Retinoic acid-induced gene expression in normal and leukemic myeloid cells.

Retinoic acid has been shown to induce large accumulations of tissue transglutaminase in cultured myeloid cells. Addition of retinoic acid to mouse resident peritoneal macrophages increased the level of tissue transglutaminase mRNA within 30-60 min. Retinoic acid also increased tissue transglutaminase mRNA levels in human promyelocytic leukemia (HL-60) cells. These studies show that retinoic acid can induce acute alterations in specific gene expression in both normal and leukemic myeloid cells.

Primary sequence of ovomucoid messenger RNA as determined from cloned complementary DNA.

Ovomucoid messenger RNA (mRNAom) comprises approximately 8% of the total mRNA in the estrogen-stimulated oviduct. The recombinant plasmid pOM100 contained DNA complementary to the 3' end of mRNAom. DNA complementary to the 5' end of mRNAom was obtained from a partially purified preparation of mRNAom by polymerization by reverse transcriptase in the presence of a restriction fragment primer from pOM100. The complementary DNA mixture was amplified by molecular cloning using poly dG/dC tailing to form recombinant bacterial plasmids. Recombinant plasmids containing ovomucoid DNA sequences were selected by in situ hybridization to 32P-labeled pOM100 fragments. The longest plasmid containing ovomucoid DNA sequences was designated pOM502. The complete DNA sequence of both pOM100 and pOM502 was determined. The two plasmids appear to contain sequences complementary to the entire length of mRNAom. The nucleic acid sequence agrees with the known amino acid sequences for both ovomucoid and its N-terminal signal peptide. Highly homologous sequences occur in two regions that coincide with structural domains of the protein. Comparison of the sequence of mRNAom with that for other eucaryotic mRNAs allowed identification of possible functional regions in the mRNA molecule.

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival.

We sought to evaluate the biological function of the receptor tyrosine kinase EphB4 in bladder cancer. All of the nine bladder cancer cell lines examined express EphB4 and the receptor could be phosphorylated following stimulation with its cognate ligand, EphrinB2. Out of the 15 fresh bladder cancer specimens examined, 14 expressed EphB4 with a mean sevenfold higher level of expression compared to adjacent normal urothelium. EphB4 expression was regulated by several mechanisms: EPHB4 gene locus was amplified in 27% tumor specimens and 33% cell lines studied; inhibition of EGFR signaling downregulated EphB4 levels; and forced expression of wild-type p53 reduced EphB4 expression. EphB4 knockdown using specific siRNA and antisense oligodeoxynucleotides molecules led to a profound inhibition in cell viability associated with apoptosis via activation of caspase-8 pathway and downregulation of antiapoptotic factor, bcl-xl. Furthermore, EphB4 knockdown significantly inhibited tumor cell migration and invasion. EphB4 knockdown in an in vivo murine tumor xenograft model led to a nearly 80% reduction in tumor volume associated with reduced tumor proliferation, increased apoptosis and reduced tumor microvasculature. EphB4 is thus a potential candidate as a predictor of disease outcome in bladder cancer and as target for novel therapy.

Complications of radical cystectomy.

