Inhibitors of C5 complement enhance vaccinia virus oncolysis.

Genetically engineered tumor-selective vaccinia virus (VV) has been demonstrated to be a highly effective oncolytic agent, but immune clearance may limit its therapeutic potential. As previously demonstrated, immunosuppression can lead to significant enhancement of viral recovery and therapeutic effect, but the magnitude of complement-mediated viral inactivation has not been fully elucidated and warrants further investigation. Using fluorescent microscopy and quantitative plaque assays, we have determined complement's key role in viral clearance and its multi-faceted means to pathogen destruction. Complement can lead to direct viral destruction and inhibition of viral uptake into cells, even in the absence of anti-vaccinia antibodies. Our data demonstrate C5 to be integral to the clearance pathway, and its inhibition by Staphylococcal superantigen-like protein leads to a 90-fold and 150-fold enhancement of VV infectivity in both the presence and absence of anti-VV antibodies, respectively. This study suggests that complement inhibition may reduce vaccinia viral neutralization and may be critical to future in vivo work.

Oncolytic poxvirus armed with Fas ligand leads to induction of cellular Fas receptor and selective viral replication in FasR-negative cancer.

Tumor necrosis factor superfamily members, including Fas ligand and TRAIL, have been studied extensively for cancer therapy, including as components of gene therapy. We examined the use of FasL expression to achieve tumor-selective replication of an oncolytic poxvirus (vFasL), and explored its biology and therapeutic efficacy for FasR- and FasR+ cancers. Infection of FasR+ normal and MC38 cancer cells by vFasL led to abortive viral replication owing to acute apoptosis and subsequently showed both reduced pathogenicity in non-tumor-bearing mice and reduced efficacy in FasR+ tumor-bearing mice. Infection of FasR- B16 cancer cells by vFasL led to efficient viral replication, followed by late induction of FasR and subsequent apoptosis. Treatment with vFasL as compared with its parental virus (vJS6) led to increased tumor regression and prolonged survival of mice with FasR- cancer (B16) but not with FasR+ cancer (MC38). The delayed induction of FasR by viral infection in FasR- cells provides for potential increased efficacy beyond the limit of the direct oncolytic effect. FasR induction provides one mechanism for tumor-selective replication of oncolytic poxviruses in FasR- cancers with enhanced safety. The overall result is both a safer and more effective oncolytic virus for FasR- cancer.

Lymph node growth rate in testicular germ cell tumours: implications for computed tomography surveillance frequency.

AIM: To estimate the growth rate of lymph nodes in patients on surveillance for testicular cancer who developed recurrent disease. MATERIALS AND METHODS: During a 7-year period, 318 patients at our institution were managed by surveillance and 39 relapsed (12.3%). The computed tomography scans of 28 patients (median age 32 years; range 19-51 years) who met our inclusion criteria and who developed recurrent disease in the abdomen/pelvis were retrospectively reviewed. Thirteen patients had non-seminoma and 15 had seminoma. To estimate the lymph node growth rate, the slope of lymph node size over time was calculated. RESULTS: The median length of time from orchiectomy to the recurrence computed tomography was 131 days (range 49-520) or about 4.4 months for non-seminoma patients and 373 days (range 129-675) or about 12.3 months for seminoma patients. The median size of the involved lymph node at final computed tomography for seminoma patients was 12 mm (range 9-31 mm) and for non-seminoma patients was 15 mm (range 10-56 mm). The median lymph node growth rate for patients with seminoma was 1.35 mm/month (range 0.62-4.56) and for patients with non-seminoma 2.99 mm/month (range 0.77-7.06); the difference in growth rates was statistically significant (P=0.029). CONCLUSIONS: There is a statistically significant faster growth rate of lymph nodes in patients with recurrent non-seminoma compared with patients with seminoma. This finding supports a more frequent computed tomography schedule during the first 2 years of surveillance in non-seminoma patients compared with seminoma patients.

The combination of immunosuppression and carrier cells significantly enhances the efficacy of oncolytic poxvirus in the pre-immunized host.

