The Relationship Between the Endoscopic Healing Index, Fecal Calprotectin, and Magnetic Resonance Enterography in Crohn's Disease.

INTRODUCTION: The serum-based endoscopic healing index (EHI) test identifies endoscopic Crohn's disease (CD) activity. Data are lacking on the relationship between EHI with other endpoints. We assessed the relationship between EHI and the simplified Magnetic Resonance Index of Activity. MATERIALS AND METHODS: Data were prospectively collected on patients with CD with either an EHI or fecal calprotectin (FCAL) within 90 days of magnetic resonance enterography (MRE). Diagnostic accuracy was assessed using area under the receiver operator characteristics. Proportions with any, severe, and terminal ileum MR inflammation were compared above/below identified thresholds for both EHI and FCAL. RESULTS: A total of 241 MREs paired to either EHI or FCAL from 155 patients were included. Both EHI and FCAL had similar accuracy to diagnose inflammation (area under the receiver operator characteristics: EHI: 0.635 to 0.651, FCAL: 0.680 to 0.708). Optimal EHI values were 42 and 26 for inflammation on MRE and endoscopy, respectively. Patients with EHI ≥42 (100% vs. 63%, P=0.002), FCAL >50 µg/g (87% vs. 64%, P<0.001) and FCAL >250 µg/g (90% vs. 75%, P=0.02) had higher rates of simplified Magnetic Resonance Index of Activity ≥1 compared with lower values. EHI differentiated ileitis numerically more than FCAL (delta: 24% to 25% vs. 11% to 21%). Patients with FCAL ≥50 µg/g had higher rates of severe inflammation compared with FCAL <50 µg/g (75% vs. 47%, P<0.001), whereas smaller differentiation existed for EHI threshold of 42 (63% vs. 49%, P=0.35). CONCLUSION: Both EHI and FCAL were specific in their confirmation of inflammation and disease activity on MRE in patients with CD. However, MRE-detected inflammation was frequently present in the presence of low EHI and FCAL in similar proportions.

Quantitative Ultrasound Biomarkers to Assess Nonalcoholic Fatty Liver Disease.

PURPOSE: To assess diagnostic performance of quantitative ultrasound (QUS) biomarkers in assessing hepatic steatosis. METHODS: We prospectively recruited 125 participants (mean age 54 years) who underwent liver QUS, magnetic resonance imaging (MRI), and laboratory tests within 30 days in this IRB approved study. Based on MRI-proton density fat fraction (MRI-PDFF) and MRE, we divided 125 participants into normal liver, nonalcoholic fatty liver (NAFL) and liver fibrosis (≥F1) groups. We examined diagnostic performance of ultrasound attenuation coefficient (AC), normalized local variance (NLV), superb microvascular imaging-based vascularity index (SMI-VI), and shear wave velocity (SWV) for determining hepatic steatosis and fibrosis using area under receiver operating characteristic curve (AUC). We also analyzed correlations of QUS biomarkers to MRI using Spearman correlation coefficient. RESULTS: We observed significant differences in AC, NLV, and SMI-VI among the three groups (22 participants with normal liver, 78 with NAFL, and 25 with liver fibrosis). AUC of AC, NLV, and SMI-VI for determining ≥ mild steatotic livers (MRI-PDFF ≥5%) was 0.95, 0.90, and 0.92, respectively. AUC of SWV for determining ≥ F1 liver fibrosis was 0.93. The correlation of MRI-PDFF was positive to AC (r = 0.91) and negative to NLV (r = -0.74), SMI-VI (r = -0.8) in NAFL group. There was a significant difference in regression slope of AC to MRI-PDFF in livers with and without ≥F1 (0.84 vs 0.91, P = .02). CONCLUSIONS: QUS biomarkers have high sensitivity and specificity to determine and grade hepatic steatosis and detect liver fibrosis. The effect of liver fibrosis on the performance of QUS biomarkers in quantifying liver fat content warrants further investigation.

Magnetic Resonance Imaging Radiomics-Based Machine Learning Prediction of Clinically Significant Prostate Cancer in Equivocal PI-RADS 3 Lesions.

