Christina Kalogeropoulou

Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study

Objective. To assess the efficacy of rituximab (RTX) in SSc. Methods. Fourteen patients with SSc were evaluated. Eight patients were randomized to receive two cycles of RTX at baseline and 24 weeks [each cycle consisted of four weekly RTX infusions (375 mg/m2)] in addition to standard treatment, whereas six patients (control group) received standard treatment alone. Lung involvement was assessed by pulmonary function tests (PFTs) and chest high-resolution CT (HRCT). Skin involvement was assessed both clinically and histologically. Results. There was a significant increase of forced vital capacity (FVC) in the RTX group compared with baseline (mean ± s.d.: 68.13 ± 19.69 vs 75.63 ± 19.73, at baseline vs 1-year, respectively, P = 0.0018). The median percentage of improvement of FVC in the RTX group was 10.25%, whereas that of deterioration in the controls was 5.04% (P = 0.002). Similarly, diffusing capacity of carbon monoxide (DLCO) increased significantly in the RTX group compared with baseline (mean ± s.d.: 52.25 ± 20.71 vs 62 ± 23.21, at baseline vs 1-year respectively, P = 0.017). The median percentage of improvement of DLCO in the RTX group was 19.46%, whereas that of deterioration in the control group was 7.5% (P = 0.023). Skin thickening, assessed with the Modified Rodnan Skin Score (MRSS), improved significantly in the RTX group compared with the baseline score (mean ± s.d.: 13.5 ± 6.84 vs 8.37 ± 6.45 at baseline vs 1-year, respectively, P < 0.001). Conclusion. Our results indicate that RTX may improve lung function in patients with SSc. To confirm our encouraging results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

Externally coated ureteral metallic stents: an unfavorable clinical experience.

Abstract Objective: The purpose of the present study was to evaluate the use of externally coated stents in patients with malignant ureteral obstruction. Materials and Methods: We have prospectively evaluated 16 patients, 10 men and 6 women, with malignant ureteral obstruction treated successfully by placement of Passager metal stents (Boston Scientific, Natick, MA, USA) bypassing the stricture. Mean patient age was 65.6 years (range 62–78 years). Ureteral patency was confirmed 24 and 48 hours by injection of contrast material through the nephrostomy tube, and after patency confirmation the nephrostomy catheter was removed. Results: All stents were positioned successfully, and the postoperative course was uneventful. In 13 cases (81.2%) the prostheses finally migrated into the bladder hindering overall ureteral patency (mean time of migration: 1.5 months). Patency was achieved in the remaining ureters ( n =3), during the follow-up period (mean: 8 months, range 6–16 months), without any need for further intervention. Conclusion: The inappropriate anchorage and the increased ureteral peristalsis are the main causes of migration towards the bladder, thus, minimizing the usefulness of this stent for the treatment of ureteral strictures.

Texture classification‐based segmentation of lung affected by interstitial pneumonia in high‐resolution CT

Accurate and automated lung field (LF) segmentation in high-resolution computed tomography (HRCT) is highly challenged by the presence of pathologies affecting lung borders, also affecting the performance of computer-aided diagnosis (CAD) schemes. In this work, a two-dimensional LF segmentation algorithm adapted to interstitial pneumonia (IP) patterns is presented. The algorithm employs k-means clustering followed by a filling operation to obtain an initial LF order estimate. The final LF border is obtained by an iterative support vector machine neighborhood labeling of border pixels based on gray level and wavelet coefficient statistics features. A second feature set based on gray level averaging and gradient features was also investigated to evaluate its effect on segmentation performance of the proposed method. The proposed method is evaluated on a dataset of 22 HRCT cases spanning a range of IP patterns such as ground glass, reticular, and honeycombing. The accuracy of the method is assessed using area overlap and shape differentiation metrics (d(mean), d(rms), and d(max)), by comparing automatically derived lung borders to manually traced ones, and further compared to a gray level thresholding-based (GLT-based) method. Accuracy of the methods evaluated is also compared to interobserver variability. The proposed method incorporating gray level and wavelet coefficient statistics demonstrated the highest segmentation accuracy, averaged over left and right LFs (overlap=0.954, d(mean)=1.080 mm, d(rms)=1.407 mm, and d(max)=4.944 mm), which is statistically significant (two-tailed students t test for paired data, p<0.0083) with respect to all metrics considered as compared to the proposed method incorporating gray level averaging and gradient features (overlap=0.918, d(mean)=2.354 mm, d(rms)=3.711 mm, and d(max)=14.412 mm) and the GLT-based method (overlap=0.897, d(mean)=3.618 mm, d(rms)=5.007 mm, and d(max)=16.893 mm). The performance of the three segmentation methods, although decreased as IP pattern severity level (mild, moderate, and severe) was increased, did not demonstrate statistically significant difference (two-tailed students t test for unpaired data, p>0.0167 for all metrics considered). Finally, the accuracy of the proposed method, based on gray level and wavelet coefficient statistics ranges within interobserver variability. The proposed segmentation method could be used as an initial stage of a CAD scheme for IP patterns.