Pre-existing antipoxvirus immunity in cancer patients presents a severe barrier to poxvirus-mediated oncolytic virotherapy. We have explored strategies of immunosuppression (IS) and/or immune evasion for efficient delivery of an oncolytic double-deleted vaccinia virus (vvDD) to tumors in the pre-immunized mice. Transient IS using immunosuppressive drugs, including tacrolimus, mycophenolate mofetil and methylprednisolone sodium succinate, have been used successfully in organ transplantation. This drug cocktail alone did not enhance viral recovery from subcutaneous tumor after systemic viral delivery. Using B-cell knockout mice, we confirmed that the neutralizing antibodies had a significant role in preventing poxvirus infection. Using a MC38 peritoneal carcinomatosis model, we found that the combination of IS and tumor cells as carriers led to the most effective viral delivery, viral replication and viral spread inside the tumor mass. We found that our immunosuppressive drug cocktail facilitated recruitment of tumor-associated macrophages and conversion into an immunosuppressive M2 phenotype (interleukin (IL)-10(hi)/IL-12(low)) in the tumor microenvironment. A combination of IS and carrier cells led to significantly prolonged survival in the tumor model. These results showed the feasibility of treating pre-vaccinated patients with peritoneal carcinomatosis using an oncolytic poxvirus and a combined immune intervention strategy.

TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer.

We have explored a unique combination therapy for metastatic colorectal cancer. This strategy combines a potent and new oncolytic poxvirus expressing a membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or TNFSF10) and oxaliplatin (Ox) chemotherapy. We hypothesized that TRAIL expression would increase the efficacy of the oncolytic poxvirus, and that the therapeutic efficacy would be further enhanced by combination with chemotherapy. The cytotoxicity to cancer cells by Ox, oncolytic vaccinia virus (VV) and trail gene-armed VV alone or in combination was tested in vitro. The trail gene armed oncolytic VV-expressed high levels of TRAIL in infected cancer cells and had greater potency as a cytotoxic agent compared with the parent VV. Ox alone exerted concentration-dependent cytotoxicity. In vitro, the combination of the two agents applied at suboptimal concentrations for individual therapy displayed synergy in inducing cancer cells into enhanced levels of apoptosis/necrosis. Western blot analyses were consistent with the notion that TRAIL induced cancer cell death mainly through apoptosis, whereas Ox and vJS6 induced cell death more through non-apoptotic death pathways. In two aggressive colorectal carcinomatosis models derived from human HCT116 and murine MC38 cells, the combination therapy displayed synergistic or additive antitumor activity and prolonged the survival of the tumor-bearing mice compared with either Ox chemotherapy or vvTRAIL-mediated oncolytic gene therapy alone. This combination strategy may provide a new avenue to treating peritoneal carcinomatosis and other types of metastases of colorectal cancer.

Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene.

In this study, we assessed the ability of a highly tumor-selective oncolytic vaccinia virus armed with a yeast cytosine deaminase gene to infect and lyse human and murine ovarian tumors both in vitro and in vivo. The virus vvDD-CD could infect, replicate in and effectively lyse both human and mouse ovarian cancer cells in vitro. In two different treatment schedules involving either murine MOSEC or human A2780 ovarian carcinomatosis models, regional delivery of vvDD-CD selectively targeted tumor cells and ovarian tissue, effectively delaying the development of either tumor or ascites and leading to significant survival advantages. Oncolytic virotherapy using vvDD-CD in combination with the prodrug 5-fluorocytosine conferred an additional long-term survival advantage upon tumor-bearing immunocompetent mice. These findings demonstrate that a tumor-selective oncolytic vaccinia combined with gene-directed enzyme prodrug therapy is a highly effective strategy for treating advanced ovarian cancers in both syngeneic mouse and human xenograft models. Given the biological safety, tumor selectivity and oncolytic potency of this armed oncolytic virus, this dual therapy merits further investigation as a promising new treatment for metastatic ovarian cancer.

A new recombinant vaccinia with targeted deletion of three viral genes: its safety and efficacy as an oncolytic virus.

