Microwave assisted the short time clean synthesis of 1,3-diketones as building blocks in heterocyclic synthesis: a facile synthesis and antimicrobial evaluation of new dihydropyridine, 4H-pyrane, dihydropyridazine, pyrimidine and pyrazole derivatives.

The compounds bearing naphthalene moiety can be used as medical preparations because of their wide spectrum of biological activity and low toxicity. In this study, a new series of azoles or azines were synthesized from the reaction of the key intermediate 1-(1-hydroxynaphthalen-2-yl)-3-phenylpropane-1,3-dione 3 with a variety of electrophilic and nucleophilic reagents under a variety of mild conditions. The chemical structures of these compounds were confirmed by various spectroscopic methods such as (IR, 1H-NMR, 13C-NMR, mass spectra and elemental analyses). The prepared compounds were screened in vitro for their anti-microbial activity against some species of Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeuroginosa). Anti-fungal activities of the compounds were tested against yeast and mycelial fungi,Candida albicans and Aspergillus flavus. The antimicrobial activity of this series was showed either weak or moderate activities.

Right-Sided Ectopic Intrathoracic Kidney Associated With Symptomatic Bochdalek Hernia in an Adult Indian Female: Case Report and Review of Literature.

Bochdalek hernia is an inherited posterior lateral defect in the diaphragm that allows the abdominal organs to herniate into the thoracic cavity. In addition to being the most prevalent variety of congenital diaphragmatic hernia (CDH), it is also the type that is observed on the left hemithorax the majority of the time. Ectopic kidney is an uncommon condition, and the occurrence of ectopic intrathoracic kidney is even more uncommon, accounting for only a few of all the cases of renal ectopias. The occurrence of intrathoracic kidney associated with Bochdalek hernia is infrequent among adult individuals and is typically an incidental finding. A 52-year-old obese female patient presented to the pulmonology outpatient unit and reported experiencing the symptoms of coughing, wheezing, and difficulty in breathing since three years. A chest radiograph revealed an elevated dome of the diaphragm on the right side. A computed tomography (CT) of the chest revealed a defect in the posterior aspect of the right hemi-diaphragm with herniation of the right kidney and retroperitoneal fat into the right hemi-thorax. CT urography showed normal size and enhancement of the intrathoracic kidney with prompt excretion of contrast into the pelvicalyceal system. With regard to the small size of the hernia and considering the absence of complications on CT urography, a conservative treatment was proposed to the patient. The patient was followed up every year. There was no occurrence of renal complications during the follow-up period. When evaluating patients with 'elevated hemi-diaphragm' or thoracic 'mass', it is essential to check for the presence of intrathoracic kidney to avoid undesirable surgical procedures and image-guided biopsies.

Does preoperative silodosin administration facilitate ureteral dilatation during flexible ureterorenoscopy? A randomized clinical trial.

PURPOSE: To assess whether preoperative administration of silodosin can facilitate the placement of ureteral access sheath (UAS) prior to flexible ureteroscopy (F-URS) and reduce the occurrence of ureteric injury in challenging cases. METHODS: This prospective randomized clinical trial was carried out on 147 patients diagnosed with upper ureteric stone or stone kidney, non-stented. The patients were randomly divided into two equal groups. Group A (silodosin group) included patients in whom F-URS was done with daily preoperative intake of 8 mg silodosin for 1 week and group B (placebo/control group) included patients in whom F-URS was done with daily preoperative intake of placebo tablets. RESULTS: In group A, a total of 23 (33.3%) experienced ureteral wall injury following UAS insertion, while in group B, this occurred in 40 patients (59.7%). There was a statistically significant difference in the grade of ureteral wall injury between the two groups (P < 0.001). In the multiple regression analysis, age, operative time and silodosin were found to be significant risk factors for ureteral wall injury (P = 0.007, 0.041 and < 0.001, respectively). CONCLUSIONS: The administration of silodosin prior to retrograde intrarenal surgery (RIRS) effectively prevented significant ureteral wall damage and reduced initial postoperative discomfort.