Is There a Role for B-cell Depletion as Therapy for Scleroderma? A Case Report and Review of the Literature

OBJECTIVES Rituximab (RTX) has been successfully used in the treatment of several rheumatic diseases with an acceptable safety profile. We present herein a patient with systemic sclerosis (SSc) who exhibited significant improvement of his lung function and skin fibrosis following RTX administration, and review the literature regarding the role of B-cells in SSc and the potential efficacy of RTX in its treatment. METHODS We performed an internet search using the keywords systemic sclerosis, scleroderma, rituximab, B-cells, fibrosis, interstitial lung disease (ILD), and therapy. RESULTS Our patient, a 40-year old man with severe SSc-associated ILD, received 4 courses of RTX. The patients lung function improved; forced vital capacity and diffusing capacity of carbon monoxide reached values of 35% and 33%, respectively, compared with 30% and 14% of pretreatment values. Skin thickening assessed clinically and histologically improved as well. Several lines of evidence suggest that B-cells may have a pathogenic role in SSc. B-cells from tight skin mice--an animal model of SSc--exhibit chronic hyperactivity; likewise, B-cells from patients with SSc overexpress CD19 and are chronically activated. Furthermore, studies have revealed that B-cell genes were specifically transcribed in SSc skin and that B-cell infiltration was a prominent feature of SSc-associated ILD. The potential clinical efficacy of RTX in SSc has been explored in a limited number of patients with encouraging results. Preliminary data suggest that RTX may favorably affect skin as well as lung disease in SSc. CONCLUSIONS Several basic research data underscore the potential pathogenic role of B-cells in SSc and clinical evidence suggests that RTX might be a therapeutic option in SSc. Large-scale multicenter studies are needed to evaluate the potential clinical efficacy of RTX in SSc.

Metallic stents in gynecologic cancer: an approach to treat extrinsic ureteral obstruction.

Objective: We report on our experience with the use of self–expandable metal stents for the treatment of extramural ureteral obstruction in patients with gynecologic cancer to restore ureteral patency and to alleviate the ureterectasis and hydronephrosis proximal to the ureteral narrowing.Methods: Fourteen women (mean age 48 years) with obstructive uropathy secondary to gynecologic malignancies were treated successfully by placement of Wallstent self–expandable intraureteral metallic stents. The patients were followed for a mean period of 15 (range 9–24) months.Results: Obstructive uropathy was resolved in all cases. In 1 patient placement of an additional, totally coaxial, stent was considered necessary because of tumor ingrowth, occurring 6 months after the procedure. In another patient, tumor overgrowth invading the borderline area between the proximal ureteric end and the metallic prosthesis was seen 12 months after stent placement causing obstruction. Thus, an additional Wallstent was implanted overlapping the initially placed stent. Patency was achieved in all the remaining ureters, during the follow–up period, without any need for further intervention.Conclusion: Implantation of self–expandable metal stents is a safe and effective method for bypassing ureteral obstruction due to gynecologic malignancies.

Imaging in Percutaneous Nephrolithotomy

Image guidance is a critical factor for the performance of urologic interventions. Percutaneous minimally invasive procedures have been developed and are being used with constantly increasing frequency. Procedures such as percutaneous nephrolithotomy (PCNL) are not performed without any image guidance. Recent developments in medical imaging, such as three-dimensional radiographic fluoroscopy, CT, and magnetic resonance (MR) fluoroscopy, four-dimensional ultrasonography, and image fusion techniques, propose a new generation of image-guidance tools that promise to improve patient care. These developments have been used or have the potential to be used in PCNL and other urologic interventional procedures. Moreover, advanced needles and needle guidance systems provide a new perspective for the nephrolithotomy suite of the future. The current review presents existing imaging technology in PCNL and interventional urology as well as advanced imaging techniques that are being or are expected to be evaluated in PCNL practice.

