Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study

Purpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopatho-logic variables with survival was evaluated in a large multi-institutional European cohort. Experimental Design: Data from 185 patients were retrospec-tively collected in 23 European GIST reference centers. Propen-sity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Uni-variate and multivariate unweighted and weighted Cox propor-tional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival. Results: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79- 2.28]. The variables consistently associated with worse survival out-comes were high mitotic index and nongastric tumor location. Conclusions: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.Peer reviewe

“What makes every work perfect is cooking and grinding”: the ancient roots of mechanochemistry

This paper explores the historical significance of milling in various technological areas from ancient times, emphasizing its role beyond the simple ingredient reduction. The study focuses on sources from the 1st to the 10th centuries: philologists selected, studied, and translated ancient sources, while chemists provided chemical interpretations by replicating the recipes in the laboratory. The study delves into the synthesis of cinnabar from mercury and sulphur, or mineral ores such as orpiment, realgar, and stibnite. While the mercury–sulphur reaction is known, the synthesis from sulphide ores is not reported in the literature. Chemical replication assessed the reactions' feasibility and confirmed the fundamental role of grinding for the yield of the reaction, which was already recognized by the alchemist Zosimus of Panopolis (3rd–4th cent. CE) who claimed “what makes every work perfect is cooking and griding”

Incidental enhancing lesions found on preoperative breast MRI: management and role of second-look ultrasound.

This study prospectively assessed second-look ultrasound (US) for the evaluation of incidental enhancing lesions identified on preoperative breast magnetic resonance imaging (MRI). Between 2004 and 2007, 182 patients with malignant breast lesions detected on US and/or X-ray mammography and confirmed by cytology/histology underwent preoperative breast contrast-enhanced (CE)-MRI. Patients with incidental lesions on breast MRI underwent second-look high-resolution US directed at the site of the incidental finding. Diagnosis of incidental lesions was based on biopsy or 24-month follow-up. Breast MRI detected 55 additional lesions in 46/182 (25.2%) patients. Forty-two of 55 (76.3%) lesions were detected on second-look US in 38/46 (82.6%) patients. Malignancy was confirmed for 24/42 (57.1%) correlate lesions compared with 7/13 (53.8%) noncorrelate lesions. Second-look US depicted 8/9 (88.8%) Breast Imaging Reporting and Data System (BI-RADS) 5, 16/22 (72.7%) BI-RADS 4 and 18/24 (75%) BI-RADS 3 lesions. Sensitivity, specificity, accuracy and positive and negative predictive values for lesion detection/diagnosis was 100%, 88.9%, 94.6%, 90.3% and 100% for MRI and 64.3%, 70.4%, 67.3%, 69.2% and 65.5% for second-look US. Improved performance for US was obtained when masslike lesions only were considered. Second-look US is a confirmatory method for incidental findings on breast MRI, particularly for mass-like lesions

Prolonged sporadic hemiplegic migraine associated with a novel de novo missense ATP1A2 gene mutation

Hemiplegic migraine is a rare form of migraine characterized by periodic attacks of migraine with neurologic aura and transient hemiplegia. There are familial and sporadic cases, both on a genetic basis; we describe the case of a 6-year-old boy affected by sporadic hemiplegic migraine, showing a novel ATP1A2 gene missense mutation (p.Gly715Arg) in exon 16. Long-term treatment with flunarizine resulted in good clinical response and prevention of further attacks

Role of breast MR imaging for predicting malignancy of histologically borderline lesions diagnosed at core needle biopsy: prospective evaluation.

Purpose: To prospectively determine the diagnostic performance of breast magnetic resonance (MR) imaging in predicting the malignancy of breast lesions classified as borderline at core needle biopsy (CNB). Materials and Methods: This prospective study was approved by the local ethics committee, and all patients provided written informed consent. Between February 2007 and October 2009, 193 patients underwent ultrasonography (US)-guided CNB. Thirty-two lesions in 32 patients were classified as "borderline" ("lesions of uncertain malignant potential" according to the United Kingdom National Health Service Breast Screening program or those that are "probably benign" according to the Breast Imaging Reporting and Data System [BI-RADS] lexicon) at pathologic examination and were evaluated. All 32 patients underwent contrast agent-enhanced breast MR imaging 1-3 weeks after CNB; surgical biopsy was performed within 60 days of MR imaging. Results were compared with histologic findings. Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated. Results: Findings from surgical biopsy confirmed the diagnosis of seven atypical ductal hyperplasia lesions, four atypical lobular hyperplasia (ALH) lesions, five papillary lesions, two fibroepithelial lesions, three radial scars, three lobular carcinomas in situ, three ductal carcinomas in situ (DCIS), four invasive ductal carcinomas, and one invasive lobular carcinoma. With regard to malignancy, breast MR imaging helped correctly classify 22 of the 32 lesions as negative and seven as positive. Two of the lesions confirmed to be ALH were incorrectly classified as suspicious (BI-RADS category IV; false-positive finding), whereas one small DCIS was incorrectly classified as nonsuspicious (BI-RADS category II; false-negative finding). The sensitivity, specificity, accuracy, and positive and negative predictive values for the correct demonstration of malignancy at MR imaging were 88% (seven of eight lesions), 92% (22 of 24 lesions), 91% (29 of 32 lesions), 78% (seven of nine lesions), and 96% (22 of 23 lesions), respectively. Conclusion: Breast MR imaging can improve the evaluation of lesions classified as borderline at CNB. In cases of nonsuspicious enhancement or no enhancement at breast MR imaging, follow-up rather than surgical biopsy might be performed. (C)RSNA, 201