BACKGROUND: While Prostate Imaging Reporting and Data System (PI-RADS) 4 and 5 lesions typically warrant prostate biopsy and PI-RADS 1 and 2 lesions may be safely observed, PI-RADS 3 lesions are equivocal. PURPOSE: To construct and cross-validate a machine learning model based on radiomics features from T2 -weighted imaging (T2 WI) of PI-RADS 3 lesions to identify clinically significant prostate cancer (csPCa), that is, pathological Grade Group ≥ 2. STUDY TYPE: Single-center retrospective study. POPULATION: A total of 240 patients were included (training cohort, n = 188, age range 43-82 years; test cohort, n = 52, age range 41-79 years). Eligibility criteria were 1) magnetic resonance imaging (MRI)-targeted biopsy between 2015 and 2020; 2) PI-RADS 3 index lesion identified on multiparametric MRI; (3) biopsy performed within 1 year of MRI. The percentages of csPCa lesions were 10.6% and 15.4% in the training and test cohorts, respectively. FIELD STRENGTH/SEQUENCE: A 3 T; T2 WI turbo-spin echo, diffusion-weighted spin-echo echo planar imaging, dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging. ASSESSMENT: Multislice volumes-of-interest (VOIs) were drawn in the PI-RADS 3 index lesions on T2 WI. A total of 107 radiomics features (first-order histogram and second-order texture) were extracted from the segmented lesions. STATISTICAL TESTS: A random forest classifier using the radiomics features as input was trained and validated for prediction of csPCa. The performance of the machine learning classifier, prostate specific antigen (PSA) density, and prostate volume for csPCa prediction was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The trained random forest classifier constructed from the T2 WI radiomics features good and statistically significant area-under-the-curves (AUCs) of 0.76 (P = 0.022) for prediction of csPCa in the test set. Prostate volume and PSA density showed moderate and nonsignificant performance (AUC 0.62, P = 0.275 and 0.61, P = 0.348, respectively) for csPCa prediction in the test set. CONCLUSION: The machine learning classifier based on T2 WI radiomic features demonstrated good performance for prediction of csPCa in PI-RADS 3 lesions. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 2.

Imaging and Treatment of Complications of Abdominal and Pelvic Mesh Repair.

Surgical mesh is used most frequently for tension-free repair of abdominal wall hernias in adults, because the rate of hernia recurrence is lower with mesh than with primary soft-tissue repair. Since the introduction of polypropylene mesh in the middle of the 20th century, many mesh materials and configurations for specific surgical procedures have been developed. In addition to abdominal wall hernia repair, mesh may be used for repair of diaphragmatic hernias, urinary incontinence in women (female slings), genitourinary prolapse (vaginal mesh and sacrocolpopexy), rectal prolapse (rectopexy), and postprostatectomy male urinary incontinence (male slings). General mesh repair complications include chronic pain; fluid collections such as seromas, hematomas, and abscesses; adhesions that may lead to intestinal blockage; erosion into solid or hollow viscera including enterocutaneous fistulizing disease; and mesh failure characterized by mesh shrinkage, detachment, and migration with repair malfunction. Several mesh complications are often diagnosed with imaging, primarily with CT and less frequently with MRI and US, despite variable mesh visibility at imaging. This article reviews the common surgical mesh applications in the abdomen and pelvis, discusses imaging of mesh repair complications, and provides complication treatment highlights.©RSNA, 2020.

Ultrasound Strain Imaging to Assess the Biceps Brachii Muscle in Chronic Poststroke Spasticity.

OBJECTIVES: The aim of the study was to assess the feasibility of ultrasound strain imaging in characterizing the biceps brachii muscle in chronic poststroke spasticity. METHODS: We prospectively analyzed strain imaging data from bilateral biceps brachii muscles in 8 healthy volunteers and 7 patients with poststroke chronic spasticity. Axial deformations of the biceps brachii muscle and overlying subcutaneous tissue were produced by external compression using a sandbag (1.0 kg) attached to a transducer. The lengthening and shortening of the biceps brachii muscle and subcutaneous tissue were produced by manual passive elbow extension (from 90° to 0°) and flexion (from 0° to 90°), respectively. We used offline 2-dimensional speckle tracking to estimate axial and longitudinal strain ratios (biceps brachii strain/subcutaneous tissue strain), and the longitudinal tissue velocity of the biceps brachii muscle. Statistical analyses included analysis of variance for testing differences in strain imaging parameters among healthy, nonspastic, and spastic biceps brachii muscles, the Bonferroni correction for further testing differences in US strain imaging among paired groups (healthy versus spastic, nonspastic versus spastic, and healthy versus nonspastic), and the Pearson correlation coefficient for assessing the intraobserver reliability of performing strain imaging in stroke survivors. RESULTS: The differences in strain imaging parameters between healthy and spastic and between nonspastic and spastic biceps brachii muscles were significant at both 90° elbow flexion and maximal elbow extension (P < .01). There was no significant difference in axial strain ratios at 90° of elbow flexion or longitudinal tissue velocities between healthy and nonspastic muscles (P > .05). The intraobserver reliability of performing strain imaging in stroke survivors was good (r = 0.85; P < .01). CONCLUSIONS: Ultrasound strain imaging seems to be feasible for characterizing the biceps brachii muscle in chronic poststroke spasticity.

