Discovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling.

Leiomyosarcoma (LMS) is a soft tissue tumor with a significant degree of morphologic and molecular heterogeneity. We used integrative molecular profiling to discover and characterize molecular subtypes of LMS. Gene expression profiling was performed on 51 LMS samples. Unsupervised clustering showed three reproducible LMS clusters. Array comparative genomic hybridization (aCGH) was performed on 20 LMS samples and showed that the molecular subtypes defined by gene expression showed distinct genomic changes. Tumors from the 'muscle-enriched' cluster showed significantly increased copy number changes (P=0.04). A majority of the muscle-enriched cases showed loss at 16q24, which contains Fanconi anemia, complementation group A, known to have an important role in DNA repair, and loss at 1p36, which contains PRDM16, of which loss promotes muscle differentiation. Immunohistochemistry (IHC) was performed on LMS tissue microarrays (n=377) for five markers with high levels of messenger RNA in the muscle-enriched cluster (ACTG2, CASQ2, SLMAP, CFL2 and MYLK) and showed significantly correlated expression of the five proteins (all pairwise P<0.005). Expression of the five markers was associated with improved disease-specific survival in a multivariate Cox regression analysis (P<0.04). In this analysis that combined gene expression profiling, aCGH and IHC, we characterized distinct molecular LMS subtypes, provided insight into their pathogenesis, and identified prognostic biomarkers.

Providing location-independent access to patient clinical narratives using Web browsers and a tiered server approach.

Health care today depends upon timely access to patient medical data and the latest medical knowledge. As we make the transition from a hospital-based organization to an integrated health care delivery system, patient care information must move throughout the organization quickly and efficiently over increasing distances. The emergence of widely-dispersed referral networks demands novel solutions to the problems of delivering patient care information to providers. We have developed a mechanism to provide location-independent access to clinical narrative reports using a multi-tiered server model and World Wide Web technologies for delivery. To successfully deploy such a system to sites separated by large distances, it is important to reduce complexity at the client site. Using a "thin client", such as a web browser, in our design facilitates deployment and support while reducing cost per user. This architecture allows the application to be updated without modification to the end-user software and eases maintenance over long distances.

Intravenous urographic technique.

In these times of rapid advances in radiographic imaging, intravenous urography should be performed in an optimal way. The urographic examination should involve consultation between the referring physician and the radiologist. Necessary patient information should be accessible. McClennan said "patient selection for urographic studies should be efficacious with the radiologist exerting appropriate control so that the urogram is truly a consultative imaging service integrated into the total patient management." We share this view, and it is an extension of the philosophy of practice emphasized by other leaders in uroradiology. Cost containment, new imaging technologies, risk/benefit considerations, and evolving patterns of patient care have had a significant influence on genitourinary tract imaging. In addition, current debate about contrast media, digital radiography, efficacy, and utilization will undoubtedly have an influence on imaging during the next decade. Utilization of intravenous urography has decreased significantly in the past 15 years. Our volume of examinations has declined approximately 50% since 1970. This decline in our practice is attributed to several complex factors such as previous overutilization of screening urography for hypertension; the impact of US and CT for evaluation of obstruction, retroperitoneal disease (adenopathy and fibrosis), renal failure, and renal masses; concern about contrast medium-induced renal failure; and fewer repeat studies because of improved quality of intravenous urography in general radiology practice. In addition, overutilization of urography in patients with hematuria, prostatism, history of urinary tract infection, etc, continues to be debated in the medical community. In our integrated group practice, we have also observed overutilization of "high-tech" procedures in lieu of urography for evaluation of suspected urinary tract disease. Swings of the pendulum are inevitable in diagnostic imaging because of evolving technology and the art of medical practice. Although some differences of opinion about the details of urographic technique and indications for urography may exist, most would agree on the philosophy of producing a high-quality urographic examination. That philosophy focuses on producing the highest quality examination in each patient so that a diagnosis of normal or abnormal can be made accurately and confidently. Failure to demonstrate the entire urinary tract is a common cause of diagnostic error and one that can largely be eliminated by careful attention to the technical details of the examination.

