Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Cutaneous squamous cell carcinoma (CSCC) accounts for ∼20%-25% of all skin tumors. Its precise incidence is often challenging to determine due to limited statistics and its incorporation with mucosal forms. While most cases have a favorable prognosis, challenges arise in patients presenting with locally advanced or metastatic forms, mainly appearing in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties. Traditionally, chemotherapy and targeted therapy were the mainstays for advanced cases, but recent approvals of immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options. These guidelines, developed by the Italian Association of Medical Oncologists (AIOM) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, aim to guide clinicians in diagnosing, treating, and monitoring patients with CSCC, covering key aspects from primitive tumors to advanced stages, selected by a panel of experts selected by AIOM and other national scientific societies. The incorporation of these guidelines into clinical practice is expected to enhance patient care and address the evolving landscape of CSCC management.

Guidelines for the diagnosis and treatment of basal cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.

Prediction of patient-specific post-operative outcomes of TAVI procedure: The impact of the positioning strategy on valve performance.

Prosthesis positioning in transcatheter aortic valve implantation procedures represents a crucial aspect for procedure success as demonstrated by many recent studies on this topic. Possible complications, device performance, and, consequently, also long-term durability are highly affected by the adopted prosthesis placement strategy. In the present work, we develop a computational finite element model able to predict device-specific and patient-specific replacement procedure outcomes, which may help medical operators to plan and choose the optimal implantation strategy. We focus in particular on the effects of prosthesis implantation depth and release angle. We start from a real clinical case undergoing Corevalve self-expanding device implantation. Our study confirms the crucial role of positioning in determining valve anchoring, replacement failure due to intra or para-valvular regurgitation, and post-operative device deformation.

Simulation of transcatheter aortic valve implantation through patient-specific finite element analysis: two clinical cases.

Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure introduced to treat aortic valve stenosis in elder patients. Its clinical outcomes are strictly related to patient selection, operator skills, and dedicated pre-procedural planning based on accurate medical imaging analysis. The goal of this work is to define a finite element framework to realistically reproduce TAVI and evaluate the impact of aortic root anatomy on procedure outcomes starting from two real patient datasets. Patient-specific aortic root models including native leaflets, calcific plaques extracted from medical images, and an accurate stent geometry based on micro-tomography reconstruction are key aspects included in the present study. Through the proposed simulation strategy we observe that, in both patients, stent apposition significantly induces anatomical configuration changes, while it leads to different stress distributions on the aortic wall. Moreover, for one patient, a possible risk of paravalvular leakage has been found while an asymmetric coaptation occurs in both investigated cases. Post-operative clinical data, that have been analyzed to prove reliability of the performed simulations, show a good agreement with analysis results. The proposed work thus represents a further step towards the use of realistic computer-based simulations of TAVI procedures, aiming at improving the efficacy of the operation technique and supporting device optimization.

Complete recovery from paraparesis in spinal cord compression due to extramedullary haemopoiesis in beta-thalassaemia by emergency radiation therapy.

Extramedullary haemopoiesis (EMH) is a complication commonly associated with beta-thalassaemia intermedia; it is frequently asymptomatic but can sometimes lead to symptomatic tumour-like masses. No guidelines or common consensus are available in literature regarding the different treatment strategies and only single cases have been reported. We describe a case of spinal cord compression due to intrathoracic EMH masses treated with combined radiotherapy and hydroxyurea.

Simulation of transcatheter aortic valve implantation: a patient-specific finite element approach.

Until recently, heart valve failure has been treated adopting open-heart surgical techniques and cardiopulmonary bypass. However, over the last decade, minimally invasive procedures have been developed to avoid high risks associated with conventional open-chest valve replacement techniques. Such a recent and innovative procedure represents an optimal field for conducting investigations through virtual computer-based simulations: in fact, nowadays, computational engineering is widely used to unravel many problems in the biomedical field of cardiovascular mechanics and specifically, minimally invasive procedures. In this study, we investigate a balloon-expandable valve and we propose a novel simulation strategy to reproduce its implantation using computational tools. Focusing on the Edwards SAPIEN valve in particular, we simulate both stent crimping and deployment through balloon inflation. The developed procedure enabled us to obtain the entire prosthetic device virtually implanted in a patient-specific aortic root created by processing medical images; hence, it allows evaluation of postoperative prosthesis performance depending on different factors (e.g. device size and prosthesis placement site). Notably, prosthesis positioning in two different cases (distal and proximal) has been examined in terms of coaptation area, average stress on valve leaflets as well as impact on the aortic root wall. The coaptation area is significantly affected by the positioning strategy (- 24%, moving from the proximal to distal) as well as the stress distribution on both the leaflets (+13.5%, from proximal to distal) and the aortic wall (- 22%, from proximal to distal). No remarkable variations of the stress state on the stent struts have been obtained in the two investigated cases.

Patient-specific simulation of a stentless aortic valve implant: the impact of fibres on leaflet performance.

