Downgrading and Upgrading Gray-Scale Ultrasound BI-RADS Categories of Benign and Malignant Masses With Optoacoustics: A Pilot Study.

OBJECTIVE: False-positive findings remain challenging in breast imaging. This study investigates the incremental value of optoacoustic imaging in improving BI-RADS categorization of breast masses at ultrasound. SUBJECTS AND METHODS: The study device is an optoacoustic breast imaging device with a handheld duplex laser and internal gray-scale ultrasound probe, fusing functional and morphologic information (optoacoustic ultrasound). In this prospective multisite study, breast masses assessed as BI-RADS category 3, 4A, 4B, 4C, or 5 by site radiologists underwent both gray-scale ultrasound and optoacoustic imaging with the study device. Independent reader radiologists assessed internal gray-scale ultrasound and optoacoustic ultrasound features for each mass and assigned a BI-RADS category. The percentage of mass reads for which optoacoustic ultrasound resulted in a downgrade or upgrade of BI-RADS category relative to internal gray-scale ultrasound was determined. RESULTS: Of 94 total masses, 39 were biopsy-proven malignant, 44 were biopsy-proven benign, and 11 BI-RADS category 3 masses were stable at 12-month follow-up. The sensitivity of both optoacoustic ultrasound and internal gray-scale ultrasound was 97.1%. The specificity was 44.3% for optoacoustic ultrasound and 36.4% for internal gray-scale ultrasound. Using optoacoustic ultrasound, 41.7% of benign masses or BI-RADS category 3 masses that were stable at 12-month follow-up were downgraded to BI-RADS category 2 by independent readers; 36.6% of masses assigned BI-RADS category 4A were downgraded to BI-RADS category 3 or 2, and 10.1% assigned BI-RADS category 4B were downgraded to BI-RADS category 3 or 2. Using optoacoustic ultrasound, independent readers upgraded 75.0% of the malignant masses classified as category 4A, 4B, 4C, or 5, and 49.4% of the malignant masses were classified as category 4B, 4C, or 5. CONCLUSION: Optoacoustic ultrasound resulted in BI-RADS category downgrading of benign masses and upgrading of malignant masses compared with gray-scale ultrasound.

A Pivotal Study of Optoacoustic Imaging to Diagnose Benign and Malignant Breast Masses: A New Evaluation Tool for Radiologists.

Purpose To compare the diagnostic utility of an investigational optoacoustic imaging device that fuses laser optical imaging (OA) with grayscale ultrasonography (US) to grayscale US alone in differentiating benign and malignant breast masses. Materials and Methods This prospective, 16-site study of 2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging Reporting and Data System (BI-RADS) categories assigned by seven blinded independent readers to benign and malignant breast masses using OA/US versus US alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven histologic findings and BI-RADS 3 masses stable at 12 months were eligible. Independent readers reviewed US images obtained with the OA/US device, assigned a probability of malignancy (POM) and BI-RADS category, and locked results. The same independent readers then reviewed OA/US images, scored OA features, and assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were calculated for US and OA/US. Benign and malignant mass upgrade and downgrade rates, positive and negative predictive values, and positive and negative likelihood ratios were compared. Results Of 2105 consented subjects with 2191 masses, 100 subjects (103 masses) were analyzed separately as a training population and excluded. An additional 202 subjects (210 masses) were excluded due to technical failures or incomplete imaging, 72 subjects (78 masses) due to protocol deviations, and 41 subjects (43 masses) due to high-risk histologic results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%] malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%) for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI: 12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99% CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI-RADS 4B) to a posttest probability of 2% (BI-RADS 3). Conclusion OA/US increases the specificity of breast mass assessment compared with the device internal grayscale US alone. Online supplemental material is available for this article. © RSNA, 2017.

Intraluminal duodenal diverticula: collective review with report of a laparoscopic excision.

A comprehensive review of intraluminal duodenal diverticulum (IDD) is presented, along with a report of a completely laparoscopic excision of this duodenal abnormality as well as a report of magnetic resonance cholangiopancreatography demonstrating the classic fluoroscopic "wind sock sign" pathognomonic appearance of IDD. IDD may easily be missed unless one specifically considers this entity in patients presenting with symptoms of foregut disease. Patients with IDD typically present in the fourth decade of life with duration of symptoms less than 5 years that typically include pain, nausea and vomiting, pancreatitis, and gastrointestinal bleeding. Diagnosis usually requires imaging studies and upper gastrointestinal endoscopy. Laparoscopic excision is recommended because of superior visualization of significant intestinal anatomic abnormalities, the need for accurate ampullary localization, and the ability to facilitate complete diverticular excision while maintaining biliary and pancreatic ductal integrity. Review of surgical literature suggests that IDD results from congenital duodenal developmental abnormalities matured by long-term duodenal peristalsis.

