Typical values of z-resolution for different Digital Breast Tomosynthesis systems evaluated in a multicenter study.

PURPOSE: The aim of the present study, conducted by a working group of the Italian Association of Medical Physics (AIFM), was to define typical z-resolution values for different digital breast tomosynthesis (DBT) models to be used as a reference for quality control (QC). Currently, there are no typical values published in internationally agreed QC protocols. METHODS: To characterize the z-resolution of the DBT models, the full width at half maximum (FWHM) of the artifact spread function (ASF), a technical parameter that quantifies the signal intensity of a detail along reconstructed planes, was analyzed. Five different commercial phantoms, CIRS Model 011, CIRS Model 015, Modular DBT phantom, Pixmam 3-D, and Tomophan, were evaluated on reconstructed DBT images and 82 DBT systems (6 vendors, 9 models) in use at 39 centers in Italy were involved. RESULTS: The ASF was found to be dependent on the detail size, the DBT angular acquisition range, the reconstruction algorithm and applied image processing. In particular, a progressively greater signal spread was observed as the detail size increased and the acquisition angle decreased. However, a clear correlation between signal spread and angular range width was not observed due to the different signal reconstruction and image processing strategies implemented in the algorithms developed by the vendors studied. CONCLUSIONS: The analysis led to the identification of typical z-resolution values for different DBT model-phantom configurations that could be used as a reference during a QC program.

Consensus Report of the Technical-Scientific Associations of Italian Dental Hygienists and the Academy of Advanced Technologies in Oral Hygiene Sciences on the Non-Surgical Treatment of Peri-Implant Disease.

BACKGROUND: The recent publication of the new classification of periodontal and peri-implant disease has given clear indications on the parameters to be taken into consideration to correctly diagnose the different phases of these diseases. To date, however, there are no equally clear indications on the treatments to be implemented to solve these diseases. The objective of this Consensus Report is to provide guidance for the non-surgical management of peri-implant mucositis and peri-implantitis. For the drafting of the consensus, the most recent scientific literature was analysed. MATERIALS AND METHODS: A group of 15 expert Italian dental hygienists were selected by the Italian technical-scientific societies (AIDI, UNID and ATASIO) and, starting from the literature review, they formulated indications according to the GRADE method (Grading of Recommendations, Assessment, Development, and Evaluation, a tool for rating the quality of evidence, used to draw up systematic reviews and clinical guidelines) on the treatment of peri-implant mucositis, peri-implantitis and on management of the various implanting surfaces. CONCLUSIONS: in accordance with the international literature, non-surgical therapy alone can resolve peri-implant mucositis, but not peri-implantitis. Several adjunctive therapies have been considered and some appear to be helpful in managing inflammation.

Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis.

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Stearoyl-CoA desaturase 1 and paracrine diffusible signals have a major role in the promotion of breast cancer cell migration induced by cancer-associated fibroblasts.

BACKGROUND: Despite the recognised contribution of the stroma to breast cancer development and progression, the effective targeting of the tumor microenvironment remains a challenge to be addressed. We previously reported that normal fibroblasts (NFs) and, notably, breast cancer-associated fibroblasts (CAFs) induced epithelial-to-mesenchymal transition and increases in cell membrane fluidity and migration in well- (MCF-7) and poorly-differentiated (MDA-MB-231) breast cancer cells. This study was designed to better define the role played, especially by CAFs, in promoting breast tumor cell migration. METHODS: Fibroblast/breast cancer cell co-cultures were set up to investigate the influence of NFs and CAFs on gene and protein expression of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating membrane fluidity, as well as on the protein level and activity of its transcription factor, the sterol regulatory element-binding protein 1 (SREBP1), in MCF-7 and MDA-MB-231 cells. To assess the role of SREBP1 in the regulation of SCD1 expression, the desaturase levels were also determined in tumor cells treated with an SREBP1 inhibitor. Migration was evaluated by wound-healing assay in SCD1-inhibited (by small-interfering RNA (siRNA) or pharmacologically) cancer cells and the effect of CAF-conditioned medium was also assessed. To define the role of stroma-derived signals in cancer cell migration speed, cell-tracking analysis was performed in the presence of neutralising antibodies to hepatocyte growth factor, transforming growth factor-ß or basic fibroblast growth factor. RESULTS: A two to three fold increase in SCD1 mRNA and protein expression has been induced, particularly by CAFs, in the two cancer cell lines that appear to be dependent on SREBP1 activity in MCF-7 but not in MDA-MB-231 cells. Both siRNA-mediated and pharmacological inhibition of SCD1 impaired tumor cells migration, also when promoted by CAF-released soluble factors. Fibroblast-triggered increase in cancer cell migration speed was markedly reduced or abolished by neutralising the above growth factors. CONCLUSION: These results provide further insights in understanding the role of CAFs in promoting tumor cell migration, which may help to design new stroma-based therapeutic strategies.