Radical cystectomy has become a standard and arguably the best definitive form of therapy for high-grade, invasive bladder cancer. Lower urinary tract reconstruction, particularly orthotopic diversion, has been a major component in enhancing the quality of life of patients requiring cystectomy. As with any major surgery, however, complications do arise. It is important for all surgeons to be familiar with the presentation, prevention and treatment of the major causes of morbidity and mortality associated with radical cystectomy and lower urinary tract reconstruction. The complications discussed are among the most common of the complications seen with cystectomy and urinary-intestinal diversion. There are, in fact, many others that may be encountered, as the published literature testifies, and a thorough understanding as to their presentation, prevention and treatment is equally essential for a successful patient outcome. Adherence to proper surgical technique, familiarization with recent data regarding the most successful treatment methods, and attention to detail in the perioperative period are crucial for minimizing complications in any surgical undertaking. Radical cystectomy with orthotopic neobladder as well as total pelvic exenteration and its modifications need to be considered among the treatment options for patients with muscle invasive bladder cancer or advanced pelvic malignancies. Recent advances in patient selection, surgical technique, and perioperative care have led to decreased morbidity. Despite this, these procedure remain complex with the potential for both short and long-term complications. There is abundant evidence that radical cystectomy for bladder malignancies and pelvic exenteration for primary rectal cancer and cervical cancer can lead to meaningful long-term survival; however, the prognosis after pelvic exenteration for recurrent rectal cancer is not as good. The recent introduction of combined chemoradiotherapy is likely to improve local recurrence rates and may translate into more durable long-term survival. Pelvic exenteration continues to have an important role in the multimodality approach to patients with advanced pelvic malignancies. In conclusion, pelvic exenteration appears to be a safe and effective option for an experienced multi specialty surgical team in the treatment of complex locally advanced pelvic malignancy. The success of pelvic exenteration is highly dependent on good patient selection where an en bloc resection may result in prolonged disease-free survival and long term cure. In recent times the morbidity and mortality of this operation has decreased so that palliative exenteration has a role to help improve quality of life for this difficult group of patients.

Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression.

BACKGROUND: Thrombospondin-1 (TSP) is a 430-kd glycoprotein that is an important component of the extracellular matrix and is known to be a potent inhibitor of angiogenesis (i.e., formation of new blood vessels) both in vitro and in vivo. Several reports suggest that TSP possesses tumor suppressor function, possibly through its ability to inhibit tumor neovascularization. It has recently been shown that TSP expression is enhanced by the product of the p53 gene (also known as TP53). PURPOSE: We examined the role of TSP expression in tumor recurrence and overall survival in patients with invasive bladder cancer. We also examined the relationship between alterations in p53 protein expression, TSP expression, and tumor angiogenesis. METHODS: Tumors from 163 patients (with a median follow-up of 7.7 years) who underwent radical cystectomy for invasive transitional cell carcinoma of the bladder (63 patients with organ-confined disease and no lymph node involvement, 48 patients with extravesical extension of the disease and no lymph node involvement, and 52 patients with metastasis to regional lymph nodes) were examined for TSP expression by immunohistochemistry, utilizing monoclonal antibody MA-II, which recognizes an epitope in the amino-terminal region of TSP. For each tumor, microvessel density counts and p53 protein expression status (via immunohistochemistry) were also determined. TSP expression was graded as low, moderate, or high without knowledge of clinical outcome, p53 status, and microvessel density count; tumors with moderate and high TSP levels were considered as one group. Groups of patients were compared by Kaplan-Meier product limit estimates of overall survival, the complement of cumulative incidence curves for recurrence-free survival, and the stratified logrank test. Reported P values are two-sided. RESULTS: TSP expression was significantly associated with disease recurrence (P = .009) and overall survival (P = .023). Patients with low TSP expression exhibited increased recurrence rates and decreased overall survival. TSP expression was an independent predictor of disease recurrence (P = .002) and overall survival (P = .01) after stratifying for tumor stage, lymph node status, and histologic grade, but it was not independent of p53 status. TSP expression was significantly associated with p53 expression status (P = .001) and microvessel density counts (P = .001). Tumors with p53 alterations were significantly more likely to demonstrate low TSP expression, and tumors with low TSP expression were significantly more likely to demonstrate high microvessel density counts. Results of an analysis of variance were compatible with the hypothesis that p53 affects tumor angiogenesis by regulating the level of TSP expression. CONCLUSIONS AND IMPLICATIONS: These data support the concept that TSP may possess a tumor-inhibitory function. TSP may act, in part, through the regulation of tumor neovascularity. These results may also provide insight into one mechanism by which p53 exerts its tumor suppressor effects, i.e., through the control of tumor angiogenesis.

Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer.

BACKGROUND: Altered expression of p53 protein is an important predictor of progression in bladder cancer. The action of p53 on cell cycle regulation is mediated, in part, through expression of the cyclin-dependent kinase inhibitor p21WAF/CIP1 (p21). Loss of p21 expression may, therefore, contribute to tumor progression. We sought to determine the relationship between p21 expression in bladder cancer and disease progression. METHODS: Tumor specimens were obtained from 242 patients who underwent cystectomy for bladder cancer. Median follow-up was 8.5 years (range, 0.1-11.8 years). Nuclear p21 status was determined by immunohistochemistry and was then analyzed in relationship to the probability of tumor recurrence, overall survival, and tumor p53 status. Reported P values are two-sided. RESULTS: Nuclear p21 expression was detected in the tumors of 156 (64%) of the 242 patients. Patients with p21-positive tumors had a decreased probability of tumor recurrence (P<.00001) and an increased probability of overall survival (P<.00001) in comparison with patients with p21-negative tumors. In a multivariable analysis, p21 expression was an independent predictor of tumor recurrence (P = .0017) and of survival (P = .006) when assessed with tumor grade, tumor stage, lymph node status, and p53 status. p21 expression was associated with p53 status (P<.001); 56% of tumors with p53 alterations showed loss of p21 expression, whereas 79% of tumors expressing wild-type p53 were p21 positive. Patients with p53-altered/p21-negative tumors demonstrated a higher rate of recurrence and worse survival compared with those with p53-altered/p21-positive tumors (P<.0001). Patients with 53-altered/p21-positive tumors demonstrated a similar rate of recurrence and survival as those with p53-wild type tumors. CONCLUSION: Loss of p21 expression is a statistically significant and independent predictor of bladder cancer progression. Maintenance of p21 expression appears to abrogate the deleterious effects of p53 alterations on bladder cancer progression.

Elevated and absent pRb expression is associated with bladder cancer progression and has cooperative effects with p53.

Rb protein (pRb) expression was evaluated in 185 cases of transitional cell carcinoma of the bladder from patients that underwent radical cystectomy. Tumors were stratified into three categories based on the percentage of nuclei expressing pRb: (a) 0, 0% of tumor cells showing nuclear reactivity; (b) 1+, 1-50% of tumor cells showing nuclear reactivity; and (c) 2+, >50% of tumor cells showing nuclear reactivity. Cases with undetectable (pRb 0) and high (pRb 2+) pRb reactivity had identical rates of recurrence. These cases had significantly higher recurrence (P = 0.0001) and lower survival rates (P = 0.0002) compared to cases with moderate (pRb 1+) pRb reactivity, indicating that high levels of pRb expression may reflect a dysfunctional (altered) Rb pathway. The tumors were also examined for alterations in p53 expression; patients with tumors altered in both p53 and pRb had significantly increased rates of recurrence (P < 0.0001) and survival (P < 0.0001) compared to patients with no alterations in either p53 or pRb; patients with alterations in only one of these proteins had intermediate rates of recurrence and survival. These results suggest that: (a) bladder cancers with high pRb expression do not show the tumor suppressor effects of the protein; and (b) alteration in both p53 and pRb may act in cooperative or synergistic ways to promote tumor progression.

The promoter of the mouse tissue transglutaminase gene directs tissue-specific, retinoid-regulated and apoptosis-linked expression.

