Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial.

BACKGROUND: Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. METHODS: We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. FINDINGS: We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. INTERPRETATION: Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. FUNDING: Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

Trigeminal Neuralgia Secondary to Intracranial Lesions: A Prospective Series of 17 Consecutive Cases

Object: The purpose of the study was to assess the role of Gamma Knife surgery (GKS) in secondary trigeminal neuralgia (TN) caused by space-occupying lesions. Methods: From July 2010 till January 2015, 17 patients had GKS for secondary TN caused by intracranial lesions. The primary outcome was tumor control. The secondary outcomes were the alleviation of pain and the eventual secondary effects. Covariates were the age, duration of symptoms, duration till alleviation etc. Results: The mean age in this series was 63.3 years (range 39-79). The mean follow-up period was 1.85 years (range 0.5-3). Nine (52.9%) were meningiomas, five (29.4%) trigeminal schwannomas, two (11.8%) brain metastases and one (5.9%) arteriovenous malformation (AVM). Eight were located on the right side and nine on the left side. The mean duration of TN was 13.5 months (range 0.5-160). Follow-up was available for 16 patients (94.1%). Pain alleviation appeared after a mean time of 4.6 months (1-11) in 15 patients (88.2%). Five (29.4%) patients completely stopped medication in a mean time of 7 months (range 1-13) and three (17.6%) decreased it at half of the initial doses. No patient developed new hypoesthesia or other cranial nerve complication. The marginal doses for meningiomas and trigeminal schwannomas were 12 Gy (12-14), for metastasis 20 (20-20) and for AVM 24 Gy. The mean target volume was 1.84 cc (range 0.12-8.10). The mean prescription isodose volume was 2.65 cc (0.19-11.90). The mean maximal diameter was 19.9 (range 9-36). The mean number of isocenters was 14.2 (4-27). The mean duration was 76.9 minutes (range 25-172). The mean conformity, selectivity, Paddick and gradient index were: 0.99 (range 0.955-1), 0.701 (range 0.525-0.885), 0.694 (range 0.525-0.885) and 2.904 (range 2.654-3.371). At last follow-up, tumor decreased in 10 (58.8%) patients, was stable in 6 (35.3%) and increased in one (5.9%), the latest at 6 months. Conclusions: Gamma Knife surgery is safe and effective in treating intracranial lesions presenting with secondary TN. The initial pain freedom response was close to 90%, while having no secondary effect. Pain alleviation is achieved even in the absence of a volume variation of the lesions.

Mammographic density in asymptomatic menopausal women: correlation with clinical and sonographic findings

OBJECTIVE: To evaluate mammographic breast density in asymptomatic menopausal women in correlation with clinical and sonographic findings. MATERIALS AND METHODS: Mammograms and clinical and sonographic findings of 238 asymptomatic patients were retrospectively reviewed in the period from February/2022 to June/2006. The following variables were analyzed: mammographic density patterns, sonographic findings, patients' age, parity, body mass index and use of hormone replacement therapy. RESULTS: Age, parity and body mass index showed a negative correlation with breast density pattern, while use of hormone replacement therapy showed a positive correlation. Supplementary breast ultrasonography was performed in 103 (43.2%) patients. Alterations which could not be visualized at mammography were found in 34 (33%) of them, most frequently in women with breast density patterns 3 and 4. CONCLUSION: The authors concluded that breast density patterns were influenced by age, parity, body mass index and time of hormone replacement therapy. Despite not having found any malignant abnormality in the studied cases, the authors have observed a predominance of benign sonographic abnormalities in women with high breast density patterns and without mammographic abnormalities, proving the relevance of supplementary ultrasonography to identify breast lesions in such patients.

A web-based tool to aid the identification of chemicals potentially posing a health risk through percutaneous exposure