Genotypes B and C hepatocellular carcinoma-associated hepatitis B virus pre-S mutants: their detection among F1b and A2 - but not F4 - isolates from Argentina.

Prevalence rates of hepatocellular carcinoma (HCC)-associated hepatitis B virus (HBV) pre-S mutants among most genotypes are still lacking. In this study, viral (sub)genotypes of 70 Argentine nucleotide sequences (33 newly obtained) were determined by phylogenetic analysis, and the presence of such mutants was assessed in the American continent for the first time. Nucleotide substitutions of the pre-S2 start codon were observed in 10% of the HBV/A2 sequences. Ten per cent of the HBV/A2 and 12.5% of the HBV/F1b - but none of HBV/F4 - exhibited a deletion in the pre-S1/pre-S2 region. The contribution of these variants to liver cirrhosis (LC) and/or HCC development among HBV/F and HBV/A isolates deserves further prospective clinical studies.

Metachronous contralateral Leydig-cell tumour in an 8-year-old boy.

Leydig-cell tumours of the testis are rare and usually benign in children. The possibility of metachronous bilateral tumours should be considered not only for testicular teratomas but also in the follow up of a Leydig-cell tumour. Testis-sparing surgery is feasible and safe in prepubertal boys after exclusion of a malignant tumour.

Effective count rates for PET scanners with reduced and extended axial field of view.

We investigated the relationship between noise equivalent count (NEC) and axial field of view (AFOV) for PET scanners with AFOVs ranging from one-half to twice those of current clinical scanners. PET scanners with longer or shorter AFOVs could fulfill different clinical needs depending on exam volumes and site economics. Using previously validated Monte Carlo simulations, we modeled true, scattered and random coincidence counting rates for a PET ring diameter of 88 cm with 2, 4, 6, and 8 rings of detector blocks (AFOV 7.8, 15.5, 23.3, and 31.0 cm). Fully 3D acquisition mode was compared to full collimation (2D) and partial collimation (2.5D) modes. Counting rates were estimated for a 200 cm long version of the 20 cm diameter NEMA count-rate phantom and for an anthropomorphic object based on a patient scan. We estimated the live-time characteristics of the scanner from measured count-rate data and applied that estimate to the simulated results to obtain NEC as a function of object activity. We found NEC increased as a quadratic function of AFOV for 3D mode, and linearly in 2D mode. Partial collimation provided the highest overall NEC on the 2-block system and fully 3D mode provided the highest NEC on the 8-block system for clinically relevant activities. On the 4-, and 6-block systems 3D mode NEC was highest up to ∼300 MBq in the anthropomorphic phantom, above which 3D NEC dropped rapidly, and 2.5D NEC was highest. Projected total scan time to achieve NEC-density that matches current clinical practice in a typical oncology exam averaged 9, 15, 24, and 61 min for the 8-, 6-, 4-, and 2-block ring systems, when using optimal collimation. Increasing the AFOV should provide a greater than proportional increase in NEC, potentially benefiting patient throughput-to-cost ratio. Conversely, by using appropriate collimation, a two-ring (7.8 cm AFOV) system could acquire whole-body scans achieving NEC-density levels comparable to current standards within long, but feasible, scan times.

A robust state-space kinetics-guided framework for dynamic PET image reconstruction.

Dynamic PET image reconstruction is a challenging issue due to the low SNR and the large quantity of spatio-temporal data. We propose a robust state-space image reconstruction (SSIR) framework for activity reconstruction in dynamic PET. Unlike statistically-based frame-by-frame methods, tracer kinetic modeling is incorporated to provide physiological guidance for the reconstruction, harnessing the temporal information of the dynamic data. Dynamic reconstruction is formulated in a state-space representation, where a compartmental model describes the kinetic processes in a continuous-time system equation, and the imaging data are expressed in a discrete measurement equation. Tracer activity concentrations are treated as the state variables, and are estimated from the dynamic data. Sampled-data H(∞) filtering is adopted for robust estimation. H(∞) filtering makes no assumptions on the system and measurement statistics, and guarantees bounded estimation error for finite-energy disturbances, leading to robust performance for dynamic data with low SNR and/or errors. This alternative reconstruction approach could help us to deal with unpredictable situations in imaging (e.g. data corruption from failed detector blocks) or inaccurate noise models. Experiments on synthetic phantom and patient PET data are performed to demonstrate feasibility of the SSIR framework, and to explore its potential advantages over frame-by-frame statistical reconstruction approaches.

