Non-invasive molecular detection of bladder cancer recurrence

Transitional cell carcinoma (TCC) is the most common bladder tumor and approximately 90% of bladder TCC are superficial at initial diagnosis. High recurrence rate and possible progression to muscle invasive disease that is eventually indicated for radical cystectomy are established features of these tumors. Therefore, reliable predictors of tumor recurrence are of critical importance for management of superficial bladder TCC. Successful molecular diagnosis of bladder cancer by detecting genetic lesions: loss of heterozygosity (LOH) or microsatellite instability (MSI) in cells exfoliated in urine has been reported by several groups including ours. The aim of our study was to evaluate the predictive potential of microsatellite analysis of cells exfoliated in urine in the detection of superficial bladder TCC recurrence. We studied 47 Caucasian patients with confirmed superficial bladder TCC (37 pTa, 10 pT1) at initial diagnosis. Blood samples were obtained once from every patient whereas urine samples were collected before each cystoscopy (initial and follow-up). Matched DNAs from blood and urine were subjected to microsatellite analysis in a blinded fashion. The follow-up period ranged 12-48 months after tumor resection. Microsatellite analysis correctly identified 94% (44/47) of primary tumors and 92% (12/13) of tumor recurrences. Interestingly enough, 75% (9/12) of tumor recurrences were molecularly detected 1-9 months before cystoscopic evidence of recurrent disease. This study demonstrated clearly that not only urine microsatellite analysis reliably detected superficial bladder tumors, but also was a reliable test for detecting and predicting tumor recurrence in Caucasian patients. These results warrant multicenter randomized trials.     

Nerve growth factor and enhancement of proliferation,invasion, and tumorigenicity of pancreatic cancer cells

Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain non-neuronal tumors. In pancreatic cancer NGF is overexpressed, and this overexpression is associated with increased perineural invasion. NGF has the potential to stimulate the growth of some pancreatic cancer cell lines, and this effect is mediated by the phosphorylation of tyrosine kinase receptor A and mitogen-activated protein kinase activation; it is dependent on the expression levels of tyrosine kinase receptor A and p75 receptors. To determine whether cancer cell-derived NGF can participate in the regulation of pancreatic cancer cell proliferation, PANC-1 human pancreatic cancer cells were stably transfected with a full-length human beta-NGF expression vector. In vitro and in vivo growth characteristics were analyzed by proliferation assays and invasion assays and in a nude mouse tumor model. Stable transfection of NGF in PANC-1 cells resulted in enhanced anchorage-dependent growth, with a decrease in doubling times of up to 50%, and in an approximately twofold increase in anchorage-independent cell growth and cell invasion. Furthermore, stably transfected PANC-1 cells showed enhanced tumorigenicity in nude mice. These results suggest that NGF has the capacity to act in a paracrine and/or an autocrine manner in pancreatic cancer and that it enhances cancer cell growth and invasion in vivo, thereby contributing to the aggressiveness and poor prognosis of this disease.     

Coccidioidal meningitis: incidental diagnosis 3 y after ventriculo-peritoneal shunt placement for hydrocephalus

A patient from the American Midwest developed hydrocephalus after a trip to southwest California, necessitating placement of a ventriculo-peritoneal shunt. Coccidioidal meningitis was diagnosed incidentally 3 y later, during evaluation for shunt malfunction.     

Severe cholestatic hepatitis caused by thiazolidinediones: risks associated with substituting rosiglitazone for troglitazone

Troglitazone maleate (Rezulin) has been associated with severe hepatotoxicity, which led to its withdrawal from the U.S. market in March 2000. Rosiglitazone maleate (Avandia) is being marketed as a safe alternative in the treatment of type 2 diabetes mellitus. We report a case of severe thiazolidinedione-induced cholestatic hepatitis in a 56-year-old female patient at a university hospital who was given rosiglitazone, 8 mg/day, after she developed milder hepatotoxicity while taking troglitazone. Rosiglitazone was discontinued, and the patient was treated with prednisone, azathioprine, and ursodiol. Clinical evaluation and liver biopsy were performed and liver function tests were monitored. After being switched from troglitazone to rosiglitazone the patient developed a severe cholestatic hepatitis with marked jaundice and moderate increases in serum alkaline phosphatase and -glutamyltranspeptidase but only mild increases in serum aminotransferases. Discontinuation of rosiglitazone and treatment with prednisone, azathioprine, and ursodiol led to improvement, albeit with residual injury, dropout of intrahepatic bile ducts, and persisting elevations of serum alkaline phosphatase. Rosiglitazone is not always a safe alternative in patients who have had hepatotoxicity to troglitazone. It is important to monitor the serum alkaline phosphatase in addition to the serum aminotransferases in patients taking thiazolidinediones.     

