Diagnostics, Volume 7, Issue 2 (June 2017) – 19 articles

Neurogenic thoracic outlet syndrome (nTOS) is characterized by arm and hand pain, paresthesias, and sometimes weakness resulting from compression of the brachial plexus within the thoracic outlet. While it is the most common subtype of TOS, nTOS can be difficult to diagnose. Furthermore, patient selection for surgical treatment can be challenging as symptoms may be vague and ambiguous, and diagnostic studies may be equivocal. Herein, we describe some approaches to aid in identifying patients who would be expected to benefit from surgical intervention for nTOS. We describe the role of physical examination, physical therapy, and imaging in the evaluation and diagnosis of nTOS. Full article

The creation of any patient database requires substantial planning. In the case of thoracic outlet syndrome, which is a rare disease, the Society for Vascular Surgery has defined reporting standards to serve as an outline for the creation of a patient registry. Prior to undertaking this task, it is critical that designers understand the basics of registry planning and a priori establish plans for data collection and analysis. Full article

Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured. Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy and the evaluation CT scan, leaving twelve patients for analysis. Early changes in perfusion parameters using DCE-US did not correlate well with subsequent CT changes. A subgroup analysis of eight patients receiving bevacizumab, however, demonstrated a statistically significant correlation (p = 0.045) between early changes in perfusion measures of peak enhancement at DCE-US and tumor shrinkage at CT scan. The study indicates that early changes in DCE-US perfusion measures may predict subsequent treatment response of colorectal liver metastases in patients receiving bevacizumab. Full article

Thoracic Outlet Syndrome (TOS) describes a set of disorders that arise from compression of the neurovascular structures that exit the thorax and enter the upper extremity. This can present as one of three subtypes: neurogenic, venous, or arterial. The objective of this section is to outline our current practice at a single, high-volume institution for venous and arterial TOS. VTOS: Patients who present within two weeks of acute deep vein thrombosis (DVT) are treated with anticoagulation, venography, and thrombolysis. Those who present later are treated with a transaxillary first rib resection, then a two-week post-operative venoplasty. All patients are anticoagulated for 2 weeks after the post-operative venogram. Those with recurrent thrombosis or residual subclavian vein stenosis undergo repeat thrombolysis or venoplasty, respectively. ATOS: In patients with acute limb ischemia, we proceed with thrombolysis or open thrombectomy if there is evidence of prolonged ischemia. We then perform a staged transaxillary first rib resection followed by reconstruction of the subclavian artery. Patients who present with claudication undergo routine arterial duplex and CT angiogram to determine the pathology of the subclavian artery. They then undergo decompression and subclavian artery repair in a similar staged manner. Full article

In some radiology departments, the lack of alignment between administrators and radiologists can pose significant challenges. This article describes how differences in background and priorities between administrators and radiologists can contribute to conflict and presents strategies on how to manage the conflict in a way that can leverage positive change. Strategies to build relations between radiologists and radiology administrators are described. Full article

Background: The aim of this study was to assess and compare the performance of different ultrasound-based International Ovarian Tumor Analysis (IOTA) strategies and subjective assessment for the diagnosis of early stage ovarian malignancy. Methods: This is a secondary analysis of a prospective multicenter cross-sectional diagnostic accuracy study that included 1653 patients recruited at 18 centers from 2009 to 2012. All patients underwent standardized transvaginal ultrasonography by experienced ultrasound investigators. We assessed test performance of the IOTA Simple Rules (SRs), Simple Rules Risk (SRR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model and subjective assessment to discriminate between stage I-II ovarian cancer and benign disease. Reference standard was histology after surgery. Results: 230 (13.9%) patients proved to have stage I–II primary invasive ovarian malignancy, and 1423 (86.1%) had benign disease. Sensitivity and specificity with respect to malignancy (95% confidence intervals) of the original SRs (classifying all inconclusive cases as malignant) were 94.3% (90.6% to 96.7%) and 73.4% (71.0% to 75.6%). Subjective assessment had a sensitivity and specificity of 90.0% (85.4% to 93.2%) and 86.7% (84.9% to 88.4%), respectively. The areas under the receiver operator characteristic curves of SRR and ADNEX were 0.917 (0.902 to 0.933) and 0.905 (0.920 to 0.934), respectively. At a 1% risk cut-off, sensitivity and specificity for SRR were 100% (98.4% to 100%) and 38.0% (35.5% to 40.6%), and for ADNEX were 100% (98.4% to 100%) and 19.4% (17.4% to 21.5%). At a 30% risk cut-off, sensitivity and specificity for SRR were 88.3% (83.5% to 91.8%) and 81.1% (79% to 83%), and for ADNEX were 84.5% (80.5% to 89.6%) and 84.5% (82.6% to 86.3%). Conclusion: This study shows that all three IOTA strategies have good ability to discriminate between stage I-II ovarian malignancy and benign disease. Full article

