Radiation Therapy in Non-Melanoma Skin Cancers: An Italian Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology.

AIMS: The National Palliative Care and Interventional Radiotherapy Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) carried out a survey whose aim was to obtain a "snapshot" of the real-world practice of nonmelanoma skin cancer (NMSC) treatments in Italy. MATERIALS AND METHODS: The survey was conducted on SurveyMonkey's online interface and was sent via e-mail to our society Radiation Oncologists. RESULTS: Fifty-eight Italian radiation oncologists (ROs), representing 54 centers, answered the survey. Thirteen percent of the ROs declared they treat fewer than 10 NMSC lesions annually, 36% treat between 11 and 20, and 51% treat more than 20 lesions annually. Interventional radiotherapy (IRT) was offered by 25% of the ROs, and every case was reportedly discussed by a multidisciplinary team (71%). Electrons (74%), volumetric modulated arc therapy (V-MAT) (57%), three-dimensional conformal radiotherapy (3D-CRT) (43%), and IRT (26%) were the main treatment options. With external beam radiotherapy (EBRT), 46 and 53 different RT schedules were treated for curative and palliative intent, respectively; whereas for IRT, there were 21 and 7 for curative and palliative intent, respectively. The most popular EBRT curative options were 50-70.95/22-35 fractions (fx) and 50-70 Gy/16-20fx and for EBRT palliative settings, 30Gy/10fx, and 20-35Gy/5fx. For IRT, the most popular curative options were 32-50Gy/8-10fx and 30-54Gy/3-5fx, whereas 30Gy/6fz was the palliative option. Less than 10 re-RT cases were reported in one year in 42.5%, 11-20 cases in 42.5%, and >20 cases annually in 15%. Electrons (61%), VMAT (49%), and BRT (25%) were the most widely used approaches: 20-40Gy in 10fx and 20-25Gy in 5fx were the recommended fractionations. CONCLUSION: The survey shows a variegated reality. A national registry with more detailed data could help in undercover its causes.

Osteoradionecrosis incidence in pre-radiation teeth extractions: A prospective study.

AIMS: To evaluate osteoradionecrosis (ORN) incidence in a cohort of patients undergoing tooth extraction (TE) before radiotherapy (RT) for head and neck cancers. METHODS: The study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (ID-2132) and registered at clinicaltrials.gov (ID: NCT04009161). TE was performed in case of signs of pericoronitis, periapical lesions, restorative impossibility, severe periodontitis. ORN was defined as exposed bone at an unhealed post-extraction socket in the absence of oncological recurrence. The RT plans were reviewed, and each post-extractive socket was contoured to calculate the received radiation dose. RESULTS: In total, 156 patients with 610 TE were enrolled. The mean follow-up was 567 days. ORN was diagnosed in four patients (2.6% of patients and 0.7% of TE). Need for osteotomy and radiation dose at the extraction site were associated with ORN (OR for osteotomy: 21.9, 95% CI: 2.17-222.2, p = 0.009; OR for RT dose: 1.1, 95% CI: 1-1.15, p = 0.05). CONCLUSIONS: TE appears to be a significant risk factor for ORN, particularly when osteotomy is required, and post-extraction sockets receive a high RT dosage. This study proposes a decision-making algorithm for TE and outlines a straightforward surgical protocol.

The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

BACKGROUND: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. AIMS: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). METHODS: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). RESULTS: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) µg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 µg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. DISCUSSION: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. CONCLUSION: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

Brain gliomas and growth factors: immunohistochemical, immunofluorescence, flow cytometry and RT-PCR profile in pediatric age.

Gliomas represent over 50% of tumors occurring in children. Evidence suggests that glioma stem cells (GSCs), maintained by the transforming growth factor-beta (TGF-ß1) pathway, and vascularization substantially contribute to tumor aggressiveness. The identification of important angiogenic factors such as vascular endothelial growth factor (VEGF) may represent a crucial step in the therapeutic approach against tumor growth and metastatic diffusion. The aim of this study was to identify the expression of TGF-ß1, VEGF and VEGF-receptors in brain gliomas. Specimens of 16 gliomas and 4 controls from children aged 0.2-14 years were used in the study. Immunohistochemical analysis and gene expression study from specimens was performed. Flow cytometry analysis on GSCs was performed to ascertain the expression of VEGF and VEGF-R2 in the tumor stem cell compartment. Newly diagnosed gliomas mainly showed moderate to strong VEGF immunostaining and increased expression of pro-inflammatory molecules in glioma cells. The proportion of TGF-ß1 positive endothelial cells was markedly lower in normal brain vessels compared to tumor vessels. These findings demonstrate that the glioma mass is constituted by a phenotypically immature anoxic central area with a proliferating hypoxic layer; the peripheral area is characterized by cell types with a higher degree of differentiation expressing pro-angiogenic factors. Our data have proven that GSCs play a central role in promoting glioma neovascularization. These findings are useful to understand glioma vascularization, have relevant implications in the therapeutic options and may favor new insights into stem cells biology and suggest therapeutic opportunities for the anti-vascular treatment strategy.

