Urological outcomes following pelvic exenteration for non-urological malignancies.

Background: Pelvic exenteration (PE) is a major surgical procedure used as a salvage therapy for patients with locally advanced or recurrent pelvic malignancies. Urinary reconstruction is a major part of PE and is often associated with high rates of post-operative complications. In the current study we evaluate the short and long-term urological outcomes following PE for Colo-Rectal (CR) and gyneco-oncological (GO) malignancies. Methods: Study included 22 patients who underwent PE for recurrent or locally advanced CR and GO malignancies in our institution between the years 2010-2018. The endpoint was post-operative freedom from urological complications. Results: Of 22 patients included, 13 (59 %) and 9 (41 %) underwent PE for CR and GO malignancies respectively. The mean age of the patients was 54 years. The median follow-up was 19 months. Seven (78 %) patients with GO malignancy and 11 (85 %) with CR malignancy underwent PE for local recurrence. Hydronephrosis prior to surgery existed in 8 (36.3 %) patients, of which, 5 patients required kidney drainage via nephrostomy tube. Two patients underwent posterior pelvic exenteration (PPE) with bladder preservation whereas the remaining 20 underwent cystectomy with urinary diversion by ileal conduit. Hydronephrosis post PE developed in 13 patients (59 %). eight (36 %) patients needed kidney drainage by nephrostomy tubes post PE, of these, 6 (75 %) had disease recurrence. The 2 years freedom from kidney drainage was 68 %, however the median time for kidney drainage was 0.5 months. The median overall survival was 12.5 months. Conclusion: The rate of urological complications following PE is relatively high and associated with disease recurrence.

Ureteric stent versus percutaneous nephrostomy for acute ureteral obstruction - clinical outcome and quality of life: a bi-center prospective study.

BACKGROUND: To compare quality of life (QoL) indices between ureteral stent (DJS) and nephrostomy tube (PCN) inserted in the setting of acute ureteral obstruction. METHODS: Prospective bi-centered study. Over the span of 2 years, 45 DJS and 30 PCN patients were recruited. Quality of life was assessed by 2 questionnaires, EuroQol EQ-5D and 'Tube symptoms' questionnaire, at 2 time points (at discharge after drainage and before definitive treatment). RESULTS: Patients' demographics and pre-drainage data were similar. There were no clinically significant differences in patient's recovery between the groups, including post procedural pain, defeverence, returning to baseline renal function, and septic shock complications. More DJS patients presented to the emergency room with complaints related to their procedure compared to PCN patients. At first, DJS patients complained more of urinary discomfort while PCN patients had worse symptoms relating to mobility and personal hygiene, with both groups achieving similar overall QoL score. At second time point, PCN patients' symptoms ameliorated while symptoms in the DJS group remained similar, translating to higher overall QoL score in the PCN group. CONCLUSIONS: The two techniques had a distinct and significantly different impact on quality of life. Over time, PCN patients' symptoms relieve and their QoL improve, while DJS patients' symptoms persist. Specific tube related symptoms, and their dynamics over time, should be a major determinant in choosing the appropriate drainage method, especially when definitive treatment is not imminent.

Postoperative Urinary Leakage Following Partial Nephrectomy for Renal Mass: Risk Factors and a Proposed Algorithm for the Diagnosis and Management.

