Contrast-enhanced mammography for the assessment of screening recalls: a two-centre study.

OBJECTIVES: To evaluate the potential of contrast-enhanced mammography (CEM) for reducing the biopsy rate of screening recalls. METHODS: Recalled women were prospectively enrolled to undergo CEM alongside standard assessment (SA) through additional views, tomosynthesis, and/or ultrasound. Exclusion criteria were symptoms, implants, allergy to contrast agents, renal failure, and pregnancy. SA and CEM were independently evaluated by one of six radiologists, who recommended biopsy or 2-year follow-up. Biopsy rates according to SA or recombined CEM (rCEM) were compared with the McNemar's test. Diagnostic performance was calculated considering lesions with available final histopathology. RESULTS: Between January 2019 and July 2021, 220 women were enrolled, 207 of them (median age 56.6 years) with 225 suspicious findings analysed. Three of 207 patients (1.4%) developed mild self-limiting adverse reactions to iodinated contrast agent. Overall, 135/225 findings were referred for biopsy, 90/225 by both SA and rCEM, 41/225 by SA alone and 4/225 by rCEM alone (2/4 being one DCIS and one invasive carcinoma). The rCEM biopsy rate (94/225, 41.8%, 95% CI 35.5-48.3%) was 16.4% lower (p < 0.001) than the SA biopsy rate (131/225, 58.2%, 95% CI 51.7-64.5%). Considering the 124/135 biopsies with final histopathology (44 benign, 80 malignant), rCEM showed a 93.8% sensitivity (95% CI 86.2-97.3%) and a 65.9% specificity (95% CI 51.1-78.1%), all 5 false negatives being ductal carcinoma in situ detectable as suspicious calcifications on low-energy images. CONCLUSIONS: Compared to SA, the rCEM-based work-up would have avoided biopsy for 37/225 (16.4%) suspicious findings. Including low-energy images in interpretation provided optimal overall CEM sensitivity. KEY POINTS: • The work-up of suspicious findings detected at mammographic breast cancer screening still leads to a high rate of unnecessary biopsies, involving between 2 and 6% of screened women. • In 207 recalled women with 225 suspicious findings, recombined images of contrast-enhanced mammography (CEM) showed a 93.8% sensitivity and a 65.9% specificity, all 5 false negatives being ductal carcinoma in situ detectable on low-energy images as suspicious calcifications. • CEM could represent an easily available one-stop shop option for the morphofunctional assessment of screening recalls, potentially reducing the biopsy rate by 16.4%.

Pulmonary Covid Fibrosis a New Pharmaceutic Approach.

BACKGROUND: Patient's post-COVID may develop chronic irreversible respiratory failure with "widespread signs of pulmonary fibrosis." Our study analyzed the causes of this fibrosis to propose a therapeutic protocol. METHODS: Identification of the biochemical causes of fibrosis in COVID-19 analysing the literature and chest CT. RESULTS: The CT imaging shows pulmonary fibrosis. The viral infection produces "interleukin-6", which binds to its receptor, in MUC1 of lung epithelial cells. The biochemical response of the cells promotes an over-expression of MUC1 with fibrosis. Interleukin6 also causes a metabolic imbalance in NO that promotes clots and atherosclerosis of the pulmonary vessels. These results show to promote NO endothelia's formation to block both the excessive expression of MUC1 and the atherosclerosis effect of the vessels. CONCLUSIONS: This study proposes to inhibit phosphodiesterase by vasodilatation of the pulmonary vascular bed and the MUC1 over expression by interleukin6, the Sildenafil with the SGLT2 and N-Acetylcysteine.

Chest x-ray in the COVID-19 pandemic: Radiologists' real-world reader performance.

