Embolization of high flow arteriovenous malformations: experience with use of superabsorbent polymer microspheres

PURPOSE: To determine efficacy, safety, and requirements for adjunctive embolization or surgery in the treatment of symptomatic arteriovenous malformations (AVMs) with superabsorbent polymer microsphere (SAP-MS) particles. MATERIALS AND METHODS: SAP-MS particles (sodium acrylate and vinyl alcohol copolymer) are nonbiodegradable spheres with a precisely calibrated diameter. SAP-MS particles swell by absorbing fluids and become soft and deformable. Twenty-five patients (16 men, nine women; mean age, 32 y; range 12-66 y) with symptomatic facial (n = 5), upper- (n = 8) and lower- (n = 12) extremity AVMs were treated primarily (n = 23) or preoperatively (n = 2) by transarterial embolization (TAE) treatment with use of SAP-MS particles. Direct puncture embolization (DPE; n = 4) and/or surgical intervention (n = 5; ie, skin graft, resection, or amputation) were required. Surgical specimens from the resected (n = 2) and the amputated (n = 2) patients were evaluated histologically. Follow-up study, including clinical findings and imaging studies, was performed at intervals ranging from 3 months to 1 year. Clinical outcome was evaluated retrospectively, depending on the subjective improvement of symptoms and signs, according to the medical records. RESULTS: Seventy-two TAEs (range, 1-11; mean, 2.8) and 12 DPEs (range, 1-3; mean, 2.4) were performed during the mean follow-up period of 38 months (range, 7-110 mo). Twenty patients (80%) experienced symptom improvement by embolotherapy alone (n = 17) or in combination with surgery (n = 3). One lip and two finger AVMs were totally removed by surgical excision or amputation after TAE treatment. In diffuse upper- (n = 1) and lower- (n = 1) extremity AVMs, the symptoms were uncontrolled. No nerve injury or skin necrosis was observed after TAE treatment with SAP-MS particles. Mucosal necrosis was induced by DPE with ethanol in one patient. Histologically, SAP-MS particles penetrated intralesional vessels and conformed to the vessel lumen, resulting in tight vessel occlusion. Minimal perivascular reaction was observed. CONCLUSION: SAP-MS particles were used safely in TAE treatment of AVM. TAE treatment with use of SAP-MS particles was suitable for certain symptomatic AVMs, but diffuse AVMs remain a challenge and a combination of alternative methods will be necessary for further strategy.     

Small hypervascular hepatocellular carcinoma revealed by double arterial phase CT performed with single breath-hold scanning and automatic bolus tracking

OBJECTIVE: The purpose of this study was to evaluate the usefulness of double arterial phase CT for the detection of small hypervascular hepatocellular carcinomas, using an automated bolus-tracking technique to initiate the hepatic arterial phase CT. MATERIALS AND METHODS: Double arterial and late phase contrast-enhanced helical CT scans were obtained on 287 consecutive patients suspected of having hepatocellular carcinoma. These included 56 patients with 90 small (< or 3 cm) hepatocellular carcinomas and 50 patients with no hepatocellular carcinomas. CT scans of these patients were interpreted by three reviewers. The first arterial phase scan was initiated automatically 10 sec after the bolus-tracking program detected the threshold enhancement of 50 H in the abdominal aorta. Three reviewers interpreted the late phase CT scans in combination with the first, second, or both hepatic arterial phases. Measures of the reviewers' detection of hepatocellular carcinoma included analysis of interobserver variation, sensitivity, specificity, and area under receiver operating characteristic curve (A(z)). RESULTS: The time elapsed from bolus initiation to threshold aortic enhancement ranged from 10 to 24 sec (mean, 13 sec), resulting in initiation of the first arterial phase CT scan from 20 to 34 sec (mean, 23 sec). The combination of late phase CT and both first and second arterial phase images showed significantly better performance than the combination of the late phase and either the first or second arterial phases, although the difference was most evident in comparison with the combination of second arterial and late phases. CONCLUSION: An automated bolus-tracking program can be used to optimize the timing of hepatic arterial phase CT. Multiphasic CT performed using this technique is useful in detection of small hepatocellular carcinoma.     

Incremental value of assessment of regional wall motion for detection of multivessel coronary artery disease in exercise (201)Tl gated myocardial perfusion imaging.