To enhance further the safety and efficacy of oncolytic vaccinia virus, we have developed a new virus with targeted deletions of three viral genes encoding thymidine kinase and antiapoptotic/host range proteins SPI-1 and SPI-2 (vSPT). Infection of human and murine tumor cell lines yielded nearly equivalent or a log lower virus recovery in comparison to parental viruses. Viral infection activated multiple caspases in cancer cells but not in normal cells, suggesting infected cells may die via different pathways. In tumor-bearing mice, vSPT recovery from MC38 tumor was slightly reduced in comparison to two parental viruses. However, no virus was recovered from the brains and livers of mice injected with vSPT in contrast to control viruses. vSPT demonstrated significantly lower pathogenicity in nude mice. Systemic delivery of vSPT showed significant tumor inhibition in subcutaneous MC38 tumor, human ovarian A2780 and murine ovarian MOSEC carcinomatosis models; however, the tumor inhibition by vSPT was reduced compared with parental viruses. These results demonstrated that although deletion of these three viral genes further enhanced tumor selectivity, it also weakened the oncolytic potency. This study illustrates the complexity of creating a tumor-selective oncolytic virus by deleting multiple viral genes involved in multiple cellular pathways.

Imaging of hepatic infections.

Imaging plays a significant role in the detection, characterization and treatment of hepatic infections. Infectious diseases of the liver include pyogenic and amoebic abscesses and parasitic, fungal, viral and granulomatous infections. With increases in worldwide travel, immunosuppression and changing population demographics, identification of cases of hepatic infection is becoming more common in daily practice. Knowledge of the imaging features seen with hepatic infections can assist in early diagnosis and timely initiation of appropriate therapy. This review presents the imaging appearances of hepatic infections, emphasizing specific features that may contribute to the diagnosis. Examples of the imaging findings seen with pyogenic and amoebic abscesses, infection with Echinococcus granulosus (Hydatid), schistosomiasis, candidiasis and tuberculosis (TB) are presented.

Triple-phase MDCT of hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to describe the appearances of hepatocellular carcinoma including intralesional contrast washout using a triple-phase liver protocol on an MDCT scanner. MATERIALS AND METHODS: Fifty-one patients with newly diagnosed hepatocellular carcinoma underwent standardized triple-phase CT using a multidetector scanner. Pathologic proof was obtained in 35 patients (69%); in 16 patients (31%), hepatocellular carcinoma was diagnosed on clinical and laboratory findings. Two radiologists independently reviewed the CT studies for the appearance and attenuation of the lesions. Intralesional washout of contrast material was evaluated subjectively and objectively. Statistical analysis was performed using Fisher's exact test to analyze the relationships between tumor appearance and alpha-fetoprotein level, tumor grade, and risk factor. Correlation between tumor size and appearance was analyzed using the Student's t test and Wilcoxon's rank sum test. RESULTS: The most common enhancement pattern for hepatocellular carcinoma was hypervascularity on hepatic arterial phase images with a mosaic pattern on both arterial and portal venous images; this finding was seen in 86% and 78% of lesions by the two observers, respectively. A hypervascular component was seen in 96% of lesions by both observers, and the observers recorded 86% and 63% of lesions as showing washout, respectively. Objective washout was present in 76% of lesions. Both subjective and objective washout correlated with an elevated alpha-fetoprotein level (p = 0.01). CONCLUSION: The appearances of hepatocellular carcinoma on images obtained using MDCT scanners are similar to those described for images obtained using single-detector helical scanners. However, the prevalence of hypervascular hepatocellular carcinoma on MDCT images is higher than previously described on single-detector helical images and most lesions showed washout on portal venous MDCT images.

Comparison of excretory phase, helical computed tomography with intravenous urography in patients with painless haematuria.

AIM: To compare excretory phase, helical computed tomography (CT) with intravenous (IV) urography for evaluation of the urinary tract in patients with painless haematuria. MATERIALS AND METHODS: Ninety-one out-patients had IV urography followed by helical CT limited to the urinary tract. Both IV urograms and CT images were evaluated for abnormalities of the urinary tract in a blinded, prospective manner. The clinical significance of abnormalities was scored subjectively and receiver operator characteristic curve analysis was performed. RESULTS: In 69 of 91 patients (76%), no cause of haematuria was identified. In 22 of 91 patients (24%), the cause of haematuria was identified as follows: transitional cell cancer of the bladder (n=15), urinary tract stones (n=3), cystitis (n=2), haemorrhagic pyelitis (n=1) and benign ureteral stricture (n=1). With IV urography, there were 15 true-positive, seven false-negative and three false-positive interpretations. With CT, there were 18 true-positive, four false-negative and two false-positive interpretations. There was no significant difference between IV and CT urography for the significance of the positive interpretations (n=0.47). CONCLUSION: Excretory phase CT urography was comparable with IV urography for evaluation of the urinary tract in patients with painless haematuria. However, the study population did not include any upper tract cancers.