PURPOSE: To report real-world diagnostic performance of chest x-ray (CXR) readings during the COVID-19 pandemic. METHODS: In this retrospective observational study we enrolled all patients presenting to the emergency department of a Milan-based university hospital from February 24th to April 8th 2020 who underwent nasopharyngeal swab for reverse transcriptase-polymerase chain reaction (RT-PCR) and anteroposterior bedside CXR within 12 h. A composite reference standard combining RT-PCR results with phone-call-based anamnesis was obtained. Radiologists were grouped by CXR reading experience (Group-1, >10 years; Group-2, <10 years), diagnostic performance indexes were calculated for each radiologist and for the two groups. RESULTS: Group-1 read 435 CXRs (77.0 % disease prevalence): sensitivity was 89.0 %, specificity 66.0 %, accuracy 83.7 %. Group-2 read 100 CXRs (73.0 % prevalence): sensitivity was 89.0 %, specificity 40.7 %, accuracy 76.0 %. During the first half of the outbreak (195 CXRs, 66.7 % disease prevalence), overall sensitivity was 80.8 %, specificity 67.7 %, accuracy 76.4 %, Group-1 sensitivity being similar to Group-2 (80.6 % versus 81.5 %, respectively) but higher specificity (74.0 % versus 46.7 %) and accuracy (78.4 % versus 69.0 %). During the second half (340 CXRs, 81.8 % prevalence), overall sensitivity increased to 92.8 %, specificity dropped to 53.2 %, accuracy increased to 85.6 %, this pattern mirrored in both groups, with decreased specificity (Group-1, 58.0 %; Group-2, 33.3 %) but increased sensitivity (92.7 % and 93.5 %) and accuracy (86.5 % and 81.0 %, respectively). CONCLUSIONS: Real-world CXR diagnostic performance during the COVID-19 pandemic showed overall high sensitivity with higher specificity for more experienced radiologists. The increase in accuracy over time strengthens CXR role as a first line examination in suspected COVID-19 patients.

Chest x-ray severity score in COVID-19 patients on emergency department admission: a two-centre study.

BACKGROUND: Integration of imaging and clinical parameters could improve the stratification of COVID-19 patients on emergency department (ED) admission. We aimed to assess the extent of COVID-19 pulmonary abnormalities on chest x-ray (CXR) using a semiquantitative severity score, correlating it with clinical data and testing its interobserver agreement. METHODS: From February 22 to April 8, 2020, 926 consecutive patients referring to ED of two institutions in Northern Italy for suspected SARS-CoV-2 infection were reviewed. Patients with reverse transcriptase-polymerase chain reaction positive for SARS-CoV-2 and CXR images on ED admission were included (295 patients, median age 69 years, 199 males). Five readers independently and blindly reviewed all CXRs, rating pulmonary parenchymal involvement using a 0-3 semiquantitative score in 1-point increments on 6 lung zones (range 0-18). Interobserver agreement was assessed with weighted Cohen's κ, correlations between median CXR score and clinical data with Spearman's ρ, and the Mann-Whitney U test. RESULTS: Median score showed negative correlation with SpO2 (ρ = -0.242, p < 0.001), positive correlation with white cell count (ρ = 0.277, p < 0.001), lactate dehydrogenase (ρ = 0.308, p < 0.001), and C-reactive protein (ρ = 0.367, p < 0.001), being significantly higher in subsequently dead patients (p = 0.003). Considering overall scores, readers' pairings yielded moderate (κ = 0.449, p < 0.001) to almost perfect interobserver agreement (κ = 0.872, p < 0.001), with better interobserver agreement between readers of centre 2 (up to κ = 0.872, p < 0.001) than centre 1 (κ = 0.764, p < 0.001). CONCLUSIONS: Proposed CXR pulmonary severity score in COVID-19 showed moderate to almost perfect interobserver agreement and significant but weak correlations with clinical parameters, potentially furthering CXR integration in patients' stratification.

The Question on the Potential Cancerous Effects of Hair Dyes: The Monitoring of the Oxidative Stress Induced by the Hair Dyes with the Dosage of the Salivary Free Radicals.

