Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.

BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087). SETTING: Done during 2021 to 2022 among 127 U.S. hospitals. PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for 30 days. MEASUREMENTS: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. RESULTS: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. LIMITATIONS: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. CONCLUSION: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. PRIMARY FUNDING SOURCE: National Institutes of Health.

Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

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).

Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy.

PURPOSE: The aim of this study was to analyze the safety, treatment characteristics and survival outcomes of Yttrium-90 (Y90) radioembolization for unresectable colorectal carcinoma (CRC) liver metastases refractory to standard of care therapy. METHODS: A total of 214 patients with CRC metastases were treated with Y90 radioembolization over 12 years. Toxicity was assessed using National Cancer Institute common terminology criteria. Overall survival was analyzed from date of diagnosis of primary cancer, hepatic metastases and from the first Y90. Uni/multivariate analyses were performed. Substratification by era of chemotherapeutics was performed. RESULTS: Most patients were male (60 %) and <65 years old (61 %). Of them, 98 % had been exposed to chemotherapy. Grade 3 lymphocyte, bilirubin, albumin, ALP and AST toxicities were observed in 39 %, 11 %, 10 %, 8 % and 4 % of patients, respectively. Grade 4 lymphocyte and ALP toxicities were observed in 5 % and 3 % of patients, respectively. Median overall survival was 43.0, 34.6, and 10.6 months from date of diagnosis of primary cancer, hepatic metastases and first Y90, respectively. Survival was significantly longer in patients: (1) who received ≤2 cytotoxic drugs (n = 104) than those who received 3 (n = 110) (15.2 vs. 7.5 months, p = 0.0001); and (2) who received no biologic agents (n = 52) compared with those that did (n = 162) (18.6 vs. 9.4 months, p = 0.0001). Multivariate analyses identified ≤2 cytotoxic agents, no exposure to biologics, ECOG 0, tumor burden <25 %, lack of extrahepatic disease and albumin >3 g/dL as independent predictors of survival. CONCLUSION: In this largest metastatic CRC series published to date, Y90 radioembolization was found to be safe; survival varied by prior therapy. Further studies are required to further refine the role of Y90 in metastatic CRC.

Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Chemoembolization is one of several standards of care treatment for hepatocellular carcinoma (HCC). Radioembolization with Yttrium-90 microspheres is a novel, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC. METHODS: We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up time points. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multivariate analyses were performed. RESULTS: Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P < .05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs 36%, respectively, P = .104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, respectively, P = .046), median survival times were not statistically different (20.5 months vs 17.4 months, respectively, P = .232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P = .42). CONCLUSIONS: Patients with HCC treated by chemoembolization or radioembolization with Yttrium-90 microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post hoc analyses of sample size indicated that a randomized study with > 1000 patients would be required to establish equivalence of survival times between patients treated with these two therapies.

Cancer Diagnoses during Active Conflict: Experience from a Cancer Program in Northwest Syria.

Background Protracted conflict has destroyed Syria's health system with severe impacts on the diagnosis and treatment of chronic and high-cost diseases including cancer. Here, we review the type and (where possible) the stage of cancers diagnosed in a pathology laboratory serving Northwest Syria. Methods We retrospectively reviewed all pathology reports which reported a diagnosis of cancer from a pathology department in Northwest Syria from January to December 2020. Results A total of 397 new cancers were diagnosed during 2020 of which 191 were among males (48.1%) and 20 cases were in children aged 17 years or under (5%). The most common cancer in men was bladder cancer (15.7%) and skin cancers (14.7%) followed by cancers in the lymph nodes (includes primary and secondary; 9.9%.) In women, breast cancer (38.3%) followed by skin cancer skin (9.7%) and uterine cancer (8.7%) was the most common. The overall proportion of cancer diagnoses were breast cancer (20.2%), skin cancer (12.1%), cancer affecting lymph nodes (8.8%), and urinary bladder (8.3%) and colorectal cancer (7.3%). Discussion This preliminary analysis is the first report of cancer types and demographics in areas outside of government control in Syria since the onset of the conflict. Despite limitations, it presents some indication of the burden of oncological diagnoses in this area. Further research which aims to describe and address the burden of cancer on populations under ongoing conflict and humanitarian crises remains essential, especially in Northwest Syria given ongoing attacks and severe underfunding. There is a particular need to investigate how best to apply interventions and support health systems and cancer services within conflict settings. More support and resources need to be allocated to cancer centers with long-term health partnership models. The underresourced and understaffed conditions of the hospital are significant limits to a more detailed report.

Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has limited treatment options; long-term outcomes following intra-arterial radiation are unknown. We assessed clinical outcomes of patients treated with intra-arterial yttrium-90 microspheres (Y90). METHODS: Patients with HCC (n = 291) were treated with Y90 as part of a single-center, prospective, longitudinal cohort study. Toxicities were recorded using the Common Terminology Criteria version 3.0. Response rate and time to progression (TTP) were determined using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) guidelines. Survival by stage was assessed. Univariate/multivariate analyses were performed. RESULTS: A total of 526 treatments were administered (mean, 1.8; range, 1-5). Toxicities included fatigue (57%), pain (23%), and nausea/vomiting (20%); 19% exhibited grade 3/4 bilirubin toxicity. The 30-day mortality rate was 3%. Response rates were 42% and 57% based on WHO and EASL criteria, respectively. The overall TTP was 7.9 months (95% confidence interval, 6-10.3). Survival times differed between patients with Child-Pugh A and B disease (A, 17.2 months; B, 7.7 months; P = .002). Patients with Child-Pugh B disease who had portal vein thrombosis (PVT) survived 5.6 months (95% confidence interval, 4.5-6.7). Baseline age; sex; performance status; presence of portal hypertension; tumor distribution; levels of bilirubin, albumin, and alpha-fetoprotein; and WHO/EASL response rate predicted survival. CONCLUSIONS: Patients with Child-Pugh A disease, with or without PVT, benefited most from treatment. Patients with Child-Pugh B disease who had PVT had poor outcomes. TTP and overall survival varied by patient stage at baseline. These data can be used to design future Y90 trials and to describe Y90 as a potential treatment option for patients with HCC.

Does multidetector CT attenuation change in colon cancer liver metastases treated with 90Y help predict metabolic activity at FDG PET?

PURPOSE: To evaluate the correlation between change in attenuation and tumor metabolic activity assessed by using fluorodeoxyglucose (FDG) positron emission tomography (PET) in colon cancer liver metastases treated with yttrium 90 ((90)Y) radioembolization. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant retrospective study was approved by the institutional review board; patient informed consent was waived. Unresectable chemorefractory colon cancer liver metastases treated with (90)Y radioembolization in 28 patients were evaluated at pre- and posttreatment multidetector computed tomographic (CT) and FDG PET scans. Maximum cross-sectional diameter, volume, and overall attenuation of target lesions were calculated. The percentage change (%Delta) in these parameters after treatment was calculated and correlated with the standardized uptake value (SUV) analysis at FDG PET. The accuracy of the radiologic parameters in helping predict response to treatment at FDG PET was assessed. Data were analyzed by using the Student t, Wilcoxon matched pair, Mann-Whitney, Spearman rank correlation, and chi(2) tests. The significance level was set at .05. RESULTS: Seventy-four metastatic lesions in 10 women and 18 men (mean age, 61.5 years +/- 14.3 [standard deviation]) were evaluated. Mean follow-up interval for multidetector CT after treatment was 30 days. A significant reduction in maximum cross-sectional diameter, volume, and attenuation was observed from pre- to posttreatment multidetector CT (P < .05). The %Delta in attenuation had higher correlation with %Delta in SUV (r = 0.61) than diameter (r = 0.39) or volume (r = 0.49) and also predicted the metabolic activity at FDG PET with higher sensitivity (P < .001). By using a threshold level of a reduction in attenuation of 15% or greater, attenuation showed 84.2% sensitivity and 83.3% specificity in predicting response at FDG PET evaluation. CONCLUSION: Changes in attenuation of colon cancer liver metastases treated with (90)Y radioembolization correlate highly with metabolic activity at FDG PET and may be useful as an early surrogate marker for assessing treatment response.

Yttrium-90 radioembolization for liver malignancies: prognostic factors associated with survival.

