Development and validation of an optimal GATE model for proton pencil-beam scanning delivery.

OBJECTIVE: To develop and validate a versatile Monte Carlo (MC)-based dose calculation engine to support MC-based dose verification of treatment planning systems (TPSs) and quality assurance (QA) workflows in proton therapy. METHODS: The GATE MC toolkit was used to simulate a fixed horizontal active scan-based proton beam delivery (SIEMENS IONTRIS). Within the nozzle, two primary and secondary dose monitors have been designed to enable the comparison of the accuracy of dose estimation from MC simulations with respect to physical QA measurements. The developed beam model was validated against a series of commissioning measurements using pinpoint chambers and 2D array ionization chambers (IC) in terms of lateral profiles and depth dose distributions. Furthermore, beam delivery module and treatment planning has been validated against the literature deploying various clinical test cases of the AAPM TG-119 (c-shape phantom) and a prostate patient. RESULTS: MC simulations showed excellent agreement with measurements in the lateral depth-dose parameters and spread-out Bragg peak (SOBP) characteristics within a maximum relative error of 0.95 mm in range, 1.83% in entrance to peak ratio, 0.27% in mean point-to-point dose difference, and 0.32% in peak location. The mean relative absolute difference between MC simulations and measurements in terms of absorbed dose in the SOBP region was 0.93% ±â€¯0.88%. Clinical phantom studies showed a good agreement compared to research TPS (relative error for TG-119 planning target volume PTV-D95 ∼ 1.8%; and for prostate PTV-D95 ∼ -0.6%). CONCLUSION: We successfully developed a MC model for the pencil beam scanning system, which appears reliable for dose verification of the TPS in combination with QA information, prior to patient treatment.

Association between methyl donor nutrients and metabolic health status in overweight and obese adolescents.

Limited evidence is available regarding the association of methyl donor nutrients and adolescents' metabolic health. Therefore, we investigated the relation between a combination of methyl donor nutrients and metabolic health status of overweight and obese Iranian adolescents. In this cross-sectional study, 203 overweight/obese adolescents were included, using a multistage cluster random-sampling method. Dietary intakes were assessed by a validated food frequency questionnaire. Methyl donor nutrient score (MDNS) was constructed based on deciles of vitamins B2, B6, B9, B12, methionine, choline and betaine. Glycemic profile, lipid profile, blood pressure and anthropometric indices were collected. Participants were classified as metabolically healthy obese or unhealthy obese (MUO) based on International Diabetes Federation (IDF) and IDF/Homeostasis Model Assessment Insulin Resistance (HOMA-IR) definitions. Mean age of adolescents was 13.98 [Formula: see text] 1.61 y and 50.2% of them was girls. After controlling all of the confounders, individuals in the top tertile of MDNS, had lower odds of MUO (OR 0.36; 95% CI 0.13-0.95) according to IFD criteria. Considering IDF/HOMA-IR criteria, an inverse marginally significant association was observed between the highest tertile of MDNS and odds of MUO (OR 0.36; 95% CI 0.12-1.02) in the fully-adjusted model. Furthermore, significant inverse association was found between each unit increase in MDNS and odds of MUO based on IDF criteria, but not for IDF/HOMA-IR definition. We found that overweight/obese adolescents with higher dietary intakes of methyl donor nutrients were less likely to be metabolically unhealthy. Further studies are needed to confirm the findings.

Dietary total antioxidant capacity in relation to metabolic health status in overweight and obese adolescents.

