The excretion of small quantities of urinary albumin (microalbuminuria) may predict renal failure in diabetes. The measurement of microalbuminuria with radioimmunoassays has been based on 24-h, overnight, and 3- to 4-h collections. To determine whether single-void urine samples can be used to estimate 24-h excretion, we compared the results of 24-h outpatient urine collections with single-void samples corrected for creatinine from diabetic and nondiabetic subjects. The overall correlation of single-void sample results expressed as microgram albumin per milligram creatinine with 24-h excretion (mg/24 h) was excellent (r = .82, P less than .001). More important, in the diabetic patients the sensitivity and specificity of detecting 24-h microalbuminuria in the abnormal range were at least 94 and 96%, respectively. Single-void urine specimens adjusted for creatinine discriminate between normal and abnormal levels of microalbuminuria, as determined in 24-h urine collection, with high specificity and sensitivity.

Randomized controlled trials are investigating the benefit of hepatic radioembolization added to systemic therapy in the first-and second-line treatment of patients with colorectal liver metastases (CRLM). Remarkably, administered activity may still be suboptimal, because a dose-response relationship has not been defined. The purpose of this study was to characterize the relationship between tumor-absorbed dose and response after 90 Y radioembolization treatment for CRLM. Methods: Thirty patients with unresectable chemorefractory CRLM were treated with resin 90 Y-microspheres in a prospective phase II clinical trial. Tumor-absorbed dose was quantified on 90 Y PET. Metabolic tumor activity, defined as tumor lesion glycolysis (TLG*) on 18 F-FDG PET, was measured at baseline and 1 mo after treatment. The relationship between tumor-absorbed dose and posttreatment metabolic activity was assessed per metastasis with a linear mixed-effects regression model. Results: Treated metastases (n 5 133) were identified. The mean tumorabsorbed dose was 51 ± 28 Gy (range, 7-174 Gy). A 50% reduction in TLG* was achieved in 46% of metastases and in 11 of 30 (37%) patients for the sum of metastases. The latter was associated with a prolonged median overall survival (11.6 vs. 6.6 mo, P 5 0.02). A strong and statistically significant dose-response relationship was found (P , 0.001). The dose effect depended on baseline TLG* (P , 0.01). The effective tumor-absorbed dose was conservatively estimated at a minimum of 40-60 Gy. Conclusion: A strong dose-response relationship exists for the treatment of CRLM with resin microsphere 90 Y radioembolization. Treatment efficacy is, however, still limited, because the currently used pretreatment activity calculation methods curb potentially achievable tumor-absorbed dose values. A more personalized approach to radioembolization is required before concluding on its clinical potential.

Currently, there is no consensus on the use of 90 Y radioembolization for salvage patients with colorectal cancer liver metastases. The purpose of this study was to provide a comprehensive overview of the available data on tumor response and survival after 90 Y radioembolization for this group of patients. Methods: A systematic literature search was conducted in PubMed (Medline), Excerpta Medica (EMBASE), and the Cochrane Library (September 2012) with synonyms for "radioembolization" and "colorectal cancer liver metastases." Results were described separately for patient cohorts treated with 90 Y radioembolization as monotherapy and with 90 Y radioembolization in combination with chemotherapy. Results: The search yielded 13 relevant articles for systematic review on 90 Y radioembolization as monotherapy and 13 relevant articles on 90 Y radioembolization combined with chemotherapy. Disease control rates (i.e., complete response, partial response, and stable disease) ranged from 29% to 90% for 90 Y radioembolization as monotherapy and from 59% to 100% for 90 Y radioembolization combined with chemotherapy. Heterogeneity in the data prohibited pooling of response rates. Survival proportions at 12 mo ranged from 37% to 59% for 90 Y radioembolization as monotherapy and from 43% to 74% for 90 Y radioembolization combined with chemotherapy. Conclusion: In the studies included in this systematic review, approximately 50% of salvage patients with colorectal cancer liver metastases survive more than 12 mo after treatment with 90 Y radioembolization, either as monotherapy or in combination with chemotherapy. Heterogeneity between studies has unfortunately prohibited pooling of data. Future research will discern the precise role of 90 Y radioembolization in general clinical practice in comparison with chemotherapy.

No abstract

No abstract

PurposeTo evaluate the incidence of extrahepatic deposition of technetium-99m–labeled albumin macroaggregates (99mTc-MAA) after pretreatment angiography, before yttrium-90 radioembolizaton (90Y-RE), and to report on technical solutions that can be used to ensure safe delivery of 90Y-microspheres in patients with initial extrahepatic deposition.Materials and MethodsA retrospective analysis of 26 patients with primary and secondary liver malignancies, who were scheduled for treatment with 90Y-RE in our institution in 2009, was performed. The angiograms and single-photon emission computed tomography images of all patients were reviewed by an interventional radiologist and a nuclear medicine physician, respectively, to identify and localize extrahepatic deposition of 99mTc-MAA when present. Subsequently, the technical solutions were used to successfully perform 90Y-RE in these patients were evaluated and described.ResultsExtrahepatic deposition of 99mTc-MAA was observed in 8 of 26 patients (31%). In 7 of 8 patients, a second pretreatment angiography was performed to detect the cause of extrahepatic deposition. The technical solutions to enable safe 90Y microspheres delivery included more distal placement of the microcatheter in the proper/right hepatic artery in 4 of 7 (57%) patients; (super)selective catheterization of multiple segmental branches in 2 of 7 (29%); and additional coiling of a newly detected branch in the remaining patient (14%). This was confirmed by a second MAA procedure. 90Y-RE was eventually performed in 25 of 26 (96%) patients. No procedure-related complications (<30 days) were observed.ConclusionExtrahepatic deposition of 99mTc-MAA after pretreatment angiography did occur in 8 of 26 (31%) patients. The technical solutions as presented allowed safe 90Y-RE delivery in 25 of 26 (96%) patients.

In patients with CRCLM referred for Y90-RE, FDG-PET showed significantly more EHD and led to a considerable change of management.

BackgroundYttrium-90 radioembolization (90Y-RE) as a treatment for liver tumours induces radiation damage and hypoxia in liver tissue, which is also a trigger for systemic release of angiogenic factors, potentially stimulating tumour growth. We examined changes in circulating angiogenic factors following 90Y-RE and investigated the association between response and angiogenic factors. In this prospective study, 42 patients with unresectable, chemorefractory metastatic colorectal cancer (CRCLM) were treated with 90Y-RE. Blood samples were collected pre-treatment and at 0, 1, 3, 7 and 30 days of follow-up. Response was measured with MRI according to RECIST 1.1 at 1 month and subsequently 3-month interval until progressive disease (PD) occurred. Associations between circulating angiogenic factors and response were examined with linear mixed model analysis.ResultsFollowing 90Y-RE, three angiogenic factors demonstrated an increase in plasma levels, i.e., vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and angiopoietin-2 (Ang-2). Non-responders (= PD at 1-month follow-up, n = 10) had a significant increase of Ang-2 and HGF at 3 and 7 days post treatment compared to responders (= stable disease or better, n = 32), who showed little to no changes in plasma levels (respectively p = 0.01 and p = 0.007). Median overall survival was 9.2 months (95% confidence interval 6.1–12.4).ConclusionsSignificant increases in plasma levels of Ang-2 and HGF in the first week after treatment were associated with rapid progressive disease of liver lesions at 1 month after 90Y-RE. Combination of 90Y-RE with anti-angiogenic therapy may reduce these effects and result in better response.