Trabectedin in advanced synovial sarcomas: A multicenter retrospective study from four European institutions and the Italian Rare Cancer Network

Treatment options for patients with metastatic synovial sarcoma are limited. Over recent years, trabectedin has emerged as an effective agent for patients with advanced soft tissue sarcomas resistant to anthracyclines and ifosfamide. The aim of this retrospective analysis was to study the efficacy of trabectedin in the subgroup of synovial sarcomas. A retrospective analysis was carried out on patients with advanced synovial sarcoma treated with trabectedin at four European reference sarcoma centers and within the Italian Rare Cancer Network between 2000 and 2013. Radiological response, progression-free, and overall survival, as well as serious and unexpected adverse events were retrospectively assessed. Sixty-one patients with metastatic synovial sarcoma were identified. The median number of previous chemotherapy regimens was 2 (range 1-6). Nine patients had a partial response, in addition to two minor responses, and 19 patients had stable disease, for an overall response rate of 15% and a tumor control rate of 50%. The median progression-free survival was 3 months, with 23% of patients free from progression at 6 months. The median progression-free survival in responding patients was 7 months. Trabectedin is a therapeutic option for palliative treatment of a subset of patients with metastatic synovial sarcoma

Validity of the wall goniometer as a screening tool to detect postural abnormalities in Parkinson's disease

INTRODUCTION: Software-based measurements of postural abnormalities in Parkinson's disease (PD) are the gold standard but may be time-consuming and not always feasible in clinical practice. Wall goniometer (WG) is an easier, quicker, and inexpensive instrument for screening patients with postural abnormalities, but no studies have investigated its validity so far. The aim of this study was to investigate the validity of the WG to measure postural abnormalities. METHODS: A total of 283 consecutive PD outpatients with ≥5° forward trunk, lateral trunk or forward neck bending (FTB, LTB, FNB, respectively) were recruited from seven centers for movement disorders. Postural abnormalities were measured in lateral and posterior view using a freeware program (gold standard) and the WG. Both angles were expressed in degrees (°). Sensitivity and specificity for the diagnosis of camptocormia, Pisa syndrome, and anterocollis were assessed. RESULTS: WG showed good to excellent agreement (intraclass correlation coefficient from 0.80 to 0.98) compared to the gold standard. Bland-Altman plots showed a mean difference between the methods from -7.4° to 0.4° with limits of agreements from -17.7° to 9.5°. Sensitivity was 100% for the diagnosis of Pisa syndrome, 95.74% for anterocollis, 76.67% for upper camptocormia, and 63.64% for lower camptocormia. Specificity was 59.57% for Pisa syndrome, 71.43% for anterocollis, 89.80% for upper camptocormia, and 100% for lower camptocormia. Overall, the WG underestimated measurements, especially in lower camptocormia with an average of -8.7° (90% of cases). CONCLUSION: WG is a valid tool for screening Pisa syndrome and anterocollis, but approximately 10° more should be added for camptocormia

Augmented reality (AR) in minimally invasive surgery (MIS) training: where are we now in Italy? The Italian Society of Endoscopic Surgery (SICE) ARMIS survey

Minimally invasive surgery (MIS) is a widespread approach in general surgery. Computer guiding software, such as the augmented reality (AR), the virtual reality (VR) and mixed reality (MR), has been proposed to help surgeons during MIS. This study aims to report these technologies' current knowledge and diffusion during surgical training in Italy. A web-based survey was developed under the aegis of the Italian Society of Endoscopic Surgery (SICE). Two hundred and seventeen medical doctors' answers were analyzed. Participants were surgeons (138, 63.6%) and residents in surgery (79, 36.4%). The mean knowledge of the role of the VR, AR and MR in surgery was 4.9 ± 2.4 (range 1-10). Most of the participants (122, 56.2%) did not have experience with any proposed technologies. However, although the lack of experience in this field, the answers about the functioning of the technologies were correct in most cases. Most of the participants answered that VR, AR and MR should be used more frequently for the teaching and training and during the clinical activity (170, 80.3%) and that such technologies would make a significant contribution, especially in training (183, 84.3%) and didactic (156, 71.9%). Finally, the main limitations to the diffusion of these technologies were the insufficient knowledge (182, 83.9%) and costs (175, 80.6%). Based on the present study, in Italy, the knowledge and dissemination of these technologies are still limited. Further studies are required to establish the usefulness of AR, VR and MR in surgical training