OBJECTIVES: To evaluate the current incidence, risk factors, management, and long-term follow-up of urinary leakage following partial nephrectomy, in order to propose an algorithm for diagnosis and evaluation of postoperative urinary leakage. MATERIALS AND METHODS: The study included 752 patients who underwent elective partial nephrectomies for renal masses between the years 1988 and 2013. Patients' demographics, clinico-pathologic variables, and operative details were collected retrospectively. The associations between urinary leakage and patients' variables were assessed by univariate and multivariate analyses. RESULTS: Of the 752 patients, 21 (2.8%) experienced urinary leakage; 4 of the 21 patients with urinary leakage had spontaneous resolution, 1 patient underwent nephrectomy, and 16 patients were treated by retrograde ureteral stents insertion. One of them necessitated insertion of an additional percutaneous nephrostomy and another one deserved concomitant percutaneous drainage of a perirenal urinoma. The average period of time that elapsed from the operation until the insertion of stent was 8.5 ± 4.5 days. Stents were removed 68 ± 20.5 days postoperatively. None of the patients had either persistent or repeated leakage. On univariate analysis, hilar renal masses (p < 0.04) and higher preoperative creatinine levels (p < 0.01) were found to be associated with higher rates of urinary leakage. None of these variables was significant on a multivariate analysis. Review of the urinary leakage rate over time revealed it has been constantly decreasing over time, from 4% in early cases to 1.3% among the most recent ones. CONCLUSION: None of the preoperative variables that were examined in this study was significantly associated with increased risk of urinary leakage. However, cumulative surgical experience was associated with lower rates of urinary leakage, suggesting that the decrease in its incidence is related to the improved surgical skills, rather than to differences in tumors' or patients' characteristics.

Age-related differences in susceptibility to cisplatin-induced renal toxicity.

Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague-Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg(-1) i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were >or= 25 days old. Several serum, urinary and 'omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 >or= 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers.

Use of diagnostic accuracy as a metric for evaluating laboratory proficiency with microarray assays using mixed-tissue RNA reference samples.

Effective use of microarray technology in clinical and regulatory settings is contingent on the adoption of standard methods for assessing performance. The MicroArray Quality Control project evaluated the repeatability and comparability of microarray data on the major commercial platforms and laid the groundwork for the application of microarray technology to regulatory assessments. However, methods for assessing performance that are commonly applied to diagnostic assays used in laboratory medicine remain to be developed for microarray assays. A reference system for microarray performance evaluation and process improvement was developed that includes reference samples, metrics and reference datasets. The reference material is composed of two mixes of four different rat tissue RNAs that allow defined target ratios to be assayed using a set of tissue-selective analytes that are distributed along the dynamic range of measurement. The diagnostic accuracy of detected changes in expression ratios, measured as the area under the curve from receiver operating characteristic plots, provides a single commutable value for comparing assay specificity and sensitivity. The utility of this system for assessing overall performance was evaluated for relevant applications like multi-laboratory proficiency testing programs and single-laboratory process drift monitoring. The diagnostic accuracy of detection of a 1.5-fold change in signal level was found to be a sensitive metric for comparing overall performance. This test approaches the technical limit for reliable discrimination of differences between two samples using this technology. We describe a reference system that provides a mechanism for internal and external assessment of laboratory proficiency with microarray technology and is translatable to performance assessments on other whole-genome expression arrays used for basic and clinical research.

Fatty acid production in Schizochytrium sp.: Involvement of a polyunsaturated fatty acid synthase and a type I fatty acid synthase.

Schizochytrium sp. is a marine microalga that has been developed as a commercial source for docosahexaenoic acid (DHA, C22:6 (omega-3), enriched biomass, and oil. Previous work suggested that the DHA, as well as docosapentaenoic acid (DPA, C22:5 omega-6), that accumulate in Schizochytrium are products of a multi-subunit polyunsaturated fatty acid (PUFA) synthase (1). Here we show data to support this view and also provide information on other aspects of fatty acid synthesis in this organism. Three genes encoding subunits of the PUFA synthase were isolated from genomic DNA and expressed in E. coli along with an essential accessory gene encoding a phosphopantetheinyl transferase (PPTase). The resulting transformants accumulated both DHA and DPA. The ratio of DHA to DPA was approximately the same as that observed in Schizochytrium. Treatment of Schizochytrium cells with certain levels of cerulenin resulted in inhibition of 14C acetate incorporation into short chain fatty acids without affecting labeling of PUFAs, indicating distinct biosynthetic pathways. A single large gene encoding the presumed short chain fatty acid synthase (FAS) was cloned and sequenced. Based on sequence homology and domain organization, the Schizochytrium FAS resembles a fusion of fungal FAS beta and alpha subunits.

Gene expression profiles and genetic damage in benzo(a)pyrene diol epoxide-exposed TK6 cells.