PURPOSE: To identify key prognostic clinical and imaging variables in patients undergoing yttrium-90 radioembolization ((90)Y) for liver malignancies. MATERIALS AND METHODS: Patients with liver malignancies that progressed despite standard-of-care therapy were treated with (90)Y from 2002 to 2006. Baseline functional status, laboratory values, and diagnostic imaging were assessed before therapy. Imaging follow-up was performed 1 month after treatment and subsequently at 3-month intervals. Patients were followed for survival from the time of their first (90)Y treatment. RESULTS: Patients with follow-up imaging after radioembolization (N = 130) were included in this analysis. Primary malignancies included colon, neuroendocrine, and others. The following clinical variables had a significant effect on survival on multivariate analysis: Eastern Cooperative Oncology Group (ECOG) performance status (PS) greater than 0 (hazard ratio [HR], 7.98; 95% CI, 3.98-16), hepatic tumor burden of 51%-75% (HR, 2.46; 95% CI, 1.01-6.02), bilirubin level greater than 1.3 mg/dL (HR, 2.60; 95% CI, 1.27-5.34), hepatic metastases from breast cancer (HR, 2.51; 95% CI, 1.13-5.61), response on imaging based on World Health Organization (WHO) criteria (HR, 0.48; 95% CI, 0.24-0.94), and lymphocyte depression (HR, 0.56; 95% CI, 0.31-0.96). Among patients with colorectal cancer metastases to the liver, the HR for survival on univariate analysis for responders compared with nonresponders (per WHO criteria) was 0.26 (95% CI, 0.10-0.69). CONCLUSIONS: Cancer-related symptoms (ie, ECOG PS > 0), hepatic tumor burden greater than 50%, increased bilirubin levels, and hepatic metastases from breast cancer were found to be negative prognostic factors. Tumor response to therapy and lymphocyte depression were associated with favorable prognosis. Additionally, WHO response was identified to be a favorable prognostic factor in patients with colorectal cancer metastases. These findings may be useful when counseling patients regarding prognosis of their hepatic disease.

Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis.

UNLABELLED: This study was undertaken to present data from a phase 2 study in which patients with unresectable hepatocellular carcinoma (HCC) with and without portal vein thrombosis underwent radioembolization with Yttrium ((90)Y) microspheres. Patients treated were stratified by Okuda, Child-Pugh, baseline bilirubin, tumor burden, Eastern Cooperative Oncology Group (ECOG), presence of cirrhosis and portal vein thrombosis (PVT) (none, branch, and main). Clinical and biochemical data were obtained at baseline and at 4-week intervals following treatment for up to 6 months. Tumor response was obtained using computed tomography (CT). Patients were followed for survival. One hundred eight patients were treated during the study period. Thirty-seven (34%) patients had PVT, 12 (32%) of which involved the main PV. The cumulative dose for those with and without PVT was 139.7 Gy and 131.9 Gy, respectively. The partial response rate using world Health Organization (WHO) criteria was 42.2%. Using European Association for the Study of the Liver (EASL), the response rate was 70%. Kaplan-Meier survival varied depending on location of PVT and presence of cirrhosis. The adverse event (AE) rates were highest in patients with main PVT and cirrhosis. There were no cases of radiation pneumonitis. CONCLUSION: The use of minimally embolic (90)Y glass microspheres to treat patients with HCC complicated by branch/lobar PVT may be clinically indicated and appears to have a favorable toxicity profile. Further investigation is warranted in patients with main PVT.

Transcatheter intraarterial perfusion: MR monitoring of chemoembolization for hepatocellular carcinoma--feasibility of initial clinical translation.

PURPOSE: To prospectively test the hypothesis that intraprocedural transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging can be used to successfully measure reductions in perfusion to the targeted hepatocellular carcinoma (HCC) and the adjacent surrounding liver tissue during MR-interventional radiology (IR)-monitored transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: This HIPAA-compliant prospective study was approved by the institutional review board. An MR-IR unit was used to perform TACE in 10 patients with HCC (seven male, three female; eight younger than 69 years, two older than 69 years). Intraprocedural reductions in tumor perfusion before and after TACE were monitored with TRIP MR imaging. Time-signal intensity curves were derived, and semiquantitative spatially resolved area under the time-signal intensity curve maps of tumor perfusion before and after TACE were produced. Mean perfusion values before and after TACE for liver tumors and adjacent liver tissue were compared by using a mixed-model analysis, with alpha = .05. RESULTS: Perfusion reductions were measured successfully with TRIP MR imaging in 18 separate tumors during 13 treatment sessions. Perfusion maps showed significant perfusion reductions for tumors (P < .013) but not for adjacent nontumorous liver tissue (P = .21). For tumors, the mean perfusion value was 193 arbitrary units (AU) +/- 223 (standard deviation) before TACE and 45.3 AU +/- 91.9 after TACE, with a mean reduction in baseline perfusion of 74.6% +/- 24.8. For adjacent liver tissue, the mean perfusion value was 124 AU +/- 93.5 before TACE and 93.2 AU +/- 72.3 after TACE, with a mean reduction in baseline perfusion of 24.2% +/- 14.5. CONCLUSION: TRIP MR imaging can be used to detect intraprocedural changes in perfusion to HCC and surrounding liver parenchyma during MR-IR-monitored TACE.

Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival.

PURPOSE: To prospectively evaluate the safety, efficacy, and survival of patients with chemorefractory liver metastases who have been treated with yttrium 90 ((90)Y) glass microspheres. MATERIALS AND METHODS: Institutional review boards from two institutions approved the HIPAA-compliant study; all patients provided informed consent. One hundred thirty-seven patients underwent 225 administrations of (90)Y microspheres by using intraarterial infusion. Primary sites (origins) included colon, breast, neuroendocrine, pancreas, lung, cholangiocarcinoma, melanoma, renal, esophageal, ovary, adenocarcinoma of unknown primary, lymphoma, gastric, duodenal, bladder, angiosarcoma, squamous cell carcinoma, thyroid, adrenal, and parotid. Patients underwent evaluation of baseline and follow-up liver function and tumor markers and computed tomographic or magnetic resonance imaging. Patients were observed for survival from first treatment. Median survival (in days) and corresponding 95% confidence intervals were computed by using the Kaplan-Meier method. The log-rank statistic was used for statistical significance testing of survival distributions between various subgroups of patients. RESULTS: There were 66 men and 71 women. All patients were treated on an outpatient basis. Median age was 61 years. The mean number of treatments was 1.6. The median activity and dose infused were 1.83 GBq and 112.8 Gy, respectively. Clinical toxicities included fatigue (56%), vague abdominal pain (26%), and nausea (23%). At follow-up imaging, according to World Health Organization criteria, there was a 42.8% response rate (2.1% complete response, 40.7% partial response). There was a biologic tumor response (any decrease in tumor size) of 87%. Overall median survival was 300 days. One-year survival was 47.8%, and 2-year survival was 30.9%. Median survival was 457 days for patients with colorectal tumors, 776 days for those with neuroendocrine tumors, and 207 days for those with noncolorectal, nonneuroendocrine tumors. CONCLUSION: (90)Y hepatic treatments are well tolerated with acceptable toxicities; tumor response and median survival are promising.

Tumor response after yttrium-90 radioembolization for hepatocellular carcinoma: comparison of diffusion-weighted functional MR imaging with anatomic MR imaging.

PURPOSE: Anatomic magnetic resonance (MR) imaging assessment of hepatocellular carcinoma (HCC) response to yttrium-90 ((90)Y) radioembolization may require 3 months before therapeutic effectiveness can be determined. The relationship between anatomic MR and diffusion-weighted imaging (DWI) changes after (90)Y therapy is unclear. The present study tested the hypothesis that apparent diffusion coefficient (ADC) values on DWI at 1 month precede anatomic tumor size change at 3 months after (90)Y radioembolization. MATERIALS AND METHODS: In this prospective study, 20 patients with HCC (16 men) enrolled between April 2005 and July 2006 underwent lobar (90)Y therapy with mean doses of 141 Gy (right lobe) and 98 Gy (left lobe). Anatomic 1.5-T MR imaging (gadolinium-enhanced T1-weighted gradient-recalled echo) and DWI (single-shot spin-echo echo-planar imaging; b value of 0, 500 sec/mm(2)) were performed at baseline (0-3 weeks before (90)Y therapy) and at 1 and 3 months after (90)Y therapy. Tumor size and ADC values were measured and compared, and the percentage change in ADC was compared to the change in tumor size (minimum >5% change in size), with use of a paired t test (alpha = .05). RESULTS: Yttrium-90 therapy was successfully delivered in all patients. The mean baseline ADC of 1.64 x 10(-3) mm(2)/sec +/- 0.30 significantly increased to 1.81 x 10(-3) mm(2)/sec +/- 0.37 at 1 month (P = .02), and to 1.82 x 10(-3) mm(2)/sec +/- 0.23 at 3 months (P = .02). The mean baseline tumor size of 83.0 cm(2) +/- 63.7 did not change statistically at 1 month (84.1 cm(2) +/- 62.1; P = .75) or 3 months (74.0 cm(2) +/- 57.0; P = .10). The overall mean ADC percentage change at 1 month of 10.5% +/- 23.1% preceded an overall mean tumor size percentage change at 3 months of -18.5% +/- 31.5% (P = .03). CONCLUSIONS: HCC tumor response assessed with DWI at 1 month preceded anatomic size changes at 3 months after (90)Y therapy. DWI may assist in early determination of the response or failure of (90)Y therapy for HCC.

Multimodality imaging following 90Y radioembolization: a comprehensive review and pictorial essay.