BACKGROUND: Although several studies evaluated the relationship between individual dietary antioxidants and metabolic health conditions, data on the association between dietary total antioxidant capacity and metabolic health among children and adolescents is limited. This study investigated the relationship between dietary total antioxidant capacity and metabolic health status in Iranian overweight/obese adolescents. METHODS: This cross-sectional study was conducted on 203 overweight/obese adolescents. Dietary intakes were evaluated by a validated food frequency questionnaire. Ferric Reducing-Antioxidant Power (FRAP) was considered to indicate dietary total antioxidant capacity. Anthropometric parameters and blood pressure status were measured. Fasting blood samples were obtained to determine circulating insulin, glucose, and lipid profile. Two different methods (modified International Diabetes Federation (IDF) criteria and IDF criteria along with insulin resistance) were applied to classify participants as metabolically healthy obese (MHO) or metabolically unhealthy obese (MUO). RESULTS: According to IDF and IDF/HOMA definitions, a total of 79 (38.9%) and 67 (33.0%) adolescents were respectively defined as MUO. Considering IDF criteria, the highest tertile of FRAP was related to lower odds of being MUO in the maximally-adjusted model (OR: 0.40; 95%CI: 0.16-0.96), compared to the lowest tertile. However, based on the IDF/HOMA-IR criteria, no significant relation was found between FRAP and odds of MUO (OR: 0.49; 95%CI: 0.19-1.23) after considering all possible confounders. CONCLUSIONS: Adolescents with higher intakes of dietary antioxidants have a lower possibility of being MUO based on IDF criteria. However, no substantial relation was found considering HOMA-IR/IDF definition. Further prospective cohort studies need to be done to confirm these findings.

Post-embolization outcomes of splenic artery pseudoaneurysms: A single-center experience.

PURPOSE: Splenic artery pseudoaneurysms (PSA) are relatively rare but associated with high mortality/morbidity when presenting acutely. Embolization has emerged as the treatment of choice. We aim to evaluate the outcomes of embolization for the treatment of splenic artery PSAs. METHODS: From 2007 to 2019, all patients that underwent embolization for splenic artery PSAs were included in this IRB-approved review. Evaluated outcomes included complications, morbidity/mortality rates, and 30-day white blood cell count. Student t-tests were performed to compare laboratory values before and after embolization. 5-year survival rates were estimated using Kaplan Meier methodology. RESULTS: A retrospective analysis of 24 patients (14 males, mean age 51 ± 19 years) who underwent splenic artery PSA embolization was performed. Fifteen PSA embolizations were performed in an emergent setting. There was technical success in 23/24 patients. Etiologies included trauma (10), pancreatitis (9), post-surgical (3), and malignancy (2). Post-embolization patients had a mean length of stay of 19 days and within 30 days, 9 patients developed leukocytosis (median of 14,800/µl). The 5-year survival rate of these patients was 89% [95% CI 75% - 100%]. Post-procedure, 4 patients developed grade 2 complications. Grade 3 complications were observed in 5 patients. One (4.2%) splenic abscess was identified. Of the 19 patients with follow-up imaging, 14 patients had splenic infarcts (5 infarcts were >50% of splenic volume). CONCLUSIONS: Splenic artery PSAs are encountered in the emergent setting and are most frequently secondary to trauma or pancreatitis. Embolization can be life-saving in these critically ill patients.

Analysis of adjuvant chemotherapy in patients undergoing curative-intent resection of localized adrenocortical carcinoma.

BACKGROUND: Studies evaluating the role of adjuvant chemotherapy (ACT) in Adrenocortical Carcinoma (ACC) are limited due to its rarity. The objective of this study was to evaluate if ACT provides a survival benefit in patients who underwent curative-intent resection of localized ACC and to determine factors associated with receipt of ACT. METHODS: The National Cancer Data Base was queried to identify patients (2010-2016) with curative-intent resection of localized ACC (T1-T3, N0, M0). RESULTS: Of 577 patients with adrenalectomy, 389 (67%) had adrenalectomy alone, and 188 (33%) received ACT. Private insurance, lymphovascular invasion, stage II, and radiotherapy were predictors of ACT (P < 0.05). Advanced (T3) stage lymphovascular invasion, and being uninsured were associated with decreased OS (P < 0.05). There was no association between ACT and OS. CONCLUSIONS: For patient who underwent curative-intent resection of localized ACC, there was no association between ACT and OS. Private insurance, lymphovascular invasion, stage II disease, and radiotherapy were associated with receipt of ACT.