Corticomedullary strain ratio: a quantitative marker for assessment of renal allograft cortical fibrosis.

OBJECTIVES: To quantitatively assess the correlation between the corticomedullary strain ratio and cortical fibrosis in renal transplants. METHODS: Using quasistatic ultrasound elasticity imaging, we prospectively assessed the corticomedullary strain ratio in renal allografts of 33 patients who underwent renal transplant sonography and biopsy. Based on Banff score criteria for renal cortical fibrosis, 33 allografts were divided into 2 groups: group 1 (n = 19), with mild (<25%) fibrosis; and group 2 (n = 14), with moderate (>26%) fibrosis. We used 2-dimensional speckle-tracking software to perform offline analysis of cortical and medullary strain induced by external compression by the ultrasound transducer. We then calculated the corticomedullary strain ratio (cortical normalized strain/medullary normalized strain; normalized strain = developed strain/applied strain [deformation from the abdominal wall to the pelvic muscles]). An unpaired 2-tailed t test was used to determine differences in normalized strain and the strain ratio between the groups. Receiver operating characteristic curve analysis was performed to determine the best strain ratio cutoff value for identifying moderate fibrosis. RESULTS: Normalized strain differed between the cortex and medulla (mean ± SD: group 1, 4.58 ± 2.02 versus 2.58 ± 1.38; P = .002; group 2, 1.71 ± 0.42 versus 2.60 ± 0.87; P = .0011). The strain ratio in group 1 was higher than in group 2 (2.06 ± 1.33 versus 0.70 ± 0.20; P = .0007). The area under the receiver operating characteristic curve was 0.964. The sensitivity and specificity of a strain ratio cutoff value of 0.975 for determining moderate fibrosis were 92.9% and 94.7%, respectively. CONCLUSIONS: Strain values vary in different compartments of the kidney. The corticomedullary strain ratio on ultrasound elasticity imaging decreases with increasing renal cortical fibrosis, which makes it potentially useful as a noninvasive quantitative marker for monitoring the progression of fibrosis in renal transplants.

Spleen stiffness and splenoportal venous flow: assessment before and after transjugular intrahepatic portosystemic shunt placement.

OBJECTIVES: To prospectively assess changes in spleen stiffness and splenoportal venous flow before and after transjugular intrahepatic portosystemic shunt (TIPS) placement. METHODS: We prospectively evaluated spleen stiffness measured by the mean shear wave velocity with acoustic radiation force impulse imaging and the splenoportal venous velocity with color Doppler sonography in 12 patients (mean age ± SD, 42.6 ± 11.0 years; range, 29-65 years) who underwent TIPS placement for portal hypertension and gastroesophageal bleeding. The mean shear wave velocity and angle-corrected splenoportal venous velocity at the main portal and splenic veins were measured 1 day before and 3 to 9 days after TIPS placement (mean interval, 6.0 ± 1.95 days; range, 4-10 days) and were compared with portal vein pressure measured during the procedure. RESULTS: There was a significant difference in portal vein pressure before and after TIPS (25.34 ± 6.21 versus 15.66 ± 6.07 mm Hg; P = .0005). After TIPS, the mean shear wave velocity decreased significantly in all 12 cases (3.50 ± 0.46 versus 3.15 ± 0.39 m/s before and after TIPS; P = .00015). The flow velocity at the main portal vein increased significantly after TIPS (22.21 ± 4.13 versus 47.25 ± 12.37 cm/s; P = .0000051). The splenic vein velocity and spleen index measured 25.57 ± 6.98 cm/s and 55.99 ± 21.27 cm(2), respectively, before TIPS and 35.72 ± 11.10 cm/s and 50.11 ± 21.12 cm(2) after TIPS (P = .0004 and .003). CONCLUSIONS: A significant decrease in the mean shear wave velocity and increase in the splenoportal venous velocity occurred with reduced portal vein pressure after TIPS placement. Hence, both parameters can be used as noninvasive quantitative markers for monitoring TIPS function after placement.