Use of preputial skin as cutaneous graft after nevus excision.

We report a four-year-old boy with a nevus covering all the plantar side of his second finger on the left foot. He was also affected by congenital phimosis. Surgical excision of the nevus was indicated, but the skin defect would have been too large to be directly closed. The foreskin was taken as a full-thickness skin graft to cover the cutaneous defect of the finger. The graft intake was favourable and provided a functional repair with good aesthetic characteristic.

[Definitive treatment of anal canal carcinoma with radiotherapy: adverse impact of a pre-radiation resection. A retrospective study of 57 patients treated with curative intent]. / Radiothérapie à visée curative du carcinome du canal anal : impact défavorable d'une résection préalable. Etude rétrospective de 57 patients traités en intention curative.

PURPOSE: To describe retrospectively the overall survival, the cancer specific survival and the tumor control in an homogeneous series of patients with epidermoid carcinoma of the anal canal treated with definitive radiotherapy; to assess the impact of brachytherapy, chemotherapy and pre-radiotherapy resection on the risk of recurrence. PATIENTS AND METHODS: From 1997 to 2007, 57 patients (pts) presenting with an epidermoid carcinoma of the anal canal (T1: 14, T2: 33, T3-4: 10, N0: 31, N1: 19, N2: 3, N3: 4, M0: 57) were treated with definitive radiotherapy by the same radiation oncologist. The treatment included an external beam irradiation (EBRT) given to the posterior pelvis (45Gy/25 fractions) and, six weeks later, a boost delivered with interstitial brachytherapy (37/57) or external beam irradiation (20/57). Twelve pts had undergone a surgical resection of the tumour before radiotherapy. A belly board was used for EBRT in 13 pts. A concurrent platinum based chemotherapy was done in 42 pts. The mean follow-up was 57 months. RESULTS: The overall survival rate at 5 years was 89% with a cause specific survival of 96%. Five patients recurred (5-year rate: 12%: four had local relapse (5-year rate: 8%), four had groin recurrence, and distant metastases were seen in two. In univariate analysis, the risk of relapse was higher in patients who had undergone a pre-radiation excision (p=0.018), in those who did not receive chemotherapy (p=0.076) and in those who were irradiated on a belly board (p=0.049). In multivariate analysis, a pre-radiotherapy resection (p=0.084) had an inverse impact on the tumour control reaching the level of statistical significance and the use of a belly board was of marginal influence (p=0.13). CONCLUSION: Radiotherapy and chemoradiation with cisplatine-based chemotherapy cure a vast majority of patients with epidermoid carcinoma of the anal canal. Therapeutic factors that may interfere with the definition of the target volume and the patients' repositioning may decrease the efficacy of radiotherapy. Pre-radiotherapy surgical resection should be avoided.

EEG spike source localization before and after surgery for temporal lobe epilepsy: a BOLD EEG-fMRI and independent component analysis study

Simultaneous measurements of EEG-functional magnetic resonance imaging (fMRI) combine the high temporal resolution of EEG with the distinctive spatial resolution of fMRI. The purpose of this EEG-fMRI study was to search for hemodynamic responses (blood oxygen level-dependent - BOLD responses) associated with interictal activity in a case of right mesial temporal lobe epilepsy before and after a successful selective amygdalohippocampectomy. Therefore, the study found the epileptogenic source by this noninvasive imaging technique and compared the results after removing the atrophied hippocampus. Additionally, the present study investigated the effectiveness of two different ways of localizing epileptiform spike sources, i.e., BOLD contrast and independent component analysis dipole model, by comparing their respective outcomes to the resected epileptogenic region. Our findings suggested a right hippocampus induction of the large interictal activity in the left hemisphere. Although almost a quarter of the dipoles were found near the right hippocampus region, dipole modeling resulted in a widespread distribution, making EEG analysis too weak to precisely determine by itself the source localization even by a sophisticated method of analysis such as independent component analysis. On the other hand, the combined EEG-fMRI technique made it possible to highlight the epileptogenic foci quite efficiently.