Occupational hygiene practitioners typically assess the risk posed by occupational exposure by comparing exposure measurements to regulatory occupational exposure limits (OELs). In most jurisdictions, OELs are only available for exposure by the inhalation pathway. Skin notations are used to indicate substances for which dermal exposure may lead to health effects. However, these notations are either present or absent and provide no indication of acceptable levels of exposure. Furthermore, the methodology and framework for assigning skin notation differ widely across jurisdictions resulting in inconsistencies in the substances that carry notations. The UPERCUT tool was developed in response to these limitations. It helps occupational health stakeholders to assess the hazard associated with dermal exposure to chemicals. UPERCUT integrates dermal quantitative structure-activity relationships (QSARs) and toxicological data to provide users with a skin hazard index called the dermal hazard ratio (DHR) for the substance and scenario of interest. The DHR is the ratio between the estimated 'received' dose and the 'acceptable' dose. The 'received' dose is estimated using physico-chemical data and information on the exposure scenario provided by the user (body parts exposure and exposure duration), and the 'acceptable' dose is estimated using inhalation OELs and toxicological data. The uncertainty surrounding the DHR is estimated with Monte Carlo simulation. Additional information on the selected substances includes intrinsic skin permeation potential of the substance and the existence of skin notations. UPERCUT is the only available tool that estimates the absorbed dose and compares this to an acceptable dose. In the absence of dermal OELs it provides a systematic and simple approach for screening dermal exposure scenarios for 1686 substances.

Positive predictive values of Breast Imaging Reporting and Data System (BI-RADS®) categories 3, 4 and 5 in breast lesions submitted to percutaneous biopsy

Objective To evaluate the BI-RADS as a predictive factor of suspicion for malignancy in breast lesions by correlating radiological with histological results and calculating the positive predictive value for categories 3, 4 and 5 in a breast cancer reference center in the city of São Paulo. Materials and Methods Retrospective, analytical and cross-sectional study including 725 patients with mammographic and/or sonographic findings classified as BI-RADS categories 3, 4 and 5 who were referred to the authors' institution to undergo percutaneous biopsy. The tests results were reviewed and the positive predictive value was calculated by means of a specific mathematical equation. Results Positive predictive values found for categories 3, 4 and 5 were respectively the following: 0.74%, 33.08% and 92.95%, for cases submitted to ultrasound-guided biopsy, and 0.00%, 14.90% and 100% for cases submitted to stereotactic biopsy. Conclusion The present study demonstrated high suspicion for malignancy in lesions classified as category 5 and low risk for category 3. As regards category 4, the need for systematic biopsies was observed.

Correlation between PET/CT results and histological and immunohistochemical findings in breast carcinomas

Objective To correlate the results of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) performed with a specific protocol for assessment of breasts with histological/immunohistochemical findings in breast carcinoma patients. Materials and Methods Cross-sectional study with prospective data collection, where patients with biopsy-confirmed breast carcinomas were studied. The patients underwent PET/CT examination in prone position, with a specific protocol for assessment of breasts. PET/CT findings were compared with histological and immunohistochemical data. Results The authors identified 59 malignant breast lesions in 50 patients. The maximum diameter of the lesions ranged from 6 to 80 mm (mean: 32.2 mm). Invasive ductal carcinoma was the most common histological type (n = 47; 79.7%). At PET/CT, 53 (89.8%) of the lesions demonstrated anomalous concentrations of 18F-FDG, with maximum SUV ranging from 0.8 to 23.1 (mean: 5.5). A statistically significant association was observed between higher values of maximum SUV and histological type, histological grade, molecular subtype, tumor diameter, mitotic index and Ki-67 expression. Conclusion PET/CT performed with specific protocol for assessment of breasts has demonstrated good sensitivity and was associated with relevant histological/immunohistochemical factors related to aggressiveness and prognosis of breast carcinomas.

Bosniak classification of renal cystic lesions according to multidetector computed tomography findings

Renal cystic lesions are usually diagnosed in the radiologists' practice and therefore their characterization is crucial to determine the clinical approach to be adopted and prognosis. The Bosniak classification based on computed tomography findings has allowed for standardization and categorization of lesions in increasing order of malignancy (I, II, IIF, III and IV) in a simple and accurate way. The present iconographic essay developed with multidetector computed tomography images of selected cases from the archives of the authors' institution, is aimed at describing imaging findings that can help in the diagnosis of renal cysts.

The role of gadoxetic acid as a paramagnetic contrast medium in the characterization and detection of focal liver lesions: a review

Recent studies have demonstrated that the use of paramagnetic hepatobiliary contrast agents in the acquisition of magnetic resonance images remarkably improves the detection and differentiation of focal liver lesions, as compared with extracellular contrast agents. Paramagnetic hepatobiliary contrast agents initially show the perfusion of the lesions, as do extracellular agents, but delayed contrast-enhanced images can demonstrate contrast uptake by functional hepatocytes, providing further information for a better characterization of the lesions. Additionally, this intrinsic characteristic increases the accuracy in the detection of hepatocellular carcinomas and metastases, particularly the small-sized ones. Recently, a hepatobiliary contrast agent called gadolinium ethoxybenzyl dimeglumine, that is simply known as gadoxetic acid, was approved by the National Health Surveillance Agency for use in humans. The authors present a literature review and a practical approach of magnetic resonance imaging utilizing gadoxetic acid as contrast agent, based on patients' images acquired during their initial experiment.