Non-invasive imaging biomarkers to assess nonalcoholic fatty liver disease: A review.

This review summarizes the current state of non-invasive diagnosis of non-alcoholic fatty liver disease (NAFLD). This begins with a brief discussion of blood-based analysis (serum biomarkers) then progresses through various imaging modalities (imaging biomarkers) including magnetic resonance (MR), computed tomography (CT), and ultrasound-based imaging methods. The review concludes with comment on the advantages, disadvantages, and prospects of commercially available modalities and the impact they may have on diagnosis and management of patients with NAFLD.

Ultrasound Elastography to Assess Botulinum Toxin A Treatment for Post-stroke Spasticity: A Feasibility Study.

The aim of the study was to evaluate the feasibility of using ultrasound elastography to assess the effect of botulinum toxin A (BoNT-A) treatment on post-stroke spasticity of the upper limb. In this prospective study, we performed ultrasound elastography (strain imaging and acoustic radiation force impulse-based shear wave elastography) of the spastic biceps brachii muscle in seven patients (five men and two women, mean age: 45y) who underwent BoNT-A injection treatment for post-stroke spasticity of the upper limb. We measured ultrasound elasticity parameters including axial strain ratio (SR) (SR = muscle strain/reference strain), longitudinal SR and shear wave velocity of the biceps muscle immediately before and 17-30 d (mean: 22 d) after BoNT-A injection. Statistical analyses included a two-tailed paired t-test to examine the difference in ultrasound elasticity parameters of bilateral biceps muscles before and after BoNT-A treatment and a Spearman rank correlation coefficient (rs) to analyze the correlation of ultrasound elasticity parameters to clinical assessment with the Modified Ashworth Scale (MAS) and Tardieu Scale (TS). The difference in ultrasound elasticity parameters before and after BoNT-A treatment was significant (p < 0.05) in the treated spastic muscle. The correlation of ultrasound elasticity parameters with MAS and the angle of catch and range of motion in TS were also significant (rs = 0.55-0.95, p < 0.05). Our results suggest that ultrasound elastography is feasible in assessment of the effectiveness of BoNT-A treatment for post-stroke spasticity of the upper limb.

Serum Ustekinumab Concentrations Are Associated With Improved Outcomes With the Magnetic Resonance Index of Activity for Crohn's Disease.

Higher ustekinumab concentrations were associated with improved radiologic (Simplified Magnetic Resonance Index of Activity for Crohn's Disease) and stringent biomarker (calprotectin) outcomes. The high concentration needed for these novel endpoints validates previous studies using the same assay.

Quantitative Ultrasound Imaging to Assess the Biceps Brachii Muscle in Chronic Post-Stroke Spasticity: Preliminary Observation.

We prospectively investigated the feasibility of using quantitative ultrasound imaging (QUI) to assess the biceps brachii muscle (BBM) in individuals with chronic post-stroke spasticity. To quantify muscle echogenicity and stiffness, we measured QUI parameters (gray-scale pixel value and shear wave velocity [SWV, m/s]) of the BBM in three groups: 16 healthy BBMs; 12 post-stroke, non-spastic BBMs; and 12 post-stroke, spastic BBMs. The QUI results were compared with the Modified Ashworth Scale and Tardieu Scale. A total of 20 SWVs were measured in each BBM, once at elbow in 90° flexion and again at maximally achievable extension using acoustic radiation force impulse imaging. BBM pixel value was measured in gray-scale images captured at 90° elbow flexion using ImageJ software. Statistical analyses included analysis of variance for examining the difference in SWV and pixel values among the three groups; Bonferroni correction for testing the difference in SWV and pixel values in a paired group; t-test for examining the difference in SWV values measured at two elbow angles; and Pearson correlation coefficient for analyzing the correlation of QUI to Modified Ashworth Scale and Tardieu Scale. SWV significantly differed between spastic BBMs and non-spastic or healthy BBMs. For pixel values, each of the three groups significantly differed from the others at elbow 90° flexion. The difference in SWV measured between the two elbow angles was also significant (p <0.01). A strong negative correlation was found between SWV and passive range of motion (R2 = -0.88, p <0.0001) in spastic upper limbs. These results suggest that the use of QUI is feasible in quantitative assessment of spastic BBM.

