Can radiomic feature analysis differentiate adrenal metastases from lipid-poor adenomas on single-phase contrast-enhanced CT abdomen?

AIM: To assess if radiomic feature analysis could help to differentiate between the lipid-poor adenomas and metastases to the adrenal glands. MATERIALS AND METHODS: Eighty-six patients (women:men 42:44; mean age 66 years) with biopsy-proven adrenal metastases and 55 patients (women:men 39:16; mean age 67 years) with lipid-poor adenomas who underwent contrast-enhanced, portal-venous phase CT of the abdomen. Radiomic features were extracted using the PyRadiomics extension for 3D Slicer. Following elastic net regularisation, seven of 1,132 extracted radiomic features were selected to build a radiomic signature. This was combined with patient demographics to create a predictive nomogram. The calibration curves in both the training and validation cohorts were assessed using a Hosmer-Lemeshow test. RESULTS: The radiomic signature alone yielded an area under the curve of 91.7% in the training cohort (n=93) and 87.1% in the validation cohort (n=48). The predictive nomogram, which combined age, a previous history of malignancy, and the radiomic signature, had an AUC of 97.2% in the training cohort and 90.4% in the validation cohort. CONCLUSION: The present nomogram has the potential to differentiate between a lipid-poor adrenal adenoma and adrenal metastasis on portal-venous CT.

The role of percutaneous CT-guided biopsy of an adrenal lesion in patients with known or suspected lung cancer.

PURPOSE: To determine the sensitivity, specificity, and complication rate of percutaneous adrenal biopsy in patients with known or suspected lung cancer. METHODS: This study was approved by the Institutional Review Board at our institution as a retrospective analysis; therefore, the need for informed consent was waived. All percutaneous adrenal biopsies performed between April 1993 and May 2019 were reviewed. 357 of 582 biopsies were performed on 343 patients with known or suspected lung cancer (M:F 164:179; mean age 66 years). The biopsy results were classified into malignant, benign, or non-diagnostic. The final diagnosis was established by pathology (biopsy and/or surgical resection) or imaging follow-up on CT for at least 12 months following the biopsy. Patients with less than 12 months follow-up were excluded (n = 44). Complications were recorded. RESULTS: The final diagnosis was metastatic lung cancer in 235 cases (77.8%), metastasis from an extrapulmonary primary in 2 cases (0.7%), pheochromocytoma in 2 cases (0.7%), and benign lesions in 63 cases (20.9%). Percutaneous adrenal gland biopsy had a sensitivity of 97% and specificity of 100% for lung cancer metastases. The non-diagnostic rate was 0.6%. Larger lesions were more likely to be malignant (p = 0.0000) and to be correctly classified as a lung metastasis (p = 0.025). The incidence of minor complications was 1.1%. There were no major complications. CONCLUSION: Over 20% of adrenal lesions in patients with known or suspected lung cancer were not related to lung cancer. Percutaneous adrenal gland biopsy is a safe procedure, with high sensitivity and specificity for lung cancer metastases.

Comparison of 18F-FDG avidity at PET of benign and malignant pure ground-glass opacities: a paradox? Part II: artificial neural network integration of the PET/CT characteristics of ground-glass opacities to predict their likelihood of malignancy.

AIM: To assess the ability of artificial neural networks (ANNs) to predict the likelihood of malignancy of pure ground-glass opacities (GGOs), using observations from computed tomography (CT) and 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) images and relevant clinical information. MATERIALS AND METHODS: One hundred and twenty-five cases of pure GGOs described in a previous article were used to train and evaluate the performance of an ANN to predict the likelihood of malignancy in each of the GGOs. Eighty-five cases selected randomly were used for training the network and the remaining 40 cases for testing. The ANN was constructed from the image data and basic clinical information. The predictions of the ANN were compared with blinded expert estimates of the likelihood of malignancy. RESULTS: The ANN showed excellent predictive value in estimating the likelihood of malignancy (AUC = 0.98±0.02). Employing the optimal cut-off point from the receiver operating characteristic (ROC) curve, the ANN correctly identified 11/11 malignant lesions (sensitivity 100%) and 27/29 benign lesions (specificity 93.1%). The expert readers found 23 lesions indeterminate and correctly identified 17 lesions as benign. CONCLUSION: ANNs have potential to improve diagnostic certainty in the classification of pure GGOs, based upon their CT appearance, intensity of FDG uptake, and relevant clinical information, and may therefore, be useful to help direct clinical and imaging follow-up.