Tissue transglutaminase is a multifunctional enzyme that accumulates to high levels in cells undergoing apoptosis. Retinoids act as an acute and direct regulator of tissue transglutaminase gene transcription. The studies reported here were carried out to elucidate the molecular mechanisms involved in the regulation of tissue transglutaminase expression. We have isolated and characterized the mouse tissue transglutaminase gene promoter and 3.8 kb of 5'-flanking DNA. A large fragment of the promoter that includes both the core promoter and 3.8 kb of 5'-flanking DNA shows retinoid-dependent transcriptional activity when stably transfected into HeLa cells. In these stably transfected HeLa cells both the endogenous tissue transglutaminase gene and transfected mouse tissue transglutaminase promoter are activated by all-trans retinoic acid and by retinoic acid receptor (RAR)-specific and retinoid X receptor (RXR)-specific retinoids. In embryos made transgenic with a transglutaminase promoter-beta-galactosidase reporter gene, the transgene shows specific patterns of expression during limb development. The transglutaminase transgene is expressed in cartilage, the cells of the apical ectodermal ridge, and in regions of apoptotic cell death of the interdigital mesenchyme. It appears that cis-acting elements responsible for the complex retinoid regulation, tissue- and apoptosis-specific expression are embedded within the proximal 3.8 kb of DNA flanking the 5'-end of the mouse tissue transglutaminase gene.

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.

PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

Synergistic induction of gene 33 expression by retinoic acid and insulin.

The expression of gene 33 in rat liver and hepatoma cells is regulated by multiple hormones and other bioactive agents. Previous studies have demonstrated a 15-fold increase in gene 33 mRNA after 1 h of insulin treatment. We demonstrate in this report that retinoic acid (RA) also controls the expression of this gene. Gene 33 mRNA levels are rapidly elevated by RA, with maximal accumulation (19-fold over control) attained after just 1 h of RA treatment. The transcription rate of gene 33 was increased by RA to a maximum level 6-fold greater than control values. Studies with inhibitors of RNA synthesis demonstrated no increase in the stability of gene 33 mRNA in response to RA or insulin. In addition, a synergistic induction of both gene 33 mRNA levels and the transcription rate of gene 33 was observed when both RA and insulin were added together. In the presence of both hormones, the transcription rate was induced almost 20-fold in 30 min, followed by a 49-fold increase in mRNA levels after 1 h. Thus, gene 33 represents the first example of a gene whose transcription rate is elevated directly by both insulin and RA, and synergistically elevated by treatment with both hormones together.

Molecular prognostication in bladder cancer--a current perspective.

The optimal management of bladder cancer depends on the accurate assessment of the tumour's biological potential. Advances in molecular biology and cytogenetics have spurred intense research in identifying and characterising prognostic markers for patients with transitional cell carcinoma (TCC) of the bladder. The molecular changes that occur can be categorised into (1) chromosomal alterations leading to carcinogenesis, (2) cellular proliferation as a result of dysregulation of cell cycle control, and (3) growth control processes such as angiogenesis leading to metastasis. The accumulation of these changes ultimately determines a tumour's clinical behaviour and response to therapy. As the understanding of bladder cancer evolves, novel molecular markers for prognostication will make their way from the research laboratory to the clinical setting with the promise to improve patient care and outcomes.

Enhanced apoptosis and radiosensitization by combined 13-cis-retinoic acid and interferon-alpha2a; role of RAR-beta gene.

PURPOSE: Combined use of 13-cis-retinoic acid (cRA) and interferon-alpha2a (IFNalpha) induced significant radiosensitization in human cervical cancer ME-180 cell line, whereas it failed to achieve similar radiation enhancement in HeLa cells. The differential radiosensitization could be from the difference of retinoic acid receptor (RAR) expression because RAR-beta was highly expressed in ME-180 cells in contrast to the HeLa cells where RAR-beta was not detectable. We examined the role of this gene in mediating radiosensitization by cRA and IFNalpha, and explored the mechanism of radiation-induced cell killing. METHODS AND MATERIALS: Human cervical cancer cell lines, ME-180 and HeLa, were treated with cRA and IFNalpha followed by radiation. Apoptosis and radiosensitization were quantitated by TUNEL assay (in situ DNA nick end labeling) and colony-forming ability of surviving cells. The cells were transfected with bcl-2 gene and RAR-beta gene to test the role of these genes in mediating radiosensitization and apoptosis. RESULTS: Synergistic radiosensitization and apoptosis was observed by combined use of cRA and IFNalpha with radiation in ME-180 cells which express high level of RAR-beta mRNA, whereas these were not seen in HeLa cells where RAR-beta mRNA is not detectable. Both radiosensitization and apoptosis were abolished by bcl-2 gene in ME-180 cells. RAR-beta gene transfection induced similar radiation enhancement and apoptosis in HeLa cells. CONCLUSION: Apoptosis and radiation response were enhanced in the cells with high level of RAR-beta mRNA expression. The RAR-beta gene appears to mediate the radiation-induced apoptosis by cRA and IFNalpha. These findings indicate that presence of RAR-beta in the cancer cells could be exploited for patient selection in using these drugs for apoptosis and radiosensitization.