Correction to: Prognosticating Survival in Hepatocellular Carcinoma with Elevated Baseline Alpha-fetoprotein Treated with Radioembolization Using a Novel Laboratory Scoring System: Initial Development and Validation.

The name of the eleventh author is listed incorrectly in the published article as Nitin Kataraya. The correct name is Nitin Katariya.

Safety and efficacy of radioembolization with glass microspheres in hepatocellular carcinoma patients with elevated lung shunt fraction: analysis of a 103-patient cohort.

BACKGROUND: Technetium-99m macroaggregated albumin is used to estimate lung shunt fraction (LSF) prior to yttrium-90 (Y90). Studies have debated the safety and efficacy of Y90 in patients with LSF > 15%. We aimed to assess the role of Y90 in hepatocellular carcinoma (HCC) with LSF > 15%. METHODS: With IRB approval, we searched our prospectively acquired database of HCC patients with Y90 treated with LSF > 15%. Median LSF and liver and lung doses were calculated. The response was assessed using RECIST. Overall survival (OS) was calculated from date of first Y90. RESULTS: A total of 103 HCC patients underwent Y90. The median baseline LSF was 24.4% (IQR 18.1-28.8). Patients exhibited multifocal disease (59/103, 60%) and median tumor size of 7.85 cm (IQR 5.2, 10.57). BCLC class was A, B, C, and D in 7 (7%), 5 (5%), 85 (83%), and 6 (6%) patients, respectively. The median liver dose was 84.6 Gy (IQR 57.4, 107.55). The median lung dose per session and cumulatively was 22.9 Gy (IQR 15-28) and 29.5 Gy (IQR 20.5-44.3). Thirty-three patients (32%) demonstrated partial response, 57 stable disease, and 13 (13%) had progressive disease. The median OS was 7.3 months (95% CI 5.3, 11.47). Twenty patients (19%) had non-specific pulmonary symptoms (cough, shortness of breath, wheezing) in the 1-year post-Y90. The median time to the appearance of non-specific pulmonary symptoms was 63 days (range 7-224). Thoracic imaging demonstrated no pulmonary fibrosis/injury following treatment in any patient. CONCLUSION: Y90 can be performed in patients with LSF > 15%. The RECIST response was identified in 32% of the patients. In isolation, LSF > 15% should not deter from treatment with Y90.

AAV GCG-EGFP, a new tool to identify glucagon-secreting α-cells.

The study of primary glucagon-secreting α-cells is hampered by their low abundance and scattered distribution in rodent pancreatic islets. We have designed a double-stranded adeno-associated virus containing a rat proglucagon promoter (700 bp) driving enhanced green fluorescent protein (AAV GCG-EGFP), to specifically identify α-cells. The administration of AAV GCG-EGFP by intraperitoneal or intraductal injection led to EGFP expression selectively in the α-cell population. AAV GCG-EGFP delivery to mice followed by islet isolation, dispersion and separation by FACS for EGFP resulted in an 86% pure population of α-cells. Furthermore, the administration of AAV GCG-EGFP at various doses to adult wild type mice did not significantly alter body weight, blood glucose, plasma insulin or glucagon levels, glucose tolerance or arginine tolerance. In vitro experiments in transgene positive α-cells demonstrated that EGFP expression did not alter the intracellular Ca2+ pattern in response to glucose or adrenaline. This approach may be useful for studying purified primary α-cells and for the in vivo delivery of other genes selectively to α-cells to further probe their function or to manipulate them for therapeutic purposes.

Technical Aspects and Practical Approach Toward Same-Day Y90 Radioembolization in the Management of Hepatocellular Carcinoma.