Comparison of the 18F-FDG avidity at PET of benign and malignant pure ground-glass opacities: a paradox?

AIM: To determine if pure ground-glass opacities (GGOs) and the subgroup of ground-glass nodules (GGNs) typically demonstrate higher 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake at positron-emission tomography (PET) when benign than when malignant. MATERIALS AND METHODS: Informed consent was waived for this institutional review board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA) compliant, retrospective study. A review of all 1,864 combined PET/computed tomography (CT) examinations performed in 2011 on a single system to identify pure GGOs with mean diameter ≥1 cm yielded 166 GGOs. Two blinded subspecialty-trained thoracic radiologists independently assessed GGO size, morphology, attenuation, and location on CT. A blinded nuclear radiologist procured the SUVmax for each GGO. Final diagnosis of malignancy (n=21) was made based on histopathology or upon increased size and attenuation; a final diagnosis of benignity (n=106) was made if GGO resolved, was new within 3 months, evolved in a manner consistent with pulmonary fibrosis, or was stable for ≥60 months; 29 were indeterminate and were excluded, along with 10 cases with unreliable SUVmax measurements, yielding 127 GGOs, of which 68 were GGNs, in 76 patients. RESULTS: The SUVmax was significantly higher in benign than malignant GGOs (p=0.0017) and in the GGN subgroup (p=0.03). A threshold SUVmax >1.5 for GGOs, including GGNs, assured benignity in this cohort. CONCLUSION: Benign GGOs and the benign GGN subgroup demonstrated significantly higher FDG uptake at PET than malignant GGOs/GGNs. Awareness of this finding may prevent misinterpretation of highly 18FDG-avid pure GGOs/GGNs as definitively malignant, which could lead to unnecessary thoracic surgery and its associated risks.

Population-based mortality data suggests remediation is modestly effective in two Montana Superfund counties.

The health effects of living in proximity to Superfund sites with ongoing remediation were evaluated for residents of two contiguous Montana counties, Deer Lodge and Silver Bow. Deer Lodge and Silver Bow are home to the Anaconda Smelter and Silver Bow Creek/Butte Area Superfund sites, respectively. Established by the Environmental Protection Agency in 1983, both sites have had ongoing remediation for decades. Employing county level death certificate data obtained from the Centers for Disease Control and Prevention WONDER site, sex and age-adjusted standardized mortality ratios (SMRs) for composite targeted causes of death were calculated using observed versus expected mortality for both counties, and compared to the expected mortality from the remaining Montana counties. Cancers, cerebro- and cardiovascular diseases (CCVD), and organ failure were elevated for the two counties during the study period, 2000-2016, with SMRs of 1.19 (95% CI 1.10, 1.29); 1.36 (95% CI 1.29, 1.43); and 1.24 (95% CI 1.10, 1.38), respectively. Neurological conditions were not elevated for the two counties (SMR = 1.01; 95% CI 0.89, 1.14). Time trend analyses performed using Cox regression models indicate that deaths from cancers (HR = 0.97; p = 0.0004), CCVDs (HR = 0.95; p ≤ 0.0001), and neurological conditions (HR = 0.97; p = 0.01) decreased over the study period. While the ecological approach applied limits the interpretation of our results, our study suggests that while mortality is elevated, it is also decreasing over time for these two Superfund sites.

EMP2 is a novel therapeutic target for endometrial cancer stem cells.

Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1). ALDH expression significantly promotes tumor initiation and correlates with the levels of EMP2 expression in both patient samples and tumor cell lines. As therapy against cancer stem cells in endometrial cancer is lacking, the ability of anti-EMP2 IgG1 therapy to reduce primary and secondary tumor formation using xenograft HEC1A models was determined. Anti-EMP2 IgG1 reduced the expression and activity of ALDH and correspondingly reduced both primary and secondary tumor load. Our results collectively suggest that anti-EMP2 therapy may be a novel method of reducing endometrial cancer stem cells.

Imaging the Abdominal Manifestations of Cystic Fibrosis.