BACKGROUND: Many studies indicate the difficulty on assessing the possible carcinogenic effects of hair dyes, for their high time of the latence. OBJECTIVES: Our objective is to determine their prognostic index, by monitoring the oxidative stress, produced exposed to hair dyes, in hairdressers, and in consumers, by measuring the concentration of salivary malondialdehyde. MATERIALS AND METHODS: Saliva samples are provided by the hairdressers, working in private (NP) or shopping center (CC), by users of hair dyes, for at least 10 years, and by a control group. The values of malondialdehyde are determined using the thiobarbituric acid method. The results are statistically analyzed by Kruskal-Wallis and Mann-Whitney test. RESULTS: Comparing the three groups with tests for K-independent Kruskal-Wallis samples (dyed vs. control vs. dyed at least 10 years), there is a significant difference for the amount of MDA (P < 0.001). Proceeding for the median MDA in the subgroups by testing for two independent U-samples of Mann-Whitney: control versus dyed, P < 0.001; control versus CC, P = 0.013; control versus NP, P < 0.001; control versus 10 years, P = 0.111; CC versus NP, P = 0.001; CC versus 10 years, P = 0.462; and NP versus 10 years, P < 0.001. DISCUSSION: In hairdressers, the increase of the salivary MDA versus control group is statistically significant (P ≤ 0.05), with an accentuation in small workplace, for age, probably for a more direct exposure to dyes' gas. Another statistically significant increase of salivary MDA is for the consumers versus control group, also function of the increasing age. CONCLUSIONS: The results of this study show a significant increase of oxidative stress in the hairdressers. This factor involves a potential carcinogenic risk, especially for the bladder, difficult to assess in the short term.

Abdominal CT: a radiologist-driven adjustment of the dose of iodinated contrast agent approaches a calculation per lean body weight.

BACKGROUND: The contrast agent (CA) dose for abdominal computed tomography (CT) is typically based on patient total body weight (TBW), ignoring adipose tissue distribution. We report on our experience of dosing according to the lean body weight (LBW). METHODS: After Ethics Committee approval, we retrospectively screened 219 consecutive patients, 18 being excluded for not matching the inclusion criteria. Thus, 201 were analysed (106 males), all undergoing a contrast-enhanced abdominal CT with iopamidol (370 mgI/mL) or iomeprol (400 mgI/mL). LBW was estimated using validated formulas. Liver contrast-enhancement (CEL) was measured. Data were reported as mean ± standard deviation. Pearson correlation coefficient, ANOVA, and the Levene test were used. RESULTS: Mean age was 66 ± 13 years, TBW 72 ± 15 kg, LBW 53 ± 11 kg, and LBW/TBW ratio 74 ± 8%; body mass index was 26 ± 5 kg/m2, with 9 underweight patients (4%), 82 normal weight (41%), 76 overweight (38%), and 34 obese (17%). The administered CA dose was 0.46 ± 0.06 gI/kg of TBW, corresponding to 0.63 ± 0.09 gI/kg of LBW. A negative correlation was found between TBW and CA dose (r = -0.683, p < 0.001). CEL (Hounsfield units) was 51 ± 18 in underweight patients, 44 ± 8 in normal weight, 42 ± 9 in overweight, and 40 ± 6 in obese, with a significant difference for both mean (p = 0.004) and variance (p < 0.001). A low but significant positive correlation was found between CEL and CA dose in gI per TBW (r = 0.371, p < 0.001) or per LBW (r = 0.333, p < 0.001). CONCLUSIONS: The injected CA dose was highly variable, with obese patients receiving a lower dose than underweight patients, as a radiologist-driven 'compensation effect'. Diagnostic abdomen CT examinations may be obtained using 0.63 gI/kg of LBW.

Industrial Pollutants and Nasopharyngeal Cancer: An Open Question.

INTRODUCTION AND OBJECTIVES: Nasopharyngeal Carcinoma represents 0.7% of the total cancer cases in the world with an ASR index of 1.7 and is widely associated with Epstein-Barr virus. It is not common in Italy (ASR index of 0.5) while in China (ASR 1.9), one third of the clinical cases are observed in Guangdong (ASR index 11.3). It is also quite common in Malaysia and Indonesia. The activation of the cancerogenesis process happens after the exposure to some environmental parameters that epidemiological studies have indicated with various dietary habits, mainly for salted fish consumption. The purpose of this work is to highlight such as exposure to compounds, such as formaldehyde, which is present in the different working conditions of these countries and may lead to the real cause to establish the carcinogenic process. MATERIALS AND METHODS: The most recent publications regarding the impact of various external factors on Pub Med, Google, TOXLINE, Chem Abstract, were analyzed with the radiological data that were found in Milan hospitals database. RESULTS: The relationship between food consumption and nasopharyngeal cancer are not clear and statistically insignificant in Indonesia. In Malaysia, the preparation of natural rubber for the use of formaldehyde is a dangerous environmental factor. The same exposure is a risk factor in Guangdong, where many workers are employed in the wood panel industry. Incidence of cancer in these Chinese ethnic groups decreases when they migrate to other countries. In the last 5 years, few cases were recorded in Italy, without any apparent change in ethnic environmental factors or HBV infection Discussion: In the production of natural rubber, a lot of people are exposed to formaldehyde during the various steps of preparation and production such as stripping, drying and coagulation without observing proper environmental hygiene precautions. The same working conditions are present in industrial production of wood panels in Guangdong, China. The relationship between exposure to formaldehyde and nasopharyngeal cancer is demonstrated by the fact that epidemiological studies on the population of this Chinese district whose immigrant populations were not exposed to these pollutants, the appearance of these tumors decreases. Also an examination of our radiological data in Italy shows that in about one hundred sixty cases of nasopharyngeal cancer none of the patients were Indonesian or Chinese Conclusion: The preliminary results of our study suggest that EPST-BARR virus could be a risk factor if associated with exposure to compounds such as formaldehyde which is present in industrial productions of countries like Indonesia, Malaysia, and China.