Radioembolization with Yttrium-90 (Y90) has been proven safe and effective for the treatment of primary and secondary hepatic malignancies. Standard protocols have necessitated planning angiography with Technetium-99m macroaggregated albumin (Tc99m MAA) administration/scan typically 1-2 weeks prior to the radioembolization therapy. The intent of this practice is to ensure appropriate patient selection and treatment candidacy while also confirming best dosimetry approaches. At our center, we started performing "same-day Y90" in 2008; in a subset of international patients with travel hardship, we performed the planning and treatment procedures consecutively on the same day. In this article, we reveal our practical approach to treating patients on the same day as planning angiography. With more than 160 same-day procedures completed between 2008 and 2017, the safety and efficacy of such a paradigm has been established at our center. This approach is appealing to patients, their families, and referring physicians. Appropriate patient selection and proper preprocedure planning based on baseline imaging are key elements in successful same-day radioembolization treatments.

Prognosticating Survival in Hepatocellular Carcinoma with Elevated Baseline Alpha-fetoprotein Treated with Radioembolization Using a Novel Laboratory Scoring System: Initial Development and Validation.

AIMS: To investigate laboratory parameters as predictors of overall survival (OS) for hepatocellular carcinoma (HCC) treated with radioembolization and develop/validate a scoring system. METHODS: With IRB approval, we included all patients with baseline alpha-fetoprotein (AFP) > 100 ng/dL from our prospectively acquired HCC radioembolization database. Neutrophil-lymphocyte ratio, albumin-bilirubin (ALBI), and AFP were measured at baseline and at 1-, 3-, and 6-month post-radioembolization Landmarks. OS was assessed from these Landmarks. Univariate/multivariate analyses were performed to evaluate OS predictability of these parameters. Baseline Imaging, Laboratory, and Combination scoring systems were developed. Developing/validating groups were created to investigate/validate the score's OS predictability. Time-dependent receiver operating characteristics (ROC) were evaluated. Patients were stratified into groups I, II, and III by using 25th and 75th percentile cutoffs according to change in Laboratory Score from baseline. RESULTS: 345/401 (86%), 238/401 (59%), and 167/401 (42%) patients had laboratory parameters available at the 1-, 3-, and 6-month Landmarks, respectively. ALBI and AFP were significant OS prognosticators at all Landmarks. The Laboratory Score [ALBI + (0.3 × LnAFP)] was developed/internally validated to predict OS from these Landmarks. Areas under the curve of time-dependent ROCs of the Baseline Imaging vs. Laboratory scores in predicting patient OS post 3 and 6 months Landmarks were 0.56 versus 0.82 and 0.57 versus 0.77, respectively. OS differences in groups I, II, and III according to change in Laboratory Score from baseline were significant (p < 0.001). CONCLUSIONS: Post-radioembolization AFP and ALBI scores were significant OS prognosticators. A decrease in post-therapeutic Laboratory Score, which combines AFP and ALBI, correlates with an improved OS.

Coexisting Sources of False-Positive Reflux on a Direct Radionuclide Cystography Scan.

Direct radionuclide cystography is currently a popular method for evaluation of vesicoureteral reflux, despite its pitfalls and drawbacks in producing false-positive results. In this article, we present a case with 2 sources of false-positive reflux on a direct radionuclide cystography scan.

Radiation Segmentectomy: Potential Curative Therapy for Early Hepatocellular Carcinoma.