Cystic fibrosis (CF) is a multisystem disease with a range of abdominal manifestations including those involving the liver, pancreas, and kidneys. Recent advances in management of the respiratory complications of the disease has led to a greater life expectancy in patients with CF. Subsequently, there is increasing focus on the impact of abdominal disease on quality of life and survival. Liver cirrhosis is the most important extrapulmonary cause of death in CF, yet significant challenges remain in the diagnosis of CF related liver disease. The capacity to predict those patients at risk of developing cirrhosis remains a significant challenge. We review representative abdominal imaging findings in patients with CF selected from the records of two academic health centres, with a view to increasing familiarity with the abdominal manifestations of the disease. We review their presentation and expected imaging findings, with a focus on the challenges facing diagnosis of the hepatic manifestations of the disease. An increased familiarity with these abdominal manifestations will facilitate timely diagnosis and management, which is paramount to further improving outcomes for patients with cystic fibrosis.

Molecular imaging-its current role in cancer.

Medical imaging has undergone extensive growth over the last few decades and now plays a central role in clinical oncology. The future of imaging in the management of oncology patients is molecularly targeted imaging agents. Molecular imaging differs from conventional anatomical imaging in that imaging probes are utilized to visualize target molecules-of-interest. It is envisioned that molecular imaging will have a major impact on oncology and personalized medicine by allowing earlier diagnosis, assessing early response to treatment and by predicting treatment response. It will, hopefully, also have an impact on drug development by streamlining preclinical and clinical tests for new drug candidates.

Utility of positron emission tomography/CT in the evaluation of small bowel pathology.

We describe the management principles and different roles of positron emission tomography (PET)/CT in the evaluation of patients with small bowel tumours (adenocarcinoma, gastrointestinal stromal tumour, lymphoma, metastases) from initial staging, monitoring response to treatment, to detection of recurrent disease. We also discuss the various non-malignant aetiologies of small bowel fludeoxyglucose (FDG) PET uptake, and other pitfalls in FDG PET/CT interpretation. Awareness of the imaging appearances of small bowel tumours, patterns of disease spread and potential PET/CT interpretation pitfalls are of paramount importance to optimise diagnostic accuracy.

Plastic wound retractors as bacteriological barriers in gastrointestinal surgery: a prospective multi-institutional trial.

BACKGROUND: Surgical site infection remains a significant problem, and peri-operative strategies to reduce wound exposure to bacteria are needed urgently. Plastic ring wound retractors, used to gain access to the abdominal cavity, may shield the incision site from bacteria. AIM: To evaluate exposure of the surgical incision site to bacteria using a plastic ring wound retractor in gastrointestinal surgery. METHODS: Prospective, observational, multi-centre study. Patients undergoing clean-contaminated gastrointestinal surgery with standard antibiotic prophylaxis were included (N = 250 patients, 500 samples). A plastic wound retractor was used to facilitate access to the abdominal cavity. Samples were taken for bacterial culture from the inside (luminal) and outside (wound) surfaces of the retractor at the end of the operation. FINDINGS: Bacteria were found on 56% (140/250) of samples from the inside surface of the retractor compared with 34% (85/250) of samples from the outside surface of the retractor (P < 0.0001). There was no significant difference in skin-derived organisms from the inside [34/245 (14%)] and outside [27/250 (11%)] surfaces of the retractor (P = 0.108). However, enteric organisms were cultured twice as often from the inside surface of the retractor compared with the outside surface of the retractor (49% vs 26%, respectively; P < 0.0001). CONCLUSION: Plastic wound retractors reduce wound exposure to enteric bacteria in gastrointestinal surgery.

18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Management of Aggressive Non-Hodgkin's B-Cell Lymphoma.

18-Fluorodeoxyglucose (FDG-PET/CT) is an established imaging modality that has been proven to be of benefit in the management of aggressive B-cell non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and advanced stage follicular lymphoma. The combination of anatomic and functional imaging afforded by FDG-PET/CT has led to superior sensitivity and specificity in the primary staging, restaging, and assessment of response to treatment of hematological malignancies when compared to FDG-PET and CT alone. The use of FDG-PET/CT for posttreatment surveillance imaging remains controversial, and further study is needed to ascertain whether this modality is cost effective and appropriate for use in this setting.

Radiological evaluation of adrenal incidentalomas: current methods and future prospects.

Incidental adrenal lesions are very common. Computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) all have a role to play in characterizing adrenal lesions. The purpose of this review is to discuss the rationale behind both established and emerging imaging techniques. We also discuss how to follow up incidentally found lesions.

Reference urodynamic values for stress incontinent women.

