Assessment of automated cone-beam CT vessel identification software during transarterial hepatic embolisation: radiation dose, contrast medium volume, processing time, and operator perspectives compared to digital subtraction angiography.

AIM: To evaluate arterial cone-beam computed tomography (A-CBCT) automated analysis software for identification of vessels supplying tumours during transarterial hepatic embolisation (TAE). MATERIALS AND METHODS: This study was approved by the institutional review board, with waiver of consent. Consecutive TAE procedures using arterial mapping software (AMS), and performed between February 2014 and August 2014, were reviewed. Hepatic arteries were imaged using digital subtraction angiography (DSA) as well as A-CBCT processed with AMS. Interventional radiologists reported1 potential embolisation target vessels computed using AMS versus DSA alone,2 modification of the embolisation plan based on AMS, and3 operator confidence related to technical success. Imaging set-up, processing time, radiation dose, and contrast media volume were recorded. RESULTS: Thirty of 34 consecutive procedures were evaluated retrospectively. At least one additional embolisation target vessel was identified using AMS in 13 procedures (43%, 95% confidence interval [CI]: 26-61%) and embolisation plan modified in 11 (37%, 95% CI: 19-54%). Radiologists reported AMS increased operator confidence and reduced the number of DSA acquisitions in 25 (83%, 95% CI: 70-97%) and 15 cases (50%, 95% CI: 32-68%), respectively. The average A-CBCT acquisition and processing time was 4 minutes 53 seconds and 3 minutes 45 seconds, respectively. A-CBCT contributed to 11% of the radiation dose and 18% of the contrast media volume. CONCLUSION: Physicians report increased tumour supplying vessel detection and intraprocedural confidence using AMS during TAE without substantial impact on radiation dose, contrast media volume, and procedure time.

Genetic background and sex influence somatosensory sensitivity and oxycodone analgesia in the Hybrid Rat Diversity Panel.

Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h2 = 0.23-0.40). All strains displayed oxycodone-induced analgesia that peaked at 15-30 min and returned to baseline by 2 h. There were significant differences between the strains in the magnitude and duration of their analgesic response to oxycodone, although the heritability estimates were quite modest (h2 = 0.10-0.15). These data demonstrate that genetic background confers differences in mechanical sensitivity, thermal sensitivity, and oxycodone-induced analgesia.

Prospective study of outcomes after percutaneous biliary drainage for malignant biliary obstruction.

BACKGROUND: Percutaneous biliary drainage (PBD) is used to relieve malignant bile duct obstruction (MBO) when endoscopic drainage is not feasible. Little is known about the effects of PBD on the quality of life (QoL) in patients with MBO. The aim of this study was to evaluate changes in QoL and pruritus after PBD and to explore the variables that impact these changes. MATERIALS AND METHODS: Eligible patients reported their QoL and pruritus before and after PBD using the Functional Assessment of Cancer Therapy-Hepatobiliary instrument (FACT-HS) and the Visual Analog Scale for Pruritus (VASP). Instruments were completed preprocedure and at 1 and 4 weeks following PBD. RESULTS: A total of 109 (60 male/49 female) patients enrolled; 102 (94%) had unresectable disease. PBD was technically successful (hepatic ducts cannulated at the conclusion of procedure) in all patients. There were 2 procedure-related deaths. All-cause mortality was 10% (N = 11) at 4 weeks and 28% (N = 31) at 8 weeks post-PBD with a median survival of 4.74 months. The mean FACT-HS scores declined significantly (P < .01) over time (101.3, 94.8, 94.7 at baseline, 1 week, 4 weeks, respectively). The VASP scores showed significant improvement at 1 week with continued improvement at 4 weeks (P < .01). CONCLUSIONS: PBD improves pruritus but not QoL in patients with MBO and advanced malignancy. There is high early mortality in this population.

Indirect costs of federally supported research.

