Radioembolization with 90Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory gastrointestinal cancers: final report of a prospective pilot study.

BACKGROUND: This prospective pilot single-institution study was undertaken to document the feasibility, safety, and efficacy of radioembolization of liver-dominant metastatic gastrointestinal cancer using 90Y glass microspheres. METHODS: Between June 2010 and October 2013, 42 adult patients (26 men, 16 women; median age 60 years) with metastatic chemotherapy-refractory unresectable colorectal (n=21), neuroendocrine (n=11), intrahepatic bile duct (n=7), pancreas (n=2), and esophageal (n=1) carcinomas underwent 60 lobar or segmental administrations of 90Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for up to 5.5 years after radioembolization. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Time to maximum response, response duration, progression-free survival (PFS) (hepatic and extrahepatic), and overall survival (OS) were measured. RESULTS: Median target dose and activity were 109.4 Gy and 2.6 GBq per treatment session, respectively. Majority of clinical AE were grade 1 or 2 in severity. Patients with colorectal cancer had hepatic objective response rate (ORR) of 25% and a hepatic disease control rate (DCR) of 80%. Median PFS and OS were 1.0 and 4.4 months, respectively. Patients with neuroendocrine tumors (NET) had hepatic ORR and DCR of 73% and 100%, respectively. Median PFS was 8.9 months for this cohort. DCR and median PFS and OS for patients with cholangiocarcinoma were 86%, 1.1 months, and 6.7 months, respectively. CONCLUSIONS: 90Y glass microspheres device has a favorable safety profile, and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort.

90Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory gastrointestinal cancers: a pilot study.

PURPOSE: This prospective pilot single-institution study was undertaken to document the feasibility, safety, and efficacy of treatment of liver-dominant metastatic gastrointestinal cancer using (90)Y glass microspheres. METHODS: Between June 2010 and November 2012, 30 adult patients (22 men, eight women; median age 61 years) with metastatic chemotherapy-refractory unresectable colorectal (n = 15), neuroendocrine (n = 9), intrahepatic cholangiocarcinoma (n = 3), pancreas (n = 2), and esophageal (n = 1) carcinomas underwent 45 lobar or segmental administrations of (90)Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for 6 months after each treatment. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors, version 1.1. Time to maximum response, response duration, progression-free survival (hepatic and extrahepatic), and overall survival were measured. RESULTS: Median target dose and activity were 111.6 Gy and 2.5 GBq per treatment session, respectively. All but three clinical AE were grade 1 or 2 in severity. Serious AE included an unplanned hospital admission for carcinoid crisis, grade 3 vomiting, and grade 4 gastric ulcer. Patients with colorectal cancer had hepatic objective response rate (ORR) of 27 % and a disease control rate (DCR) of 73 %. Median progression-free and overall survival were 1.0 and 4.9 months, respectively. Patients with neuroendocrine tumors had hepatic ORR and DCR of 78 % and 100 %, respectively. Median progression-free survival was 18.5 months for this cohort. CONCLUSIONS: Y glass microspheres device has a favorable safety profile and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort.

Self-assessed sleep quality in chronic kidney disease.

BACKGROUND: Although sleep complaints are commonly reported in persons with end stage renal disease (ESRD), little is known about the prevalence of sleep complaints in chronic kidney disease (CKD), and the relation of sleep quality to the severity of kidney disease. METHODS: We administered the Kidney Disease Quality of Life (KDQOL) sleep scale to 156 subjects, 78 with ESRD and 78 with CKD. Glomerular filtration rate (GFR) was estimated using the six variable Modification of Diet in Renal Disease (MDRD) equation and used to stratify subjects with CKD as mild-moderate (GFR >25 ml/min/1.73 m(2)) and advanced (GFR <25 ml/min/1.73 m(2)). We used multivariable linear regression to determine independent predictors of KDQOL sleep scale scores. Higher scores indicate higher self-reported quality of sleep. RESULTS: Median scores on the KDQOL sleep scale were 59 (interquartile range 40-80) in subjects with ESRD and 69 (interquartile range 53-80) in subjects with CKD (P=0.04). Thirty-four percent of subjects with ESRD, 27% of subjects with advanced CKD, and 14% of subjects with mild to moderate CKD had sleep maintenance disturbances (P=0.05). Thirteen percent of subjects with ESRD, 11% of subjects with advanced CKD, and no subjects with mild-moderate CKD had complaints of daytime somnolence (P=0.03). There was no significant difference in the prevalence of sleep adequacy complaints in persons with ESRD versus CKD. In multivariable analyses, only age and ESRD status (vs. CKD) were significant predictors of lower KDQOL sleep scores. Among subjects with CKD, there was a significant direct association between estimated GFR and scores on the KDQOL sleep scale in non-African American subjects (P=0.01). CONCLUSIONS: Sleep complaints are common in persons with CKD and ESRD and may be associated with the severity of kidney disease.

