How to Integrate Cell-Free DNA Screening With Sonographic Markers for Aneuploidy: An Update.

OBJECTIVE: The sonologist detects a so-called "soft marker" during approximately 10% of routine second-trimester anatomy examinations and is often uncertain about what further management is appropriate. This article will specifically address the management of patients with sonographic markers for six common entities: choroid plexus cysts (CPCs), ventriculomegaly (VM), echogenic intracardiac focus (EIF), urinary tract dilation (UTD), fetal echogenic bowel (FEB), and femoral and humeral shortening. The use of cell-free DNA screening and its relationship to these sonographic findings will be reviewed. CONCLUSION: The era of ultrasound markers as a screen for fetal aneuploidy is coming to a close. The detection of these markers on an ultrasound examination should simply serve as a reminder to ensure that the patient was offered cell-free DNA screening or conventional analyte screening. Cell-free DNA testing is revolutionizing screening. With normal results on a cell-free DNA test, many isolated soft markers-including CPCs, EIF, mild rhizomelic limb shortening, and mild pyelectasis-are irrelevant from a genetic standpoint. However, further counseling and workup are indicated for VM, true FEB, femur or humerus length measurement that is less than 2.5-percentile value, and pyelectasis to evaluate for the nongenetic associations with these findings. Finally, cell-free DNA testing is currently a screening test; positive results require definitive diagnostic testing with amniocentesis or chorionic villus sampling.

Testicular Microlithiasis: What Should You Recommend?

OBJECTIVE: Ultrasound surveillance of patients with testicular microlithiasis (TM) has been recommended because of the reported association between TM and testicular cancer (TC). The purpose of this review is to summarize what is known about TM and discuss recent recommendations. CONCLUSION: The most recent recommendations do not support the use of routine ultrasound surveillance for patients with TM who are at low risk for TC. A template for possible use in reporting TM is also provided.

Holoprosencephaly: a survey of the entity, with embryology and fetal imaging.

Structural malformations of the brain are an important cause of childhood mortality and morbidity, with the latter having long-term financial and psychosocial implications for the affected child and family. Holoprosencephaly (HPE) is a severe brain malformation characterized by abnormal cleavage of the prosencephalon in the 5th gestational week. Aprosencephaly and atelencephaly occur earlier because of failure in the formation of the prosencephalon and telencephalon, respectively. The HPE holoprosencephaly spectrum classically includes alobar, semilobar, and lobar forms, although there are no clear-cut defining features. The middle interhemispheric variant (MIH), also known as syntelencephaly, is classified as a variant of HPE holoprosencephaly with midline interhemispheric fusion. Other conditions sometimes included in the spectrum of HPE holoprosencephaly include septo-optic dysplasia (SOD); "minimal" HPE holoprosencephaly , which is associated with subtle craniofacial malformations and mild developmental delay; and microform HPE holoprosencephaly , which by definition excludes brain involvement. The focus of this article will be on the spectrum of findings visible in fetal manifestation of the HPE holoprosencephaly spectrum. Brain embryology; the imaging characteristics, epidemiology, and embryology of HPE; and the more common associated anomalies, particularly those of the face ("the face predicts the brain") are reviewed. Recognition of these anomalies is important for accurate parental counseling, since the prognosis is poor but not invariably lethal; children with the milder forms may live well into their teens with severe developmental delays, endocrine dysfunction, and disrupted homeostasis. Available data on outcome in surviving children are summarized. Illustrative fetal ultrasonographic and magnetic resonance images are presented with clinical, autopsy, and postnatal imaging correlation.

You see what you know gas bubbles in the inferior vena cava, an unusual presentation of necrotizing soft tissue infection.

Gas detected within the systemic circulation as an unexpected finding is a very rare phenomenon. A case of multiple bubbles within the inferior vena cava detected incidentally during a sonogram requested to assess for portal vein thrombosis is presented. These were eventually determined to be sequelae of a fatal, clinically silent necrotizing soft tissue infection. The differential diagnosis for gas within the inferior vena cava is reviewed, and teaching points that may help future patients are presented.

Should small sliding hiatal hernias be reported at CT colonography?