Indirect costs of federally supported research have increased steadily and dramatically since the current indirect cost policy became effective in 1966. The amount of research supported by any given level of federal funding has thus been markedly reduced, and this has become a critical factor limiting research support in the United States. The current policy has had multiple adverse effects that threaten the health of both the federal research program and the universities in which most of the research is conducted. This article examines the background and nature of the current policy, describes its consequences, and proposes simplifying modifications.

Beveling of fine micropipette electrodes by a rapid precision method.

A technique has been developed for embedding alumina particles 0.05 micrometer in size in the surface of a polyurethane film laid on glass. This abrasive surface is used for rapid, precise, and reliable beveling of Pyrex micropipettes with tip diameters at least as small as 0.1 micrometer. In the snapping turtle retina the beveled electrodes give much better cell penetration and intracellular response stability than unbeveled electrodes of considerably higher proach to this problem.

Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis.

INTRODUCTION: The purpose of this study was to compare rates and patterns of disease progression following percutaneous, image-guided radiofrequency ablation (RFA) and nonanatomic wedge resection for solitary colorectal liver metastases. METHODS: We identified 30 patients who underwent nonanatomic wedge resection for solitary liver metastases and 22 patients who underwent percutaneous RFA because of prior major hepatectomy (50%), major medical comorbidities (41%), or relative unresectability (9%). Serial imaging studies were retrospectively reviewed for evidence of local tumor progression. RESULTS: Patients in the RFA group were more likely to have undergone prior liver resection, to have a disease-free interval greater than 1 year, and to have had an abnormal carcinoembryonic antigen (CEA) level before treatment. Two-year local tumor progression-free survival (PFS) was 88% in the Wedge group and 41% in the RFA group. Two patients in the RFA group underwent re-ablation, and two patients underwent resection to improve the 2-year local tumor disease-free survival to 55%. Approximately 30% of patients in each group presented with distant metastasis as a component of their first recurrence. Median overall survival from the time of resection was 80 months in the Wedge group vs 31 months in the RFA group. However, overall survival from the time of treatment of the colorectal primary was not significantly different between the two groups. CONCLUSIONS: Local tumor progression is common after percutaneous RFA. Surgical resection remains the gold standard treatment for patients who are candidates for resection. For patients who are poor candidates for resection, RFA may help to manage local disease, but close follow-up and retreatment are necessary to achieve optimal results.

Radiofrequency ablation in the management of liver metastases from breast cancer.

OBJECTIVE: Systemic chemotherapy remains the standard treatment for patients with breast cancer hepatic metastases. Resection of metastases has survival advantages in a small percentage of selected patients. Radiofrequency ablation has been used in small numbers of selected patients. This small series was undertaken to review our experience with radiofrequency ablation in the management of patients with breast cancer hepatic metastases. CONCLUSION: Radiofrequency ablation of breast cancer hepatic metastases is safe and may be used to control hepatic deposits in patients with stable or no extrahepatic disease.

Effects of the rod receptor potential upon retinal extracellular potassium concentration.

It has been hypothesized that the light-evoked rod hyperpolarization (the receptor potential) initiates the light-evoked decrease in extracellular potassium ion concentration, [K+]o, in the distal retina. The hypothesis was tested using the isolated, superfused retina of the toad, Bufo marinus; the receptor potential was recorded intracellularly from red rods, and [K+]o was measured in the photoreceptor layer with K+-specific microelectrodes. In support of the hypothesis, variations in stimulus irradiance or duration, or in retinal temperature, produced qualitatively similar effects on both the receptor potential and the decrease in [K+]o. A mechanism for the relationship between the receptor potential and the decrease in [K+]o was suggested by Matsuura et al. (1978. Vision Res. 18:767-775). In the dark, the passive efflux of K+ out of the rod is balanced by an equal influx of K+ fromthe Na+/K+ pump. The light-evoked rod hyperpolarization is assumed to reduce the passive efflux, with little effect on the pump. Thus, the influx will exceed the efflux, and [K+]o will decrease. Consistent with this mechanism, the largest and most rapid decrease in [K+]o was measured adjacent to the rod inner segments, where the Na+/K+ pump is most likely located; in addition, inhibition of the pump with ouabain abolished the decrease in [K]o more rapidly than the rod hyperpolarization. Based upon this mechanism, Matsuura et al. (1978) developed a mathematical model: over a wide range of stimulus irradiance, this model successfully predicts the time-course of the decrease in [K+]o, given only the time-course of the rod hyperpolarization.