Baropodometry on patients after total knee arthroplasty.

PURPOSE: It is well known that total knee replacement surgery decreases pain and improves function, but the effect on postural assessment needs to be studied better with the use of new technological devices. Total knee arthroplasty (TKA) improves motor coordination and stability of the knee. On the other hand, changing joint functionality can modify the balance. The aim of this trial is to record and analyze the static and dynamic baropodometric data of patients in the first few months following joint replacement. For the physiatrist, this tool can be useful to check if the rehabilitation treatment protocols and times are correct. METHODS: We designed a prospective observation longitudinal study to assess postural stability following TKA. Between December 2014 and May 2015, sixty consecutive patients were recruited through local orthopedic physician offices and hospitals. The patients scheduled to undergo TKA were recruited and were monitored before surgery (T0) and at 1 (T1), 3 (T2) and 6 months (T3) after knee surgery. The correction of varus/valgus deviation at X-ray and the Knee Society Score were performed to verify the functional recovery. We used static and dynamic baropodometric analysis to evaluate postural assessment. RESULTS: After surgery, there was a significant improvement in physiological alignment of knee axes (p < 0.0001) and of Knee and Function Scores (excellent, mean values 80.5 and 80.7, respectively, p < 0.0001). The static analysis showed that the center of gravity and the pressure on the foot of the operated limb were corrected toward the physiological center (p < 0.0001) and the body weight displaced to the forefeet and to the hindfeet reduced bilaterally (p < 0.0001). The type of footprint did not change. The dynamic analysis confirmed the significant normalization of the pressure on the foot of the operated limb at all follow-ups (p < 0.0001). The percentage of load was reduced on the operated limb (p = 0.0096) and speed of step, cadence and semi-step length increased (p < 0.0001). CONCLUSION: These data show the progressive recovery of stability after TKA from the immediate postoperative to the subsequent months. The clinical and functional improvement correlated with a load redistribution between the two limbs. The baropodometry could be an excellent noninvasive method for monitoring effects of rehabilitation treatment.

Age-related ultrastructural and monoamine oxidase changes in the rat optic nerve.

The aim of this paper is to study the morphology and the distribution of the monoamine oxidase enzymatic system in the optic nerve of 4 month-old Wistar (young) and 28 month-old Wistar (old) rats. The optic nerve was harvested from 20 young and old rats. The segment of optic nerve was divided longitudinally into two pieces, each 0.1 mm in length. The first piece was used for transmission electron microscopy. The second piece was stained with histochemical reaction for monoamine oxidase. The agerelated changes in the optic nerve of rats include micro-anatomical details, ultrastructure and monoamine oxidase histochemical staining. A strong decrease of the thin nerve fibers and a swelling of the thick ones can be observed in optic nerve fibers of old rats. Increased monoamine oxidase histochemical staining of the optic nerve of aged rats is well demonstrated. The increase of meningeal shealth and the decrease of thin nerve fibers of the optic nerve in old rats are well documented. Morphological, ultrastructural and histochemical changes observed in optic nerve fibers of the old rats show a close relation with aging.

Three dimensional myocardial deformation and diagnosis of stable coronary artery disease.

To date, only one third of patients, with stable angina, undergoing coronary angiography demonstrated obstructive coronary artery disease (CAD). Thus, identifying high sensitivity and specificity, low-cost, non invasive tests is crucial. Here we present the case of a patient, at a high risk of CAD, undergoing coronary angiography because of positive exercise test and stress imaging results, with non obstructive coronary artery disease at angiography, confirmed by FFR. Interestingly, 3D speckle tracking, performed before angiography, assessed normal left ventricle deformation, predicting the absence of severe coronary artery lesions.

Genetic Test for the Channelopaties: Useful or Less Than Useful for Patients? (Part II).

The advanced knowledge about genetic diseases and their mutations has widened the possibility to have a more precise and definitive diagnosis in many patients, but the use of genetic testing is still controversial. Actually, many cardiomyopathies show the availability of genetic testing. The clinical utility of this testing has been widely debated, but it is evident that the use of genetics must be put in a more organic diagnostic pathway that includes the evaluation of risks and benefits for the patient and his relatives, as well as the costs of the procedure. This review aims to clarify the role of genetic in clinics regarding Channelopaties, less frequent but equally important than other Cardiomyopathies because patients can often be asymptomatic until the first fatal manifestation.

Ventricular septal defect: the three-dimensional point of view.