EEG spike source localization before and after surgery for temporal lobe epilepsy: a BOLD EEG-fMRI and independent component analysis study.

Simultaneous measurements of EEG-functional magnetic resonance imaging (fMRI) combine the high temporal resolution of EEG with the distinctive spatial resolution of fMRI. The purpose of this EEG-fMRI study was to search for hemodynamic responses (blood oxygen level-dependent--BOLD responses) associated with interictal activity in a case of right mesial temporal lobe epilepsy before and after a successful selective amygdalohippocampectomy. Therefore, the study found the epileptogenic source by this noninvasive imaging technique and compared the results after removing the atrophied hippocampus. Additionally, the present study investigated the effectiveness of two different ways of localizing epileptiform spike sources, i.e., BOLD contrast and independent component analysis dipole model, by comparing their respective outcomes to the resected epileptogenic region. Our findings suggested a right hippocampus induction of the large interictal activity in the left hemisphere. Although almost a quarter of the dipoles were found near the right hippocampus region, dipole modeling resulted in a widespread distribution, making EEG analysis too weak to precisely determine by itself the source localization even by a sophisticated method of analysis such as independent component analysis. On the other hand, the combined EEG-fMRI technique made it possible to highlight the epileptogenic foci quite efficiently.

Lymphatic preservation using methylene blue dye during varicocele surgery: a single-center retrospective study.

OBJECTIVE: Hydrocele and testicular edema caused by division of lymphatic vessels during varicocelectomy could lead to decrease in testicular function. In-vivo methylene blue mapping of testicular lymphatic vessels should prevent damage to the lymphatic system. MATERIALS AND METHODS: We retrospectively compared outcomes for 46 patients who received an intraparenchymal injection of 0.25 ml of vital dye (isosulphan blue) before a laparoscopic or an inguinal/subinguinal spermatic vein ligation with 93 controls in whom no mapping technique was adopted. RESULTS: Methylene blue mapping of testicular lymphatics reduced the incidence of postvaricocelectomy hydrocele from 6.4% (6/93) to 2.1% (1/46); the incidence of hydrocele was 0% in all cases of successful lymphatic mapping. CONCLUSION: Mapping of testicular lymphatic drainage with intraparenchymal vital dye is an easy, safe, rapid and cost-free technique. We stress the importance of sparing the lymphatic system to ensure the best andrological outcome.

The tyrosine phosphatase Shp-2 mediates intracellular signaling initiated by Ret mutants.

The Src homology 2-containing tyrosine phosphatase, Shp-2, is a crucial enzyme that mediates intracellular signaling and is implicated in cell proliferation and differentiation. Here we investigated the involvement of the Shp-2 tyrosine phosphatase in determining the downstream signaling pathways initiated by the Ret oncogene, carrying either the cysteine 634 to tyrosine or the methionine 918 to threonine substitutions. These mutations convert the receptor tyrosine kinase, Ret, into a dominant transforming protein and induce constitutive activation of its intrinsic tyrosine kinase activity leading to congenital and sporadic cancers in neuroendocrine organs. Using the PC12, rat pheochromocytoma cell line, as model system, we show that Shp-2 mediates immediate-early gene expression if induced by either of the mutant alleles. Furthermore, we show that Shp-2 activity is required for RetM918T-induced Akt activation. The results indicate that Shp-2 is a downstream mediator of the mutated receptors RetC634Y and RetM918T, thus suggesting that it may act as a limiting factor in Ret-associated endocrine tumors, in the neoplastic syndromes multiple endocrine neoplasia types 2A and 2B.

[Biological monitoring of occupational exposure to desflurane]. / Monitoraggio biologico dell'esposizione occupazionale a desflurane.