After the introduction of antiretroviral therapy (ART) the life expectancy of patients infected with human immunodeficiency virus (HIV) is now approaching that of the general population and the importance of non-AIDS co-morbidities is increasing. Specifically, the risk of coronary artery disease (CAD) seems to be higher in HIV-infected patients and an accurate risk prediction of CAD is of high importance for optimal long term treatment. In this study, we assessed the correlation of the endoPAT, which is an office-based CVD screening tool with the myocardial perfusion reserve by ⁸²-rubidium PET/CT. We measured the reactive hyperemia index, which is a measure of the endothelial responsiveness, by the use of an endoPAT device (Itamar Medical, Caesarea, Israel) in 48 ART treated HIV-infected patients with high CD 4 cell counts and viral suppression (HIV-RNA < 20 copies/mL), who had previously undergone measurement of the myocardial perfusion reserve by ⁸²-rubidium PET/CT for study purposes. We found an inverse correlation between the reactive hyperemia index and the myocardial perfusion reserve which most likely indicates different vascular physiology. This study did not find evidence to suggest the immediate implementation of the reactive hyperemia index as a screening tool for early coronary artery disease in well-treated HIV-infected patients pending further validation in larger prospective studies. Full article

Mammographic breast density (MBD) has been proven to be an important risk factor for breast cancer and an important determinant of mammographic screening performance. The measurement of density has changed dramatically since its inception. Initial qualitative measurement methods have been found to have limited consistency between readers, and in regards to breast cancer risk. Following the introduction of full-field digital mammography, more sophisticated measurement methodology is now possible. Automated computer-based density measurements can provide consistent, reproducible, and objective results. In this review paper, we describe various methods currently available to assess MBD, and provide a discussion on the clinical utility of such methods for breast cancer screening. Full article

Immunochromatographic or lateral flow assays (LFAs) are inexpensive, easy to use, point-of-care medical diagnostic tests that are found in arenas ranging from a doctor’s office in Manhattan to a rural medical clinic in low resource settings. The simplicity in the LFA itself belies the complex task of optimization required to make the test sensitive, rapid and easy to use. Currently, the manufacturers develop LFAs by empirical optimization of material components (e.g., analytical membranes, conjugate pads and sample pads), biological reagents (e.g., antibodies, blocking reagents and buffers) and the design of delivery geometry. In this paper, we will review conventional optimization and then focus on the latter and outline analytical tools, such as dynamic light scattering and optical biosensors, as well as methods, such as microfluidic flow design and mechanistic models. We are applying these tools to find non-obvious optima of lateral flow assays for improved sensitivity, specificity and manufacturing robustness. Full article

Neurogenic thoracic outlet syndrome is a widely recognized, yet controversial, syndrome. The lack of specific objective diagnostic modalities makes diagnosis difficult. This is compounded by a lack of agreed upon definitive criteria to confirm diagnosis. Recent efforts have been made to more clearly define a set of diagnostic criteria that will bring consistency to the diagnosis of neurogenic thoracic syndrome. Additionally, advancements have been made in the quality and techniques of various imaging modalities that may aid in providing more accurate diagnoses. Surgical decompression remains the mainstay of operative treatment; and minimally invasive techniques are currently in development to further minimize the risks of this procedure. Medical management continues to be refined to provide non-operative treatment modalities for certain patients, as well. The aim of the present work is to review these updates in the diagnosis and treatment of neurogenic thoracic outlet syndrome. Full article