This case highlights the clinical usefulness of three-dimensional (3D) echocardiography. The diagnosis of inter-ventricular septal defect associated with aortic regurgitation has been performed in a 50-year-old man using 3D echocardiography. This advanced echocardiography could accurately reproduce the anatomy of the defect and provide further insights in the mechanisms of aortic regurgitation showing an unusual non-coronary cusp prolapse. The routinely use of 3D echocardiography in clinics might allow a better characterization of cardiac anatomy, especially of aortic valve disorders.

Genetic test for dilated and hypertrophic cardiomyopathies: useful or less than useful for patients?

Genetic testing for potentially heritable cardiomyopathies has advanced from basic scientific discovery to clinical application. Nowadays, genetic diagnostic tests for cardiomyopathies are clinically available. As a consequence is fundamental the understanding of the clinical utility, in terms of diagnosis and prognosis, of genetic test results. In addition, the genetic counselling, regarding risks, benefits and options, is recommended for all patients and their relatives. However the relation between genotype and phenotype remains often unclear, and there is frequently a variance of uncertain significance. Consequently, the genetic test should always be approached as one component of a comprehensive cardio-genetic evaluation. This review aims to explore when genetic tests are indicated in patients with dilated and hypertrophic cardiomyopathy.

Neurotrophins, their receptors and KI-67 in human GH-secreting pituitary adenomas: an immunohistochemical analysis.

Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM.

"Il corpo ritrovato": dermocosmetological skin care project for the oncologic patient.

Neoplastic disease and its therapeutic options have a huge impact on the patient's quality of life from both the emotional and the working point of view. The project "Il Corpo Ritrovato" aims at creating an interdisciplinary network of physicians to improve the quality of life of the oncologic patient, focusing on such important aspects as dermocosmetological skin care but also on the evaluation of new therapeutic and diagnostic algorithms in order to make further progress in the field of prevention.

A new classification and clinical predictivity for some naevus variants.

Background. The incidence of cutaneous melanoma is rapidly increasing in Europe. Active research is directed toward the identification of naevi as a risk factor. Objective. The aim of our case-control study was to observe different numbers of moles and different mole typology associations in order to evaluate clinical predictivity and to establish a new classification for some naevus variants. Methods. A case-control study was carried out, enrolling 64 cases affected by melanoma and 183 controls, between October 2009 and February 2011. Each patient was interviewed and subjected to clinical examination. The resulting data were analysed using the statistical elaboration program SPSS 16.0. Results. The association of target naevus with other variants increases the degree of risk (target + small brown Odds Ratio 5.25; confidence interval 1.8-15.4); (target + small brown + small black + large brown odds ratio 5.0; confidence interval 1.1-22.4). Therefore, other variants and/or other variant combinations do not significantly increase risk. Conclusion. People presenting two naevus variants in association with other naevus variants seem to run a major risk. The general nonuniformity of the whole naevus panorama should be carefully considered.

Teledermatology: from prevention to diagnosis of nonmelanoma and melanoma skin cancer.

Telemedicine is a rapidly developing application of clinical medicine where medical information is transferred through interactive audiovisual media for the purpose of consulting remote medical procedures or examinations, reducing the time of consultation for patients. Teledermatology as an application of telemedicine was developed in 1995: it turns out to be a gradually more ordinary mean of delivering dermatologic healthcare worldwide and will almost certainly have a greater medical function in the future. In particular, teledermatology can aid in the prevention and diagnosis of nonmelanoma and melanoma skin cancer; telemedicine and teledermatology offer the opportunity to make available consultations with experts also by long distance. Overall, patients seem to accept teledermatology, considering it as an excellent mean to obtain healthcare, particularly in those areas with no expert dermatologists available. Clinicians have also generally reported affirmative experiences with teledermatology in the skin cancer field. Further studies focusing on cost effectiveness, patient outcomes, and patient and clinician satisfaction will facilitate to delineate the potential of teledermatology as a mean of prevention and diagnosis of nonmelanoma and melanoma skin cancer.

Skin needling to enhance depigmenting serum penetration in the treatment of melasma.

Melasma is a common hypermelanotic disorder affecting the facial area which has a considerable psychological impact on the patient. Managing melasma is a difficult challenge that requires long-term treatment with a number of topical agents, such as rucinol and sophora-alpha. Aims. We aim to compare the combined treatment of skin needling and depigmenting serum with that using depigmenting serum alone in the treatment of melasma, in order to evaluate the use of microneedles as a means to enhance the drug's transdermal penetration. Methods. Twenty patients were treated with combined skin needling and depigmenting serum on one side of the face and with depigmenting serum alone on the other side. The outcome was evaluated periodically for up to two months using the Melasma Area Severity Index score and the Spectrocolorimeter X-Rite 968. Results. The side with combined treatment (skin needling + depigmenting serum) presented a statistically significant reduction in MASI score and luminosity index (L) levels compared to the side treated with depigmenting serum alone, and clinical symptoms were significantly improved. Conclusions. Our study suggests the potential use of combining skin needling with rucinol and sophora-alpha compounds to achieve better results in melasma treatment compared to rucinol and sophora-alpha alone.