URETEROPELVIC JUNCTION OBSTRUCTION: AN INNOVATIVE APPROACH COMBINING METALLIC STENTING AND VIRTUAL ENDOSCOPY

PURPOSE We report our experience with auto-expandable metallic stents for treating ureteropelvic junction obstruction. MATERIALS AND METHODS We treated 4 patients with a mean age of 45 years who had ureteropelvic junction obstruction with placement of a self-expandable intraureteral metallic stent (Wallstent, Schneider, Zurich, Switzerland). All patients presented with recurrent ureteropelvic junction obstruction after open pyeloplasty. Excretory urography and 3-dimensional reconstruction computerized tomography were performed 1 and 6 months after stent insertion. Virtual endoscopy images were obtained at followup due to the need to define ureteral patency. RESULTS Mean followup was 16 months (range 9 to 24). Wallstent placement was successful and immediate patency was achieved in all cases. During followup 3 patients required no further intervention and the stented ureteropelvic junction remained patent. In the remaining patient stricture recurred 2 months after initial stent insertion due to the ingrowth of scar tissue through the prosthesis. Additional intervention was deemed necessary after placing a longer 6 cm., completely coaxial overlapping metal stent. Virtual endoscopy and excretory urography findings concurred. Virtual endoscopy allows visualization of the stented ureteropelvic junction lumen cephalad and caudal to the prosthesis. It also enables easy navigation within the stent at different angles of view. CONCLUSIONS The concept of applying metallic stents for ureteropelvic junction obstruction and adjacent adynamic ureteral segments combined with virtual endoscopy is strengthened by the results of this study.

Coated v Noncoated Ureteral Metal Stents: An Experimental Model

PURPOSE The purpose of the present study was to compare the standard metal stents with internally and externally coated metal stents in the pig model. MATERIALS AND METHODS In nine female pigs weighing between 25 and 30 kg, the metal stents were randomly placed in either the right or left ureter, for a total of 18 stented ureters. Six ureters were stented with a Wallstent (Schneider, Zurich, Switzerland), six with a Passager stent (Boston Scientific, Natick, MA, USA), and six with a Corvita endoluminal graft (CEG) (Boston Scientific, Natick, MA, USA). Patency was examined by nephrostotomography 24 hours and 21 days after the initial procedure. RESULTS Free flow of urine through the stents into the bladder was revealed in all ureters with the exemption of four cases where a Passager stent migrated into the bladder, jeopardizing ureteral patency. The Wallstent generated mild inflammation with metaplasia of the urothelium; the CEG a more pronounced inflammatory response in the adjacent ureter; and the Passager stent severe inflammatory reaction with necrosis of the urothelium. The sections of the Wallstents revealed the presence of a mild polypoid reaction adherent to the internal surface of the devices. The coated stents showed no tissue ingrowth through the lining material into the ureteral lumen, and thus, the urothelium was compressed beneath the prostheses. CONCLUSIONS Our experimental results suggest that the standard Wallstent generates less inflammation of the surrounding tissues than coated stents. The coated stents have the advantage of minimal tissue ingrowth but have a tendency to migrate toward the bladder.

A novel radiological approach for the experimental study of angiogenesis: angiography of the chick embryo and its chorioallantoic membrane

We use a modification of the digital substraction angiography (DSA) technique to visualize the vascular system of the chorioallantoic membrane (CAM) of the developing chick embryo. After catheterization of the central vein of the CAM with a metallic needle and injection of contrast medium, angiography was performed at specified follow-up intervals (1-2.5 images per second) using the Philips DVI-S Angiography Unit. By applying the vascular casting technique we were able to visualize the vessels of the CAM and to study the existing complex vascular-anatomical relationships. Our results show that DSA demonstrates the development of the circulatory system of the chick embryo (heart and vessels) and the vessels of its CAM effectively. By applying for the first time interventional radiology techniques on the chick embryo system, it has been possible to study morphological changes of the vessels during angiogenesis in vivo. These results suggest that this technique can be a proven and valuable tool in the quantitative assessment of angiogenesis.

Gorlin-Goltz syndrome: incidental finding on routine ct scan following car accident.

IntroductionGorlin-Goltz syndrome is a rare hereditary disease. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and loss or mutations of human patched gene (PTCH1 gene). Multiple basal cell carcinomas (BCCs), odontogenic keratocysts, skeletal abnormalities, hyperkeratosis of palms and soles, intracranial ectopic calcifications of the falx cerebri and facial dysmorphism are considered the main clinical features. Diagnosis is based upon established major and minor clinical and radiological criteria and ideally confirmed by DNA analysis. Because of the different systems affected, a multidisciplinary approach team of various experts is required for a successful management.Case presentationWe report the case of a 19 year-old female who was involved in a car accident and found to present imaging findings of Gorlin-Goltz syndrome during a routine whole body computed tomography (CT) scan in order to exclude traumatic injuries.ConclusionRadiologic findings of the syndrome are easily identifiable on CT scans and may prompt to early verification of the disease, which is very important for regular follow-up and better survival rates from the co-existent diseases.