Interstitial microwave thermal therapy for prostate cancer: method of treatment and results of a phase I/II trial.

PURPOSE: Interstitial microwave thermal therapy is experimental treatment for prostate cancer with the goal of curing disease, while causing fewer complications than standard treatment options. We present a method for delivering interstitial microwave thermal therapy using microwave radiating helical antennae inserted percutaneously under transrectal ultrasound guidance. We report the results of a trial of this method in 25 patients in whom primary external beam radiation therapy had previously failed. This patient group currently has limited curative options that are associated with a high complication rate. However, these recurrent tumors often remain localized to the prostate, and so they may be amenable to localized therapy. MATERIALS AND METHODS: Patients with proved prostatic adenocarcinoma were candidates for treatment when prostate specific antigen (PSA) was 15 ng./ml. or less and prostate volume was 50 cc. or less. Followup included PSA measurement, digital rectal examination, urinalysis, and documentation of adverse events at 4, 8, 12 and 24 weeks. Sextant biopsy was performed at week 24. The procedure involved the insertion of 5 antennae percutaneously through a modified brachytherapy template. The antenna arrangement was determined based on computer simulated predictions of temperature throughout the prostate. The prostate was dissected away from the rectum by an injection of sterile saline to provide a thermal barrier that protected the rectum from thermal damage. Temperatures were monitored using interstitial mapping thermistor probes that were also inserted through the template. A minimum peripheral target temperature of 55C but less than 70C was maintained for 15 to 20 minutes, while the urethra, rectum and hydrodissection space remained below 42C. The urethra and rectum were actively cooled in addition to hydrodissection. RESULTS: Peripheral target temperatures of 55C were achieved. The urethra and rectum remained at a safe temperature. The procedure, including setup and treatment, required approximately 2.5 hours of operating room time. At 24 weeks the PSA nadir was 0.5 ng./ml. or less in 52% of patients and 0.51 to 4 ng./ml. was achieved in an additional 40%. The negative biopsy rate at 24 weeks was 64%, assuming that 3 patients lost to followup would have had positive results. No major complications were observed and in most cases minor complications resolved within 3 months. CONCLUSIONS: Interstitial microwave thermal therapy for prostate cancer was developed to heat the prostate safely to a cytotoxic temperature. Experience with 25 patients in whom external beam radiation therapy for prostate cancer had failed indicates that the treatment is safe. Although our series indicates that this therapy may be effective, further studies and longer followup are required in larger patient groups to confirm the potential role of this therapy as an option for recurrent and primary prostate cancer.

Helical CT protocols for the abdomen and pelvis: a survey.

OBJECTIVE: We surveyed members of the Society of Computed Body Tomography/Magnetic Resonance to evaluate current techniques used for helical CT in the abdomen and pelvis. MATERIALS AND METHODS: The survey was distributed to 70 members (36 institutions) of the Society of Computed Body Tomography/Magnetic Resonance. The survey included general questions related to abdominal and pelvic helical CT and also asked the members to write a protocol for 12 hypothetical requisitions. RESULTS: Thirty-two members (46%) responded, representing 28 institutions (78%). The number of protocols for helical CT of the abdomen and pelvis at each institution ranges from 2 to 35 (median, 11). IV contrast material is administered for 90% (median) of abdominal and pelvic CT examinations. Nonionic contrast material is used for 68% (median) of these examinations. IV contrast material is used by 100% of institutions for tumor staging protocols except for one institution that does not use IV contrast material for lymphoma staging. Fifty percent of the institutions obtain two- or three-phases of liver images for breast cancer staging. For all protocols, the average collimation and reconstruction interval is 7 mm except for renal (5 mm) and adrenal (4 mm) protocols. Rectal contrast material is administered most commonly for colon cancer staging (39% of institutions). CONCLUSION: There is a wide range in the number of protocols used for helical CT in the abdomen and pelvis among the responding institutions. Most protocols include use of nonionic IV contrast material injected at a rate of 3 ml/sec and a collimation of 7 mm.

Adenocarcinoma of the head of the pancreas: determination of surgical unresectability with thin-section pancreatic-phase helical CT.