Acne scars: pathogenesis, classification and treatment.

Acne has a prevalence of over 90% among adolescents and persists into adulthood in approximately 12%-14% of cases with psychological and social implications. Possible outcomes of the inflammatory acne lesions are acne scars which, although they can be treated in a number of ways, may have a negative psychological impact on social life and relationships. The main types of acne scars are atrophic and hypertrophic scars. The pathogenesis of acne scarring is still not fully understood, but several hypotheses have been proposed. There are numerous treatments: chemical peels, dermabrasion/microdermabrasion, laser treatment, punch techniques, dermal grafting, needling and combined therapies for atrophic scars: silicone gels, intralesional steroid therapy, cryotherapy, and surgery for hypertrophic and keloidal lesions. This paper summarizes acne scar pathogenesis, classification and treatment options.

Bronchodilator activity of (3R)-3-[[[(3-fluorophenyl)[(3,4,5-trifluorophenyl)methyl]amino] carbonyl]oxy]-1-[2-oxo-2-(2-thienyl)ethyl]-1-azoniabicyclo[2.2.2]octane bromide (CHF5407), a potent, long-acting, and selective muscarinic M3 receptor antagonist.

The novel quaternary ammonium salt (3R)-3-[[[(3-fluorophenyl)[(3,4,5-trifluorophenyl)methyl]amino]carbonyl]oxy]-1-[2-oxo-2-(2-thienyl)ethyl]-1-azoniabicyclo[2.2.2]octane bromide (CHF5407) showed subnanomolar affinities for human muscarinic M1 (hM1), M2 (hM2), and M3 (hM3) receptors and dissociated very slowly from hM3 receptors (t(½) = 166 min) with a large part of the receptorial complex (54%) remaining undissociated at 32 h from radioligand washout. In contrast, [(3)H]CHF5407 dissociated quickly from hM2 receptors (t(½) = 31 min), whereas [(3)H]tiotropium dissociated slowly from both hM3 (t(½) = 163 min) and hM2 receptor (t(½) = 297 min). In the guinea pig isolated trachea and human isolated bronchus, CHF5407 produced a potent (pIC(50) = 9.0-9.6) and long-lasting (up to 24 h) inhibition of M3 receptor-mediated contractile responses to carbachol. In the guinea pig electrically driven left atrium, the M2 receptor-mediated inhibitory response to carbachol was recovered more quickly in CHF5407-pretreated than in tiotropium-pretreated preparations. CHF5407, administered intratracheally to anesthetized guinea pigs, potently inhibited acetylcholine (Ach)-induced bronchoconstriction with an ED(50) value of 0.15 nmol/kg. The effect was sustained over a period of 24 h, with a residual 57% inhibition 48 h after antagonist administration at 1 nmol/kg. In conscious guinea pigs, inhaled CHF5407 inhibited Ach-induced bronchoconstriction for at least 24 h as did tiotropium at similar dosages. Cardiovascular parameters in anesthetized guinea pigs were not significantly changed by CHF5407, up to 100 nmol/kg i.v. and up to 1000 nmol/kg i.t. In conclusion, CHF5407 shows a prolonged antibronchospastic activity both in vitro and in vivo, caused by a very slow dissociation from M3 receptors. In contrast, CHF5407 is markedly short-acting at M2 receptors, a behavior not shared by tiotropium.

The effect of aminolevulinic acid photodynamic therapy on microcomedones and macrocomedones.

BACKGROUND: Photodynamic therapy (PDT) with aminolevulinic acid (ALA) has been shown to be an effective treatment for acne. However, the effect of ALA PDT on comedo formation has never been objectively evaluated. Cyanoacrylate follicular biopsy (CFB), a noninvasive procedure, has been proposed as the most reliable tool for studying follicular casts. OBJECTIVE: To determine the possible effect of ALA and red light (550-700 nm) on macro- and microcomedones in acne patients. PATIENTS AND METHODS: 10 patients with mild-to-moderate facial and/or chest/back acne resistant to conventional therapies received ALA PDT at 2-week intervals in 3 sessions. The severity of acne had been estimated by a system of points, the Global Acne Grading System. The patients underwent PDT utilizing ALA 10% (face) or 15% (back/chest) and red light (15 J/cm(2) each session). CFBs were performed. RESULTS: Four weeks after their last PDT session, the patients showed an average global score reduction of 50%. CFBs demonstrated a reduction in the total area, the average area and the density of macrocomedones. CONCLUSION: The results obtained in this study using CFB evaluation demonstrate that ALA PDT exerts an action on the comedogenic phase as well.