Validation of the Kidney Disease Quality of Life (KDQOL) cognitive function subscale.

BACKGROUND: Formal cognitive function testing is cumbersome, and no self-administered instruments for estimating cognitive function in persons with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been validated. The goal of this study was to determine the validity of the Kidney Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of cognitive impairment in persons with kidney disease. METHODS: We administered the KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross-sectional study of cognitive function. Scores on the Modified Mini-Mental State Exam (3MS) were considered the gold standard measure of global cognitive function. Performance characteristics of the KDQOL-CF were assessed using correlation coefficients, Bland-Altman plots, and receiver operating characteristic curves. RESULTS: Median scores on the KDQOL-CF were 73 (interquartile range 60-87) for subjects with ESRD and 87 (interquartile range 73-100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global cognitive impairment as a 3MS score < 80, a cut-point of 60 on the KDQOL-CF accurately classified 76% of subjects, with 52% sensitivity and 81% specificity. On multivariable analysis, cerebral and peripheral vascular disease, benzodiazepine use, and higher serum phosphorus concentrations were associated with lower KDQOL-CF scores, while beta blocker use, education, and higher serum albumin concentrations were associated with higher KDQOL-CF scores. CONCLUSION: The KDQOL-CF is a valid instrument for estimating cognitive function in patients with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected individuals may prove to be an effective and efficient strategy for identifying cognitive impairment in patients with kidney disease.

Cognitive impairment in chronic kidney disease.

OBJECTIVES: To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD. DESIGN: Cross-sectional study. SETTING: University-affiliated ambulatory nephrology and dialysis practices. PARTICIPANTS: Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end-stage renal disease (ESRD)) with a mean age+/-standard deviation of 62.5+/-14.3. MEASUREMENTS: Three standardized cognitive tests, the Modified Mini-Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six-variable Modification of Diet in Renal Disease equation. RESULTS: There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms (P<.001 for all comparisons). Scores on the Trails B (P<.001) and CVLT immediate (P=.01) and delayed (P<.001) recall were significantly worse for subjects with CKD not requiring dialysis than for published norms. In addition, the fraction of subjects with impairment on the 3MS and Trails B increased with decreasing kidney function. CONCLUSION: Cognitive impairment is associated with the severity of kidney disease. Further studies are needed to determine the reasons for cognitive impairment in subjects with CKD and ESRD.

Early OspA immune complex formation in animal models of Lyme disease.

Infection with Borrelia burgdorferi, the cause of Lyme disease, has been accompanied by a puzzling delayed antibody (Ab) response to B. burgdorferi antigens (Ags) including the abundant organism-specific outer surface proteins, such as the 31-kD OspA. In humans the response to nonspecific B. burgdorferi Ags has required 3-6 weeks. The response to OspA has rarely been detected by conventional methodology until months after infection, despite demonstrable T cell reactivity. Tick inoculation and low-dose intradermal inoculation animal models have been characterized by a comparable response to OspA. Using more sensitive biotin-avidin immunoblots and immune complex (IC) dissociation techniques, we demonstrated in humans that Ab to OspA is formed early but may remain at low levels or bound in IC. To see if this was a universal biologic response, animal models were analyzed by these methods. The results with mice, monkeys and rabbits show that IC Ab to OspA may be detected at the onset of infection. The data suggest that these animal models may be used to understand the immune response to B. burgdorferi and the pathogenesis of Lyme disease. With attention to unique B. burgdorferi Ags, these results are likely to have both clinical and diagnostic importance.