OBJECTIVE: The objective of our study was to determine whether colonic distention at CT colonography (CTC) induces small incidental sliding hiatal hernias. MATERIALS AND METHODS: This study evaluated for the presence and, if present, the size (small, moderate, or large) of sliding (type 1) hiatal hernias in 3126 consecutive asymptomatic adults (mean age ± SD, 57.0 ± 7.4 years) undergoing screening CTC. Colonic distention was achieved with automated continuous CO(2) delivery. As an internal control, standard CT studies (i.e., without colonography technique) were available for comparison in 123 individuals with a hernia present at CTC. In addition, the prevalence of hiatal hernia was assessed in an external control group of 488 adults (mean age, 60.8 years) undergoing abdominal CT without colonic distention. The Fisher exact test was used to test for statistical significance. RESULTS: Hiatal hernias were present in 47.8% (1495/3126) of adults at screening CTC (86% small, 13% moderate, 1% large). Abdominal CT of the 123 internal control subjects showed resolution of the hernia in 64.2% (79/123) of cases and was smaller in an additional 12 cases. The prevalence of sliding hiatal hernias in the external control group was 23.8% (116/488), significantly lower than in the CTC screening cohort (p < 0.0001). After applying an empiric correction factor based on results from the internal control group to account for technique-induced hernias, the estimated prevalence for the CTC cohort more closely matched that for the external control subjects. CONCLUSION: Our findings suggest that small sliding hiatal hernias are commonly induced by colonic distention at CTC and should probably not be reported to avoid inappropriate diagnosis, workup, or treatment.

Effect of computer-aided detection for CT colonography in a multireader, multicase trial.

PURPOSE: To assess the effect of using computer-aided detection (CAD) in second-read mode on readers' accuracy in interpreting computed tomographic (CT) colonographic images. MATERIALS AND METHODS: The contributing institutions performed the examinations under approval of their local institutional review board, with waiver of informed consent, for this HIPAA-compliant study. A cohort of 100 colonoscopy-proved cases was used: In 52 patients with findings positive for polyps, 74 polyps of 6 mm or larger were observed in 65 colonic segments; in 48 patients with findings negative for polyps, no polyps were found. Nineteen blinded readers interpreted each case at two different times, with and without the assistance of a commercial CAD system. The effect of CAD was assessed in segment-level and patient-level receiver operating characteristic (ROC) curve analyses. RESULTS: Thirteen (68%) of 19 readers demonstrated higher accuracy with CAD, as measured with the segment-level area under the ROC curve (AUC). The readers' average segment-level AUC with CAD (0.758) was significantly greater (P = .015) than the average AUC in the unassisted read (0.737). Readers' per-segment, per-patient, and per-polyp sensitivity for all polyps of 6 mm or larger was higher (P < .011, .007, .005, respectively) for readings with CAD compared with unassisted readings (0.517 versus 0.465, 0.521 versus 0.466, and 0.477 versus 0.422, respectively). Sensitivity for patients with at least one large polyp of 10 mm or larger was also higher (P < .047) with CAD than without (0.777 versus 0.743). Average reader sensitivity also improved with CAD by more than 0.08 for small adenomas. Use of CAD reduced specificity of readers by 0.025 (P = .05). CONCLUSION: Use of CAD resulted in a significant improvement in overall reader performance. CAD improves reader sensitivity when measured per segment, per patient, and per polyp for small polyps and adenomas and also reduces specificity by a small amount.

Accuracy of routine nontargeted CT without colonography technique for the detection of large colorectal polyps and cancer.

