The Natural History of Splenic Artery Aneurysms: Factors That Predict Aneurysm Growth.

PURPOSE: To examine the natural history of splenic artery aneurysms (SAAs) at a single institution and assess the effect of patient factors and aneurysm characteristics on aneurysm growth. MATERIALS AND METHODS: This single-center retrospective study included patients with SAAs who underwent serial imaging over 30 years (1990-2020). Data regarding patient demographics and aneurysm characteristics were collected. The variables contributing to aneurysm growth were assessed using nonparametric tests for continuous variables and chi-square test for categorical variables. Multivariable linear regression was performed using aneurysm growth rate as a continuous dependent variable. RESULTS: A total of 132 patients were included in this study. The median maximum diameter of the SAAs was 15.8 mm (range, 4.0-50.0 mm). Growth over time was observed in 39% of the aneurysms, whereas the remaining 61% were stable in size. Of aneurysms that increased in size, the median aneurysm growth rate was 0.60 mm/y (range, 0.03-5.00 mm/y). Maximum aneurysm diameter of >2 cm and the presence of >50% mural thrombus were significant positive predictors for aneurysm growth (P = .020 and P = .022, respectively). Greater than 50% rim calcification was a significant negative predictor for aneurysm growth (P = .009) in multivariate analysis. CONCLUSIONS: A larger baseline SAA size, presence of mural thrombus, and lack of rim calcification are associated with increased aneurysm growth rate.

Synergizing Thermal Ablation Modalities with Immunotherapy: Enough to Induce Systemic Antitumoral Immunity?

Thermal ablation modalities (cryoablation, radiofrequency ablation, and microwave ablation) have long been noted to occasionally induce a systemic antitumoral response. With the widespread use of checkpoint inhibitors, there is a significant interest in whether thermal ablation can promote immune system tumor recognition and increase checkpoint inhibitor response rates. In this review, we examine the current state of preclinical and clinical evidence examining the combination of checkpoint inhibitor therapies and thermal ablation modalities as well as discuss remaining the unanswered questions and directions for future research.

Percutaneous Intratumoral Immunoadjuvant Gel Increases the Abscopal Effect of Cryoablation for Checkpoint Inhibitor Resistant Cancer.

Percutaneous cryoablation is a common clinical therapy for metastatic and primary cancer. There are rare clinical reports of cryoablation inducing regression of distant metastases, known as the "abscopal" effect. Intratumoral immunoadjuvants may be able to augment the abscopal rate of cryoablation, but existing intratumoral therapies suffer from the need for frequent injections and inability to confirm target delivery, leading to poor clinical trial outcomes. To address these shortcomings, an injectable thermoresponsive gel-based controlled release formulation is developed for the FDA-approved Toll-like-receptor 7 (TLR7) agonist imiquimod ("Imigel") that forms a tumor-resident depot upon injection and contains a contrast agent for visualization under computed tomography (CT). The poly-lactic-co-glycolic acid-polyethylene glycol-poly-lactic-co-glycolic acid (PLGA-PEG-PLGA)-based amphiphilic copolymer gel's underlying micellar nature enables high drug concentration and a logarithmic release profile that is additive with the neo-antigen release from cryoablation, requiring only a single injection. Rheological testing demonstrated the thermoresponsive increase in viscosity at body temperature and radio-opacity via microCT. Its ability to significantly augment the abscopal rate of cryoablation is demonstrated in otherwise immunotherapy resistant metastatic tumors in two aggressive colorectal and breast cancer dual tumor models with an all or nothing response, responders generally demonstrating complete regression of bilateral tumors in 90-day survival studies.

MIDOS: a novel stochastic model towards a treatment planning system for microsphere dosimetry in liver tumors.