Randomized study of paclitaxel and tamoxifen deposition into human brain tumors: implications for the treatment of metastatic brain tumors.

PURPOSE: Drug resistance in brain tumors is partially mediated by the blood-brain barrier of which a key component is P-glycoprotein, which is highly expressed in cerebral capillaries. Tamoxifen is a nontoxic inhibitor of P-glycoprotein. This trial assessed, in primary and metastatic brain tumors, the differential deposition of paclitaxel and whether tamoxifen could increase paclitaxel deposition. EXPERIMENTAL DESIGN: Patients for surgical resection of their primary or metastatic brain tumors were prospectively randomized to prior paclitaxel alone (175 mg/m(2)/i.v.) or tamoxifen for 5 days followed by paclitaxel. Central and peripheral tumor, surrounding normal brain and plasma, were analyzed for paclitaxel and tamoxifen. RESULTS: Twenty-seven patients completed the study. Based on a multivariate linear regression model, no significant differences in paclitaxel concentrations between the two study arms were found after adjusting for treatment group (tamoxifen versus control). However, in analysis for tumor type, metastatic brain tumors had higher paclitaxel concentrations in the tumor center (1.93-fold, P = 0.10) and in the tumor periphery (2.46-fold, P = 0.039) compared with primary brain tumors. Pharmacokinetic analyses showed comparable paclitaxel areas under the serum concentration between treatment arms. CONCLUSIONS: Paclitaxel deposition was not increased with this tamoxifen schedule as the low plasma concentrations were likely secondary to concurrent use of P-450-inducing medications. However, the statistically higher paclitaxel deposition in the periphery of metastatic brain tumors provides functional evidence corroborating reports of decreased P-glycoprotein expression in metastatic versus primary brain tumors. This suggests that metastatic brain tumors may respond to paclitaxel if it has proven clinical efficacy for the primary tumor's histopathology.

Ultrasound Strain Imaging in Assessment of Biceps Muscle Stiffness and Dynamic Motion in Healthy Adults.

We prospectively evaluated the feasibility of using ultrasound strain imaging (USI) to assess biceps brachii muscle (BBM) stiffness and dynamic motion in 10 healthy adults. The BBM axial deformation was produced by external compression with a sandbag (1.0 kg) tied onto the transducer. The BBM lateral movement was produced by manual passive elbow flexion and extension. By use of 2-D speckle tracking, captured 5-s real-time ultrasound data of BBM were processed to estimate axial strain, representing muscle stiffness, and lateral strain and tissue velocity, representing muscle dynamic motion. Axial (lateral) strain ratio was defined as BBM strain divided by subcutaneous soft tissue strain. There was no significant difference in lateral strain or tissue velocity between the left and right BBM (lateral strain ratio: 4.69 ± 0.07 vs. 4.51 ± 0.08 for extension, 4.82 ± 0.09 vs. 4.69 ± 0.11 for flexion; tissue velocity: 1.58 ± 0.32 cm/s vs. 1.78 ± 0.85 cm/s for extension, -2.03 ± 0.63 vs. -2.03 ± 0.59 for flexion; all p values > 0.05) or between men and women (lateral strain ratio: 4.52 ± 0.06 vs. 4.67 ± 0.1 for extension, 4.71 ± 0.11 vs. 4.83 ± 0.09 for flexion; tissue velocity, cm/s: 1.76 ± 0.76 vs. 1.66 ± 0.65 for extension, -2.21 ± 0.65 vs. -1.88 ± 0.52 for flexion, all p values > 0.05). The difference in axial stain between men and women was significant (axial strain ratio: 3.09 ± 0.43 vs. 3.52 ± 0.26, p = 0.02). Inter- and intra-observer reliability in performing USI of the BBM was good (all intra-class correlation coefficients [ICCs] >0.75). Our results suggest that USI seems to be feasible for and reproducible in estimating BBM mechanical properties and motion dynamics in healthy adults.