In some cases of aortic valve leaflet disease, the implant of a stentless biological prosthesis represents an excellent option for aortic valve replacement (AVR). In particular, if compared with the implant of mechanical valves, it provides a more physiological haemodynamic performance and a reduced thrombogeneticity, avoiding the use of anticoagulants. The clinical outcomes of AVR are strongly dependent on an appropriate choice of both prosthesis size and replacement technique, which is, at present, strictly related to surgeon's experience and skill. This represents the motivation for patient-specific finite element analysis able to virtually reproduce stentless valve implantation. With the aim of performing reliable patient-specific simulations, we remark that, on the one hand, it is not well established in the literature whether bioprosthetic leaflet tissue is isotropic or anisotropic; on the other hand, it is of fundamental importance to incorporate an accurate material model to realistically predict post-operative performance. Within this framework, using a novel computational methodology to simulate stentless valve implantation, we test the impact of using different material models on both the stress pattern and post-operative coaptation parameters (i.e. coaptation area, length and height). As expected, the simulation results suggest that the material properties of the valve leaflets affect significantly the post-operative prosthesis performance.

Is there a role for postoperative radiotherapy following open partial laryngectomy when prognostic factors on the pathological specimen are unfavourable? A survey of head and neck surgical/radiation oncologists.

Our aim was to survey the opinions of Italian radiation and ENT oncologists regarding the role of postoperative radiotherapy (PRT) and the appropriate dose to be given to patients with remnant larynx (RL) after open partial laryngectomy (OPL). The radio-oncologists (ROs) of the Italian Radiation-Oncologist Association (AIRO) and the ENTs of the Head-Neck Oncology Society (AIOCC-IHNS) were contacted through a SurveyMonkey online interface questionnaire. There were 148 usable responses. The majority of ROs recommended PRT in the case of positive/close margins (R(+)/R(close)) or in the case of initial involvement of thyroid cartilage (pT3(tci)). In the same cases, ENTs prefer a "watch and wait" policy (w&w). Both disciplines recommended w&w in the case of negative margins (R(-)). Finally, the majority of RO s recommended irradiating RL with 62-66 Gy in R(+), with 56-66 Gy (61.4%) in R(close) and with 56-60 Gy (34%) in pT3(tci). In Conclusion, OPL raises new considerations about PRT.

Patient-specific finite element analysis of carotid artery stenting: a focus on vessel modeling.

Finite element analysis is nowadays a well-assessed technique to investigate the impact of stenting on vessel wall and, given the rapid progression of both medical imaging techniques and computational methods, the challenge of using the simulation of carotid artery stenting as procedure planning tool to support the clinical practice can be approached. Within this context, the present study investigates the impact of carotid stent apposition on carotid artery anatomy by means of patient-specific finite element analysis. In particular, we focus on the influence of the vessel constitutive model on the prediction of carotid artery wall tensional state of lumen gain and of vessel straightening. For this purpose, we consider, for a given stent design and CA anatomy, two constitutive models for the CA wall, that is, a hyperelastic isotropic versus a fiber-reinforced hyperelastic anisotropic model. Despite both models producing similar patterns with respect to stress distribution, the anisotropic model predicts a higher vessel straightening and a more evident discontinuity of the lumen area near the stent ends as observed in the clinical practice. Although still affected by several simplifications, the present study can be considered as further step toward a realistic simulation of carotid artery stenting.

Patient-specific aortic endografting simulation: from diagnosis to prediction.

Traditional surgical repair of ascending aortic pseudoaneurysm is complex, technically challenging, and associated with significant mortality. Although new minimally invasive procedures are rapidly arising thanks to the innovations in catheter-based technologies, the endovascular repair of the ascending aorta is still limited because of the related anatomical challenges. In this context, the integration of the clinical considerations with dedicated bioengineering analysis, combining the vascular features and the prosthesis design, might be helpful to plan the procedure and predict its outcome. Moving from such considerations, in the present study we describe the use of a custom-made stent-graft to perform a fully endovascular repair of an asymptomatic ascending aortic pseudoaneurysm in a patient, who was a poor candidate for open surgery. We also discuss the possible contribution of a dedicated medical images analysis and patient-specific simulation as support to procedure planning. In particular, we have compared the simulation prediction based on pre-operative images with post-operative outcomes. The agreement between the computer-based analysis and reality encourages the use of the proposed approach for a careful planning of the treatment strategy and for an appropriate patient selection, aimed at achieving successful outcomes for endovascular treatment of ascending aortic pseudoaneurysms as well as other aortic diseases.

Evaluation of carotid stent scaffolding through patient-specific finite element analysis.