PURPOSE: Transarterial radioembolization (TARE) procedures treat liver tumors by injecting radioactive microspheres into the hepatic artery. Currently, there is a critical need to optimize TARE towards a personalized dosimetry approach. To this aim, we present a novel microsphere dosimetry (MIDOS) stochastic model to estimate the activity delivered to the tumor(s), normal liver, and lung. METHODS: MIDOS incorporates adult male/female liver computational phantoms with the hepatic arterial, hepatic portal venous, and hepatic venous vascular trees. Tumors can be placed in both models at user discretion. The perfusion of microspheres follows cluster patterns, and a Markov chain approach was applied to microsphere navigation, with the terminal location of microspheres determined to be in either normal hepatic parenchyma, hepatic tumor, or lung. A tumor uptake model was implemented to determine if microspheres get lodged in the tumor, and a probability was included in determining the shunt of microspheres to the lung. A sensitivity analysis of the model parameters was performed, and radiation segmentectomy/lobectomy procedures were simulated over a wide range of activity perfused. Then, the impact of using different microspheres, i.e., SIR-Sphere®, TheraSphere®, and QuiremSphere®, on the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), and mean absorbed dose was analyzed. RESULTS: Highly vascularized tumors translated into increased TNR. Treatment results (TNR and LSF) were significantly more variable for microspheres with high particle load. In our scenarios with 1.5 GBq perfusion, TNR was maximum for TheraSphere® at calibration time in segmentectomy/lobar technique, for SIR-Sphere® at 1-3 days post-calibration, and regarding QuiremSphere® at 3 days post-calibration. CONCLUSION: This novel approach is a decisive step towards developing a personalized dosimetry framework for TARE. MIDOS assists in making clinical decisions in TARE treatment planning by assessing various delivery parameters and simulating different tumor uptakes. MIDOS offers evaluation of treatment outcomes, such as TNR and LSF, and quantitative scenario-specific decisions.

Machine Learning-Based Radiomic Features on Pre-Ablation MRI as Predictors of Pathologic Response in Patients with Hepatocellular Carcinoma Who Underwent Hepatic Transplant.

BACKGROUND: The aim was to investigate the role of pre-ablation tumor radiomics in predicting pathologic treatment response in patients with early-stage hepatocellular carcinoma (HCC) who underwent liver transplant. METHODS: Using data collected from 2005-2015, we included adult patients who (1) had a contrast-enhanced MRI within 3 months prior to ablation therapy and (2) underwent liver transplantation. Demographics were obtained for each patient. The treated hepatic tumor volume was manually segmented on the arterial phase T1 MRI images. A vector with 112 radiomic features (shape, first-order, and texture) was extracted from each tumor. Feature selection was employed through minimum redundancy and maximum relevance using a training set. A random forest model was developed based on top radiomic and demographic features. Model performance was evaluated by ROC analysis. SHAP plots were constructed in order to visualize feature importance in model predictions. RESULTS: Ninety-seven patients (117 tumors, 31 (32%) microwave ablation, 66 (68%) radiofrequency ablation) were included. The mean model for end-stage liver disease (MELD) score was 10.5 ± 3. The mean follow-up time was 336.2 ± 179 days. Complete response on pathology review was achieved in 62% of patients at the time of transplant. Incomplete pathologic response was associated with four features: two first-order and two GLRM features using univariate logistic regression analysis (p < 0.05). The random forest model included two radiomic features (diagnostics maximum and first-order maximum) and four clinical features (pre-procedure creatinine, pre-procedure albumin, age, and gender) achieving an AUC of 0.83, a sensitivity of 82%, a specificity of 67%, a PPV of 69%, and an NPV of 80%. CONCLUSIONS: Pre-ablation MRI radiomics could act as a valuable imaging biomarker for the prediction of tumor pathologic response in patients with HCC.

The double-balloon technique: a safe and effective adjunctive technique in patients undergoing arterial therapy for hepatic malignancies with vascular supply not amenable to selective administration.

PURPOSE: During catheter directed intraarterial therapy for liver lesions, challenging hepatic vascular anatomy can sometimes prevent selective administration of treatment delivery to liver tumors leading to increased toxicity to normal liver parenchyma. The objective of this study is to describe a variation of the double balloon technique that isolates the feeding artery to liver tumors proximally and distally to provide treatment delivery in lesions that cannot be otherwise selected. MATERIALS AND METHODS: An IRB-approved retrospective review of 7 patients who had undergone either radioembolization, chemoembolization, or bland embolization and the double balloon technique was employed. The devices used for flow augmentation were two 2.1 French balloon microcatheters (Sniper™, Embolx). One balloon was inflated distal to target vessel and the second was inflated proximal to protect from reflux. RESULTS: DEB-TACE was performed in 3 cases, 90Y was performed in 4, and bland embolization was performed in the last patient. There were no adverse effects from the procedure or clinically evident effects from non-target embolization. Mean follow up time was 286.4 +/- 200.1 days. Six of the 7 patients are alive. One patient passed away on post-procedure day 121 from septic shock unrelated to the procedure. One patient was bridged to transplant with an additional TACE of a separate lesion. CONCLUSION: Double-balloon technique for patients undergoing 90Y or chemoembolization is a safe adjunctive technique for super selective treatment of hepatic lesions where direct selection via catheter is not feasible. This may increase the range of lesions that can be both safely and effectively treated by catheter directed therapies.