Purpose To report long-term outcomes of radiation segmentectomy (RS) for early hepatocellular carcinoma (HCC). The authors hypothesized that outcomes are comparable to curative treatments for patients with solitary HCC less than or equal to 5 cm and preserved liver function. Materials and Methods This retrospective study included 70 patients (median age, 71 years; range, 22-96 years) with solitary HCC less than or equal to 5 cm not amenable to percutaneous ablation who underwent RS (dose of >190 Gy) between 2003 and 2016. Patients who underwent subsequent curative liver transplantation were excluded to eliminate this confounding variable affecting survival. Radiologic response of time to progression and median overall survival were estimated by using the Kaplan-Meier method per the guidelines of the European Association for the Study of the Liver (EASL) and the World Health Organization (WHO). Results Seventy patients were treated with RS over 14 years. Sixty-three patients (90%) showed response by using EASL criteria, of which 41 (59%) showed complete response. Fifty patients (71%) achieved response by using WHO criteria, of which 11 (16%) achieved complete response. Response rates at 6 months were 86% and 49% by using EASL and WHO criteria, respectively. Median time to progression was 2.4 years (95% confidence interval: 2.1, 5.7), with 72% of patients having no target lesion progression at 5 years. Median overall survival was 6.7 years (95% confidence interval: 3.1, 6.7); survival probability at 1, 3, and 5 years was 98%, 66%, and 57%, respectively. Overall survival probability at 1, 3, and 5 years was 100%, 82%, and 75%, respectively, in patients with baseline tumor size less than or equal to 3 cm (n = 45) and was significantly longer than in patients with tumors greater than 3 cm (P = .026). Conclusion RS provides response rates, tumor control, and survival outcomes comparable to curative-intent treatments for selected patients with early-stage HCC who have preserved liver function. © RSNA, 2018 Online supplemental material is available for this article.

Survival Analysis of Advanced HCC Treated with Radioembolization: Comparing Impact of Clinical Performance Status Versus Vascular Invasion/Metastases.

PURPOSE: In this study, we aim to compare the effects of prognostic indicators on survival analysis for Barcelona Clinic Liver Cancer (BCLC) C patients undergoing yttrium-90 radioembolization (Y-90). METHODS: A prospectively acquired database (2003-2017) for BCLC C hepatocellular carcinoma (HCC) patients that underwent radioembolization with Y-90 was searched. The criteria for BCLC C status (Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or 2, metastases, and/or portal vein thrombosis (PVT)) were recorded. Kaplan-Meier survival analyses were performed from the date of the first radioembolization with Y-90, censored to curative treatment, to determine median overall survival (OS). Cox regression hazards model was used for multivariate analyses. Significance was set at P < 0.05. RESULTS: 547 BCLC C patients treated with radioembolization with Y-90 had a median OS of 10.7 months (range: 9.5-12.9). 43% (233 of 547) patients classified as BCLC C solely by their ECOG PS had a median OS of 19.4 months (14.7-23.7); 57% (314 of 547) patients with PVT/metastases had a median OS of 7.7 months (6.7-8.7). On multivariate analysis, ECOG PS was not found to be a statistically significant prognostic indicator of OS in BCLC C whereas metastases and PVT exhibited hazards ratios (95%CI) of 0.51 (0.38-0.69) and 0.49 (0.38-0.63), respectively (P < 0.0001). CONCLUSION: Patients classified as BCLC C due to ECOG PS 1 demonstrated longer survival when compared to those presenting with PVT, metastases and/or ECOG PS 2. Hence, ECOG PS 1, as an isolated variable, may not be a true indicator of advanced disease.

Radioembolization for hepatocellular carcinoma: Statistical confirmation of improved survival in responders by landmark analyses.