Thiopurine intolerance and treatment-related toxicity, such as fatal myelosuppression, is related to non-function genetic variants encoding thiopurine S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). Genetic testing of the common variants NUDT15:NM_018283.2:c.415C>T (Arg139Cys, dbSNP rs116855232 T allele) and TPMT: NM_000367.4:c.719A>G (TPMT*3C, dbSNP rs1142345 G allele) in East Asians including Chinese can potentially prevent treatment-related complications. Two complementary genotyping approaches, real-time PCR-high resolution melt (PCR-HRM) and PCR-restriction fragment length morphism (PCR-RFLP) analysis were evaluated using conventional PCR and Sanger sequencing genotyping as the gold standard. Sixty patient samples were tested, revealing seven patients (11.7%) heterozygous for NUDT15 c.415C>T, one patient homozygous for the variant and one patient heterozygous for the TPMT*3C non-function allele. No patient was found to harbor both variants. In total, nine out of 60 (15%) patients tested had genotypic evidence of thiopurine intolerance, which may require dosage adjustment or alternative medication should they be started on azathioprine, mercaptopurine or thioguanine. The two newly developed assays were more efficient and showed complete concordance (60/60, 100%) compared to the Sanger sequencing results. Accurate and cost-effective genotyping assays by real-time PCR-HRM and PCR-RFLP for NUDT15 c.415C>T and TPMT*3C were successfully developed. Further studies may establish their roles in genotype-informed clinical decision-making in the prevention of morbidity and mortality due to thiopurine intolerance. Full article

The purpose of this study was to evaluate prediction of prognosis after first-line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL), by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (¹⁸F-FDG-PET/CT) three months after induction treatment by Iodine-131-rituximab (¹³¹I-rituximab). Objective response was determined using the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline ¹⁸F-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume (TMTV). Non-imaging studies included the Follicular lymphoma international prognostic index (FLIPI) and absolute baseline monocyte and lymphocyte counts. Patients were monitored for over ten years (median follow-up 59 months), and no patient was lost to follow-up. Complete response (CR) of 88% predicted excellent prognosis with median time-to-next-treatment (TTNT) not yet reached. Those patients (12%) who failed to achieve CR (Deauville ≤ 3) on ¹⁸F-FDG-PET/CT at three months had significantly poorer outcomes (p < 0.0001) with a median TTNT of 41 months. Requirement for re-treatment was predicted by FLIPI and absolute baseline monocyte count but not lymphocyte count. The TTNT was accurately predicted by ¹⁸F-FDG-PET/CT Deauville response at three months following first-line therapy of FL with RIT. Early response demonstrated by imaging does, therefore, foretell prognosis in the individual FL patients. Full article

Women that are positive for an ovarian abnormality in a clinical setting can have either a malignancy or a benign tumor with probability favoring the benign alternative. Accelerating the abnormality to surgery will result in a high number of unnecessary procedures that will place cost burdens on the individual and the health delivery system. Surveillance using serial ultrasonography is a reasonable alternative that can be used to discover if changes in the ovarian abnormality will occur that favor either a malignant or benign interpretation. Several ovarian cancer screening trials have had extensive experiences with changes in subclinical ovarian abnormalities in normal women that can define growth, stability or resolution and give some idea of the time frame over which changes occur. The present report examines these experiences and relates them to the current understanding of ovarian cancer ontology, presenting arguments related to the benefits of surveillance. Full article

Identifying, understanding, and curing disease is a lifelong endeavor for any medical practitioner. Equally as important is to be cognizant of the impact a disease has on the individual suffering from it, as well as on their family. Ovarian cancer is the leading cause of death from gynecologic malignancies. Symptoms are vague, and the disease is generally at an advanced stage at diagnosis. Efforts have been made to develop methods to identify ovarian cancer at earlier stages, thus improving overall mortality. Transvaginal ultrasound (TVUS), with and without laboratory tests, can be used to screen for ovarian cancer. For over thirty years, the University of Kentucky Markey Cancer Center Ovarian Cancer Screening Program has been studying the efficacy of TVUS for detecting early stage ovarian cancer. After 285,000+ TVUS examinations provided to over 45,000 women, the program has demonstrated that regular TVUS examinations can detect ovarian cancer at early stages, and that survival is increased in those women whose ovarian cancer was detected with screening and who undergo standard treatment. These results demonstrate the utility of TVUS as an efficacious method of ovarian cancer screening. Full article

Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses. To overcome this, new response criteria for evaluating these patients with morphologic imaging have been proposed. The aim of this paper is to review and discuss the current evidence for the use of molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer Tomography) with ¹⁸F-Fluorodeoxyglucoes (FDG) as an alternative imaging method for monitoring patients undergoing ICT. Following the currently available evidence, this review will primarily focus on patients with malignant melanoma. Full article