Microarray analysis is a powerful tool to identify the biological effects of drugs or chemicals on cellular gene expression. In this study, we compare the relationships between traditional measures of genetic toxicology and mutagen-induced alterations in gene expression profiles. TK6 cells were incubated with 0.01, 0.1, or 1.0 microM +/-anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) for 4 h and then cultured for an additional 20 h. Aliquots of the exposed cells were removed at 4 and 24 h in order to quantify DNA adduct levels by 32P post-labeling and measure cell viability by cloning efficiency and flow cytometry. Gene expression profiles were developed by extracting total RNA from the control and exposed cells at 4 and 24 h, labeling with Cy3 or Cy5 and hybridizing to a human 350 gene array. Mutant frequencies in the Thymidine Kinase and Hypoxanthine Phosphoribosyl Transferase genes were also determined. The 10alpha-(deoxyguanosin-N(2)-yl)-7alpha,8beta,9beta-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene (dG-N(2)-BPDE) adduct increased as a function of dose and was the only adduct identified. A dose-related decrease in cell viability was evident at 24 h, but not at 4 h. Cell death occurred by apoptosis. At 4 h, analysis of the gene expression profiles revealed that Glutathione Peroxidase and Gadd45 were consistently upregulated (greater than 1.5-fold and significantly (P < 0.001) greater than the control in two experiments) in response to 1.0 microM BPDE exposure. Fifteen genes were consistently down-regulated (less than 0.67-fold and significantly (P < 0.001) lower than the control in two experiments) at 4 h in cultures exposed to 1.0 microM BPDE. Genes with altered expression at 4 h included genes important in the progression of the cell-cycle and those that inhibit apoptosis. At 24 h post-exposure, 16 genes, involved in cell-cycle control, detoxification, and apoptosis were consistently upregulated; 10 genes were repressed in cultures exposed to the high dose of BPDE. Real-time quantitative PCR confirmed the differential expression of selected genes. These data suggest that changes in gene expression will help to identify effects of drugs and chemicals on molecular pathways in cells, and will provide useful information about the molecular responses associated with DNA damage. Of the endpoints evaluated, DNA adduct formation was the most sensitive indicator of DNA damage. DNA adduct formation was clearly evident at low doses, but the number of genes with significantly altered expression (P < 0.001) was minimal. Alterations in gene expression were more robust at doses associated with cellular toxicity and induction of mutations.

Loss of critical palindromic transgene promoter sequence in chemically induced Tg.AC mouse skin papillomas expressing transgene-derived mRNA.

The Tg.AC transgenic mouse carries a v-Ha-ras transgene. Skin papillomas develop in Tg.AC mice upon repeated dermal application of tumor promoters and carcinogens. The transgene is inserted at a single site on chromosome 11 in a multiple-copy array. Although most of the >or= 40 copies are arranged in a direct-repeat orientation, two copies of the transgene are inserted in a palindromic, inverted-repeat orientation. Deletion of the palindromic transgene promoter sequence is associated strongly with and diagnostic of loss of phenotypic responsiveness to Tg.AC papillomagens, such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Unexpectedly, a loss of palindromic transgene sequence, in the absence of an observable reduction in copy number of the direct-repeat-oriented transgene sequence, is seen in DNA from papillomas when compared to genomic DNA from tail clips or skin samples away from the application site. Transgene-derived transcripts were detectable in all Tg.AC papillomas sampled. The transgene locus was hypomethylated in papillomas but not in samples from tail clips from the same animal or from skin samples away from the application site in responder Tg.AC mice, as shown by loss of resistance to digestion by HpaII. A cell line derived from a Tg.AC squamous cell carcinoma showed complete loss of the palindromic transgene sequence, hypomethylation of the transgene locus, and strong expression of v-Ha-ras mRNA. These data indicate that the palindromic transgene sequence, which appears to be necessary for initial responsiveness to tumorigens, may be susceptible to deletion during rapid cellular proliferation and is not required for transgene expression in later phases of papilloma growth.

Abdominal aortic aneurysms and thoracic aortic atheromas.