Image-guided intratumoral immunotherapy: Developing a clinically practical technology.

Immunotherapy has revolutionized the contemporary oncology landscape, with durable responses possible across a range of cancer types. However, the majority of cancer patients do not respond to immunotherapy due to numerous immunosuppressive barriers. Efforts to overcome these barriers and increase systemic immunotherapy efficacy have sparked interest in the local intratumoral delivery of immune stimulants to activate the local immune response and subsequently drive systemic tumor immunity. While clinical evaluation of many therapeutic candidates is ongoing, development is hindered by a lack of imaging confirmation of local delivery, insufficient intratumoral drug distribution, and a need for repeated injections. The use of polymeric drug delivery systems, which have been widely used as platforms for both image guidance and controlled drug release, holds promise for delivery of intratumoral immunoadjuvants and the development of an in situ cancer vaccine for patients with metastatic cancer. In this review, we explore the current state of the field for intratumoral delivery and methods for optimizing controlled drug release, as well as practical considerations for drug delivery design to be optimized for clinical image guided delivery particularly by CT and ultrasound.

Immune Checkpoint Inhibitor-Mediated Cancer Theranostics with Radiolabeled Anti-Granzyme B Peptide.

Although immune checkpoint inhibitors (ICI) have revolutionized cancer management, patient response can be heterogeneous, and the development of ICI resistance is increasingly reported. Novel treatment strategies are necessary not only to expand the use of ICI to previously unresponsive tumor types but also to overcome resistance. Targeted radionuclide therapy may synergize well with ICIs since it can promote a pro-inflammatory tumor microenvironment. We investigated the use of a granzyme B targeted peptide (GZP) as a cancer theranostic agent, radiolabeled with 68Ga (68Ga-GZP) as a PET imaging agent and radiolabeled with 90Y (90Y-GZP) as a targeted radionuclide therapy agent for combinational therapy with ICI in murine models of colon cancer. Our results demonstrate that GZP increasingly accumulates in tumor tissue after ICI and that the combination of ICI with 90Y-GZP promotes a dose-dependent response, achieving curative response in some settings and increased overall survival.

Pre- and post-treatment image-based dosimetry in90Y-microsphere radioembolization using the TOPAS Monte Carlo toolkit.

Objective. To evaluate the pre-treatment and post-treatment imaging-based dosimetry of patients treated with 90Y-microspheres, including accurate estimations of dose to tumor, healthy liver and lung. To do so, the Monte Carlo (MC) TOPAS platform is in this work extended towards its utilization in radionuclide therapy.Approach. Five patients treated at the Massachusetts General Hospital were selected for this study. All patients had data for both pre-treatment SPECT-CT imaging using 99mTc-MAA as a surrogate of the 90Y-microspheres treatment and SPECT-CT imaging immediately after the 90Y activity administration. Pre- and post-treatment doses were computed with TOPAS using the SPECT images to localize the source positions and the CT images to account for tissue inhomoegeneities. We compared our results with analytical calculations following the voxel-based MIRD scheme.Main results. TOPAS results largely agreed with the MIRD-based calculations in soft tissue regions: the average difference in mean dose to the liver was 0.14 Gy GBq-1(2.6%). However, dose distributions in the lung differed considerably: absolute differences in mean doses to the lung ranged from 1.2 to 6.3 Gy GBq-1and relative differences from 153% to 231%. We also found large differences in the intra-hepatic dose distributions between pre- and post-treatment imaging, but only limited differences in the pulmonary dose.Significance. Doses to lung were found to be higher using TOPAS with respect to analytical calculations which may significantly underestimate dose to the lung, suggesting the use of MC methods for 90Y dosimetry. According to our results, pre-treatment imaging may still be representative of dose to lung in these treatments.

Non-invasive Detection of Immunotherapy-Induced Adverse Events.