Iatrogenic dilatation of the upper urinary tract during radiographic evaluation of patients with spinal cord injury.

Patients with upper and lower motor neuron spinal cord injuries were observed to determine whether cystography immediately before excretory urography induced iatrogenic dilatation of the upper urinary tract that was indistinguishable from true pathological dilatation. Evidence is given that such dilatation occurs. This iatrogenic dilatation is not seen in patients with normally innervated urinary tracts and appears to be caused by exaggerated bladder reflexes in patients with upper motor neuron lesions. Bladder spasms precipitated by cystographic contrast material also may create vesicoureteral obstruction and lead to dilatation of the upper urinary tract. Consequently, it is suggested that cystography should not immediately precede excretory urography. When such a sequence is necessary, room or body temperature contrast medium should be used for the cystogram, the bladder should be emptied before the excretory urogram is started and a 1-hour interval should be allowed between the 2 procedures. The findings also suggest that any factors that induce repeated or continuing bladder spasms may contribute to progressive dilatation of the upper urinary tract.

Rapid resolution of perfusion/ventilatory abnormalities in pulmonary air embolism.

A case of pulmonary air embolism is presented demonstrating a nearly total lung perfusion defect and a matching ventilation deficit. Despite advanced age, mild chronic obstructive airway disease, and congestive heart failure, the perfusion/ventilatory (V/Q) abnormalities produced by the air emboli resolved to near completion within three days. Rapid resolution of V/Q abnormalities due to air embolism is distinct when compared to the abnormalities seen with thromboembolism and the mechanism the matching V/Q defects is discussed.

Medullary sponge kidney presenting as polycystic renal disease.

We observed a 30-year-old woman in whom a large mass in the right lower quadrant and bilaterally enlarged cystic kidneys with markedly distorted collecting systems by excretory urography suggested a diagnosis of polycystic renal disease (PRD); but the linear and cystic dilatation of collecting tubules, many of which contained numerous calculi, was typical of medullary sponge kidney (MSK). Arteriography and CT scanning clearly showed that both the calcifications and the cysts were confined to the medullary portions. The cortical layer was entirely free of cysts except where large medullary cysts protruded to the surface. In patients in whom MSK imitates PRD, these conditions can be distinguished by CT scanning and arteriography.

Reticular mosaic (urticarial) pattern of the colonic mucosa in Yersinia colitis.

The colonic mucosa of a patient with Yersinia colitis exhibited a reticular mosaic pattern on an air-contrast barium enema. The authors conclude that Yersinia colitis can be added to the list of colonic lesions producing this characteristic pattern.

Mortality during excretory urography: Mayo Clinic experience.

In a series of 300,000 consecutive patients who underwent excretory urography between January 1, 1964 and January 5, 1982, four deaths were recorded (a mortality rate of 1.3:100,000). All four patients who died were 50 years of age or older, all had a history of some type of hypersensitivity, all had a respiratory component to the reaction, all received a 1 ml test dose and had no reaction, and none had received a prior injection of contrast medium. The mortality rate in this series (1:75,000) is significantly lower than recently reported rates from multiinstitutional studies and is similar to the mortality rate resulting from the parenteral administration of penicillin. Differences in reported series may relate to methods of data collection, variations in patient population, and therapeutic management.

Low risk of contrast media-induced acute renal failure in nonazotemic type 2 diabetes mellitus.

The risk of developing contrast media-induced acute renal failure was studied in 49 randomly selected nonazotemic type 2 adult diabetic patients subjected to IVU. There were 19 men and 30 women in the group whose mean age was 62 +/- 10 years (range, 38 to 82 years). In preparation for IVU, patients were neither dehydrated nor given a laxative. The IVU was performed in the morning, using sodium diatrizoate and meglumine diatrizoate. Serum creatinine levels were measured pre-IVU and on days 1, 3, and 6 after the IVU. A total of three patients (6%) had an elevation of serum creatinine greater than 25% above the baseline by post-IVU day 3. One patient developed oliguria (less than 400 ml/24 hr) that lasted 2 days. Creatinine clearances of the three patients showing contrast media toxicity were 74, 60, and 105 ml/min pre-IVU. In each of the three patients, a return to pre-IVU serum creatinine concentration was noted within 2 weeks. It is concluded that the risk of acute renal failure post-IVU is small in hydrated nonazotemic type 2 diabetic patients.