Retinoic acid induction of the tissue transglutaminase promoter is mediated by a novel response element.

We recently cloned and sequenced two kilobases of the upstream flanking region of the mouse tissue transglutaminase gene. Transfection experiments showed that this region of the transglutaminase flanking sequence was sufficient to mediate a 4-fold induction in reporter gene expression by retinoic acid. The goal of these studies was to identify retinoid receptor binding sites within this proximal 2 kilobase sequence and then to determine if these binding sites had ligand-dependent enhancer activity. To accomplish this we first employed a competitive band-shift assay using PCR-synthesized genomic DNA fragments as probes. This assay identified a receptor binding site located 1.7 Kb upstream from the transcription start site that contained three consensus hexanucleotide 'half sites' separated by 7 and 5 bp, respectively. This tripartite response element was shown to mediate retinoic acid activation of a heterologous promoter in transient transfection assays in RAW264.7 cells. Our results suggest that this novel retinoid response element is responsible for the retinoic acid induction of mouse tissue transglutaminase gene expression observed in numerous cells.

The evolution of a complex eucaryotic gene.

Two thirds of the natural chicken ovomucoid gene has been sequenced, including all exons and the intron sequences surrounding all fourteen intron/exon junctions. The junctions sequences surrounding four of the introns are redundant: however, the sequences surrounding the other three introns contain no redundancies and thus the splicing sites at either end of these three introns are unambiguous. The splicing in all cases conforms to the GT-AG rule. We compare the structural organization of the ovomucoid gene with the ovomucoid protein sequence to examine theories of the evolution of ovomucoids as well as the origin of intervening sequences. This analysis suggests that the present ovomucoid gene evolved from a primordia ovomucoid gene by two separate intragenic duplications. Furthermore, sequence analyses suggest that introns were present in the primordial ovomucoid gene before birds and mammals diverged, about 300 million years ago. Finally, the positions of the introns within the ovomucoid gene support the theory that introns separate gene segments that code for functional domains of proteins and provide insight on the manner by which eucaryotic genes were constructed during the process of evolution.

Recurrent lymphoma resulting in Kock pouch incontinence.

Incontinence following the Kock pouch continent cutaneous urinary diversion currently occurs in < 20 percent of patients undergoing the operation. Various causes of cutaneous incontinence have been identified, including efferent nipple prolapse, incompetent valve, pinhole fistula, parastomal herniation, and Marlex mesh erosion into the efferent nipple mechanism. We report the first case of a patient with recurrent lymphoma involving the small bowel utilized for the efferent continence nipple valve mechanism resulting in incontinence.

New technique of vaginal reconstruction following anterior exenteration.

Vaginal reconstruction is important in sexually active females undergoing anterior exenteration for malignant disease. We describe a technique for vaginal reconstruction used in two women who underwent radical cystectomy that required en bloc removal of the anterior vaginal wall. A polyglycolic acid mesh with a pedicle graft of greater omentum creates the anterior 270 degrees and the apex of the neovagina. The technique is simple and adds to the urologist's armamentarium of reconstructive procedures that improve quality of life following exenterative surgery.