Does imaging response predict survival in hepatocellular carcinoma (HCC)? We studied the ability of posttherapeutic imaging response to predict overall survival. Over 14 years, 948 patients with HCC were treated with radioembolization. Patients with baseline metastases, vascular invasion, multifocal disease, Child-Pugh > B7, and transplanted/resected were excluded. This created our homogeneous study cohort of 134 patients with Child-Pugh ≤ B7 and solitary HCC. Response (using European Association for Study of the Liver [EASL] and Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1] criteria) was associated with survival using Landmark and risk-of-death methodologies after reviewing 960 scans. In a subanalysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Uni/multivariate survival analyses were performed at each Landmark. At the 3-month Landmark, responders survived longer than nonresponders by EASL (hazard ratio [HR], 0.46; confidence interval [CI], 0.26-0.82; P = 0.002) but not RECIST 1.1 criteria (HR, 0.70; CI, 0.37-1.32; P = 0.32). At the 6-month Landmark, responders survived longer than nonresponders by EASL (HR, 0.32; CI, 0.15-0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.50; CI, 0.29-0.87; P = 0.021). At the 12-month Landmark, responders survived longer than nonresponders by EASL (HR, 0.34; CI, 0.15-0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.52; CI 0.27-0.98; P = 0.049). At 6 months, risk of death was lower for responders by EASL (P < 0.001) and RECIST 1.1 (P = 0.0445). In subanalyses, responders lived longer than patients with SD or PD. EASL response was a significant predictor of survival at 3-, 6-, and 12-month Landmarks on uni/multivariate analyses. CONCLUSION: Response to radioembolization in patients with solitary HCC can prognosticate improved survival. EASL necrosis criteria outperformed RECIST 1.1 size criteria in predicting survival. The therapeutic objective of radioembolization should be radiologic response and not solely to prevent progression. (Hepatology 2018;67:873-883).

Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience.

Yttrium-90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000-patient cohort acquired over a 15-year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child-Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention-to-treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty-three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty-eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5-80.3) months, BCLC B 25.0 (CI, 17.3-30.5) months, and BCLC C 15.0 (CI, 13.8-17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21-30.2) months, BCLC B 15.0 (CI, 12.3-19.0) months, and BCLC C 8.0 (CI, 6.8-9.5) months. Forty-nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. CONCLUSION: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first-line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).

90Y Radioembolization for Locally Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Long-Term Outcomes in a 185-Patient Cohort.

We report survival outcomes for patients with advanced-stage hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) treated with 90Y radioembolization. Methods: With institutional review board approval, we searched our prospectively acquired database for 90Y patients treated between 2003 and 2017. Inclusion criteria were patients who had HCC with tumor PVT. Patients with metastases were excluded. Laboratory data were collected at baseline and 1 mo after 90Y radioembolization. Toxicity grades were reported according to the Common Terminology Criteria for Adverse Events, version 4.0, and long-term survival outcomes were reported and stratified by Child-Pugh class (CP). Overall survival was calculated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. A subanalysis for patients with a high level of α-fetoprotein (AFP) (>100 ng/dL) was conducted. Results: In total, 185 patients with HCC PVT underwent 90Y radioembolization. Seventy-four (40%) were CP-A, 51 (28%) were CP-B7, and 60 (32%) were ≥CP-B8. New albumin, bilirubin, and alkaline phosphatase grade 3/4 toxicities were, respectively, 3%, 10%, and 0% for CP-A; 14%, 12%, and 6% for CP-B7; and 23%, 32%, and 3% for ≥CP-B8. Median overall survival for CP-A patients was 13.3 mo (95% confidence interval [CI], 8.7-15.7 mo). CP-B7 and ≥CP-B8 patients exhibited median overall survival of 6.9 mo (95% CI, 5.3-10.1 mo) and 3.9 mo (95% CI, 2.9-5.0 mo), respectively. Significant overall survival prognosticators on univariate analysis were albumin, bilirubin, ascites, tumor size 5 cm or smaller, focality, distribution, infiltration, Eastern Cooperative Oncology Group status, AFP level, and PVT extent. Multivariate analysis showed the prognosticators of overall survival to be bilirubin, no ascites, tumor size 5 cm or smaller, solitary lesion, baseline AFP level lower than 100 ng/dL, and Eastern Cooperative Oncology Group status. Of 123 patients with a high AFP level (>100 ng/dL), 12 patients achieved restored normal AFP levels (<13 ng/dL) and exhibited median overall survival of 23.9 mo (95% CI, 20.1-124.1 mo). AFP responders at 1 mo had better overall survival than nonresponders, at 8.5 mo versus 4.8 mo (P = 0.018); AFP responders at 3 mo had overall survival of 13.3 mo, versus 6.9 mo for nonresponders (P = 0.021). Conclusion:90Y radioembolization can serve as a safe and effective treatment for advanced-stage HCC patients with tumor PVT. Overall survival outcomes are affected by baseline liver function, tumor size, and AFP level.