Is Transnational Private Regulation Potentially an Effective Means of Promoting Collective Industrial Relations?

This paper asks whether collective industrial relations can be promoted by means other than seeking change in public policy. Recent research points to the increasing significance of transnational private regulation (TPR) in developing economies. There is an emerging consensus that market incentives to improve wages and conditions of work can have a modest positive effect on measurable outcomes like hours of work, and health and safety. However, it appears that TPR has little impact on the capacity of workers to pursue such improvements for themselves via collective action. The paper takes a closer look at the potential of TPR to enhance worker voice and participation. It argues that this potential cannot be properly evaluated without understanding how local actors mobilise the social and political resources that TPR provides. The case studies presented show how different TPR schemes have been used by unions in Africa as a means to pursue the interests of members. The authors found that the scale of the impact of TPR in all of the contexts studied depended almost entirely on the existing capacities and resources of the unions involved. TPR led to the creation of collective industrial relations processes, or helped unions to ensure that certain enterprises participated in existing industrial relations processes, but did virtually nothing to enhance the political and organisational capacity of the unions to influence the outcomes of those processes in terms of wages and conditions of employment. The paper concludes that the potential of TPR to promote the emergence of collective industrial relations systems is very low.

Receiver operating characteristic (ROC) curve for classification of18F-NaF uptake on PET/CT

Abstract Objective: To assess the cutoff values established by ROC curves to classify18F-NaF uptake as normal or malignant. Materials and Methods: PET/CT images were acquired 1 hour after administration of 185 MBq of18F-NaF. Volumes of interest (VOIs) were drawn on three regions of the skeleton as follows: proximal right humerus diaphysis (HD), proximal right femoral diaphysis (FD) and first vertebral body (VB1), in a total of 254 patients, totalling 762 VOIs. The uptake in the VOIs was classified as normal or malignant on the basis of the radiopharmaceutical distribution pattern and of the CT images. A total of 675 volumes were classified as normal and 52 were classified as malignant. Thirty-five VOIs classified as indeterminate or nonmalignant lesions were excluded from analysis. The standardized uptake value (SUV) measured on the VOIs were plotted on an ROC curve for each one of the three regions. The area under the ROC (AUC) as well as the best cutoff SUVs to classify the VOIs were calculated. The best cutoff values were established as the ones with higher result of the sum of sensitivity and specificity. Results: The AUCs were 0.933, 0.889 and 0.975 for UD, FD and VB1, respectively. The best SUV cutoffs were 9.0 (sensitivity: 73%; specificity: 99%), 8.4 (sensitivity: 79%; specificity: 94%) and 21.0 (sensitivity: 93%; specificity: 95%) for UD, FD and VB1, respectively. Conclusion: The best cutoff value varies according to bone region of analysis and it is not possible to establish one value for the whole body.

Solitary pulmonary nodule and 18F-FDG PET/CT. Part 1: epidemiology, morphological evaluation and cancer probability

Abstract Solitary pulmonary nodule corresponds to a common radiographic finding, which is frequently detected incidentally. The investigation of this entity remains complex, since characteristics of benign and malignant processes overlap in the differential diagnosis. Currently, many strategies are available to evaluate solitary pulmonary nodules with the main objective of characterizing benign lesions as best as possible, while avoiding to expose patients to the risks inherent to invasive methods, besides correctly detecting cases of lung cancer so as the potential curative treatment is not delayed. This first part of the study focuses on the epidemiology, the morfological evaluation and the methods to determine the likelihood of cancer in cases of indeterminate solitary pulmonary nodule.

Hyperechoic breast lesions: anatomopathological correlation and differential sonographic diagnosis

Abstract Hyperechoic lesions are not a frequent finding at breasts ultrasonography, and most of times are associated with benign pathologies that do not require further evaluation. However, some neoplasms such as invasive breast carcinomas and metastases may present with hyperechogenicity. Thus, the knowledge about differential diagnoses and identification of signs of lesion aggressiveness are of great relevance to avoid unnecessary procedures or underdiagnosis, and to support the correct clinical/surgical approach. On the basis of such concepts, the present essay describes and illustrates the main features of hyperechoic lesions at breast ultrasonography in different cases, with anatomopathological correlation.