The Possible Role of Diabetes in the Etiology of Laryngeal Cancer.

BACKGROUND: Laryngeal cancer and oral cancer are not always correlated with genetic mutations, HPV infection, smoking, and alcohol abuse. In the absence of these risk factors, there is an increase on these cancers with a parallel increase of diabetes. The aim of this study is to verify if diabetes could be a risk factor for the laryngeal cancer. METHODS: A questionnaire was given to a group of ninety laryngectomees to verify if these patients have presented diabetes and xerostomia before surgery. In two groups, diabetics and healthy persons, the values of the salivary mucins and the pH were evaluated. The results were statistically analysed using Fisher Exact Test and Chisquare Test Results: Diabetes is a risk factor: p= 0.0445 for laryngectomees male vs control group. Xerostomia inlaryngectomees male is a risk factor: p= 0.050. The values of mucins and pH in diabetic group show significant difference: p=0.05 vs control group Discussion: In all autoimmune diseases, a decrease in the value of pH and salivary flow consequently decreases the value of spinnbarkeit which measures the capacity of the mucous layer to adhere to the epithelium and alter the protective oral mucin layer. We find that diabetes is epidemiologically correlated with laryngeal cancer. In fact, only diabetes increases the concentration of salivary mucins with a formation of mucin layer even more reduced, and so completely ineffective in protecting the mucosa. CONCLUSIONS: The increase of mucin secretion in diabetes alters much the protective layer allowing the risk factors to promote cancer growth.

Potential predictive factors of osteoporosis in HIV-positive subjects.

Recent reports showed a high frequency of osteopenia/osteoporosis in HIV-infected subjects. Mechanism on the basis of this alteration is still unclear, as the direct effect of virus or of antiretroviral drugs. One hundred sixty-one consecutive HIV-infected outpatients aged 30-50 years, both naive and HAART-treated for >1 year, were included. An interview questionnaire was performed to establish prior pathological, toxic, epidemiological histories, medications intake, physical activity and eating habits. Blood and urinary tests were checked to exclude concomitant diseases, as were markers of bone metabolism and vitamin D3-metabolites. Each subject underwent to a lumbar spine and left hipbone mineral density by DEXA, using WHO criteria for diagnosis of osteopenia/osteoporosis. Radiologist was unaware if the subject was receiving HAART or not. For groups' homogeneity Chi-square, Fisher's exact and Student's t tests were used. Logistic regression analysis was used to find predictors of osteopenia/osteoporosis and linear regression model to find differences in bone mass density. The demographic characteristics of the 48 naive subjects and the 113 on HAART were comparable. Eighty subjects (49.7%) showed osteopenia/osteoporosis: 22 (45.8%) naive and 58 (51.3%) on HAART (P = 0.46). Independent predictors of osteopenia/osteoporosis were female gender (OR: 3.02, 95% CI: 1.26-7.25, P = 0.01 vs. male), older age (OR: 1.10, 95% CI: 1.01-1.20, P = 0.03, for each additional year), low body mass index (OR: 0.78, 95% CI: 0.68-0.91, P = 0.001 for each additional unit) and higher HIV-RNA levels at DEXA (OR: 1.97, 95% CI: 1.16-3.34, P = 0.01 for each additional Log(10)), whereas the use of HAART (OR: 2.61, 95% CI: 0.66-10.27, P = 0.17 vs. naive) and the alterations of markers of bone metabolism were not significantly related to osteopenia/osteoporosis. Similar findings were obtained using linear regression model analysis. HIV-infected subjects have a high frequency of osteopenia/osteoporosis. Traditional risk factors are predictive of osteopenia/osteoporosis also in HIV-subjects; the association with higher HIV-RNA levels can suggest a direct role of HIV itself in the occurrence of bone disease.