OBJECTIVE: This study was conducted to evaluate newly introduced criteria for unresectability of pancreatic cancer with thin-section pancreatic-phase helical CT. MATERIALS AND METHODS: Twenty-five patients with adenocarcinoma in the head of the pancreas underwent thin-section pancreatic-phase helical CT. The major peripancreatic vessels were categorized on a scale of 1-4, according to the degree of circumferential involvement by tumor. The maximum diameters of the small peripancreatic veins--gastrocolic trunk, anterosuperior pancreaticoduodenal vein, and posterosuperior pancreaticoduodenal vein--were recorded. Findings on CT were compared with the results of surgery in each patient. RESULTS: Sixteen patients had surgically resectable tumors, and nine patients had surgically unresectable tumors. CT and surgical correlation was available for 98 major peripancreatic vessels; 85 were resectable and 13 were unresectable. Of category 1 vessels, 72 (97%) of 74 were resectable at surgery. Of category 2 vessels, 12 (71%) of 17 were resectable. One (50%) of two category 3 vessels and none (0%) of five category 4 vessels were resectable at surgery. CT showed a dilated gastrocolic trunk in two patients; one of these patients had a surgically resectable tumor, but the other patient had a surgically unresectable tumor. CONCLUSION: In patients with adenocarcinoma in the head of the pancreas, the degree of circumferential vessel involvement by tumor as shown by CT is useful in predicting which patients will have surgically unresectable tumors. A dilated gastrocolic trunk should not be used as an independent sign of surgical unresectability.

Pancreatic-phase versus portal vein-phase helical CT of the pancreas: optimal temporal window for evaluation of pancreatic adenocarcinoma.

OBJECTIVE: Our objective was to use helical CT to compare the enhancement attenuation values of pancreatic adenocarcinoma, adjacent normal pancreas, and critical vascular structures during the pancreatic phase and portal vein phase. SUBJECTS AND METHODS: Forty-one patients with pathologically proven pancreatic adenocarcinoma underwent dual-phase thin-section dynamic helical CT using a pancreatic-phase and portal vein-phase protocol. The scan delay after initiation of the contrast bolus was 40 sec for the pancreatic phase and 70 sec for the portal vein phase. Attenuation values after i.v. contrast administration were calculated during both phases of scanning for normal pancreas, pancreatic tumor, celiac axis, superior mesenteric artery, superior mesenteric vein, splenic vein, and portal vein. Quantitative values were assessed using regions of interest. RESULTS: Mean differences of enhancement between tumor and normal pancreas were significantly greater in the pancreatic phase (57 H) than the portal vein phase (35 H) (p = .0001). Enhancement values of all the critical vascular structures were also significantly greater in the pancreatic phase than the portal vein phase (p < .001). CONCLUSION: With dynamic thin-section helical CT, pancreatic-phase scanning provides greater differences in contrast enhancement between normal pancreas and pancreatic tumor and between pancreatic tumors and surrounding critical vascular structures than does portal vein-phase scanning.

Herpes simplex virus type 1 vector-mediated expression of nerve growth factor protects dorsal root ganglion neurons from peroxide toxicity.

Nerve growth factor beta subunit (beta-NGF) transgene delivery and expression by herpes simplex virus type 1 (HSV-1) vectors was examined in a cell culture model of neuroprotection from hydrogen peroxide toxicity. Replication-competent (tk- K mutant background) and replication-defective (ICP4(-);tk- S mutant background) vectors were engineered to contain the murine beta-NGF cDNA under transcriptional control of either the human cytomegalovirus immediate-early gene promoter (HCMV IEp) (e.g., KHN and SHN) or the latency-active promoter 2 (LAP2) (e.g., KLN and SLN) within the viral thymidine kinase (tk) locus. Infection of rat B103 and mouse N2A neuronal cell lines, 9L rat glioma cells, and Vero cells with the KHN or SHN vectors resulted in the production of beta-NGF-specific transcripts and beta-NGF protein reaching a maximum at 3 days postinfection (p.i.). NGF protein was released into the culture media in amounts ranging from 10.83 to 352.86 ng/ml, with the highest levels being achieved in B103 cells, and was capable of inducing neurite sprouting of PC-12 cells. The same vectors produced high levels of NGF in primary dorsal root ganglion (DRG) cultures at 3 days. In contrast to HCMV IEp-mediated expression, the LAP2-NGF vectors showed robust expression in primary DRG neurons at 14 days. The neuroprotective effect of vector produced NGF was assessed by its ability to inhibit hydrogen peroxide-induced neuron toxicity in primary DRG cultures. Consistent with the kinetics of vector-mediated NGF expression, HCMV-NGF vectors were effective in abrogating the toxic effects of peroxide at 3 but not 14 days p.i. whereas LAP2-NGF vector transduction inhibited apoptosis in DRG neurons at 14 days p.i. but was ineffective at 3 days p.i. Similar kinetics of NGF expression were observed with the KHN and KLN vectors in latently infected mouse trigeminal ganglia, where high levels of beta-NGF protein expression were detected at 4 wks p.i. only from the LAP2; HCMV-NGF-driven expression peaked at 3 days but could not be detected during HSV latency at 4 weeks. Together, these results indicate that (i) NGF vector-infected cells produce and secrete mature, biologically active beta-NGF; (ii) vector-synthesized NGF was capable of blocking peroxide-induced apoptosis in primary DRG cultures; and (iii) the HCMV-IEp functioned to produce high levels of NGF for several days; but (iv) only the native LAP2 was capable of long-term expression of a therapeutic gene product in latently infected neurons in vivo.