BACKGROUND: To assess the accuracy of routine contrast-enhanced computed tomography for the detection of large colorectal polyps and cancer. METHODS: The study group consisted of 100 patients who underwent abdominal computed tomography and optical colonoscopy evaluation before any treatment or intervention. Invasive colorectal carcinoma and large polyps (>or=10mm) were found at colonoscopy in 29 and 16 patients, respectively. Computed tomography studies with oral and IV contrast were retrospectively reviewed as 5-mm thick sections in standard soft tissue windows by 3 readers. The readers scored each segment for polyp or cancer utilizing a 5-point scale for receiver operating characteristic analysis. RESULTS: By-patient sensitivity/specificity for cancer detection for each reader was 69.0%/88.7%, 65.5%/84.5%, and 82.8%/77.5%, respectively. Pooled sensitivity, specificity, and accuracy for cancer was 72.4%, 83.6%, and 80.3%, respectively. The empiric area under the receiver operating characteristic curves for the readers ranged from 0.775 to 0.857. By-patient sensitivity for large polyps was poor with a pooled sensitivity of 14.5%. CONCLUSIONS: Standard computed tomography not tailored to colorectal investigation was moderately effective for detecting invasive cancers, but insensitive for large polyps. Unsuspected cancer should be a part of the standard search pattern for routine computed tomography interpretation, but more advanced colonography techniques are necessary for detecting large polyps.

The cavum septi pellucidi: why is it important?

OBJECTIVE: The cavum septi pellucidi (CSP) is routinely imaged in the fetal brain during obstetric sonography; in fact, for well over a decade, assessment of the CSP has been considered part of the required elements of a standard examination of fetal morphology in guidelines developed by multiple specialty societies. Our objective is to present the 4 reasons why all practicing sonologists and sonographers should be familiar with this anatomic structure. METHODS: Prenatal sonograms and magnetic resonance imaging examinations are used to review the following topics: terminology, embryology, and anatomy of the CSP; pitfalls in its identification; and a wide variety of abnormalities (predominantly relating to nonvisualization) associated with the CSP. RESULTS: Embryologic development of the CSP is intimately associated with the corpus callosum (CC); thus, correct identification of the CSP essentially excludes complete agenesis of the CC. Absence of the CSP is associated with an extremely wide spectrum of neuroanatomic malformations: these range from the lethal entities of hydranencephaly and alobar holoprosencephaly; to the potentially serious but nonlethal entities of schizencephaly, porencephaly, basilar encephaloceles, severe hydrocephalus, and the less severe prosencephalic cleavage disorders (including syntelencephaly); to the normal variant, the rare and somewhat controversial entity of isolated septal deficiency. The value of noting that the absent CSP allows diagnosis of very subtle and easily overlooked abnormalities such as septo-optic dysplasia is presented. CONCLUSIONS: Correct recognition of the CSP provides welcome reassurance of proper development of the central forebrain.

Hepatic steatosis (fatty liver disease) in asymptomatic adults identified by unenhanced low-dose CT.

OBJECTIVE: The purpose of this study was to investigate the prevalence of hepatic steatosis in an asymptomatic U.S. adult population using attenuation values at unenhanced CT as the reference standard. We also assessed the utility of known clinical risk factors for diagnosis. MATERIALS AND METHODS: For 3,357 consecutive asymptomatic adults (1,865 women and 1,492 men; mean age, 57.0 years), hepatic and splenic CT attenuation values (Hounsfield units) were obtained by unenhanced CT using a low-dose colonography technique for colorectal cancer screening. Multiple attenuation criteria for steatosis were applied, including liver thresholds and comparison of liver and spleen attenuation. Relevant clinical risk factors were compared against a CT liver attenuation < or = 40 HU, which has been shown to exclude mild steatosis. RESULTS: Mean liver attenuation was 58.8 +/- 10.8 (SD) HU. The prevalence of moderate-to-severe hepatic steatosis (defined by liver attenuation < or = 40 HU) was 6.2% (208/3,357). For CT attenuation criteria that include milder degrees of steatosis, prevalence increased to as high as 45.9% (1,542/3,357) for a liver-to-spleen attenuation ratio of < or = 1.1. Overweight status (body mass index > 25) was a sensitive indicator for moderate-to-severe steatosis (92.8%) but was highly nonspecific (37.5%). Other clinical risk factors, such as diabetes, dyslipidemia, hypertension, alcohol overuse, and hepatitis, were more specific (77.6-92.4%) but highly insensitive (1.9-37.5%). Combining clinical risk factors did not substantially increase the accuracy for screening. CONCLUSION: Assessment of liver attenuation by use of unenhanced CT represents an objective and noninvasive means for detection of asymptomatic hepatic steatosis, whereas clinical risk factor assessment is unreliable. Further longitudinal investigation is needed to determine the most appropriate attenuation threshold and the risk for disease progression to steatohepatitis and cirrhosis.