Pictorial essay: imaging findings following Y90 radiation segmentectomy for hepatocellular carcinoma.

Transarterial radioembolization is a novel therapy that has gained rapid clinical acceptance for the treatment of hepatocellular carcinoma (HCC). Segmental radioembolization [also termed radiation segmentectomy (RS)] is a technique that can deliver high doses (> 190 Gy) of radiation selectively to the hepatic segment(s) containing the tumor. The aim of this comprehensive review is to provide an illustrative summary of the most relevant imaging findings encountered after radiation segmentectomy. A 62-patient cohort of Child-Pugh A patients with solitary HCC < 5 cm in size was identified. A comprehensive retrospective imaging review was done by interventional radiology staff at our institution. Important imaging findings were reported and illustrated in a descriptive account. For the purposes of completeness, specific patients outside our initial cohort with unique educational imaging features that also underwent segmentectomy were included in this pictorial essay. This review shows that response assessment after RS requires a learning curve with common drawbacks that can lead to false-positive interpretations and secondary unnecessary treatments. It is important to recognize that treatment responses and pathological changes both are time dependent. Findings such as benign geographical enhancement and initial benign pathological enhancement can easily be misinterpreted. Capsular retraction and segmental atrophy are some other examples of unique post-RS response that are not seen in any other treatment.

Clinical outcomes of Y90 radioembolization for recurrent hepatocellular carcinoma following curative resection.

PURPOSE: To assess safety/efficacy of yttrium-90 radioembolization (Y90) in patients with recurrent hepatocellular carcinoma (HCC) following curative surgical resection. METHODS: With IRB approval, we searched our prospectively acquired database for patients that were treated with Y90 for recurrent disease following resection. Baseline characteristics and bilirubin toxicities following Y90 were evaluated. Intention-to-treat overall survival (OS) and time-to-progression (TTP) from Y90 were assessed. RESULTS: Forty-one patients met study inclusion criteria. Twenty-six (63%) patients had undergone minor (≤3 hepatic segments) resection while 15 (37%) patients underwent major (>3 hepatic segments) resections. Two patients (5%) had biliary-enteric anastomoses created during surgical resection. The median time from HCC resection to the first radioembolization was 17 months (95% CI: 13-37). The median number of Y90 treatment sessions was 1 (range: 1-5). Ten patients received (entire remnant) lobar Y90 treatment while 31 patients received selective (≤2 hepatic segments) treatment. Grades 1/2/3/4 bilirubin toxicity were seen in nine (22%), four (10%), four (10%), and zero (0%) patients following Y90. No differences in bilirubin toxicities were identified when comparing lobar with selective approaches (P = 0.20). No post-Y90 infectious complications were identified. Median TTP and OS were 11.3 (CI: 6.5-15.5) and 22.1 months (CI: 10.3-31.3), respectively. CONCLUSIONS: Radioembolization is a safe and effective method for treating recurrent HCC following surgical resection, with prolonged TTP and promising survival outcomes.

Amyloid formation disrupts the balance between interleukin-1ß and interleukin-1 receptor antagonist in human islets.