Radioembolization with yttrium 90 (90Y) microspheres represents an emerging transarterial therapy for the treatment of liver malignancies that continues to generate interest in the medical community. The classic indication of treatment response is a reduction in tumor size; however, parenchymal changes (eg, necrosis, lack of enhancement, specific findings at positron emission tomography and functional magnetic resonance imaging) and other benign findings (pleural effusions, perivascular edema, contralateral hypertrophy, ring enhancement, perihepatic fluid, fibrosis) may occur following treatment, requiring proper image interpretation. With classic imaging findings and surrogates (time to progression, duration of response, disease-free interval), response rates range from 20% to 80% in patients treated for hepatocellular carcinoma or metastatic disease to the liver. Complications of 90Y radioembolization include cholecystitis, abscess, and bilomas and should be recognized early in the imaging follow-up of these patients. Radiologists who are involved in the posttreatment assessment of patients undergoing 90Y radioembolization should be familiar with the imaging findings and potential imaging pitfalls associated with this therapy.

Technical aspects of radioembolization with 90Y microspheres.

Embolotherapy with radioactive microspheres, radioembolization, is gaining clinical acceptance as a therapeutic option for patients with liver malignancies. Knowledge of the anatomic variants in the mesenteric system is critical to safely administer this therapy. The purpose of this review is to provide a thorough discussion and detailed presentation of the technical aspects of radioembolization specifically as it pertains to the implantation devices. Normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors are discussed. In addition, the basic principles described in this manuscript apply to all liver-directed transarterial therapies, such as chemoembolization and/or drug-eluting microspheres.

Metastatic Malignant Paraganglioma: A Case Report and Review of Literature.

Metastasis is a rare presentation of non-secretory paraganglioma. Consequently, there is no standard of care for the treatment of metastatic malignant paraganglioma. The most widely used chemotherapy regimen for non-resectable cases includes cyclophosphamide, vincristine, and dacarbazine (CVD). CVD has been previously studied with variable therapeutic response. However, yttrium-90 (Y90) radioembolization has not been previously studied in the treatment of hepatic metastasis in patients diagnosed with malignant paraganglioma. This case report follows the treatment of a patient with stage IV mediastinal paraganglioma with metastasis to the liver. Treatment consisted of the CVD chemotherapy regimen and Y90 radioembolization of the hepatic lesions. After 10 cycles of CVD, the tumor size has decreased from 6.0 × 8.8 to 5.5 × 3.0 × 3.4 cm on computed tomography scan. The prominent metastatic liver lesions responded after Y90 radioembolization of both the right and left hepatic arteries. The prominent right hepatic lobe lesion has decreased in size from 2.6 × 3.4 × 3.0 cm to 2.6 × 2.8 × 2.9 cm. The prominent left hepatic lobe lesion originally measuring 1.6 cm in diameter completely resolved on follow-up imaging studies. After completion of 12 cycles of chemotherapy, the most recent positron emission testing scan determined no evidence of disease regarding both the primary mass and the hepatic lesions. This study demonstrates the first case of combination chemotherapy and Y90 radioembolization with a complete response per response evaluation criteria in solid tumors criteria. The approaches toward diagnosis and treatment corresponding to this case of malignant metastatic paraganglioma are also reviewed in this study.

War is the Enemy of Health. Pulmonary, Critical Care, and Sleep Medicine in War-Torn Syria.

The Syrian crisis, now in its fifth year, has created an unprecedented strain on health services and systems due to the protracted nature of the warfare, the targeting of medics and health care infrastructure, the exodus of physicians and nurses, the shortage of medical supplies and medications, and the disruption of medical education and training. Within a few short years, the life expectancy of resident Syrians has declined by 20 years. Over the first 4 years of the conflict, more than 75,000 civilians died from injuries incurred in the violence. More than twice as many civilians, including many women and children, have died prematurely of infectious and noninfectious chronic diseases for want of adequate health care. Doctors, local administrators, and nongovernmental organizations are struggling to manage the consequences of the conflict under substandard conditions, often using unorthodox methods of health care delivery in field hospitals and remotely by telehealth communication. Much-needed medical supplies are channeled through dangerous routes across the borders from Lebanon, Jordan, and Turkey. Physicians in the United States and other western nations have helped Syrian physicians make the most of the situation by providing training on introducing innovations in technology and treatment. Portable ultrasound machines have been introduced and are being used extensively in the management of trauma and shock. This report, prepared by members of the Syrian American Medical Society, documents current needs for health care relief within Syria, focusing on pulmonary, critical care, and sleep medicine, and some of the efforts currently underway to meet those needs.