Unsuspected extracolonic findings at screening CT colonography: clinical and economic impact.

PURPOSE: To evaluate the frequency and estimated costs of additional diagnostic workup for extracolonic findings detected at computed tomographic (CT) colonography in a large screening cohort. MATERIALS AND METHODS: This retrospective HIPAA-compliant study, which had institutional review board approval, evaluated extracolonic findings in 2195 consecutive asymptomatic adults (1199 women, 996 men; age range, 40-90 years; mean age, 58.0 years +/- 8.1 [standard deviation]) undergoing low-dose CT colonographic screening performed without contrast material at a single institution over a 20-month period. All diagnostic workups generated because of extracolonic findings were reviewed. Associated costs were estimated by using 2006 Medicare average reimbursement. Testing for statistical significance was performed by using the chi(2) and t tests. RESULTS: Further diagnostic workup for unsuspected extracolonic findings was performed in 133 (6.1%) of 2195 patients, including 18 patients in whom additional workup was not recommended by the radiologist. Additional testing included ultrasonography (n = 64), CT (n = 59), magnetic resonance imaging (n = 11), other diagnostic imaging tests (n = 19), nonsurgical invasive procedures (n = 19), and surgical procedures (n = 22). Benign findings were confirmed in the majority of cases, but relevant new diagnoses were made in 55 (2.5%) patients, including extracolonic malignancies in nine patients. The mean cost per patient for nonsurgical procedures was $31.02 (95% confidence interval: $23.72, $38.94); that for surgical procedures was $67.54 (95% confidence interval: $38.62, $101.55). CONCLUSION: Detection of relevant unsuspected extracolonic disease at CT colonographic screening is not rare, accounting for a relatively large percentage of cases in which additional workup was recommended. Judicious handling of potential extracolonic findings is warranted to balance the cost of additional workup against the potential for early detection of important disease, because many findings will prove to be of no clinical consequence.

Comparison of percutaneous and laparoscopic cryoablation for the treatment of solid renal masses.

OBJECTIVE: The goal of this study was to compare the outcome, complications, and charges of percutaneous renal cryoablation and laparoscopic cryoablation of solid renal masses. MATERIALS AND METHODS: A total of 30 percutaneous renal cryoablations (mean tumor size, 2.1 cm) in 30 patients (mean age, 67.0 years) and 60 laparoscopic renal cryoablations (mean tumor size, 2.5 cm) in 46 patients (mean age, 67.4 years) were compared. The size of the tumor, procedural complications, hospital charges, length of hospital stay, and tumor follow-up parameters were recorded. Monitoring after ablation was performed every 3 months using contrast-enhanced MRI or CT. RESULTS: Both percutaneous cryoablation and laparoscopic cryoablation of solid renal masses had a high technical success rate (30/30 [100%] and 59/60 [98.3%]). There was no significant difference in the rate of residual disease (3/30 [10%] and 4/60 [6.7%], p = 0.68), and the secondary effectiveness rate is 100% for both groups to date. One renal mass treated using laparoscopic cryoablation had a local recurrence, but none of the masses treated using percutaneous cryoablation had a recurrence. The disease-specific survival is 100% in both groups with no significant difference in the mean follow-up time (14.5 vs 14.6 months, p = 1.0) or major complication rate (0/30 [0%] vs 3/60 [5.0%], p = 0.55). For the treatment of solid renal masses, percutaneous cryoablation was associated with 40% lower hospital charges (mean, $14,175 vs $23,618, p < 0.00001) and a shorter hospital stay (mean +/- SD, 1.1 +/- 0.3 vs 2.4 +/- 2.1 days; p < 0.0001) than laparoscopic cryoablation. CONCLUSION: Although certain tumors require laparoscopic intervention because of the location or size of the tumor, percutaneous renal cryoablation is safe and effective and is associated with lower charges when used for the treatment of small renal tumors.

Ultrasound-guided biopsies in the abdomen and pelvis.