Solar fuels: photoelectrosynthesis of CO from CO2 at p-type Si using Fe porphyrin electrocatalysts.

Photoelectrocatalytic conversion of CO2 to CO can be driven at a boron-doped, hydrogen terminated, p-type silicon electrode using a meso-tetraphenylporphyrin Fe(III) chloride in the presence of CF3CH2OH as a proton source and 0.1 M [NBu4][BF4]/MeCN/5% DMF (v/v) as the electrolyte. Under illumination with polychromatic light, the photoelectrocatalysis operates with a photovoltage of about 650 mV positive of that for the dark reaction. Carbon monoxide is produced with a current efficiency >90% and with a high selectivity over H2 formation. Photoelectrochemical current densities of 3 mA cm(-2) at -1.1 V versus SCE are typical, and 175 turnovers have been attained over a 6 h period. Cyclic voltammetric data are consistent with a turnover frequency of k(Si)(obs)=0.24×10(4) s(-1) for the photoelectrocatalysis at p-type Si at -1.2 V versus SCE this compares with k(Si)(obs)=1.03×10(4) s(-1) for the electrocatalysis in the dark on vitreous carbon at a potential of -1.85 V versus SCE.

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.

Solar fuels: visible-light-driven generation of dihydrogen at p-type silicon electrocatalysed by molybdenum hydrides.

We show that a robust molybdenum hydride system can sustain photoelectrocatalysis of a hydrogen evolution reaction at boron-doped, hydrogen-terminated, p-type silicon. The photovoltage for the system is about 600-650 mV and the current densities, which can be sustained at the photocathode in non-catalytic and catalytic regimes, are similar to those at a photoinert vitreous carbon electrode. The kinetics of electrocatalysed hydrogen evolution at the photocathode are also very similar to those measured at vitreous carbon-evidently visible light does not significantly perturb the catalytic mechanism. Importantly, we show that the doped (1-10â€…Ω cm) p-type Si can function perfectly well in the dark as an ohmic conductor and this has allowed direct comparison of the cyclic voltammetric behaviour of the response of the system under dark and illuminated conditions at the same electrode. The p-type Si we have employed optimally harvests light energy in the 600-700 nm region and with 37 mW cm(-2) illumination in this range; the light to electrochemical energy conversion is estimated to be 2.8 %. The current yield of hydrogen under broad tungsten halide lamp illumination at 90 mW cm(-2) is (91±5) % with a corresponding chemical yield of (98±5) %.

Early assessment of the efficacy of digital infrared thermal imaging in pediatric extremity trauma.

Young children or those with intellectual disability with trauma to an extremity often undergo radiographs of the whole limb. The objective of the study was to assess the efficacy of digital infrared thermal images (DITI) in pediatric extremity trauma. We hypothesized fractures to be associated with local hyperthermia, detectable with DITI, which could direct focused radiographs. In this exploratory study, patients seen over a 2-month period in a pediatric emergency department for limb trauma were included if an extremity radiograph was taken on the same day. Patients had DITI of symptomatic and contralateral limbs. The warmest area of each image was compared to the site of pain and/or fracture on the radiograph. Fifty-one patients were enrolled. DITI matched 73% of pain sites. Fractures were seen in 11 patients. DITI matched 7 of 11 (64%) fracture sites. DITI performance in pinpointing the site of injury, although suboptimal, is encouraging for further evaluation.

Paramagnetic bridging hydrides of relevance to catalytic hydrogen evolution at metallosulfur centers.

Paramagnetic hydrides are likely intermediates in hydrogen-evolving enzymic and molecular systems. Herein we report the first spectroscopic characterization of well-defined paramagnetic bridging hydrides. Time-resolved FTIR spectroelectrochemical experiments on a subsecond time scale revealed that single-electron transfer to the µ-hydride di-iron dithiolate complex 1 generates a 37-electron valence-delocalized species with no gross structural reorganization of the coordination sphere. DFT calculations support and (1)H and (2)H EPR measurements confirmed the formation an S = ½ paramagnetic complex (g = 2.0066) in which the unpaired spin density is essentially symmetrically distributed over the two iron atoms with strong hyperfine coupling to the bridging hydride (A(iso) = -75.8 MHz).