Assessment of reversible perfusion defects in exercise (201)Tl perfusion SPECT has low sensitivity and high specificity for detection of multivessel coronary artery disease (CAD). The goal of this study was to evaluate whether worsening of left ventricular regional wall motion assessed by an automated algorithm in exercise (201)Tl electrocardiography-gated SPECT had incremental diagnostic value over perfusion data for detection of multivessel CAD. METHODS: Two hundred one patients underwent exercise (201)Tl gated SPECT. Software that automatically analyzes left ventricular function was used to assess exercise and rest regional wall motion. Regional wall motion on initial images was compared with that on rest images, that is, delayed images for patients without reinjection images and reinjection images for patients with reinjection images. The left ventricle was divided into 9 segments, with individual segments assigned to 3 coronary territories. Worsening of wall motion was defined as worsening in any segment on initial images compared with rest images. RESULTS: Of 73 patients with multivessel CAD, 20 (27.4%) had reversible perfusion defects in multiple coronary territories, 26 (35.6%) exhibited worsening of regional wall motion in multiple territories, and 37 (50.7%) had reversible perfusion defects or worsening of regional wall motion in multiple territories. The sensitivity of the combination of reversible perfusion defect and worsening of regional wall motion was significantly higher than that of reversible perfusion defect alone for detection of multivessel CAD (50.7% vs. 27.4%, P < 0.05). The specificity of the combination of reversible perfusion defect and worsening of regional wall motion for detecting multivessel CAD did not differ from that of reversible perfusion defect alone and that of worsening of regional wall motion alone (94.5% vs. 99.2% and 97.7%, respectively, P = not statistically significant). CONCLUSION: Combined assessment of worsening of left ventricular regional wall motion by exercise and perfusion data in exercise (201)Tl gated myocardial SPECT was more sensitive, with acceptable specificity, than was assessment with perfusion data alone for detection of multivessel CAD.     

<Emphasis Type="Italic">KRAS</Emphasis> and <Emphasis Type="Italic">BRAF</Emphasis> Mutations in 203 Esophageal Squamous Cell Carcinomas: Pyrosequencing Technology and Literature Review

Background

Epidermal growth factor receptor (EGFR) signaling is one of the most promising targets for molecular-targeted therapies in esophageal squamous cell carcinoma (ESCC). Thus, the molecular diagnosis of KRAS and BRAF mutations is clinically important in therapeutic decision making. However, the frequency of KRAS and BRAF mutations in ESCCs remains inconclusive because of the limited sample sizes of previous studies (all N ≤ 80). Pyrosequencing is a nonelectrophoretic nucleotide extension sequencing technology that can be used for mutation testing.

Methods

The frequency of KRAS and BRAF mutations was examined using a nonbiased database of 203 resected ESCCs and a high-throughput pyrosequencing assay.

Results

The validity of the KRAS pyrosequencing method was initially demonstrated by detection of all 4 types of KRAS mutations [c.35G>T (codon 12 GGT>GTT), c.35G>A (codon 12 GGT>GAT), c.34G>T (codon 12 GGT>TGT), c.38G>A mutation (codon 13 GGC>GAC)], which had been previously diagnosed using Scorpion-ARMS technology, in 9 colon cancer tissues (9 of 9; 100 %). Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing. Subsequently, the KRAS mutation was found to be extremely rare (1 of 203; 0.5 %), and the BRAF mutation was absent (0 of 203; 0 %), in the dataset of 203 ESCCs.

Conclusions

These results suggest that KRAS and BRAF mutations play a limited role in the development of ESCC and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in ESCC.

     

Liver sinusoidal endothelial cells have a capacity for inducing nonresponsiveness of T cells across major histocompatibility complex barriers

Livers transplanted across major histocompatibility complex (MHC) barriers in mice are normally accepted without recipient immune suppression. To identify the cell type that contributes to induction of such a tolerance state, we established an allogeneic mixed hepatic constituent cell-lymphocyte reaction (MHLR) assay. Hepatic constituent cells were isolated from C57BL/6 (B6) and Balb/c mice as stimulators, and splenocytes were isolated from B6 mice as responders. Irradiated hepatic constituent cells were co-cultured with fluorescent dye (CFSE)-labeled B6 splenocytes. In the allogeneic MHLR using either whole hepatic constituent cells or parenchymal hepatocytes as stimulators, a lack of T-cell proliferation was observed. Only when CD105(+) cells, which are exclusively liver sinusoidal endothelial cells (LSECs), were depleted from hepatic constituent cell stimulators, the MHLR resulted in marked proliferation of both allo-reactive CD4(+) and CD8(+) T cells. These results indicate that CD105(+) LSECs have the capacity to induce nonresponsiveness of T cells across MHC barriers.     

Epidural ropivacaine anesthesia decreases the bispectral index during the awake phase and sevoflurane general anesthesia

The sedative effects of epidural anesthesia without volatile and IV anesthetics and quantification of the degree of epidural anesthesia-induced sedation have not been investigated. In the current study we evaluated the effects of epidural anesthesia on the bispectral index (BIS) during the awake phase and during general anesthesia. After placing the epidural catheter, the patients were randomly allocated to 2 groups receiving either 5 mL of epidural saline (group S) or the same volume of 0.75% ropivacaine (group R). The BIS measurements during the awake phase were performed at 7, 12, 13, 14, 22, and 23 min after the epidural injection. General anesthesia was then induced with propofol and vecuronium and maintained with 0.75% sevoflurane. From approximately 10 min after tracheal intubation, the BIS measurements were made at 1-min intervals for 10 min. The BIS during the awake phase was significantly lower in group R than in group S (P < 0.05). The BIS during general anesthesia was significantly lower in group R than in group S (P < 0.0001). Epidural anesthesia decreased the BIS during the awake phase and during general anesthesia. The decrease of the BIS associated with epidural anesthesia was more prominent during general anesthesia than during the awake phase.     