BACKGROUND: Abdominal aortic aneurysm (AAA) is associated with atherosclerosis elsewhere. Thoracic aortic atheromas (ATHs) seen on transesophageal echocardiography (TEE) are an important cause of stroke and peripheral embolization. The purposes of this study were to determine whether an association exists between AAA and ATHs and to assess the importance of screening patients with ATHs for AAA. METHODS: For the retrospective analysis, 109 patients with AAA and 109 matched controls were compared for the prevalence of ATHs on TEE and for historical variables. For the prospective analysis, screening for AAA on ultrasonography was performed in 364 patients at the time of TEE. RESULTS: Results of the retrospective analysis showed that ATHs were present in 52% of patients with AAA and in 25% of controls (odds ratio [OR] = 3.3; P =.00003). There was a significantly higher prevalence of hypertension, myocardial infarction, heart failure, smoking, and carotid or peripheral arterial disease in patients with AAA. However, only ATHs were independently associated with AAA on multivariate analysis (P =.001). Results of the prospective analysis showed that screening at the time of TEE in 364 patients revealed AAA in 13.9% of those with ATHs and in 1.4% of those without ATHs (P <.0001; OR = 11.4). CONCLUSIONS: (1) There is a strong, highly significant association between abdominal aneurysm and thoracic atheromas. (2) Patients with AAA may be at high risk for stroke because of the concomitance of thoracic aortic atheromas. (3) The high prevalence of abdominal aneurysm in patients with thoracic atheromas suggests that screening for abdominal aneurysm should be carried out in all patients with thoracic atheromas identified by TEE.

Unusual echocardiographic views of bicuspid and tricuspid pulmonic valves.

The pulmonary artery is typically seen on transthoracic echocardiography in its longitudinal axis. Therefore, short axis views of the pulmonic valve leaflets are not generally obtained, and the distinction between tricuspid and bicuspid pulmonic valves is difficult or impossible. Bicuspid pulmonic valve is one cause of pulmonic stenosis, which is especially common in tetralogy of Fallot. Presented here are 2 patients in whom the orientation of the pulmonary artery was unusual, and the pulmonic valve was seen en face. The first patient had tetralogy of Fallot and a bicuspid pulmonic valve. The severe obstruction to right ventricular outflow was infundibular. The second patient had severe stenosis of a tricuspid pulmonic valve, which was treated with balloon valvuloplasty. These unusual views of the pulmonic valve leaflets were obtained because of anterior displacement of the pulmonary artery, and precise anatomic delineation of the problem in each case was possible with transthoracic echocardiography.

Thromboembolus from a ligated left atrial appendage.

The left atrial appendage of patients with mitral valve disease is commonly a source of thromboembolus and is often ligated during mitral valve surgery to diminish this risk. However, ligation is often incomplete. We describe a patient with a stroke whose only source of embolus was an incompletely ligated left atrial appendage. Attempts to exclude the left atrial appendage from the arterial circulation by suture ligation may not decrease the risk of thromboemboli and instead may increase such risk.

Loss of palindromic symmetry in Tg.AC mice with a nonresponder phenotype.

The Tg.AC transgenic mouse carries the v-Ha-ras oncogene under the control of the zeta-globin promoter and is currently being used in a short-term carcinogenesis assay for safety testing of pharmaceuticals. A subset of hemizygous Tg.AC mice was found to be nonresponsive to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, which characteristically induces skin papillomas in these mice with repeated dermal applications. We previously showed that responder and nonresponder hemizygous Tg.AC mice carry about 40 copies of transgene but that the nonresponders had lost a 2-kb BamHI fragment containing the zeta-globin promoter sequence. The present restriction enzyme and S1 nuclease digestion experiments strongly suggested that the 2-kb BamHI fragment resulted from the orientation of two transgenes in an inverted repeat formation. Two subsets of nonresponder Tg.AC mice were identified. Restriction enzyme and S1 nuclease digestion experiments suggested that one nonresponder genotype was produced by a large deletion of one or more near complete copies of transgene sequence and the other genotype was produced by a small deletion near the apex of the "head-to-head" juncture of the inverted repeat. Polymerase chain reaction amplification, cloning, and sequencing results confirmed the palindromic orientation of transgene in Tg.AC mice. Our results indicated that, despite the presence of multiple copies of transgene in a direct repeat orientation, loss of symmetry in the palindromic array of transgene sequence results in the loss of the responder phenotype in Tg.AC mice. Mol. Carcinog. 30:99-110, 2001. Published 2001 Wiley-Liss, Inc.