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.

Synthesis of the H-cluster framework of iron-only hydrogenase.

The metal-sulphur active sites of hydrogenases catalyse hydrogen evolution or uptake at rapid rates. Understanding the structure and function of these active sites--through mechanistic studies of hydrogenases, synthetic assemblies and in silico models--will help guide the design of new materials for hydrogen production or uptake. Here we report the assembly of the iron-sulphur framework of the active site of iron-only hydrogenase (the H-cluster), and show that it functions as an electrocatalyst for proton reduction. Through linking of a di-iron subsite to a {4Fe4S} cluster, we achieve the first synthesis of a metallosulphur cluster core involved in small-molecule catalysis. In addition to advancing our understanding of the natural biological system, the availability of an active, free-standing analogue of the H-cluster may enable us to develop useful electrocatalytic materials for application in, for example, reversible hydrogen fuel cells. (Platinum is currently the preferred electrocatalyst for such applications, but is expensive, limited in availability and, in the long term, unsustainable.).

Toll-Like Receptor-4 Antagonist Enhances the Repair of Ultraviolet Radiation-Induced DNA Damage and Augments Anti-Tumor Immune Responses in Mice.

Ultraviolet (UV) irradiation of the skin is related to the development of skin cancer. UVB also causes DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), which can result in stable mutations. Toll-like receptor 4 (TLR4), a component of innate immunity, plays a key role in cancer. Previous studies from our laboratory have observed that TLR4 deficiency resulted in the repair of UVB-induced DNA damage, inhibition of UVB-induced immune suppression, and carcinogenesis. In this study, we determined the efficacy of TLR4 antagonist TAK-242 in regulation of UVB-induced DNA damage, inflammation, and tumor development. Our results indicate that TAK-242 treatment increased the expression of xeroderma pigmentosum group A (XPA) mRNA, resulting in the repair of UVB-induced CPDs in skin of SKH-1 mice. Treatment with TAK-242 also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) in UVB-exposed skin of SKH-1 mice. Cutaneous carcinogenesis was significantly reduced in mice treated with TAK-242 in comparison to vehicle-treated mice. The proinflammatory cytokines IL-1ß, IL-6, and TNF-α were also found to be significantly greater in vehicle-treated mice than TAK-242-treated mice. Finally, treatment with TAK-242 augmented anti-tumor immune responses in mice. Our data provide further evidence that activation of the TLR4 pathway promotes the development of UV-induced non-melanoma skin cancer mediated at least in part on its negative effects on DNA damage. Moreover, treatment with the TLR4 inhibitor TAK-242 may be effective for prevention of skin cancer.

Chemoembolization for hepatocellular carcinoma: comprehensive imaging and survival analysis in a 172-patient cohort.

PURPOSE: To determine comprehensive imaging and long-term survival outcome following chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred seventy-two patients with HCC treated with chemoembolization were studied retrospectively in an institutional review board approved protocol; this study was HIPAA compliant. Baseline laboratory and imaging characteristics were obtained. Clinical and laboratory toxicities following treatment were assessed. Imaging characteristics following chemoembolization were evaluated to determine response rates (size and necrosis) and time to progression (TTP). Survival from the time of first chemoembolization treatment was calculated. Subanalyses were performed by stratifying the population according to Child-Pugh, United Network for Organ Sharing, and Barcelona Clinic for Liver Cancer (BCLC) staging systems. RESULTS: Cirrhosis was present in 157 patients (91%); portal hypertension was present in 139 patients (81%). Eleven patients (6%) had metastases at baseline. Portal vein thrombosis was present in 11 patients (6%). Fifty-five percent of patients experienced some form of toxicity following treatment; 21% developed grade 3 or 4 bilirubin toxicity. Post-chemoembolization response was seen in 31% and 64% of patients according to size and necrosis criteria, respectively. Median TTP was 7.9 months (95% confidence interval: 7.1, 9.4) but varied widely by stage. Median survival was significantly different between patients with BCLC stages A, B, and C disease (stage A, 40.0 months; B, 17.4 months; C, 6.3 months; P < .0001). CONCLUSION: The determination of TTP and survival in patients with HCC is confounded by tumor biology and background cirrhosis; chemoembolization was shown to be a safe and effective therapy in patients with HCC.