Computed tomographic findings in suburothelial hemorrhage.

Retroperitoneal hemorrhage with associated intramural hemorrhage into the renal pelvis and proximal ureter is a well documented complication of coagulation defects. The urographic characteristics of this condition have been well documented by several authors [1-4], but to our knowledge the computed tomographic (CT) findings in patients with this condition have not been reported previously. We describe the CT findings in 2 such cases; one related to thrombocytopenia in leukemia, and the other to anticoagulant therapy in a patient with Budd-Chiari syndrome.

Application of computed tomography in differential diagnosis of radiographic opacities in the lower thorax and upper abdomen.

The differential diagnosis of radiographic homogeneous opacities in the lower thorax and upper abdomen is very often a dilemma for radiologists. Recently we have encountered the following 8 cases in which the correct radiologic diagnoses (confirmed pathologically) were made only by computed tomography: pyogenic liver abscesses (2 cases), subphrenic hematoma, pancreatitis with pseudocyst, adrenal cortical carcinoma, ovarian carcinoma with liver metastasis, lower lobe pulmonary infarction, and metastatic breast cancer in the peri-esophageal region. The CT findings displayed not only the anatomic location and extent of these lesions but also the unique characteristics of many of the pathologic processes that produce these otherwise nonspecific radiographic opacities. It is our purpose here to demonstrate the CT findings in such patients and to advocate CT study as a very effective diagnostic modality in those patients who present with radiographic homogeneous opacities in the lower thorax and upper abdomen.

Comprehensive renal scintillation procedures in spinal cord injury: comparison with excretory urography.

A 131iodine orthoiodohippurate comprehensive renal scintillation procedure was performed and compared to results of excretory urography in 200 spinal cord injury patients. No severe urographic abnormalities were undetected by the comprehensive renal scintillation procedure. Only 1.4 per cent of renal units had greater than minimal pyelocaliectasis or ureterectasis in the presence of a normal radionuclide examination. A relatively large number of abnormalities were detected on the renal scintillation procedure when the excretory urogram was normal. Serial followup will be required to determine the significance of these findings but present data suggest that a comprehensive renal scintillation procedure and a plain film of the kidneys, ureters and bladder may be used for screening upper urinary tract abnormalities in lieu of an excretory urogram. This is particularly advantageous for the spinal cord injury population, since there have been no toxic or allergic reactions reported, no bowel preparation or dehydration is required and there is relatively low radiation exposure.

Intraoperative roentgenography in the surgical removal of renal calculi.

Complete surgical removal of staghorn or multiple renal calculi is extremely difficult. Intraoperative roentgenography has been used to decrease the incidence of residual calculi. We herein assess the effectiveness of intraoperative roentgenography and emphasize important operative technical aspects. Between 1973 and 1979, 42 patients underwent 50 operations for the removal of staghorn or multiple renal calculi. Intraoperative roentgenography was used in 47 operations and omitted in 3. Of the 47 operations done with intraoperative roentgenography 31 units were free of stones and 12 had small retained fragments known intraoperatively with verification by postoperative tomography or plain abdominal film. In 1 case of calculus recognized intraoperatively passed during the postoperative period and tomograms demonstrated no residual calculi. Only 3 patients had residual stones postoperatively with negative intraoperative films. The 3 patients who did not have intraoperative roentgenography all had residual fragments. All 3 kidneys were thought to be free of residual stones as determined by visual inspection and nephroscopy. With the aid of intraoperative roentgenography the incidence of residual stones was 23 per cent. Followup for up to 6 years in 45 renal units showed 73 per cent to be free of stones. When properly used intraoperative roentgenography is highly accurate. Films should be obtained before any stones are removed and care should be taken to x-ray the entire kidney even if 2 films are required. Final films should be obtained after all fragments are removed.