PURPOSE: Cancer immunotherapy has markedly improved the prognosis of patients with a broad variety of malignancies. However, benefits are weighed against unique toxicities, with immune-related adverse events (irAE) that are frequent and potentially life-threatening. The diagnosis and management of these events are challenging due to heterogeneity of timing onset, multiplicity of affected organs, and lack of non-invasive monitoring techniques. We demonstrate the use of a granzyme B-targeted PET imaging agent (GZP) for irAE identification in a murine model. EXPERIMENTAL DESIGN: We generated a model of immunotherapy-induced adverse events in Foxp3-DTR-GFP mice bearing MC38 tumors. GZP PET imaging was performed to evaluate organs non-invasively. We validated imaging with ex vivo analysis, correlating the establishment of these events with the presence of immune infiltrates and granzyme B upregulation in tissue. To demonstrate the clinical relevance of our findings, the presence of granzyme B was identified through immunofluorescence staining in tissue samples of patients with confirmed checkpoint inhibitor-associated adverse events. RESULTS: GZP PET imaging revealed differential uptake in organs affected by irAEs, such as colon, spleen, and kidney, which significantly diminished after administration of the immunosuppressor dexamethasone. The presence of granzyme B and immune infiltrates were confirmed histologically and correlated with significantly higher uptake in PET imaging. The presence of granzyme B was also confirmed in samples from patients that presented with clinical irAEs. CONCLUSIONS: We demonstrate an interconnection between the establishment of irAEs and granzyme B presence and, for the first time, the visualization of those events through PET imaging.

Microwave Ablation as Bridging Therapy for Patients with Hepatocellular Carcinoma Awaiting Liver Transplant: A Single Center Experience.

PURPOSE: To determine the pathologic response of computed tomography-guided percutaneous microwave ablation as bridging therapy for patients with hepatocellular carcinoma awaiting liver transplant, and its subsequent effect on survival. MATERIALS AND METHODS: A single-center retrospective analysis was conducted on 62 patients (M:F = 50:12) with mean age of 59.6 years ± 7.2 months (SD). Sixty-four total MWA procedures were performed for hepatocellular carcinomas within Milan criteria as bridging therapy to subsequent orthotopic liver transplant between August 2014 and September 2018. The pathology reports of the explanted livers were reviewed to assess for residual disease. Residual disease was categorized as complete or incomplete necrosis. Patient demographics, tumor/procedural characteristics, and laboratory values were evaluated. Survival from time of ablation and time of transplantation were recorded and compared between cohorts using log rank tests. RESULTS: The mean tumor size was 2.4 cm ± 0.7 cm (SD), (range = 1-4.6 cm). 32 (50%) cases required hydrodissection. Histopathologic necrosis was seen in 66% of cases at time of liver transplantation. Median time to liver transplant post-MWA was 12.6 months. [IQR = 8.6-14.8 months]. The median survival from ablation was 60.8 months [IQR = 45.5-73.7 months], and the median survival from transplant was 49.3 months [IQR = 33.7-60.1 months]. There was no significant difference in survival for patients with complete versus incomplete necrosis from ablation or liver transplant (p = 0.49, p = 0.46, respectively). CONCLUSIONS: Computed tomography-guided percutaneous microwave ablation is an effective bridge to orthotopic liver transplantation for patients with hepatocellular carcinoma. CEBM LEVEL OF EVIDENCE: Level 3, non-randomized controlled cohort study/follow-up study.

HER3 PET Imaging Identifies Dynamic Changes in HER3 in Response to HER2 Inhibition with Lapatinib.