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 of yttrium-90 microsphere radioembolization in patients with biliary obstruction.

PURPOSE: There are few data on radioembolization in the setting of biliary obstruction. The present study was performed to assess the safety of yttrium-90 ((90)Y) radioembolization in the setting of tumor-related biliary obstruction and total bilirubin levels of 2 mg/dL or lower. MATERIALS AND METHODS: Twelve patients with liver tumors underwent 19 treatment sessions with (90)Y to the obstructed liver lobe or segment. Initial bilirubin level was 2 mg/dL or lower in all cases. Measured outcomes included pre- and posttreatment white blood cell (WBC) count, total bilirubin level, and alkaline phosphatase (ALP) level. Bilirubin toxicities and biliary complications were assessed according to Common Toxicity Criteria, version 3.0. RESULTS: Lobar or segmental (90)Y was successful in all cases. Pre- and posttreatment median WBC counts (5.3 vs 5.3; P = .490), bilirubin levels (1.0 vs 1.1; P = .460), and ALP levels (195 vs 146; P = .712) showed no differences. One case of grade 3 bilirubin toxicity was noted in a patient with liver hilar nodal progression and subsequent biliary obstruction requiring external drainage. Complete resolution of biliary obstruction was seen after (90)Y treatment in one case of metastatic colorectal carcinoma at 1 month follow-up. No biliary complications (infection, sepsis, biliary necrosis, biloma formation, abscess development, or biliary stricture) were encountered in this cohort during an overall median follow-up time of 22.9 months. CONCLUSIONS: The use of (90)Y glass microspheres demonstrated a good safety profile in the setting of tumor-related biliary obstruction in patients with normal or near-normal bilirubin levels in this series, without evidence of therapy-related progressive leukocytosis, bilirubin increase, or infectious or biliary complications after treatment.

Direct hepatic artery puncture for transarterial therapy in liver cancer.

In the treatment of liver malignancies, therapies such as bland embolization, chemoembolization and radioembolization require access to the hepatic artery by means of conventional transfemoral or brachial catheterization. Challenging vascular anatomy can impede selective access to tumoral vessels, preventing the safe and effective delivery of embolic material. Direct percutaneous hepatic arterial puncture under ultrasonographic guidance may be an alternative method to obtain intrahepatic arterial access for the purposes of hepatic arteriography and delivery of therapeutic agents. In this case series, the authors describe the use of direct hepatic artery puncture to successfully perform two radioembolization procedures and one bland embolization procedure.

Agreement between competing imaging measures of response of hepatocellular carcinoma to yttrium-90 radioembolization.

