Ultrasound characteristics of early-stage high-grade serous ovarian cancer.

BACKGROUND: Survival from ovarian cancer is strongly dependent on the stage at diagnosis. Therefore, when confronted with a woman with an isolated adnexal mass, clinicians worry about missing the opportunity to detect cancer at an early stage. High-grade serous ovarian cancers account for 80% of ovarian cancer deaths, largely because of their tendency to be diagnosed at a late stage. Among adnexal masses, large size and the presence of solid areas on ultrasound examination have been found to be associated with cancer, but it is unclear whether these characteristics identify early-stage cases. OBJECTIVE: This study aimed to evaluate the ultrasound findings associated with clinically detected early-stage high-grade serous ovarian cancer. STUDY DESIGN: This was a retrospective cohort study of women diagnosed with stage I or II high-grade serous ovarian or fallopian tube cancer measuring at least 1 cm at pathology from 2007 to 2017. Preoperative ultrasound examinations were independently reviewed by 3 radiologists. Adnexal masses were scored for size and volume; overall appearance; presence, thickness, and vascularity of septations; morphology and vascularity of other solid components; and degree of ascites. Characteristics were compared between masses of <5 cm and larger masses and between stage I and stage II cases. Interobserver variability was assessed. RESULTS: Among 111 women identified, 4 had bilateral ovarian involvement, for a total of 115 adnexal masses characterized by ultrasound examination. The mean age at diagnosis was 61.8 years (range, 42-91 years). The median mass size was 9.6 cm (range, 2.2-23.6 cm) with 87% of cases having a mass size of ≥5 cm. A mixed cystic and solid appearance was most common (77.4%), but a completely solid appearance was more frequently seen for tumors of <5 cm compared with larger tumors (26.7% vs 13.0%). Solid components other than septations were seen in 97.4% of cases. The characteristics of stage I and II cases were similar other than ascites, which was more commonly seen in stage II cases (18.0% vs 3.1%, respectively). Interobserver concordance was high for size and volume measurements (correlation coefficients, 0.96-0.99), with moderate agreement observed across the other ultrasound characteristics (Fleiss kappa, 0.45-0.58). CONCLUSION: In this community-based cohort, early-stage high-grade serous cancers rarely presented as masses of <5 cm or masses without solid components other than septations. Our findings provide additional support for the observation of small masses without solid areas on ultrasound examination.

Use of the probably benign (BI-RADS category 3) assessment for masses on breast MRI: Is it transferable to general clinical practice?

The purpose of this study was to identify potential BI-RADS 3 mass descriptors on breast magnetic resonance imaging by systematically defining positive predictive values (PPV). In a blinded retrospective review of BI-RADS 4 masses, reader 1 identified 132 masses and reader 2 identified 76 masses. PPV for mass descriptors and for descriptor combinations was determined. No mass descriptor resulted in a PPV ≤2% (BI-RADS 3 threshold). Descriptors with the lowest PPVs were circumscribed margin (8%), rim internal enhancement and persistent kinetics (13% each), and oval shape (15%). The results demonstrate the difficulty in transferring the theoretical concept of lesion surveillance to systematic clinical use.

Carotid atherosclerosis does not predict coronary, vertebral, or aortic atherosclerosis in patients with acute stroke symptoms.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether significant atherosclerotic disease in the carotid arteries predicts significant atherosclerotic disease in the coronary arteries, vertebral arteries, or aorta in patients with symptoms of acute ischemic stroke. METHODS: Atherosclerotic disease was imaged using CT angiography in a prospective study of 120 consecutive patients undergoing emergent CT evaluation for symptoms of stroke. Using a comprehensive CT angiography protocol that captured the carotid arteries, coronary arteries, vertebral arteries, and aorta, we evaluated these arteries for the presence and severity of atherosclerotic disease. Significant atherosclerotic disease was defined as >50% stenosis in the carotid, coronary, and vertebral arteries, or >or=4 mm thickness and encroaching in the aorta. Presence of any and significant atherosclerotic disease was compared in the different types of arteries assessed. RESULTS: Of these 120 patients, 79 had CT angiography examinations of adequate image quality and were evaluated in this study. Of these 79 patients, 33 had significant atherosclerotic disease. In 26 of these 33 patients (79%), significant disease was isolated to 1 type of artery, most often to the coronary arteries (N=14; 54%). Nonsignificant atherosclerotic disease was more systemic and involved multiple arteries. CONCLUSIONS: Significant atherosclerotic disease in the carotid arteries does not predict significant atherosclerotic disease in the coronary arteries, vertebral arteries, or aorta in patients with symptoms of acute ischemic stroke. Significant atherosclerotic disease is most often isolated to 1 type of artery in these patients, whereas nonsignificant atherosclerotic disease tends to be more systemic.

Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition.

Effective immunotherapy using T cell receptor (TCR) gene-modified T cells requires an understanding of the relationship between TCR affinity and functional avidity of T cells. In this study, we evaluate the relative affinity of two TCRs isolated from HLA-A2-restricted, gp100-reactive T cell clones with extremely high functional avidity. Furthermore, one of these T cell clones, was CD4- CD8- indicating that antigen recognition by this clone was CD8 independent. However, when these TCRs were expressed in CD8- Jurkat cells, the resulting Jurkat cells recognized gp100:209-217 peptide loaded T2 cells and had high functional avidity, but could not recognize HLA-A2+ melanoma cells expressing gp100. Tumor cell recognition by Jurkat cells expressing these TCRs could not be induced by exogenously loading the tumor cells with the native gp100:209-217 peptide. These results indicate that functional avidity of a T cell does not necessarily correlate with TCR affinity and CD8-independent antigen recognition by a T cell does not always mean its TCR will transfer CD8-independence to other effector cells. The implications of these findings are that T cells can modulate their functional avidity independent of the affinity of their TCRs.

Influence of human CD8 on antigen recognition by T-cell receptor-transduced cells.

The CD8 coreceptor on T cells has two functions. Namely, CD8 acts to stabilize the binding of the T-cell receptor (TCR) to the peptide-MHC complex while localizing p56(lck) (lck) to the TCR/CD3 complex to facilitate early signaling events. Although both functions may be critical for efficient activation of a CTL, little is known about how the structural versus signaling roles of CD8, together with the relative strength of the TCR, influences T-cell function. We have addressed these issues by introducing full-length and truncated versions of the CD8alpha and CD8beta chains into CD8(-) Jurkat cell clones expressing cloned TCRs with known antigen specificity and relative affinities. Using a combination of antigen recognition and tetramer-binding assays, we find that the intracellular lck-binding domain of CD8 is critical for enhanced T-cell activation regardless of the relative strength of the TCR. In contrast, the extracellular domain of CD8 seems to be critical for TCRs with lower affinity but not those with higher affinity. Based on our results, we conclude that there are different requirements for CD8 to enhance T-cell function depending on the strength of its TCR.

Antigen recognition and T-cell biology.

Despite the wealth of information that has been acquired regarding the way T cells recognize their targets, we are left with far more questions than answers regarding how to manipulate the immune response to better treat cancer patients. Clearly, most patients have a broad repertoire of T cells capable of recognizing their tumor cells. Despite the presence of these tumor reactive T cells and our ability to increase their frequency though vaccination or adoptive transfer, patients still progress. From the T cell side, defects in T cell signaling may account for much of our failure to achieve significant numbers of objective clinical responses. In spite of these negatives, the horizon does remain bright for T cell based immune therapy of cancer. The periodic objective clinical response tells us that immune therapy can work. Now that we know that cancer patients have the capacity to mount immune responses against their tumors, current and future investigations with agents which alter T cell function combined with vaccination or adoptive T cell transfer may help tip the balance towards effective immune therapies.

Breast MR imaging for extent of disease assessment in patients with newly diagnosed breast cancer.

Breast cancer staging and surgical planning are affected by the burden of pathologically proven cancer detected on clinical examination and/or imaging. Magnetic resonance (MR) imaging has superior sensitivity and accuracy for the detection of invasive and in situ breast cancer as compared with physical examination, mammography, and ultrasound but can be limited in specificity. The use of preoperative breast MR imaging for evaluating the extent of disease remains controversial at present because studies have not definitively shown it to improve overall survival, decrease re-excision rates, or to decrease the cost of care.

Risk of thyroid cancer based on thyroid ultrasound imaging characteristics: results of a population-based study.

