therapy on 1 year progression-free survival (PFS), among patients with high intensity and percent of SSTR2 expression on the resected tumor tissue was compared to those with low or absent SSTR2 expression. Patient population: Of the 297 patients identified with non-pituitary neuroendocrine tumor, 70 patients satisfied the inclusion criteria and a total of 52 patients had data that was completely available for analysis. Results: Mean age of study subjects was 61+1.8 years. 26 were female and 26 were male. The primary sites for NET were: pancreas 17, jejunum 16, ileum 9; paraganglioma and pheochromocytomas 3, lung and thymus 3, gastric 2, and medullary thyroid carcinoma 1. The one-year progression was not significantly different among those with low and absent SSTR2 compared to high expression of SSTR2. Step wise analysis based on the scoring of the SSRT2 did not show significant 1 year progression. Age was not associated with PFS. However, the need for additional therapy (liver embolization, surgical resection) was signigicantly reduced amongst patients with presence of SSTR2. Conclusion: In this preliminary study there was no significant association between SSTR2 expression and Progression free survival, however the need for additional therapy in patients on somatostatin analogues were reduced among subjects with presence of SSTR2 expression

Carcinoid Right Heart Disease

Carcinoid heart disease is an unusual cause of right heart failure. We present the case of a 53-year-old man with a history of metastatic carcinoid tumors originating from the appendix, status post-chemotherapy, and liver embolizations. The patient presented with a right-sided valvular disease with severe pulmonic valve regurgitation, right ventricle dilation and pulmonary hypertension. He had carcinoid syndrome well controlled with long-acting lanreotide. He underwent tricuspid valve and pulmonary valve replacement with a stented bioprosthetic valve, maze and cardio-septal right ventricular outflow tract patch with an improvement of ventricular dysfunction. These findings supported the diagnosis of carcinoid heart disease presenting with pure right heart failure. The patient was symptom-free due to lanreotide, but ultimately, valve surgery is the preferred definite treatment in suitable patients. Carcinoid heart disease requires a high index of suspicion, and valve surgery is the only definitive treatment. J Med Cases. 2020;11(3):73-76 doi: https://doi.org/10.14740/jmc3452

Inherently radiopaque polyurethane beads as potential multifunctional embolic agent in hepatocellular carcinoma therapy

The aim of the current study is to report an inherently radiopaque drug-eluted beads (DEBs) as promising embolic materials for TACE techniques. Firstly, the synthesized radiopaque iodinated polycaprolactone-polyurethanes (I-PCLUs) are synthesized by chain-extending method by using 4, 4´-isopropylidinedi-(2, 6-diiodophenol) (IBPA) as the radiopacifying agent. Then, doxorubicin (Dox) is introduced as a chemotherapeutic agent into I-PCLU beads via a double emulsification (W/O/W) method. The drug loading and controlled release behavior of two ratios of I-PCLU/Dox are found to be dependent upon the internal porous microstructure, and the radiopacity is well-retained after four weeks drug release. Besides, the I-PCLU/Dox beads exhibit positive in vitro anti-tumor effect. The in vivo intramuscular implantation and liver embolization results demonstrate that I-PCLU beads have good histocompatibility, occlusion effect and X-ray traceability. Furthermore, the drug-loaded I-PCLU beads are performed into a VX2 rabbit hepatocellular carcinoma (HCC) model using a micro-catheter, form embolization of hepatic arteries and inhibit the tumor growth after one week post-injection. Hence, this polymeric system provides a potential radiopaque chemoembolization candidate for HCC and other cancer therapies, which could bring opportunities to the next generation of multifunctional embolic agents.