PURPOSE: There are currently at least six major competing criteria used to determine response to yttrium-90 and other liver-directed therapies, including: (i) Response Evaluation Criteria in Solid Tumors (RECIST); (ii) World Health Organization (WHO), (iii) volumetric, (iv) two-dimensional (2D) European Association for the Study of the Liver (EASL), and (v) three-dimensional (3D) EASL criteria; and (vi) functional diffusion-weighted (DW) magnetic resonance (MR) imaging. This study evaluated agreement among these competing tumor response classification schemes based on quantitative measurements of tumor size, necrosis, and changes in water mobility. MATERIALS AND METHODS: In this retrospective study, 20 patients with hepatocellular carcinoma (HCC) underwent (90)Y radioembolization. The patients' tumor burden before and 3-6 months after treatment was assessed with MR imaging. The percent change in size of tumors was used to classify patients into response categories. kappa and agreement statistics were used to compare concordance among the different criteria. RESULTS: Conventional size criteria (RECIST, WHO, and volumetric) all had a substantial level of agreement (kappa = 0.76-0.78) when classifying patients into response categories. However, the conventional size criteria in relation to 2D or 3D EASL had only slight to moderate concurrence, with kappa statistics as low as 0.06. Two-dimensional EASL criteria and functional DW MR imaging resulted in the highest response rates, 55% (n = 11) and 75% (n = 15), respectively, whereas conventional size criteria produced lower response rates. CONCLUSIONS: Classification of HCC response to (90)Y radioembolization is related to which of the competing criteria are used. It is recommended that anatomic imaging criteria be used as the primary method to determine response and functional imaging criteria be used as a complementary secondary method.

Synthesis and Antimicrobial Evaluation of Some Novel Pyrimidine, Pyrazole, Chromene and Tetrahydrobenzo[b]thiophene Derivatives Bearing Pyrimidinthione Moiety.

AIM AND OBJECTIVE: A novel collection of fused pyrimidine, pyridine, pyrazole, chromene and thiophene derivatives 2-30 have been newly synthesized by using the 1a, b as starting material. Fused pyrane exhibits a range of pharmacological activity such as cancer agents [1], antimicrobial [2-4], antioxidant [5], antiproliferative [6], cytotoxic activity [7], anticipated antitumor [8], antiparkinsonian [9] and anti-inflammatory [10]. Moreover, pyrane derivatives are well known for bacterial biofilm disruptor [11], anticonvulsant [12] and inhibitors of mycobacterium bovis [13]. MATERIALS AND METHODS: All melting points were measured using the Akofler Block instrument and are uncorrected. IR spectra (KBr) were recorded on a FTIR 5300 spectrometer (υ, cm-1). The 1H-NMR spectra were recorded on a Varian Gemini spectrometer. The 1H-NMR spectra were run at 300, 400 MHz and 13C-NMR spectra were run at 100 MHz in DMSO-d6, CDCl3 as solvents. The chemical shifts are expressed in parts per million (ppm) by using tetramethylsilane (TMS) as an internal reference, 1000 EX mass spectrometer at 70 eV. The purity of synthesized compounds was checked by thin-layer chromatography (TLC) (aluminum sheets) using nhexane, EtOAc (9:1, V/V, 7:3 V/V) eluent. Elemental analyses were carried out by the Microanalytical Research Center, Faculty of Science, and Microanalytical Unit, Faculty of Pharmacy, Cairo University, Egypt. RESULTS AND DISCUSSION: A novel series of azoles and azines were designed and prepared via the reaction of 7-amino- 5-(4-chlorophenyl)-4-phenyl-2-thioxo-2,5-dihydro-1H-pyrano- [2,3-d]pyrimidine-6-carbonitrile 1a and 7-amino-4,5- diphenyl-2-thioxo-2,5-dihydro-1H-pyrano[2,3-d]-pyrimidine-6-carbonitrile 1b with some electrophilic and nucleophilic reagents. The structures of target compounds were confirmed by elemental analyses and spectral data. The novel synthesized compounds showed good antimicrobial activity against the previously mentioned microorganisms. CONCLUSION: In conclusion, compounds 1a, 1b underwent ready cyclization to give fused heterocyclic compounds through reaction with different reagents and under different conditions and subjected to antimicrobial screening.

Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization.