IMPORTANCE: There is wide variation in the management of thyroid nodules identified on ultrasound imaging. OBJECTIVE: To quantify the risk of thyroid cancer associated with thyroid nodules based on ultrasound imaging characteristics. METHODS: Retrospective case-control study of patients who underwent thyroid ultrasound imaging from January 1, 2000, through March 30, 2005. Thyroid cancers were identified through linkage with the California Cancer Registry. RESULTS: A total of 8806 patients underwent 11,618 thyroid ultrasound examinations during the study period, including 105 subsequently diagnosed as having thyroid cancer. Thyroid nodules were common in patients diagnosed as having cancer (96.9%) and patients not diagnosed as having thyroid cancer (56.4%). Three ultrasound nodule characteristics--microcalcifications (odds ratio [OR], 8.1; 95% CI, 3.8-17.3), size greater than 2 cm (OR, 3.6; 95% CI, 1.7-7.6), and an entirely solid composition (OR, 4.0; 95% CI, 1.7-9.2)--were the only findings associated with the risk of thyroid cancer. If 1 characteristic is used as an indication for biopsy, most cases of thyroid cancer would be detected (sensitivity, 0.88; 95% CI, 0.80-0.94), with a high false-positive rate (0.44; 95% CI, 0.43-0.45) and a low positive likelihood ratio (2.0; 95% CI, 1.8-2.2), and 56 biopsies will be performed per cancer diagnosed. If 2 characteristics were required for biopsy, the sensitivity and false-positive rates would be lower (sensitivity, 0.52; 95% CI, 0.42-0.62; false-positive rate, 0.07; 95% CI, 0.07-0.08), the positive likelihood ratio would be higher (7.1; 95% CI, 6.2-8.2), and only 16 biopsies will be performed per cancer diagnosed. Compared with performing biopsy of all thyroid nodules larger than 5 mm, adoption of this more stringent rule requiring 2 abnormal nodule characteristics to prompt biopsy would reduce unnecessary biopsies by 90% while maintaining a low risk of cancer (5 per 1000 patients for whom biopsy is deferred). CONCLUSIONS AND RELEVANCE: Thyroid ultrasound imaging could be used to identify patients who have a low risk of cancer for whom biopsy could be deferred. On the basis of these results, these findings should be validated in a large prospective cohort.

Endovenous laser ablation and sclerotherapy for treatment of varicose veins.

Superficial venous insufficiency is a common problem associated with varicose veins. Venous insufficiency and varicose veins can be symptomatic, but more commonly they are a cosmetic concern. In this article, we discuss the relevant anatomy and pathophysiology of superficial venous insufficiency, review the current literature for varicose vein treatment, and cover the technical aspects of diagnosing and treating superficial venous insufficiency. Saphenofemoral junction incompetence with resultant greater saphenous vein reflux is the most common cause of varicose veins; because this condition constitutes the majority of patients encountered in practice, we will concentrate on this area. Endovenous laser ablation and sclerotherapy are covered, including patient workup and selection, procedure set-up, and anesthesia.

Identification of a hepatitis C virus-reactive T cell receptor that does not require CD8 for target cell recognition.

Hepatitis C virus (HCV) has been reported to elicit B and T cell immunity in infected patients. Despite the presence of antiviral immunity, many patients develop chronic infections leading to cirrhosis, hepatocellular carcinoma, and liver failure that can require transplantation. We have previously described the presence of HLA-A2-restricted, HCV NS3-reactive cytotoxic T lymphocytes (CTL) in the blood of HLA-A2- liver transplantation patients that received an HLA-A2+ liver allograft. These T cells are analogous to the "allospecific" T cells that have been described in hematopoietic stem cell transplantation patients. It has been speculated that allospecific T cells express high-affinity T cell receptors (TCRs). To determine if our HCV-reactive T cells expressed TCRs with relatively high affinity for antigen, we identified and cloned a TCR from an allospecific HLA-A2-restricted, HCV:NS3:1406-1415-reactive CD8+ T cell clone and expressed this HCV TCR in Jurkat cells. Tetramer binding to HCV TCR-transduced Jurkat cells required CD8 expression, whereas antigen recognition did not. In conclusion, based on the reactivity of the TCR-transduced Jurkat cells, we have identified a TCR that transfers anti-HCV reactivity to alternate effectors. These data suggest this high affinity HCV-specific TCR might have potential new immunotherapic implications.