PURPOSE: Standard therapy for HER2+ breast cancers includes HER2 inhibition. While HER2 inhibitors have significantly improved therapeutic outcomes, many patients remain resistant to therapy. An important intrinsic resistance mechanism to HER2 inhibition in some breast cancers is dynamic upregulation of HER3. Increase in HER3 expression that occurs in response to HER2 inhibition allows for continued growth signaling through HER2/HER3 heterodimers, promoting tumor escape. We hypothesized that a non-invasive method to image changes in HER3 expression would be valuable to identify those breast cancers that dynamically upregulate HER3 in response to HER2 inhibition. We further hypothesized that this imaging method could identify those tumors that would benefit by additional HER3 knockdown. PROCEDURES: In a panel of HER2+ breast cancer cell lines treated with the HER2 inhibitor lapatinib, we evaluate changes in HER3 expression and viability. Mouse HER2+ breast cancer models treated with lapatinib were imaged with a peptide-based HER3-specific PET imaging agent [68Ga]HER3P1 to assess for dynamic changes in tumoral HER3 expression and uptake confirmed by biodistribution. Subsequently, HER2+ cell lines were treated with the HER2 inhibitor lapatinib as well HER3-specific siRNA to assess for changes in viability and correlate with HER3 expression upregulation. For all statistical comparisons, P<0.05 was considered statistically significant. RESULTS: Lapatinib treatment of a panel of HER2+ breast cancer cell lines increased HER3 expression in the lapatinib-resistant cell line MDA-MB 453 but not the lapatinib-resistant cell-line HCC-1569. Evaluation of [68Ga]HER3P1 uptake in mice implanted with the HER2+ breast cancer cell lines MDA-MB453 or HCC-1569 prior to and after treatment with lapatinib demonstrated a significant increase in MDA-MB453 tumors only, consistent with in vitro findings. The additional knockdown of HER3 increased therapeutic efficacy of lapatinib only in MDA-MB453 cells, but not in HCC-1569 cells. CONCLUSION: HER3 PET imaging can be used to visualize dynamic changes in HER3 expression that occur in HER2+ breast cancers with HER2 inhibitor treatment and identify those likely to benefit by the addition of combination HER3 and HER2 inhibition.

Integration of Systemic and Liver-Directed Therapies for Locally Advanced Hepatocellular Cancer: Harnessing Potential Synergy for New Therapeutic Horizons.

Treatment options in locally advanced hepatocellular carcinoma (HCC) have evolved considerably over the past few years with the recent approval of multiple systemic therapies and significant advances in locoregional therapy. Given the poor prognosis for patients with unresectable HCC, there is significant interest in rationally designed combination therapies. This article reviews the treatment options available to patients with locally advanced HCC and discusses the rationale, ongoing trials, and future prospects for combining locoregional and systemic therapy in both the definitive and neoadjuvant settings.

Yttrium-90 Hepatic Radioembolization for Advanced Chemorefractory Metastatic Colorectal Cancer: Survival Outcomes Based on Right- Versus Left-Sided Primary Tumor Location.

BACKGROUND. Primary colon cancer location affects survival of patients with metastatic colorectal cancer (mCRC). Outcomes based on primary tumor location after salvage hepatic radioembolization with 90Y resin microspheres are not well studied. OBJECTIVE. The objectives of this study are to assess the survival outcomes of patients with advanced chemorefractory mCRC treated with 90Y radioembolization, as stratified by primary tumor location, and to explore potential factors that are predictive of survival. METHODS. A total of 99 patients who had progressive mCRC liver metastases while receiving systemic therapy and who were treated with 90Y radioembolization at a single center were retrospectively analyzed. For 89 patients, tumor response on the first imaging follow-up examination (CT or MRI performed at a mean [± SD] of 1.9 ± 0.9 months after 90Y radioembolization) was evaluated using RECIST. Overall survival (OS), OS after 90Y radioembolization, and hepatic progression-free survival (PFS) were calculated using the Kaplan-Meier method. Outcomes and associations of outcomes with tumor response were compared between patients with left- and right-sided tumors. RESULTS. A total of 74 patients had left-sided colon cancer, and 25 patients had right-sided colon cancer. Median OS from the time of mCRC diagnosis was 37.2 months, median OS after 90Y radioembolization was 5.8 months, and median hepatic PFS was 3.3 months. Based on RECIST, progressive disease on first imaging follow-up was observed in 38 patients (43%) after 90Y radioembolization and was associated with shorter OS after 90Y radioembolization compared with observation of disease control on first imaging follow-up (4.0 vs 10.5 months; p < .001). Patients with right-sided primary tumors showed decreased median OS after 90Y radioembolization compared with patients with left-sided primary tumors (5.4 vs 6.2 months; p = .03). Right- and left-sided primary tumors showed no significant difference in RECIST tumor response, hepatic PFS, or extrahepatic disease progression (p > .05). Median survival after 90Y radioembolization was significantly lower among patients with progressive disease than among those with disease control in the group with left-sided primary tumors (4.2 vs 13.9 months; p < .001); however, this finding was not observed in the group with right-sided primary tumors (3.3 vs 7.2 months; p = .05). CONCLUSION. Right-sided primary tumors were independently associated with decreased survival among patients with chemorefractory mCRC after 90Y radioembolization, despite these patients having a similar RECIST tumor response, hepatic PFS, and extrahepatic disease progression compared with patients with left-sided primary tumors. CLINICAL IMPACT. Primary colon cancer location impacts outcomes after salvage 90Y radioembolization and may help guide patient selection.