Up-regulation of retinoic acid receptor beta expression in renal cancers in vivo correlates with response to 13-cis-retinoic acid and interferon-alpha-2a.

Retinoic acid receptor-beta (RAR-beta) mRNA is not expressed by retinoid-resistant renal cancer cell lines but is present in retinoid-sensitive SK-RC-06 renal cancer cells and increases following incubation with retinoic acid (RA), suggesting that the antitumor action of RA is mediated through RAR-beta (A. D. Hoffman et al., Clin. Cancer Res., 2: 1077-1082, 2996). To determine whether RAR-beta expression correlates in vivo with major clinical response to patients with renal cell carcinoma (RCC) who were treated with retinoid-based therapy, we used in situ hybridization to analyze RAR-beta expression in tumor specimens obtained from patients who were treated on a clinical trial with 13-cis-RA and IFN-alpha. Thirty-three tissue specimens were analyzed (23 pretreatment and 10 on-treatment). mRNA expression was based on staining intensity, with scores within tumor cells ranging from 0 to 2, where a score of 0 indicated absence of staining, a score of 1 indicated weak staining, and a score of 2 indicated strong staining. RAR-beta expression was present in 22 of 23 (96%) pretreatment and 9 of 10 (90%) on-treatment specimens. Pretreatment levels of expression did not associate with the site of biopsy and did not predict for major clinical response to RA plus IFN-alpha therapy (two-sided Fisher's exact test, P = 0.826). However, an increase in the intensity of RAR-beta mRNA expression was detected in four of five (80%) patients who achieved a major response but in none of the five patients with progressive disease in whom sequential biopsies were available (two-sided Fisher's exact test, P = 0.048). These data show that RAR-beta transcripts increase in tumor cells of RCC patients who clinically respond to retinoid-based therapy. Retinoids that potently induce RAR-beta expression should be evaluated in the treatment of advanced RCC.

Technique for precision beveling of relatively large micropipettes.

A technique is described for embedding various sizes of diamond dust in a film of Varathane laid upon an optically flat glass surface. This forms a precise and very durable abrasive surface. When such abrasive surfaces are used with previously described equipment, micropipettes may be beveled rapidly and reliably to tip diameters extending from 0.5 micron to indefinitely large sizes. Beveled tips formed in this manner are extremely sharp, as shown by high resolution SEM photographs. Plugging of the micropipette tip during beveling is prevented by applying pressure to the contained electrolyte. This procedure allows the micropipette's electrical resistance to be monitored accurately and continuously, so that beveling may be stopped at the electrical resistance associated with any predetermined tip diameter. The beveling of such relatively large micropipettes appears to have a variety of applications in neurophysiology, plus additional applications in kidney and capillary micropuncture work.

Micropipette puller design: form of the heating filament and effects of filament width on tip length and diameter.

Though the ultrafine short tips provided by our micropipette puller are helpful for many preparations, longer tips are still needed for some cases where target cells for intracellular work are deeply embedded in tissue. Because the original 'loop' type of heating filament proved unsuitable for widening to provide the longer tips, we studied simpler forms of heating filaments. By comparison with the common loop design, a rectangular trough filament proved to have many advantages without any significant disadvantage. In particular, this type of filament may be used at varying widths to provide long tips as well as short ones. Thus our micropipette puller can now provide tip lengths that extend upward by continuous gradations from about 6 to 27 mm, while maintaining tip diameter in the ultrafine range of 0.1 micrometer or less. These long tips have proved more reliable and free from bending than long tips traditionally provided by the Livingston puller. By using narrow filaments in conjunction with other parameters that influence tip size, tips have also formed with diameters up to 1.5 micrometers and lengths of only 2-3 mm.