Ultrasound shear wave elastography in the assessment of passive biceps brachii muscle stiffness: influences of sex and elbow position.

OBJECTIVE: To assess differences in biceps brachii muscle (BBM) stiffness as evaluated by ultrasound shear wave elastography (SWE). METHODS: The passive stiffness of the BBM was quantified with shear wave velocity (SWV) measurements obtained from 10 healthy volunteers (5 men and 5 women, mean age 50years, age range 42-63 years) with the elbow at full extension and 30° flexion in this IRB-approved study. Potential differences between two depths within the muscle, two elbow positions, the two arms, and sexes were assessed by using two-tailed t-test. The reproducibility of SWV measurements was tested by using intraclass correlation coefficient (ICC). RESULTS: Significantly higher passive BBM stiffness was found at full elbow extension compared to 30° of flexion (p≤0.00006 for both arms). Significantly higher passive stiffness in women was seen for the right arm (p=0.04 for both elbow positions). Good correlation of shear wave velocity measured at the different depths. The ICC for interobserver and intraobserver variation was high. CONCLUSIONS: SWE is a reliable quantitative tool for assessing BBM stiffness, with differences in stiffness based on elbow position demonstrated and based on sex suggested.

The evolution of adjuvant and neoadjuvant chemotherapy and radiation for advanced pancreatic cancer: from 5-fluorouracil to GTX.

This article reviews the relevant literature and reports on The Columbia University Medical Center experience with chemoradiation for pancreatic cancer.

Laparoscopic coloanal anastomosis for low rectal cancer.

OBJECTIVES: Low anterior resection with hand-sutured coloanal anastomosis for low rectal cancer is technically feasible, and it does not compromise oncologic results. We describe herein the effectiveness of the operation in treating low rectal cancer by a laparoscopic approach followed by intraanal canal dissection. METHODS: From February 1999 to October 1999, we used a laparoscopic procedure to divide the inferior mesenteric vessels and to dissect downward into the pelvic cavity as low as possible. A purse-string suture 1-cm distal to the lower margin of the tumor was secured and transection of the rectum was performed circumferentially via the anal canal near the dentate line. The specimen was removed by the pull-through method and coloanal anastomosis was completed with hand suture. A protective loop ileostomy was fashioned. RESULTS: We operated on 8 patients (4 males) with low tumor localization (average 4-cm above the dentate line). The age ranged from 45 to 83 years, with a median age of 64. The average operation time was 210 minutes (150 to 360 minutes), and the average blood loss was 250 cc (minimal to 750 cc). No operative mortalities occurred, but 2 patients had minor anastomotic slough complications. The average hospital stay was 13 days (7 to 26 days). The postoperative pathologic stage was T2N0M0 in 4 patients, T3N0M0 in 2 patients, T2N1M0 in 1 patient, and T3N2M0 in 1 patient. No local recurrence or distant metastasis occurred during the median 14 months (12 to 20 months) of follow-up. CONCLUSION: Laparoscopic coloanal anastomosis combined with intraanal canal dissection is safe and technically feasible. The oncologic results seem not to be compromised, but need further evaluation.

Fly through ultrasound imaging in assessment of carotid atherosclerosis: a pictorial essay.

To assess fly through ultrasound imaging (FTUS) in evaluation of carotid artery atherosclerosis, we prospectively performed conventional sonography and FTUS of the carotid artery on 66 patients with suspicion for atherosclerosis. Characteristics of arterial intima, atherosclerotic plaque, luminal narrowing, and carotid stent graft displayed on FTUS were compared with that on conventional sonography. On FTUS, normal carotid artery wall was smooth in appearance, mild carotid atherosclerosis appeared focal arterial wall irregularity and small plaque formation, arterial luminal reduction resulted from progressive artery plaques, and carotid stent had irregular inner lumen and tight fit against the arterial wall. A total of 38 plaques were detected by conventional sonography, while 48 plaques were depicted by FTUS in 25 patients. Using magnetic resonance angiography as a reference standard, 17 cases with >50% and 3 cases with <50% luminal reduction measured on FTUS. However, all those 20 cases were measured with >50% luminal reduction on conventional sonography. Compared with conventional sonography, FTUS can dynamically display intraluminal structure on real-time three-dimensional imaging morphologically to improve the accuracy in detecting atherosclerotic plaque and assessing luminal narrowing in the carotid artery.