Repeat Evaluation of Lung Shunt Fraction is Unnecessary: A Retrospective Observational Study of Successive Lung Shunt Fractions from Variable Arterial Distributions in Patients Undergoing Radioembolization of Primary and Secondary Liver Tumors.

PURPOSE: To evaluate whether the recalculation of lung shunt fraction (LSF) is necessary prior to next-stage or same lobe repeat radioembolization. MATERIALS AND METHODS: Retrospective chart review was performed for patients who underwent radioembolization between February 2008 and December 2018. Eighty of 312 patients had repeat mapping angiograms and LSF calculations. A total of 160 LSF calculations were made using planar imaging (155, [97%]) and single-photon emission computed tomography (5 [3%]) technetium-99m macroaggregated albumin hepatic arterial injection imaging. The mean patient age was 61.8 years ± 12.7; 69 (86%) patients had metastatic disease and 11 (14%) had hepatocellular carcinoma. RESULTS: Patients had a median LSF of 5% (interquartile range [IQR] 3%-9%) with a median absolute difference of 1.25 (IQR 0.65-3.4) and a median of 76 days (IQR 42.5-120 days) between repeat LSF calculations. There was a median change in LSF of 0.2% between mapping studies (P = .11). There was no statistical significance between the repeat LSFs regardless of the arterial distribution (P = .79) or between tumor types (P = .75). No patients exceeded lung dose limits using actual or predicted prescribed dose amounts. The actual median lung dose was 2.6 Gy (IQR 1.8-4.4 Gy, maximum = 20.5) for the first radioembolization and 2.0 Gy (IQR 1.3-3.7 Gy, maximum = 10.1) for the second radioembolization. CONCLUSIONS: No significant difference in LSF was identified between different time points and arterial distributions within the same patient undergoing repeat radioembolization. In patients who receive well under 30-Gy lung dose for the initial treatment and a 50-Gy cumulative lung dose, repeat radioembolization treatments in the same patient may not require a repeat LSF calculation.

Thermal Ablation, Embolization, and Selective Internal Radiation Therapy Combined with Checkpoint Inhibitor Cancer Immunotherapy: Safety Analysis.

PURPOSE: To describe interventional oncology therapies combined with immune checkpoint inhibitor (ICI) therapy targeting the programmed death 1 pathway in patients with different neoplasms. MATERIALS AND METHODS: This was a retrospective cohort study of patients who underwent tumor-directed thermal ablation, embolization, or selective internal radiation therapy (SIRT) between January 1, 2011, and May 1, 2019, and received anti-programmed death 1/PD-L1 agents ≤ 90 days before or ≤ 30 days after the interventional procedure. Immune-related adverse events (irAEs) and procedural complications ≤ 90 days after the procedure were graded according to the Common Terminology Criteria for Adverse Events version 5.0. The study included 65 eligible patients (49% female; age 63 years ± 11.1). The most common tumors were metastatic melanoma (n = 28) and non-small cell lung cancer (NSCLC) (n = 12). Patients underwent 78 procedures (12 patients underwent > 1 procedure), most frequently SIRT (35.9%) and cryoablation (28.2%). The most common target organs were liver (46.2%), bone (24.4%), and lung (9.0%). Most patients received ICI monotherapy with pembrolizumab (n = 30), nivolumab (n = 22), and atezolizumab (n = 6); 7 patients received ipilimumab and nivolumab. RESULTS: Seven (10.8%) patients experienced an irAE (71.4% grade 1-2), mostly affecting the skin. Median time to irAE was 33 days (interquartile range, 19-38 days). Five irAEs occurred in patients with melanoma, and no irAEs occurred in patients with NSCLC. Management required corticosteroids (n = 3) and immunotherapy discontinuation (n = 1); all irAEs resolved to grade ≤ 1. There were 4 intraprocedural and 32 postprocedural complications (77.8% grade < 3). No grade 5 irAEs and/or procedural complications occurred. CONCLUSIONS: No unmanageable or unanticipated toxicities occurred within 90 days after interventional oncology therapies combined with ICIs.