Xanthogranulomatous pyelonephritis in a pregnant woman: a case report and review of the literature.

We report a rare case of a 24-year-old woman who presented during her second trimester of pregnancy with a presumptive diagnosis of right-sided xanthogranulomatous pyelonephritis (XGP). Despite attempted conservative management, the patient ultimately required a right nephrectomy without complications to either the patient or fetus. Pathology confirmed the diagnosis of XGP of the right kidney. Herein, we present a case report and a review of the literature concerning XGP and pregnancy.

Horseshoe kidney with a retrocaval ureter.

Horseshoe kidney and retrocaval ureter are two uncommon congenital anomalies of the genitourinary system that have rarely been reported to occur in the same patient. In each case previously reported, the isthmus of the horseshoe was positioned posterior to the inferior vena cava and anterior to the aorta. In no case was the diagnosis of both anomalies made preoperatively. We report a case of simultaneous horseshoe kidney and retrocaval ureter diagnosed by preoperative imaging studies and discuss the diagnostic evaluation and surgical management of this rare entity.

Metastatic renal cell carcinoma to the contralateral ureter.

Renal cell carcinoma uncommonly metastasizes to the ureter, with only rare reports of metastatic lesions developing in the contralateral side. Recently at our institution, two patients presented with contralateral ureteral metastases from a primary renal adenocarcinoma; one was synchronous and the second metachronous. Following extensive metastatic evaluations, both lesions were believed to be solitary metastases. The involved ureters were managed with total ureterectomy and construction of an ileal ureter. We report these two cases and review the literature.

Blunt renal trauma in the pediatric population: indications for radiographic evaluation.

OBJECTIVES: The purpose of this study was to define more clearly the clinical indications for radiographic evaluation of blunt renal injury in the pediatric population. METHODS: Children evaluated for blunt abdominal trauma at the Children's Hospital of Los Angeles and Los Angeles County/University of Southern California Medical Center undergo routine physical examination, laboratory analysis, and computed tomography (CT) scan of the abdomen and pelvis regardless of urinalysis results. We retrospectively evaluated the abdominal and pelvic CT scans of 412 children sustaining blunt abdominal trauma between June 1985 and June 1990. A total of 48 children, ages 6 months to 14 years (mean 5.6 years), with CT-documented renal injuries secondary to blunt trauma were identified. The radiographic findings were correlated with clinical presentation in this group of patients. RESULTS: Of the 48 children sustaining renal injuries (12% of the group), 23 (48%) had renal contusions and 25 children (52%) sustained more serious (significant) renal injuries. Of the children with significant renal injuries, 17 (68%) had minor renal lacerations and 8 (32%) had major renal lacerations. No child sustained a renal pedicle injury. All 25 children sustaining significant renal injuries presented with hematuria: 17 (68%) had microscopic (more than 3 red blood cells per high-power field) and 8 (32%) had gross hematuria. In the 23 children with renal contusions, 4 (17%) had no hematuria, 13 (57%) had microscopic hematuria, and 6 (26%) presented with gross hematuria. Hypotension occurred in 2 of the 25 children with significant renal injuries and in 2 of 23 children with renal contusions. Fifteen of the 25 patients (60%) with significant renal injuries had associated organ injuries, and 17 of the 23 children (74%) with renal contusions had associated organ injuries. CONCLUSIONS: In adults, gross hematuria and microscopic hematuria with hypertension following blunt trauma have been correlated with significant renal injuries requiring radiographic investigation. We conclude that these clinical criteria proposed to guide the radiographic evaluation of the adult population with blunt trauma do not apply to children. In our study, the degree of hematuria did not correlate with the degree of renal injury, and significant renal injury did occur with microhematuria in the absence of hypotension. We suggest that any child with a history of blunt abdominal trauma and any evidence of hematuria should undergo abdominal and pelvic CT scanning for the proper diagnosis and staging of renal and other associated intra-abdominal injuries.