OBJECTIVES: ß-cell dysfunction and apoptosis associated with islet inflammation play a key role in the pathogenesis of type 2 diabetes (T2D). Growing evidence suggests that islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to islet inflammation and ß-cell death in T2D. We recently showed the role of interleukin-1ß (IL-1ß)/Fas/caspase-8 apoptotic pathway in amyloid-induced ß-cell death. In this study, we used human islets in culture as an ex vivo model of amyloid formation to: (1) investigate the effects of amyloid on islet levels of the natural IL-1 receptor antagonist (IL-1Ra); (2) examine if modulating the IL-1ß/IL-1Ra balance can prevent amyloid-induced ß-cell Fas upregulation and apoptosis. METHODS: Isolated human islets (n = 10 donors) were cultured in elevated glucose (to form amyloid) with or without a neutralizing human IL-1ß antibody for up to 7 days. Parallel studies were performed with human islets in which amyloid formation was prevented by adeno-siRNA-mediated suppression of hIAPP expression (as control). ß-cell levels of IL-1Ra, Fas, apoptosis as well as islet function, insulin- and amyloid-positive areas, and IL-1Ra release were assessed. RESULTS: Progressive amyloid formation in human islets during culture was associated with alterations in IL-1Ra. Islet IL-1Ra levels were higher at early stages but were markedly reduced at later stages of amyloid formation. Furthermore, IL-1Ra release from human islets was reduced during 7-day culture in a time-dependent manner. These changes in IL-1Ra production and release from human islets during amyloid formation adversely correlated with islet IL-1ß levels, ß-cell Fas expression and apoptosis. Treatment with IL-1ß neutralizing antibody markedly reduced amyloid-induced ß-cell Fas expression and apoptosis, thereby improving islet ß-cell survival and function during culture. CONCLUSIONS: These data suggest that amyloid formation impairs the balance between IL-1ß and IL-1Ra in islets by increasing IL-1ß production and reducing IL-1Ra levels thereby promoting ß-cell dysfunction and death. Restoring the IL-1ß/IL-1Ra ratio may provide an effective strategy to protect islet ß-cells from amyloid toxicity in T2D.

Comparative study of post-transplant outcomes in hepatocellular carcinoma patients treated with chemoembolization or radioembolization.

PURPOSE: To analyze long-term outcomes in patients bridged/downstaged to orthotopic liver transplantation (OLT) by transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y90) for hepatocellular carcinoma (HCC). METHODS: 172 HCC patients who underwent OLT after being treated with transarterial liver-directed therapies (LDTs) (Y90: 93; TACE: 79) were identified. Pre-LDT and pre-OLT clinical/imaging/laboratory characteristics including United Network for Organ Sharing (UNOS) staging and alpha-fetoprotein values (AFP) were tabulated. Post-OLT HCC recurrence was assessed by imaging follow-up per standard of care. Recurrence-free (RFS) and overall survival (OS) were calculated. Uni/multivariate and sub-stratification analyses were performed. RESULTS: Time-to-OLT was longer in the Y90 group (Y90: 6.5 months; TACE: 4.8 months; p=0.02). With a median post-OLT follow-up of 26.1 months (IQR: 11.1-49.7), tumor recurrence was found in 6/79 (8%) TACE and 8/93 (9%) Y90 patients. Time-to-recurrence was 26.6 (CI: 7.0-49.5) and 15.9 months (CI: 7.8-46.8) for TACE and Y90, respectively (p=0.48). RFS (Y90: 79 months; TACE: 77 months; p=0.84) and OS (Y90: 57% alive at 100 months; TACE: 84.2 months; p=0.57) were similar. 54/155 patients (Y90: 29; TACE: 25) were downstaged to UNOS T2 or less. RFS hazard ratios for patients downstaged to ≤T2 versus those that were not were 0.6 (CI: 0.33-1.1) and 1.7 (CI: 0.9-3.1) respectively (p=0.13). 17/155 patients (Y90: 8; TACE: 9) that were >T2 were downstaged to UNOS T2 or less (within transplant criteria). Distribution (unilobar/bilobar), AFP, and pre-transplant UNOS stage affected RFS on univariate analyses. CONCLUSION: Despite longer time-to-OLT for Y90 patients, post-OLT outcomes were similar between patients bridged or downstaged by TACE or Y90. A trend towards improved RFS for downstaged patients was identified.