Transjugular Intrahepatic Portosystemic Shunt Placement for Portal Hypertension: Meta-Analysis of Safety and Efficacy of 8 mm vs. 10 mm Stents.

INTRODUCTION: Hepatic encephalopathy (HE) following transjugular intrahepatic portosystemic shunt (TIPS) placement remains a leading adverse event. Controversy remains regarding the optimal stent diameter given that smaller stents may decrease the amount of shunted blood and decrease the risk of HE, but stent patency and/or clinical adequacy of portal decompression may also be affected. We aim to provide meta-analysis-based evidence regarding the safety and efficacy of 8 mm vs. 10 mm stents during TIPS placement. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched for studies comparing 8 mm and 10 mm stents during TIPS placement for portal hypertension decompression in cirrhotic patients. Randomized controlled trials and cohort studies were prioritized for inclusion. Overall evaluation of quality and bias for each study was performed. The outcomes assessed were the prevalence of HE, rebleeding or failure to control refractory ascites, and overall survival. Subgroup analysis based on TIPS indication was conducted. RESULTS: Five studies with a total number of 489 cirrhotic patients were identified. The pooled hazard ratio (HR) of post-TIPS HE was significantly lower in patients in the 8 mm stent group than in the 10 mm stent group (HR: 0.68, 95% CI: 0.51~0.92, p value < 0.0001). The combined HR of post-TIPS rebleeding/the need for paracentesis was significantly higher in patients in the 8 mm stent group than in the 10 mm stent group (HR: 1.76, 95% CI: 1.22~2.55, p value < 0.0001). There was no statistically significant difference in the overall survival between the 8 mm and 10 mm stent groups. The combined risk of HE in the variceal bleeding subgroup was statistically lower (HR: 0.52, CI: 0.34-0.80) with an 8 mm stent compared with a 10 mm stent. The combined risk of both rebleeding/paracentesis and survival was not statistically significant between 8 mm and 10 mm stent use in subgroup analysis. CONCLUSION: 8 mm stents during TIPS placement are associated with a significant lower risk of HE compared to 10 mm stents (32% decreased risk), as well as a 76% increased risk of rebleeding/paracentesis. Meta-analysis results suggest that there is not one superior stent choice for all clinical scenarios and that the TIPS indication of variceal bleeding or refractory ascites might have different appropriate selection of the shunt diameter.

Partial splenic embolization is superior to intravenous somatostatin for decreasing portal pressure in cirrhotic patients: a dynamic self-controlled cohort study.

AIMS: The efficacy of somatostatin in altering splanchnic hemodynamics in cirrhotic portal hypertension is still controversial. We aimed to establish the dynamic effect of somatostatin on portal pressure in cirrhotic patients and compared its effect with Partial Splenic Embolization (PSE). METHODS: Eighteen patients with cirrhotic portal hypertension were prospectively recruited. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were repeatedly measured at baseline, 1-, 5-, 10- and 20-min after initiating somatostatin infusion. After somatostatin infusion cessation and washout, WHVP and FHVP were measured before and after PSE. The change in all the variables between time points was analyzed. RESULTS: Decreased hepatic venous pressure gradient (HVPG) 5-min after initiation of infusion was identified compared with baseline level (19.6%; p-value: .042), which was achieved through elevated FHVP (37.5%; p-value: 9.26e - 04). There was no significant decrease in WHVP at any time point during somatostatin infusion. The HVPG (17.4%; p-value: 1.27e - 04) and WHVP (10.4%; p-value: 3.00e - 03) post-PSE significantly decreased compared to the washout level. No significant distribution differences in the number of patients with HVPG decrease by a percentage relative to the baseline level were identified between the 5-min time point and post-PSE. CONCLUSION: Our study indicates that somatostatin administration does not decrease WHVP within 20 min at clinically recommended doses. While somatostatin did decrease HVPG, this effect was achieved through increased FHVP, providing a possible explanation for its unclear efficacy. In contrast, PSE decreases both the WHVP and the HVPG.