PURPOSE: To describe volumetric changes of "radiation lobectomy," a manifestation of hepatic parenchymal response to lobar (90)Y microsphere radioembolization. METHODS: Twenty patients exhibiting this phenomenon were identified. Pre- and posttreatment absolute right and left hepatic lobar volume (HLV), relative HLV (rHLV = HLV/total liver volume), and degree of lobar atrophy (DA) or hypertrophy (DH) (DA or DH = |posttreatment rHLV - pretreatment rHLV|) were determined. Laboratory toxicities, tumor response, and patient survival were also assessed. RESULTS: Twenty patients with primary (HCC, n = 17; peripheral cholangiocarcinoma, n = 3) liver malignancies demonstrated findings of radiation lobectomy. Initial absolute right and left HLV was 955 cm(3) (range 644-1,842 cm(3), rHLV = 57%) and 719 cm(3) (range 328-1,387 cm(3), rHLV = 43%), respectively. Following (90)Y, absolute right HLV decreased to 460 cm(3) (range 185-948 cm(3), 52% reduction, rHLV = 31%, DA = 26%, P < 0.0001), while absolute left HLV increased to 1,004 cm(3) (range 560-1,558 cm(3), 40% increase, rHLV = 69%, DH = 26%, P < 0.0001). No grade 3 or 4 bilirubin toxicities were encountered. Tumor response ranged from 55% to 70% by size criteria. Forty-six percent 5-year survival was achieved in HCC patients. CONCLUSIONS: Radiation lobectomy following (90)Y radioembolization of right lobe tumors manifests extensive contralateral lobar hypertrophy, high response rates, and prolonged survival. This phenomenon was noted in 6.4% (20/315) of the entire cohort and 19.8% (20/101) of patients with unilobar right lobe tumors. Further investigation is necessary to determine contributing factors that may predict this effect.

The role of tumor vascularity in predicting survival after yttrium-90 radioembolization for liver metastases.

PURPOSE: It is unclear what role pretreatment tumor vascularity plays in determining outcomes after yttrium-90 radioembolization. A hypothesis was tested that radiographic vascularity of a tumor does not affect patient survival. MATERIALS AND METHODS: In this two-institution retrospective study, 137 patients with metastatic liver disease underwent (90)Y radioembolization. Primary sites were categorized as colon, neuroendocrine, and other. All patients underwent triphasic contrast-enhanced computed tomography (CT) or magnetic resonance imaging, as well as detailed hepatic angiography. Two board-certified interventional radiologists interpreted all images and evaluated them for the presence of enhancement. Median survival times, as well as 1- and 2-year survival rates, were compared between patients with hypervascular and hypovascular tumors on (i) cross-sectional imaging and (ii) angiography with use of the log-rank statistic (alpha = 0.05). RESULTS: On angiography, 108 patients had hypervascular tumors and 29 had hypovascular tumors. Median survival times for the two subgroups were 300 days and 261 days, respectively (P = .95). On CT, 24 patients had hypervascular tumors and 113 had hypovascular tumors. Median survival times for these subgroups were 306 days and 284 days, respectively (P = .67). Eighty-four patients' tumors that were hypovascular on CT were hypervascular on angiography. There were no statistical differences in survival between patients with hypervascular and hypovascular tumors, regardless if vascularity was defined based on CT or angiography. CONCLUSIONS: Radiographic vascular appearance of liver tumors, regardless of imaging modality, does not affect survival after radioembolization. Therefore, hypovascular tumors should not be considered contraindicated for radioembolization.

Radiologic findings following Y90 radioembolization for primary liver malignancies.

A therapy gaining rapid clinical adoption involves radioembolization with the use of Yttrium-90 (90Y) microspheres. The 20-60 microm-sized microspheres are injected trans-arterially and flow to hepatic tumors given their preferential blood supply from the hepatic artery. Once they lodge in the arterioles, they impart a very intense local radiotherapeutic effect. Given the combined radiation and embolic effect, the imaging findings imparted by this mode of action differ significantly from other treatments. This work represents a comprehensive review of the imaging findings following radioembolization in patients with primary liver tumors. The report discusses imaging response, benign secondary effects, and complications. This should help educate the radiologist on imaging findings that should be expected following radioembolization and therefore aid in the proper image interpretation.