Echo contrast-enhanced diagnosis of atrial septal defect.

Pulsed wave, continuous wave, and color flow Doppler imaging as well as intravenously administered agitated saline solution can detect intracardiac shunts during transthoracic echocardiography. Ultrasonographic contrast agents have greatly improved the visualization of left heart chambers and can enhance signals from blood flow within chambers and across valves, increasing the sensitivity of Doppler techniques. We describe a patient in whom the use of echo contrast media during transthoracic echocardiography allowed the detection of a previously unseen atrial septal defect. Combining such modalities may help to increase the sensitivity of transthoracic echocardiography and may eliminate the need for transesophageal echocardiography in selected patients.

Evaluation of in vitro reporter gene induction assays for use in a rapid prescreen for compound selection to test specificity in the Tg.AC mouse short-term carcinogenicity assay.

Under ICH guidelines, short-term carcinogenicity assays such as the Tg.AC assay are allowed alternatives for one species in the 2-year rodent bioassay. The Tg.AC transgenic mouse, which carries the v-Ha-ras oncogene under control of the zeta-globin promoter, develops skin papillomas in response to dermal application of carcinogens and tumor promoters. The appropriate specificity of the Tg.AC model for testing pharmaceuticals has not been systematically evaluated. The selection of candidate test compounds among noncarcinogenic pharmaceuticals would be aided by a high-throughput in vitro prescreen correlative of activity in the in vivo Tg.AC assay. Here we describe the development of a prescreen based on correct response to 24 compounds tested previously in Tg.AC mice. The in vitro prescreens, chosen to reflect molecular pathways possibly involved in Tg.AC papilloma formation, consisted of a zeta-globin promoter-luciferase construct stably expressed in K562 cells (Zeta-Luc) and three of the stress-response element-chloramphenicol acetyltransferase (CAT) fusion constructs stably expressed in HepG2 cells that are part of the CAT-Tox (L)iver assay. The stress response elements chosen were the c-fos promoter, the gadd153 promoter, and p53 response element repeats. Of the four assays, the gadd153-CAT assay showed the strongest concordance with activity in the Tg.AC assay, correctly classifying 78% of Tg.AC positive and 83% of Tg.AC negative compounds. The correlation was further improved by adding the Zeta-Luc assay as a second-stage screen. These cell-based assays will be used in a novel approach to selecting candidate compounds that challenge the specificity of the Tg.AC assay toward pharmaceuticals.

Aortic valve replacement in patients with aortic stenosis and severe left ventricular dysfunction.

BACKGROUND: The outcome of aortic valve replacement for severe aortic stenosis is worse in patients with impaired left ventricular function. Such dysfunction in aortic stenosis may be reversible if caused by afterload mismatch, but not if it is caused by superimposed myocardial infarction. METHODS: From our echocardiography database, 55 patients with severe aortic stenosis (valve area < or =0.75 cm2) and ejection fractions of 30% or lower who subsequently underwent aortic valve replacement were included. The operative mortality and clinical follow-up were detailed. RESULTS: There were 10 perioperative deaths (operative mortality, 18%). Twenty (36%) of the 55 patients had a prior myocardial infarction. In the 35 patients without prior myocardial infarction, there was only 1 death (3%). In contrast, 9 of 20 patients with prior myocardial infarction died (mortality rate, 45%; P< or =.001). The factors significantly associated with perioperative death on univariate analysis (functional class, mean aortic gradient, and prior myocardial infarction) were entered into a model for stepwise logistic regression. This multivariate analysis showed that only prior myocardial infarction was independently associated with perioperative death (odds ratio, 14.9; 95% confidence interval, 2.4-92.1; P = .004). CONCLUSIONS: The risk of aortic valve replacement in patients with severe aortic stenosis and severely reduced left ventricular systolic function is extremely high if the patients have had a prior myocardial infarction. This information should be factored into the risk-benefit analysis that is done preoperatively for these patients, and it may preclude operation for some.