OBJECTIVE: To determine reference urodynamic values for preoperative urodynamic studies in women undergoing surgery for pure or predominant stress urinary incontinence (SUI). MATERIALS AND METHODS: Six hundred fifty-five women with pure or predominant SUI were enrolled in a multicenter surgical trial and were randomized to undergo a Burch or autologous fascia sling procedure as part of the Urinary Incontinence Treatment Network (UITN) Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr). Preoperative free uroflowmetry, filling cystometry, and pressure flow studies were performed in all women using a standardized research protocol and standardized urodynamic interpretation guidelines. We define the normal range of urodynamic values in this population as the values that encompass 95% of the results. RESULTS: In 655 women undergoing filling cystometry in the standing position, baseline vesical and abdominal pressures were between 12 and 60 cm H(2)O. The upper limit of detrusor pressure increase during bladder filling to maximum cystometric capacity was 16 cm H(2)O. Ten percent of women who qualified for stress incontinence surgery with a positive cough stress test on physical exam did not demonstrate urodynamic stress incontinence (USI) and less than 10% of subjects in this study demonstrated detrusor overactivity. CONCLUSIONS: Results from a large cohort of women with SUI are now available for quantitative plausibility assessments or as reference values when interpreting urodynamic studies.

Juvenile syndecan-1 null mice are protected from carcinogen-induced tumor development.

We previously showed that mice with a null mutation in syndecan-1 (Sdc1; CD138) were resistant to Wnt1-induced mammary tumor initiation. The absence of Sdc1 inhibited the increase in the mammary stem cell fraction that is characteristic of preneoplasia in this model. As the tumor precursor cells are recruited from the stem/progenitor cell compartment, tumor development was also inhibited (Liu et al., 2004; PNAS 101, 4158). Although Sdc1-/- mice are grossly normal, they are systemically smaller, suggesting that developmental abnormalities may extend further than their mammary glands. We have therefore evaluated the multi-organ response of Sdc1-/- mice to carcinogen-induced tumor development (7,12-dimethylbenz[a]anthracene, DMBA), and find these mice to be resistant to tumorigenesis in all the predominant carcinogen-susceptible lineages. Thus, Sdc1-/- mice administered DMBA during juvenile development are resistant not only to epithelial tumors, including liver (60-80%) and lung tumors (C57BL6 mice, 60-80%), but also to lymphoma (over 70%, depending upon strain and carcinogen dose). We demonstrate that CD138 is expressed (heterogeneously) in the hematopoietic stem cell fraction (and not only in pre-B and plasma cells), and that tumors arise in both myeloid and lymphoid lineages. Furthermore, carcinogen-induced mammary tumors are bilineal, implying a bipotent precursor cell. Both observations imply that the DMBA-induced tumor precursor cells are drawn from the stem/progenitor fraction, and we suggest that pathogenic activation of these cells could be abnormal in Sdc1-/- mice.

Interrater reliability of filling cystometrogram interpretation in a multicenter study.

PURPOSE: As part of a continuous quality control effort to measure the interrater reliability of urodynamic studies performed at multiple centers, we compared agreement levels for urodynamic studies between central and local physician reviewers. We report interrater reliability findings for the filling cystometrogram. MATERIALS AND METHODS: Following a satisfactory interrater reliability study among 4 central physician reviewers in 33 tracings 36 urodynamic study tracings from 9 Urinary Incontinence Treatment Network continence treatment centers and 13 Urinary Incontinence Treatment Network certified urodynamic study testers were randomly selected for review. These tracings were originally interpreted by 11 local physician reviewers using standardized Urinary Incontinence Treatment Network interpretation guidelines. Each of the 4 central physician reviewers reviewed 9 randomly assigned tracings and none reviewed tracings from his or her center. Local and central physician reviewers were instructed to categorize values as invalid if specified technical quality assurance standards were not met or the signal pattern suggested implausible values because of technical deficiencies. An intraclass correlation coefficient was calculated for continuous (numerical) variables and a kappa statistic was calculated for qualitative values with acceptable agreement defined a priori as an intraclass correlation coefficient of greater than 0.6. RESULTS: Filling cystometrogram baseline pressure, Valsalva leak point pressure, and volume and pressure measurements at maximum cystometric capacity had excellent intraclass correlation coefficients of 0.74 to 0.99. There were no significant differences between local and central physician reviewer means, indicating excellent agreement. CONCLUSIONS: With proper quality control measures in place and a set of standardized interpretive guidelines excellent interrater reliability between local and central physician reviewer can be achieved for numerical cystometrogram variables.

Imaging of primary non-Hodgkin's lymphoma of the liver.