Combined time-resolved and high-spatial-resolution 3D MRA using an extended adaptive acquisition

PURPOSE: To combine the benefits of time-resolved dynamic imaging and single elliptical centric acquisitions in a reasonable scan time. MATERIALS AND METHODS: A time series of images with moderate spatial resolution was acquired using the 3D Time-Resolved Imaging of Contrast KineticS (3D TRICKS) technique with elliptical centric encoding during contrast arrival. Following venous opacification, a complete large centrically encoded k-space volume was acquired. The high-spatial-frequency portions of this volume were combined with a 3D TRICKS time frame to form a high-resolution image. An additional single image is formed by suppressing background and signal averaging all acquired data, including post-venous low-spatial-frequency data. For this image, 2D temporal correlation analysis is used to suppress low-spatial-frequency vein contributions. Arrival time and spatial correlations are used to suppress background. RESULTS: The 3D TRICKS time frame may be selected to ensure a combined high-resolution image that has optimal central k-space sampling for any vascular region. The single image formed by signal averaging all acquired data has increased contrast-to-noise (CNR) and signal-to-noise (SNR) ratios. CONCLUSION: The advantages of time-resolved and high-spatial-resolution imaging were combined using an extended dual-phase acquisition. Some SNR and CNR gain was achieved by signal averaging. This process is facilitated by background and vein suppression.     

Evaluating 90Y-glass microsphere treatment response of unresectable colorectal liver metastases by [18F]FDG PET: a comparison with CT or MRI

The purpose of this prospective study was to evaluate yttrium-90 glass microsphere treatment of unresectable liver metastases by fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET), and to compare the effectiveness of [18F]FDG PET for this purpose with that of computed tomography (CT) or magnetic resonance imaging (MRI) and determination of the serum carcinoembryonic antigen (CEA) level. Thirteen hepatic lobes from eight consecutive patients with colorectal cancer referred for 90Y-glass microsphere treatment of unresectable liver metastases who underwent both baseline (pretreatment) and 3-month posttreatment PET were studied. All patients also had correlative pre- and posttreatment CT or MRI for evaluation of the anatomic response and serum CEA determination for assessment of the total tumor load, as well as pretreatment hepatic intra-arterial technetium-99m macroaggregated albumin scan for lung shunting evaluation and hepatic arteriography for assessment of vascular anatomy and treatment. 90Y-glass microspheres were infused via an intra-arterial catheter under low pressure. Dedicated whole-body PET scans were analyzed visually and compared by lesion and by lobe with CT or MRI. A metabolic response after 90Y treatment to single or both hepatic lobes, assessed by PET, was present in a significantly higher proportion of the lobes than was an anatomic response, evaluated by CT or MRI (12 vs 2 lobes respectively, P<0.0002). Posttreatment PET showed no, stable, progressive, and new extrahepatic metastases in two, three, one, and two patients respectively. Following treatment, serum CEA decreased significantly, correlating with PET but not with CT or MRI. Thus, the study demonstrated a significant difference between the metabolic and the anatomic response after 90Y-glass microsphere treatment for unresectable liver metastases in colorectal cancer. PET appears to be an accurate indicator of treatment response.     

The role of selective computed tomography in the diagnosis and management of suspected acute appendicitis

The negative appendectomy rate in patients with clinically diagnosed acute appendicitis is 20 to 40 per cent. Recently CT has emerged as a powerful diagnostic tool in the evaluation of suspected appendicitis and its routine use has been advocated. The objective of this study was to evaluate the impact of selective use of abdominal CT on the negative appendectomy rate. Three hundred eight patients were enrolled in this prospective study. Abdominal CT was performed in patients with uncertain clinical signs of appendicitis. CT was not performed in patients with either a very high or a very low index of suspicion. The results were compared with a retrospective analysis of 85 consecutive patients operated by clinical diagnosis alone. One hundred twenty-seven patients had a final diagnosis of acute appendicitis. CT was performed in 198 patients (64%). The sensitivity, specificity, and accuracy of CT scans were 91, 92, and 91 per cent, respectively. Surgical management plans were altered in 54 patients after obtaining the CT results; unnecessary delay in surgical treatment or unnecessary operations were prevented in 28 and 26 patients, respectively. In addition CT detected unrelated pathologies in 23 patients. CT was not performed in patients with low index of suspicion and none were found to suffer from acute appendicitis. The negative appendectomy rate was 17 per cent (7% men and 24% women) in patients selected for surgery on the basis of very high clinical suspicion alone. Overall the negative appendectomy rate with the selective use of CT was 16 per cent, which is significantly lower than the rate achieved by diagnosing patients on clinical grounds alone (24%). CT is highly accurate in diagnosing or ruling out acute appendicitis and may substantially decrease the negative appendectomy rate as well as unnecessary delayed observation. We believe that CT should be performed routinely in women with suspected appendicitis and selectively in men.     