Astrocytes are the major source of nerve growth factor upregulation following traumatic brain injury in the rat.

Previous studies from our group have demonstrated an upregulation in nerve growth factor (NGF) RNA and protein in the cortex 24 h following traumatic brain injury (TBI) in a rat model. This increase in NGF is suppressed if rats are subjected to 4 h of whole-body hypothermia following TBI. In the present study we used in situ hybridization to extend our initial RNA gel-blot (Northern) hybridization findings by demonstrating that NGF RNA is increased in the cortex following TBI and that hypothermia diminishes this response. Further, by combining in situ hybridization with immunocytochemistry for glial fibrillary acidic protein we demonstrate that astrocytes are the major cellular source for the upregulation in NGF and that this upregulation can be observed in the hippocampus as early as 3 h posttrauma. The predominantly astrocytic origin suggests that the NGF upregulation is not related primarily to cholinotrophic activities. We hypothesize that its function is to stimulate upregulation of antioxidant enzymes, as part of an injury-induced cascade, and that supplementation of NGF or antioxidants may be warranted in hypothermic therapies for head injury.

MR urography: evaluation of a three-dimensional fast spin-echo technique in patients with hydronephrosis.

OBJECTIVE: The purpose of this study was to evaluate a respiratory-triggered three-dimensional (3D) fast spin-echo technique for MR urography in patients with urinary tract dilatation. SUBJECTS AND METHODS: Using a respiratory-triggered 3D fast spin-echo technique for MR urography, we obtained MR urograms in 24 patients with hydronephrosis. Images were separately reviewed by two radiologists who evaluated the images for quality, presence of, degree of, level of, and cause of urinary tract dilatation. Findings were compared with all available clinical, imaging, surgical, and pathologic data, which served as the standard of reference. Sensitivity, specificity, positive predictive value, and negative predictive value of MR urograms were calculated for each reviewer to reveal urinary tract dilatation. For each reviewer, we calculated agreement between MR urography and the standard of reference using kappa analysis. We also calculated interobserver agreement for the presence of degree of, level of, and cause of urinary tract dilatation. RESULTS: Technically adequate MR urograms were obtained in all patients. For detection of urinary tract dilatation by MR urography, the sensitivity was 100%; specificity was 96%; positive predictive value was 96%; and negative predictive value was 100%. The kappa values for the degree of dilatation seen on the MR urograms were 0.57 (moderate) and 0.43 (moderate); for the level of obstruction, 0.74 (substantial) and 0.55 (moderate); and for the cause of obstruction, 0.66 (moderate) and 0.66 (moderate). Interobserver agreement for seeing dilatation on MR urograms was 1.0 (perfect agreement); degree of dilatation, 0.48 (moderate); level of dilatation, 0.60 (moderate); and cause of dilatation, 0.74 (substantial). CONCLUSION: MR urography using a respiratory-triggered 3D fast spin-echo technique can produce high-resolution images of the urinary tract by which reviewers can achieve a high sensitivity (100%) and specificity (96%) for the detection of urinary tract dilatation. On MR urograms, reviewers also identified the cause of obstruction in most patients: 92% (reviewer 1) and 88% (reviewer 2).