Real world performance of screening breast ultrasound following enactment of Connecticut Bill 458.

The purpose of this article was to retrospectively evaluate the benefits of screening breast ultrasound in women with dense breast tissue following enactment of Connecticut Bill 458 in October 2009. This bill mandated that women be informed of their breast density and the possible benefit of ultrasound as an additional screening modality. Institutional approval was obtained from the institutional review board for this retrospective study. A total of 5519 women with dense breasts were screened with ultrasound in the year after the law went into effect from October 2009 to September 2010 (post law group). We focused on the women who had negative mammograms and biopsy recommendations based on ultrasound findings (BIRADS 4 and 5). The data were compared with those from a group of 1319 women who were screened with breast ultrasound before the law went into effect between October 2008 and September 2009 (pre law group). Prior to the law, ultrasound studies were performed only at the referring clinician's request. Of the 5,519 women in the post law group, 10 malignant lesions were found, with a cancer detection rate of 0.18%, biopsy rate of 3.3%, and a positive predictive value of 5.5%. The tumor size on ultrasound ranged from 4 to 15 mm; mean 9.7 mm. Sentinel lymph node biopsy was negative in 7 of 10 patients. Of the 1,319 women in the pre law group, 20 biopsies were recommended, all of which were benign. No malignancies were detected in the pre law group. Establishment of a formal screening breast ultrasound program as an adjunct to mammography in women with dense breasts increased our cancer detection rate following enactment of Connecticut Bill 458.

An Msh2 point mutation uncouples DNA mismatch repair and apoptosis.

Mutations in the human DNA mismatch repair gene MSH2 are associated with hereditary nonpolyposis colorectal cancer as well as a significant proportion of sporadic colorectal cancer. The inactivation of MSH2 results in the accumulation of somatic mutations in the genome of tumor cells and resistance to the genotoxic effects of a variety of chemotherapeutic agents. Here we show that the DNA repair and DNA damage-induced apoptosis functions of Msh2 can be uncoupled using mice that carry the G674A missense mutation in the conserved ATPase domain. As a consequence, although Msh2(G674A) homozygous mutant mice are highly tumor prone, the onset of tumorigenesis is delayed as compared with Msh2-null mice. In addition, tumors that carry the mutant allele remain responsive to treatment with a chemotherapeutic agent. Our results indicate that Msh2-mediated apoptosis is an important component of tumor suppression and that certain MSH2 missense mutations can cause mismatch repair deficiency while retaining the signaling functions that confer sensitivity to chemotherapeutic agents.

Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice.

The generation of protective antibodies requires somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin genes. Here we show that mice mutant for exonuclease 1 (Exo1), which participates in DNA mismatch repair (MMR), have decreased CSR and changes in the characteristics of SHM similar to those previously observed in mice mutant for the MMR protein Msh2. Exo1 is thus the first exonuclease shown to be involved in SHM and CSR. The phenotype of Exo1(-/-) mice and the finding that Exo1 and Mlh1 are physically associated with mutating variable regions support the idea that Exo1 and MMR participate directly in SHM and CSR.

Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility.

Exonuclease 1 (Exo1) is a 5'-3' exonuclease that interacts with MutS and MutL homologs and has been implicated in the excision step of DNA mismatch repair. To investigate the role of Exo1 in mammalian mismatch repair and assess its importance for tumorigenesis and meiosis, we generated an Exo1 mutant mouse line. Analysis of Exo1(-/-) cells for mismatch repair activity in vitro showed that Exo1 is required for the repair of base:base and single-base insertion/deletion mismatches in both 5' and 3' nick-directed repair. The repair defect in Exo1(-/-) cells also caused elevated microsatellite instability at a mononucleotide repeat marker and a significant increase in mutation rate at the Hprt locus. Exo1(-/-) animals displayed reduced survival and increased susceptibility to the development of lymphomas. In addition, Exo1(-/-) male and female mice were sterile because of a meiotic defect. Meiosis in Exo1(-/-) animals proceeded through prophase I; however, the chromosomes exhibited dynamic loss of chiasmata during metaphase I, resulting in meiotic failure and apoptosis. Our results show that mammalian Exo1 functions in mutation avoidance and is essential for male and female meiosis.