In these last years Desflurane (D) has become used, alone or in combination with nitrous oxide, in surgical procedures. Occupational exposed groups include anesthesiologists, other physicians, (e.g. surgeons) and operating room nurses. Desflurane is a halogenated methylethylether which is administered by inhalation. Desflurane is halogenated exclusively with fluorine. The blood/gas partition coefficient of Desflurane is 0.42. Changes in the clinical effects of Desflurane rapidly follow changes in the inspired concentration. Studies in man indicate that Desflurane washes into the body rapidly. It also washes out of the body rapidly, allowing flexibility in adjustment of the depth of anaesthesia. Desflurane is eliminated via the lungs, undergoing only minimal metabolism (0.02%). In order to investigate the role of urinary D as an indicator of occupational exposure to Desflurane (CI, ppm), CI was measured in 21 members of operating room staffs. For the measurement of environmental concentration of Desflurane (CI), the ambient air was sampled using personal passive dosimeters. The analyte was desorbed by a water-methanol mixture and was analysed by means a gas chromatograph--mass spectrometer (GC-MSD) and headspace technique. The biological monitoring of exposed workers was conducted by determining the concentration of Desflurane in urine (Cu, microgram/L). Urine concentrations of Desflurane were determined by headspace analysis using GC-MSD. Significant correlations were found between the environmental Desflurane concentration and the urinary concentrations. The correlation between CI (ppm) and Cu (microgram/L) was: Log D (Cu, microgram/L) = .191 + .922 * LogCI; r = .916 On the basis of the equation it was possible to establish tentatively the biological limit values corresponding to the respective occupational exposure limit values proposed for Desflurane.

Structure of inorganic and carbonaceous particles emitted from heavy oil combustion.

The combustion of heavy fuel oil for power generation is a great source of carbonaceous and inorganic particle emissions, even though the combustion technologies and their efficiency are improving. The information about the size distribution function of the particles originated by trace metals present into the fuels is not adequate. In this paper, we focused our attention on the larger distribution mode of both the carbonaceous and metallic particles. Isokinetic sampling was performed at the exhausts of two typical heavy oil flames and the samples were size-segregated by mean of an 8-stages Andersen impactor. Further investigation performed on the samples using electronic microscopy coupled with X-ray analysis (EDX) evidenced the presence of solid spherical particles, called plerosphere(1) as analogy with cenosphere, with typical dimensions ranging between 200 nm and 2-3 microm, whose atomic composition contains a large amount of the trace metals present in the parent oils (Fe, V, Ni, etc). EDX analyses revealed that the metal concentration increases as the plerosphere dimension decreases.

FLIP is expressed in mouse testis and protects germ cells from apoptosis.

Apoptosis control in adult testis is crucial to achieve normal spermatogenesis. In this study c-FLIP, an apoptosis-modulating protein, was investigated. In Western blot and immunohistochemical analyses, the 55 KDa c-FLIP long isoform (c-FLIP(L)) was found to be expressed strongly in spermatocytes and spermatids, at low levels in spermatogonia and at almost undetectable levels in Sertoli cells. This expression pattern was confirmed by Northern blot analyses. Further experiments carried out on GC-1spg germ cell line revealed that reducing c-FLIP(L) expression increases Fas-dependent apoptosis. Conversely, restoring c-FLIP(L) expression reduces this response to control levels. Caspase-10 expression was found to match c-FLIP(L) expression pattern; further, caspase-10 activation upon anti-Fas treatment inversely correlated with c-FLIP(L) expression. Finally, TUNEL staining of seminiferous tubules incubated with anti-Fas antibody showed that apoptosis occurs mostly in basally located germ cells, indicating that such cells, expressing low levels of c-FLIP(L), are sensitive to Fas-mediated apoptosis. These data indicate for the first time that c-FLIP(L) might control germ cell apoptosis and caspase activity in the adult testis.

The Fas system in the seminiferous epithelium and its possible extra-testicular role.

The Fas system is involved in the control of immune system homeostasis and nonfunctional Fas system leads to autoimmune disease in mice and humans. The Fas system is a mechanism through which cells expressing Fas ligand (FasL) induce apoptosis of Fas expressing cells. In mouse and rat, the testis represents the main source of constitutive FasL in the body. The roles so far proposed for this molecule in the testis, such as maintenance of immunoprivilege and regulation of physiological germ cell apoptosis, need to be reconsidered as both hypotheses are based on an erroneous cellular location of FasL in the seminiferous epithelium. Recently, we demonstrated that in rodents FasL mRNA is present in germ cells and not in Sertoli cells, and that FasL protein is displayed on the surface of spermatozoa. Here we propose that, for the mouse spermatozoa, the FasL may represent a self-defence mechanism against lymphocytes present in the female genital tract. To verify this hypothesis, we performed crossings between males gld, with nonfunctional FasL, and syngenic or nonsyngenic females. We observed a significant decrease of litter size in outbred crossings with gld males compared with wild-type males, suggesting a possible role of FasL in immunoprotection of the sperm in the female genital tract. The possibility that in humans, by analogy with mouse, FasL plays a self-protective role for the spermatozoon cannot be excluded, and awaits experimental information on the expression of FasL on human sperm cells.