Interval breast cancers: absolute and proportional incidence and blinded review in a community mammographic screening program.

PURPOSE: To evaluate the performance of the first years since the beginning of a mammographic population-based screening program. MATERIALS AND METHODS: Women aged 49-69 were invited biennially for two-view film-screen mammography and double reading without arbitration was performed. Interval cancers (ICs) from 2001 to 2006 were identified using screening archives, local pathology archives, and hospital discharge records. The proportional incidence of IC was determined considering breast cancers expected without screening. Three offsite radiologists experienced in breast cancer screening blindly evaluated mammograms prior to diagnosis, randomly mixed with negative mammograms (1:2 ratio). Cases unrecalled at review were considered as true ICs, those recalled by only one reviewer as minimal signs, and those recalled by two or three reviewers as missed cancers. T and N stage of the reviewed ICs were evaluated and compared. RESULTS: A total of 86,276 first level mammograms were performed. Mean recall rate was 6.8% at first and 4.6% at repeat screening. We had 476 screen-detected cancers and 145 ICs (10 of them ductal carcinomas in situ). Absolute incidence was 17 per 10,000 screening examinations. Invasive proportional incidence was 19% (44/234) in the first year, 39% (91/234) in the second year, and 29% (135/468) in the two-year interval. Of 145 ICs, 130 (90%) were reviewed mixed with 287 negative controls: 55% (71/130) resulted to be true ICs, 24% (31/130) minimal signs, and 22% (28/130) missed cancers. The rate of ICs diagnosed in the first year interval was 21% (15/71) for true ICs, 46% (13/28) for missed cancers, and 39% (12/31) for minimal signs, with a significant difference of true ICs rate compared to missed cancers rate (p=0.012). A higher rate of T3 and T4 stages was found for missed cancers (18%, 5/28) compared to minimal signs (6%, 2/31) or true ICs (8%, 6/71), while the rate of N2 and N3 stage for both minimal signs (19%, 6/31) or missed cancers (25%, 7/28) was higher than that for true ICs (10%, 7/71), although all these differences were not significant (p ≥ 0.480). CONCLUSION: These results showed the possibility to comply with European Community standards in the first years of a screening program implementation.

Breast vascular mapping obtained with contrast-enhanced MR imaging: implications for cancer diagnosis, treatment, and risk stratification.

The value of breast vascular maps obtained using contrast-enhanced MR imaging has recently been explored. Additional information is obtained only by evaluating maximum intensity projections of the first dynamic subtraction to achieve a form of MR angiography of the breast. No increase in acquisition time and no dedicated contrast injections are needed. Four studies have been performed to evaluate the one-sided (asymmetric) increase in vascularity associated with ipsilateral cancer in a total of 404 patients with a cancer prevalence ranging from 38% to 80%. Sensitivity ranged from 72% to 88%, specificity from 57% to 100%, positive predictive value from 85% to 100%, negative predictive value from 38% to 88%, and overall accuracy from 73% to 87%. An asymmetric increase in breast vascularity ipsilateral to a cancer may be due to reduced flow resistance in the tumour, to a high metabolic rate (more likely in large tumours) or to angiogenic stimulation of the whole breast harbouring the lesion (more likely in small tumours). Tumour size could play a specific role in determining the ipsilaterally increased vascularity, and invasive cancers might be more frequently associated with ipsilaterally increased vascularity than in situ cancers. Moreover, while a reduction in breast vasculature has anecdotically been observed in breasts with locally advanced cancers treated with neoadjuvant chemotherapy, especially when taxanes are used, the higher incidence of breast cancer in patients with size asymmetry between the breasts as determined on screening mammography suggests that a role for breast MR vascular mapping in breast cancer risk stratification should be explored. Finally, arteries and veins might be differentiated with dedicated techniques. High-relaxivity agents may be used with advantage in these future investigations.