Unusual eustachian valve function.

The eustachian valve directs oxygen-rich blood from the inferior vena cava toward the foramen ovale and away from the tricuspid valve during fetal development. Ordinarily, it does not prevent reflux of right atrial blood back into the inferior vena cava because it does not function as a true valve. Here we describe an unusual adult patient with severe tricuspid valve regurgitation in whom the eustachian valve did function as a true, albeit regurgitant, valve.

Contrast echocardiography clarifies uninterpretable wall motion in intensive care unit patients.

OBJECTIVES: The study examined the value of contrast echocardiography in the assessment of left ventricular (LV) wall motion in intensive care unit (ICU) patients. BACKGROUND: Echocardiograms done in the ICU are often suboptimal. The most common indication is the evaluation of LV wall motion and ejection fraction (EF). METHODS: Transthoracic echocardiograms were done in 70 unselected ICU patients. Wall motion was evaluated on standard echocardiography (SE), harmonic echocardiography (HE), and after intravenous (IV) contrast echocardiography (CE) using a score for each of 16 segments. A confidence score was also given for each segment with each technique (unable to judge; not sure; sure). The EF was estimated visually for each technique, and a confidence score was applied to the EF. RESULTS: Uninterpretable wall motion was present in 5.4 segments/patient on SE, 4.4 on HE (p = 0.2), and 1.1 on CE (p < 0.0001). An average of 7.8 segments were read with surety on SE, 9.2 on HE (p = 0.1), and 13.7 on CE (p < 0.0001). Ejection fraction was uninterpretable in 23% on SE, 13% on HE (p = 0.14), and 0% on CE (p = 0.002 vs. HE; p < 0.0001 vs. SE). The EF was read with surety in 56% of patients on SE, 62% on HE (p = 0.47), and 91% on CE (p < 0.0001). Thus, wall motion was seen with more confidence on CE. More importantly, the actual readings of segmental wall motion and EF significantly differed using CE. CONCLUSIONS: CE should be used in all ICU patients with suboptimal transthoracic echocardiograms.

Chromosomal localization of three human genes encoding bone morphogenetic protein receptors.

Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily that play a pivotal role in bone formation during embryogenesis and fracture repair. BMP signaling occurs via hetero-oligomeric serine/threonine kinase complexes of BMP type I (BMPR-IA or BMPR-IB) and type II receptors (BMPR-II). BMPR-IA and IB are closely related receptors, with sequence differences conserved between different species, suggesting that they serve distinct functions. Here we report the cDNA cloning of human BMPR1B and the chromosomal localization of all three BMPR genes. Using somatic cell hybrid and FISH analyses, the BMPR1A, BMPR1B, and BMPR2 genes were assigned to 10q23, 4q22-24, and 2q33-34, respectively. A processed BMPR1A pseudogene was mapped to 6q23.

The role of transesophageal echocardiography in the diagnosis and treatment of right atrial thrombi.

Twenty patients with right atrial thrombi were identified through the use of transthoracic and transesophageal echocardiography. Transesophageal echocardiography identified right atrial thrombi in all 20 cases. Transthoracic echocardiography showed definite thrombi in only 6 (30%) cases and suggested thrombus in another 2 (10%) patients. Thus transthoracic echocardiography results were false-negative for right atrial thrombus in 60% of cases. All 3 thrombi found within the right atrial appendage and 2 of 3 thrombi on pacemaker wires were missed by transthoracic echocardiography. There was no significant difference in the mean size between those thrombi seen (1.37 +/- 0.6 cm) and those missed (1.5 +/- 0.9 cm) by transthoracic echocardiography. Transesophageal echocardiography also significantly affected treatment. Anticoagulation was initiated or amplified in 13 patients. In 8 of these 13, thrombi were seen only by transesophageal echocardiography. Surgery was performed to remove thrombi in 7 cases, and in 3 (43%) cases it was because of thrombi seen only by transesophageal echocardiography. This study suggests that transesophageal echocardiography should be performed whenever right atrial thrombi are suspected. Transesophageal echocardiography has a significant effect on the diagnosis and management of patients with right atrial thrombi.