Does gender affect neonatal hyperbilirubinemia in low-birth-weight infants?

BACKGROUND: Neonatal mortality and morbidity are gender-biased in low-birth-weight (LBW) infants. The male disadvantage theory has been suggested to be responsible for these maturational differences. OBJECTIVE: To examine the impact of gender on neonatal hyperbilirubinemia. DESIGN/METHODS: A retrospective observational study. Data on all LBW infants admitted to George Washington University neonatal intensive care unit and surviving for >48 hrs from January 1992 to March 2003 were analyzed. Males and females were compared for gestational age, birth weight, race, Apgar scores at 1 and 5 mins, peak bilirubin levels, sepsis, and intraventricular hemorrhage (IVH). Significant differences were entered in a regression model to detect the influence of gender on bilirubin (Bili). Analysis was repeated after stratification of infants into: group A, <1000 g; group B, 1000-1499 g; and group C, 1500-2499 g. RESULTS: A total of 840 infants were included in this study. When comparing males (n = 407) with females (n = 433), significant differences were detected in birth weight (1,539 +/- 541 vs. 1,428 +/- 549 g; p = .003), IVH (14.2% vs. 9%; p = .025), and Bili (10.1 +/- 3.0 vs. 9.2 +/- 2.8 mg%; p < .001). No differences were detected in gestational age, sepsis, or Apgar 1 and 5. Difference in Bili for the entire group remained significant in the regression model (regression coefficient [RC] = 0.79 +/- 0.22; p < .001). In subgroup analyses: group A Bili (8.4 +/- 2.3 vs. 8.0 +/- 2.0; p = .14) and group B Bili (9.0 +/- 2.1 vs. 9.2 +/- 2.2; p = .51) did not differ in bivariate or multivariate analyses. In group C, Bili was (11.3 +/- 3.1 vs. 10.1 +/- 3.3; p < .001) and remained the only significant difference in the regression model (RC = 1.19 +/- 0.37; p = .001). CONCLUSIONS: Bili in LBW infants is significantly higher in males when compared with females. After stratification to birth weight subgroups, significance is retained in the 1500- to 2499-g group after logistic regression analysis. Bili levels in infants <1500 g are influenced more significantly by factors other than gender, such as sepsis and IVH.     

Host feeding of mosquitoes (Diptera: Culicidae) associated with the recurrence of Rift Valley fever in Egypt

In 1993, Rift Valley fever (RVF) virus reappeared in Egypt. We determined the prevalence and feeding patterns of mosquitoes in 5 villages where the virus was active. Of 10 species recovered, Aedes caspius (Pallas), Culex pipiens L., Cx. antennatus (Becker), and Cx. perexiguus Theobald constituted 99% of > 35,000 mosquitoes captured in dry ice-baited CDC light traps. Ae. caspius was most prevalent, except at Nag' El Hagar where it was replaced by Cx. perexiguus. Cx. pipiens ranked 2nd, except at Nag' El Ghuneimiya, where it was replaced by Cx. antennatus. Most blood meals analyzed by an enzyme-linked immunosorbent assay reacted to > or = 1 antiserum. Cx. pipiens was mainly anthropophagic, and therefore may have been the main vector of RVF virus among humans. Ae. caspius feeds were chiefly from humans, bovines, and equines. Cx. antennatus and Cx. perexiguus fed generally on bovines. Mixed blood meals from humans and RVF virus susceptible animals were identified in the predominant mosquitoes. Prevalence and host selection, as well as predicted probability for a blood meal being interrupted, indicated that Ae. caspius may have served as a bridge vector between humans and bovines in 4 of the villages. Cx. perexiguus may have played this role at Nag' El Hagar. Because potential vectors are abundant, susceptible domestic animals are associated closely with humans, and surveillance of imported livestock is not systematic, we conclude that RVF virus sporadically will recur in Egypt.     

Adenomyoepithelioma of the breast: Report of a case initially examined by fine-needle aspiration

This report describes the morphologic features of an adenomyoepithelioma of the breast that was first examined by fine-needle aspiration. On retrospective review of the cytology, the stromal elements of this adenomyoepithelioma showed extensive metachromasia on Diff-Quik stain, had elongated nuclei, and on Papanicolaou stain showed elongated, pale, wispy cytoplasm. Clusters of stromal cells were usually intimately associated with epithelial elements. While the main differential consideration, cystosarcoma phylloides, can show similar features, it may be possible to distinguish the two lesions in some instances.