Induction of 11beta-hydroxysteroid dehydrogenase type 2 and hyperaldosteronism are essential for enhanced sodium absorption after total colectomy in rats

BACKGROUND: Patients who undergo total colectomy with ileopouch anal reconstruction often have persistent diarrhea and frequent bowel movements. Analysis of the intestinal adaptation after total colectomy may lead to developing novel therapies for postoperative diarrhea. METHODS: Sprague-Dawley rats underwent total colectomy with ileoanal reconstruction and were sacrificed 4 and 8 weeks later. Mucosal response to aldosterone was evaluated with the use of ileal mucosa in an Ussing chamber by measuring short circuit current after in vitro stimulation with aldosterone. We investigated the expression of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD 2) in intestinal epithelial cells. To examine the role of hyperaldosteronism, we also evaluated rats treated with a sodium-deficient diet or subcutaneous aldosterone infusion. RESULTS: Aldosterone levels increased 80-fold after total colectomy. A comparable amount of aldosterone dramatically increased aldosterone-mediated, amiloride-sensitive short circuit current in the mucosa from colectomized rats, but not in control rats. We measured an increase in 11beta-HSD 2 messenger RNA and protein in the distal ileum from colectomized rats. Circulating aldosterone appears to be essential for these functional and molecular changes because similar results were obtained by using the mucosa from both dietary sodium-depleted and aldosterone-infused rats. CONCLUSIONS: Induction of 11beta-HSD 2 is essential for enhanced mineralocorticoid action in the remnant ileum after total colectomy in rats.     

Advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with oral squamous cell carcinoma

Purpose

Hypoxia, a prognostic factor in many types of cancer, can be detected by ¹⁸F-fluoromisonidazole (FMISO) positron emission tomography (PET). It is unclear whether hypoxia reflects the response to chemotherapy in patients with oral squamous cell carcinoma (OSCC). The correlations of FMISO-PET and FDG-PET with histological response to preoperative chemotherapy were therefore assessed in patients with OSCC.

Methods

This study enrolled 22 patients with OSCC undergoing preoperative chemotherapy. The T-stages were T2 in 6 patients, T3 in 3, and T4a in 13, and the N-stages were N0 in 14 patients, N1 in 3, and N2 in 5. Each patient was evaluated by both FMISO-PET and FDG-PET before surgery, and the maximum standardized uptake value (SUV_max) of FDG- and FMISO-PET and tumor-muscle ratio (TMR) of FMISO-PET were measured. The threshold for the hypoxic volume based on TMR was set at 1.25. The histological response to preoperative chemotherapy was evaluated using operative materials.

Results

FMISO-PET and FDG-PET detected uptake by primary OSCCs in 15 (68 %) and 21 (95 %) patients, respectively, and median SUV_maxs of FMISO- and FDG-PET in the primary site were 2.0 (range, 1.3–3.5) and 16.0 (range, 1.0–32.2), respectively. The median of FMISO TMR was 1.5 (range, 0.99–2.96). There were five cases whose FMISO TMR was less than 1.25. Histological evaluation showed good response to preoperative chemotherapy in 7 patients (32 %) and poor response in 15 (68 %). Good response was significantly more prevalent in patients with negative than positive FMISO uptake (P?P?=?0.04), whereas FDG uptake was not significantly correlated with response to chemotherapy response. Multivariate logistic regression analysis showed that FMISO uptake was an independent significant predictor of response to preoperative chemotherapy (P?=?0.03, odds ratio?=?0.06, 95 % confidence interval?=?0.004–0.759).

Conclusions

An advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with OSCC was observed.     

Congenital absence of a lumbar pedicle presenting with contralateral lumbar radiculopathy

The authors describe a rare case of a congenital absence of the right L5 pedicle in a 54-year-old man presenting with low back pain and radicular pain of his left leg. Plain x-ray films, computed tomography scan (CT) after myelography, and three-dimensional CT revealed the absence of the L5 pedicle and anomaly of the L4-L5 facet joint on his right side. On the left side, there were severe degenerative changes that were thought to be the result of an overload and instability. The degenerative changes led to late-onset neurologic impairment of the contralateral side, which was treated with spinal fusion. To our knowledge, this is the first report of contralateral symptoms due to unilateral defect of the facet joint accompanied by aplasia of a pedicle.     

In Vivo Molecular Imaging Characterizes Pulmonary Gene Expression During Experimental Lung Transplantation

Experimental gene therapy is a promising strategy to prevent ischemia-reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus-1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty-four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r(2) = 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.