Ultrasound-guided biopsies in the abdomen and pelvis are generally more effective, safer, faster, and cheaper than those performed under computed tomography guidance. This manuscript will discuss multiple aspects of sonographic biopsies performed between the diaphragm and the symphysis pubis. We begin with systems issues, patient preparation (including bleeding profile and anticoagulant use), pain management, and infection precautions. The procedure itself is then analyzed, including needle guidance, the role of the sonographer, image optimization, patient positioning, core- versus fine-needle aspiration, coaxial versus individual pass, needle technique, and postprocedure management. Issues specific to different sites are then discussed: liver, spleen, pancreas, kidney, adrenal, bowel, retroperitoneum and mesentery, and the pelvis. We finish with a discussion of complications, future trends, and a brief summary.

Primary 2D versus primary 3D polyp detection at screening CT colonography.

OBJECTIVE: Disparate results from the existing large CT colonography (CTC) trials suggest that 2D polyp detection is less sensitive than 3D detection, but no direct evidence exists to support this claim. Our goal was to assess the sensitivity of primary 2D polyp detection with cases from the Department of Defense CTC screening trial and compare results with the primary 3D evaluation and previous 2D CTC trials. MATERIALS AND METHODS: Ten radiologists, blinded to polyp findings, retrospectively interpreted 730 consecutive colonoscopy-proven CTC cases in asymptomatic adults using a primary 2D approach, with 3D reserved for problem solving. Primary 2D CTC performance was compared with the primary 3D CTC results from the original trial of 1,233 asymptomatic adults. The 10 2D reviewers were significantly more experienced in CTC interpretation (> 100 cases interpreted) than the six reviewers from the original 3D trial. RESULTS: Primary 2D CTC sensitivity for adenomas > or = 6 mm was 44.1% (56/127), compared with 85.7% (180/210) at 3D (p < 0.001). Sensitivity of 2D CTC for adenomas > or = 10 mm was 75.0% (27/36) compared with 92.2% (47/51) at 3D (p = 0.027). Similar sensitivity trends were seen for the by-patient analysis and for all polyps at the 6-mm and 10-mm thresholds. By-patient specificity for 2D evaluation at the 10-mm threshold was 98.1% (676/689), compared with 97.4% (1,131/1,161) at 3D evaluation (p = 0.336). CONCLUSION: Primary 2D CTC is less sensitive than primary 3D CTC for polyp detection in low-prevalence screening cohorts. The disappointing 2D sensitivity in this study was very similar to results obtained with primary 2D evaluation in previous CTC trials.

CT colonography versus colonoscopy for the detection of advanced neoplasia.

BACKGROUND: Advanced neoplasia represents the primary target for colorectal-cancer screening and prevention. We compared the diagnostic yield from parallel computed tomographic colonography (CTC) and optical colonoscopy (OC) screening programs. METHODS: We compared primary CTC screening in 3120 consecutive adults (mean [+/-SD] age, 57.0+/-7.2 years) with primary OC screening in 3163 consecutive adults (mean age, 58.1+/-7.8 years). The main outcome measures included the detection of advanced neoplasia (advanced adenomas and carcinomas) and the total number of harvested polyps. Referral for polypectomy during OC was offered for all CTC-detected polyps of at least 6 mm in size. Patients with one or two small polyps (6 to 9 mm) also were offered the option of CTC surveillance. During primary OC, nearly all detected polyps were removed, regardless of size, according to established practice guidelines. RESULTS: During CTC and OC screening, 123 and 121 advanced neoplasms were found, including 14 and 4 invasive cancers, respectively. The referral rate for OC in the primary CTC screening group was 7.9% (246 of 3120 patients). Advanced neoplasia was confirmed in 100 of the 3120 patients in the CTC group (3.2%) and in 107 of the 3163 patients in the OC group (3.4%), not including 158 patients with 193 unresected CTC-detected polyps of 6 to 9 mm who were undergoing surveillance. The total numbers of polyps removed in the CTC and OC groups were 561 and 2434, respectively. There were seven colonic perforations in the OC group and none in the CTC group. CONCLUSIONS: Primary CTC and OC screening strategies resulted in similar detection rates for advanced neoplasia, although the numbers of polypectomies and complications were considerably smaller in the CTC group. These findings support the use of CTC as a primary screening test before therapeutic OC.