AIM: To describe the radiological findings in primary liver lymphoma, which is a rare entity, presenting usually as a localized liver mass. MATERIALS AND METHODS: We reviewed retrospectively the imaging findings at presentation, of patients in whom a diagnosis of primary liver lymphoma was finally made histologically. The study period covered a 10-year period between January 1990 and December 1999. There were seven patients, all men, with a mean age of 49.6 years. Each patient presented with hepatobiliary disease without peripheral adenopathy. Imaging prior to diagnosis included ultrasonography (seven patients), computed tomography (seven patients) and magnetic resonance imaging (MRI) (two patients). Appearances during and after aggressive chemotherapy were reviewed. RESULTS: Imaging appearances were of either single or multiple liver lesions simulating liver metastases. On ultrasound all foci of primary hepatic lymphoma (PHL) were hypoechoic relative to normal liver. Computed tomography (CT) showed hypoattenuating lesions in all cases, and two cases showed rim enhancement following contrast administration. The MRI appearances were variable, and no pathognomonic feature of PHL was identified, so that histology was required in all patients to establish the diagnosis. CONCLUSIONS: This paper demonstrates the spectrum of findings encountered on various imaging modalities in PHL. We conclude that although PHL is a rare condition, it should always be considered in the differential diagnosis of liver metastases when no primary tumour is apparent.

Positive CSF HSV PCR in patients with GBM: a note of caution.

Because two patients with temporal lobe glioblastomas had herpes simplex (HSV) DNA detected in CSF using PCR at the time of their presentation, we reviewed our laboratory's experience and performed PCR on a bank of 159 frozen CSF samples from patients with glioblastoma multiforme and other neurologic disorders. Based on the inability to detect HSV in any other tumor sample, we conclude that the positive HSV PCR in our two index patients most likely represented false-positive results. A diagnosis of HSE should not be made by PCR alone when the clinical presentation is atypical.

Bladder tumor markers: need, nature and application. 1. Nucleus-based markers.

Urothelial tumors are common: their diagnosis and long-term management represent a large part of most urologists' workload. The majority of such tumors are 'superficial' and are mostly managed by repeated cystoscopic surveillance and treatment. A smaller but significant group of patients either start with, or subsequently progress to, more invasive disease, thus requiring an alternative and more invasive treatment. Maximizing the benefit/risk ratio of the diagnosis and the various treatment options of bladder tumors requires the availability of a reliable tumor marker. The concept of tumor markers encompasses the utilization of any detectable deviation from normality that is indicative of neoplasia. For bladder cancer, most of these markers are present in urine. In this part of the review we examine, from the clinician's point of view, the literature verdict on older techniques such as cytology and cytometry, as well as the current status of new nucleus-based tests such as P53, telomerase, NMP22 and Ki67.

Bladder tumor markers: need, nature and application. 2. Tumor and tumor-associated antigens.

Despite the diversity of the available markers, none is truly specific to transitional epithelium, let alone its tumors. Some of the markers used, such as hCG and CEA, are far better known in other fields and seem to be expressed in only a minority of urothelial tumors. The majority of the available markers are tumor associated and should perhaps be considered as by-products of the process of malignancy in the urinary tract. Newer tests which are simple, rapid and easy to use have a practical advantage. These are currently the Bard BTA, BTA Stat and Aura-Tek FDP tests. So far, these markers have achieved only an arguable and marginal role in daily clinical practice, challenging the role of cytology and helping decide the type of cystoscopy. A more substantial role awaits a test with higher and more consistent sensitivity and specificity, together with the capability to provide independent diagnostic and/or prognostic information. In this part of the review we examine the literature view of the above-mentioned tests, as well as other new and some older tests such as blood group-related antigens, Lewis antigen, cytokeratins and others.

Accessibility of cigarettes to minors in suburban Cook County, Illinois.

This study assessed the problem of under age sale of cigarettes, educated vendors about the law restricting the sale of tobacco to minors, and determined the effectiveness of a vendor education intervention. Twenty-one teen volunteers, 14 to 17 years in age, attempted to purchase cigarettes in suburban Cook County from over-the-counter merchants and vending machines. Of the 347 vendors that were checked, the minors were successful in 37.2% of their attempts to purchase cigarettes. After information was sent to each vendor about the State of Illinois law, follow up visits were made to all the vendors who were willing to sell cigarettes to the minors during the first visits. Approximately 50% of the vendors were again willing to sell cigarettes to minors. This study's findings suggest that minors can easily purchase cigarettes in suburban Cook County. The education intervention component of the study had a limited but promising effect on compliance rates of the vendors.