Multi-institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high-grade gliomas.

BACKGROUND: The prognosis for patients with recurrent high-grade gliomas is poor and treatment options are limited. Current chemotherapeutic regimens can improve clinical outcomes, but extend survival by only a few months. Temozolomide is a methylating agent that is typically administered once daily. Because preclinical studies suggested that a twice-daily dosing schedule might be more effective, the safety and efficacy of twice-daily dosing of temozolomide were studied in patients with recurrent gliomas at their first, second, or third recurrence. METHODS: This multi-institutional trial enrolled 120 patients with recurrent glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO). An initial oral dose of 200 mg/m(2) of temozolomide was followed by 9 consecutive doses of 90-mg/m(2) every 12 hours. Treatment cycles were repeated every 28 days. Doses were escalated to 100 mg/m(2) twice daily in the absence of unacceptable toxicity or were reduced if unacceptable toxicity occurred. RESULTS: For GBM, AA, and AO patients, respectively, the median progression-free survival (PFS) was 4.2 months, 5.8 months, and 7.7 months, whereas the median overall survival (OS) was 8.8 months, 14.6 months, and 18 months. The overall response rate (partial and complete) for the GBM, AA, and AO patients was 31%, 46%, and 46%, respectively. Grade 3/4 toxicities included neutropenia (1.1%), thrombocytopenia (3.6%), and anemia (0.3%) (graded according to the World Health Organization grading system). CONCLUSIONS: Twice-daily dosing may enhance the efficacy of temozolomide in the treatment of recurrent gliomas without increasing toxicity. This regimen compares favorably with other dosing schedules of temozolomide reported in the literature.

Tamoxifen paradoxically decreases paclitaxel deposition into cerebrospinal fluid of brain tumor patients.

BACKGROUND: P-glycoprotein (Pgp) mediates, in part, resistance to natural product chemotherapy drugs which constitute over half of the available drugs for cancer treatment. Tamoxifen (TAM) enhances intracellular deposition of natural product chemotherapy in human cell lines by inhibition of Pgp. Pgp is highly expressed in the choroid plexus and is thought to be a key component of the blood-cerebrospinal fluid barrier (BCSFB). We conducted a prospective, randomized study to assess if Pgp inhibition by TAM alters deposition of paclitaxel in cerebrospinal fluid (CSF). METHODS: Ten patients with either primary or metastatic brain tumors were randomized to: paclitaxel alone (175 mg/m2/IV) or a course of TAM (160 mg/m2 PO BID on Days 1-5) followed by paclitaxel (175 mg/m2/IV on Day 5). CSF and plasma samples were obtained following paclitaxel infusion; paclitaxel and TAM concentrations were measured by high-performance liquid chromatography assays. RESULTS: Paclitaxel was detected in the CSF of six of the 10 patients. Peak CSF paclitaxel concentrations of the paclitaxel and paclitaxel-TAM groups ranged between 3.5-57.4 and 2.3-24.6 nM, respectively. Though there was a 2.4-fold higher mean CSF paclitaxel concentration and a 3.7-fold higher median peak CSF:plasma paclitaxel ratio for those who received paclitaxel alone as compared to combined paclitaxel-TAM, it was not statistically significant (P = 0.22). In one patient enrolled to both arms, higher CSF concentrations of paclitaxel and higher paclitaxel CSF: plasma ratios were observed when given paclitaxel alone. CONCLUSIONS: The trend towards lower paclitaxel CSF concentrations when given with TAM is consistent with the published finding that Pgp's localization in the endothelial cells of the choroid plexus works in an opposite direction and keeps drugs in the CSF. Thus, agents which inhibit Pgp, such as TAM, may increase efflux of Pgp substrates out of the BCSFB and may paradoxically lower CSF concentrations of natural product chemotherapy drugs. Conceptually, this finding implies that the Pgp in the BBB and BCSFB keeps natural toxins such as paclitaxel, from entering the brain (BBB) and, if they do enter the brain, keeps them in the CSF (BCSFB) where they may be less harmful than if they re-entered the brain. Thus, our work supports this novel idea and adds to the understanding of the functions of the BCSFB.