The unique intricacies of ovarian cancer screening and perspectives of different screening methods are presented as ten considerations that are examined. Included in these considerations are: (1) Deciding on the number of individuals to be screened; (2) Anticipating screening group reductions due to death; (3) Deciding on the duration and frequency of screening; (4) Deciding on an appropriate follow-up period after screening; (5) Deciding on time to surgery when malignancy is suspected; (6) Deciding on how screen-detected ovarian cancers are treated and by whom; (7) Deciding on how to treat the data of enrolled participants; (8) Deciding on the most appropriate way to assign disease-specific death; (9) Deciding how to avoid biases caused by enrollments that attract participants with late-stage disease who are either symptomatic or disposed by factors that are genetic, environmental or social; and (10) Deciding whether the screening tool or a screening process is being tested. These considerations are presented in depth along with illustrations of how they impact the outcomes of ovarian cancer screening. The considerations presented provide alternative explanations of effects that have an important bearing on interpreting ovarian screening outcomes. Full article

Saliva has been useful as a liquid biopsy for the diagnosis of various oral or systemic diseases, and oral squamous cell carcinoma (OSCC) is no exception. While its early detection and prevention is important, salivary cytokines expression, specifically of Interleukin-8 (IL-8), Interleukin-6 (IL-6) and Tumor necrosis factor (TNF-α), does contribute to the pathogenesis of cancer and these cytokines serve as potential biomarkers. Their excessive production plays a role in cancer progression and establishment of angiogenesis. However, other inflammatory or immunological conditions may affect the levels of cytokines in saliva. This article reviews the expression of levels of specific cytokines i.e., IL-8, IL-6 and TNF-α, their signaling pathways in the development of oral cancer, and how they are essential for the diagnosis of OSCC and updates related to it. Apart from serum, the saliva-based test can be a cost-effective tool in the follow-up and diagnosis of OSCC. Moreover, large-scale investigations are still needed for the validation of salivary cytokines. Full article

Fluorothymidine is a thymidine analog labeled with fluorine-18 fluorothymidine for positron emission tomography (¹⁸F-FLT-PET) imaging. Thymidine is a nucleic acid that is used to build DNA. Fluorine-18 fluorothymidine (¹⁸F-FLT) utilizes the same metabolic pathway as does thymidine but has a very low incidence of being incorporated into the DNA (<1%). ¹⁸F-FLT-PET could have a role in the evaluation of response to targeted therapy. We present here a pilot study where we investigated cellular metabolism and proliferation in patients with prostate cancer before and after targeted therapy. Seven patients with Stage IV prostate adenocarcinoma, candidates for targeted therapy inhibiting the hepatocyte growth factor/tyrosine-protein kinase Met (HGF/C-MET) pathway, were included in this study. The HGF/C-MET pathway is implicated in prostate cancer progression, and an evaluation of the inhibition of this pathway could be valuable. ¹⁸F-FLT was performed at baseline and within four weeks post-therapy. Tumor response was assessed semi-quantitatively and using visual response criteria. The range of SUVmax for ¹⁸F-FLT at baseline in the prostate varied from 2.5 to 4.2. This study demonstrated that ¹⁸F-FLT with positron emission tomography/computerized tomography (¹⁸F-FLT PET/CT) had only limited applications in the early response evaluation of prostate cancer. ¹⁸F-FLT PET/CT may have some utility in the assessment of response in lymph node disease. However, ¹⁸F-FLT PET/CT was not found to be useful in the evaluation of the prostate bed, metastatic skeletal disease, and liver disease. Full article

Current reported incidence rates for ovarian cancer may significantly underestimate the true rate because of the inclusion of women in the calculations who are not at risk for ovarian cancer due to prior benign salpingo-oophorectomy (SO). We have considered prior SO to more realistically estimate risk for ovarian cancer. Kentucky Health Claims Data, International Classification of Disease 9 (ICD-9) codes, Current Procedure Terminology (CPT) codes, and Kentucky Behavioral Risk Factor Surveillance System (BRFSS) Data were used to identify women who have undergone SO in Kentucky, and these women were removed from the at-risk pool in order to re-assess incidence rates to more accurately represent ovarian cancer risk. The protective effect of SO on the population was determined on an annual basis for ages 5–80+ using data from the years 2009–2013. The corrected age-adjusted rates of ovarian cancer that considered SO ranged from 33% to 67% higher than age-adjusted rates from the standard population. Correction of incidence rates for ovarian cancer by accounting for women with prior SO gives a better understanding of risk for this disease faced by women. The rates of ovarian cancer were substantially higher when SO was taken into consideration than estimates from the standard population. Full article