MRI as an alternative to CT-guided biopsy of adrenal masses in patients with lung cancer.

BACKGROUND: This study was performed to assess chemical shift magnetic resonance imaging (CSMRI) for characterizing adrenal masses in patients with lung cancer, and to compare charges associated with two algorithms for assessing adrenal masses in these patients. METHODS: Forty-two patients with lung cancer underwent both CSMRI (using in-phase and opposed-phase gradient echo images) and computed tomography-guided percutaneous biopsy of adrenal masses. Adrenal-to-spleen signal intensity ratios on the opposed-phase images were correlated with histopathologic results. The normalized charges for two algorithms were compared. In algorithm A, computed tomography-guided biopsy is used first to evaluate an adrenal mass; in algorithm B, CSMRI is used first, followed by computed tomography-guided biopsy only if CSMRI findings are not diagnostic of adenoma. RESULTS: Biopsy showed 24 (57%) adrenal adenomas and 18 (43%) metastases. Chemical shift magnetic resonance imaging was 96% sensitive for adenoma and 100% specific. The average normalized charges associated with algorithm A were $1,905 per patient versus $1,890 with algorithm B. CONCLUSIONS: Initial use of CSMRI in evaluating an adrenal mass in lung cancer patients can obviate biopsy in 55% of patients, and its charges are similar to those for performing computed tomography-guided biopsy in all patients.

Hepatic neuroendocrine metastases: does intervention alter outcomes?

BACKGROUND: In most instances, advanced neuroendocrine tumors follow an indolent course. Hepatic metastases are common, and although they can cause significant pain, incapacitating endocrinopathy, and even death, they are usually asymptomatic. The appropriate timing and efficacy of interventions, such as hepatic artery embolization (HAE) and operation, remain controversial. STUDY DESIGN: The records of 85 selected patients referred for treatment of hepatic neuroendocrine tumor metastases between 1992 and 1998 were reviewed from a prospective database. A multidisciplinary group of surgeons, radiologists, and oncologists managed all patients. Overall survival among this cohort is reported and prognostic variables, which may be predictive of survival, are analyzed. RESULTS: There were 37 men and 48 women, with a median age of 52 years. There were 41 carcinoid tumors, 26 nonfunctional islet cell tumors, and 18 functional islet cell tumors. Thirty-eight patients had extrahepatic metastases, and in 84% of patients, the liver metastases were bilobar. Eighteen patients were treated with medical therapy or best supportive care, 33 patients underwent HAE, and 34 patients underwent hepatic resection. Both the HAE-related mortality and the 30-day operative mortality rates were 6%. By univariate analysis, earlier resection of the primary tumor, curative intent of treatment, and initial surgical treatment were associated with prolonged survival (p < 0.05). On multivariate analysis, only curative intent to treat remained significant (p < 0.04). Patients with bilobar or more than 75% liver involvement by tumor were least likely to benefit from surgical resection. One-, 3-, and 5-year survival rates for the entire group were 83%, 61%, and 53%, respectively. The 1-, 3-, and 5-year survivals for patients treated with medical therapy, HAE, and operation were 76%, 39%, and not available; 94%, 83%, and 50%; and 94%, 83%, and 76%, respectively. CONCLUSIONS: Hepatic metastases from neuroendocrine tumors are best managed with a multidisciplinary approach. Both HAE and surgical resection provide excellent palliation of hormonal and pain symptoms. In select patients, surgical resection of hepatic metastases may prolong survival, but is rarely curative.