After carotid artery stenting, the plaque remains contained between the stent and the vessel wall, moving consequently physicians' concerns toward the stent capability of limiting the plaque protrusion, that is, toward vessel scaffolding, to avoid that some debris is dislodged after the procedure. Vessel scaffolding is usually measured as the cell area of the stent in free-expanded configuration, neglecting thus the actual stent configuration within the vascular anatomy. In the present study, we measure the cell area of four different stent designs deployed in a realistic carotid artery model through patient-specific finite element analysis. The results suggest that after deployment, the cell area change along the stent length and the related reduction with respect to the free-expanded configuration are functions of the vessel tapering. Hence, the conclusions withdrawn from the free-expanded configuration appear to be qualitatively acceptable for comparative purposes, but they should be carefully handled because they neglect the post-implant variability, which seems to be more pronounced in open-cell designs, especially at the bifurcation segment. Even though the investigation is limited to few stent designs and one vascular anatomy, our study confirms the capability of dedicated computer-based simulations to provide useful information about complex stent features as vessel scaffolding.

Efficacy and feasibility of induction chemotherapy and radiotherapy plus cetuximab in head and neck cancer.

BACKGROUND: To determine the potential activity and tolerability of sequential treatment in head and neck cancer, we conducted a phase II trial based on induction chemotherapy of two cycles of taxotere, cisplatin and 5-fluorouracil followed by radiotherapy plus weekly cetuximab. PATIENTS AND METHODS: Thirty-six patients with stage III or IV squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx were treated and evaluated for response and acute toxicity. RESULTS: Eighty-one percent of patients had stage IV disease and 42% had hypopharyngeal and oral cavity primaries. The overall response rate was 81.8%, with 60.6% complete response and 33.3% partial response. Severe toxicities were febrile neutropenia (6%) during induction chemotherapy and dermatitis (48%), mucositis (33%) and dysphagia (12%) during the concurrent phase. CONCLUSION: Our protocol proved to be feasible, effective and well tolerated. This sequential strategy should be further investigated.

Concomitant adjuvant chemoradiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial.

AIMS: Several randomised trials have tested adjuvant regimens using concomitant high-dose cisplatin and radiotherapy to improve outcome in high-risk locally advanced squamous cell head and neck cancer (HNSCC), showing a substantial increase in locoregional control and disease-free survival, despite a higher and eventually detrimental toxicity profile. The aim of the present phase II single-stage prospective study was to investigate whether a weekly cisplatin-based chemoradiotherapy regimen might be able to improve patients' compliance compared with standard-dose cisplatin with similar outcome results. MATERIALS AND METHODS: Between January 2004 and November 2008, 54 patients with high-risk locally advanced HNSCC were enrolled on to this phase II trial. Patient characteristics were: median age 59.7 years, Eastern Cooperative Oncology Group performance status 1 in 72% of patients and stage IV disease in 82%, extracapsular nodal spread in 67% and positive/close surgical margins in 37%. Patients received cisplatin (30 mg/m(2)) once a week for 7-8 weeks concurrent with external beam radiotherapy delivered with a median dose of 66.6 Gy (1.8 Gy each day; five fractions/week) on the primary site and 50 Gy (2 Gy each day) for the lower neck. RESULTS: Major acute toxicity of the combined treatment, defined as grade 3-4 mucositis, was observed in 35.2% of patients. No fatal complications occurred, with 81.5% of patients completing the planned regimen. Late reactions were mild (total 16% with a grade 3 dysphagia rate of 12%). The locoregional control rate was 82%; 5 year overall and disease-free survival were 63 and 62%, respectively. CONCLUSIONS: Concomitant adjuvant chemoradiotherapy with weekly cisplatin seems to be a feasible and well-tolerated therapeutic approach in 'unfit' patients. Clinical results seem to be at least comparable with those previously reported. However, to draw any definitive conclusion, large confirmatory phase III randomised trials are demanded.

Nasopharyngeal polymorphous low-grade adenocarcinoma in a patient with nonfunctioning pituitary macroadenoma.

BACKGROUND: Polymorphous low grade adenocarcinoma (PLGA) is a rare malignant neoplasm of the minor salivary glands occurring in the fifth and sixth decade with a 2:1 female predominance. The nasal cavity is involved in less than 1% of cases. The incidence of clinically recognisable pituitary adenoma is 15 cases/million/year. The prevalence of non-functioning pituitary adenoma (NFPA) is estimated to be 70-90 cases/million. Both types of adenoma represent 20-45% of pituitary tumours. CASE REPORT: The report describes the first case of PLGA associated with NFPA, both incidentally diagnosed. Three months after the exeresis of the NFPA using a trans-sphenoidal approach, an endoscopic resection of the PLGA was performed. No recurrence was observed during a 13 months follow-up. CONCLUSIONS: Complete surgical excision is the preferred management for PLGA. Radiotherapy has not been demonstrated to be effective in treating PLGA. The prognosis is good with a very low rate of metastasis and local recurrence.

Perinatal nutrient restriction reduces nephron endowment increasing renal morbidity in adulthood: a review.

Perinatal malnutrition has been included among the causes of renal disease in adulthood. Here, we consider the relationships between early supply of specific nutrients (such as protein, fat, vitamins and electrolytes) and renal endowment. Prenatal and postnatal nutrition mismatch is also discussed. In addition, this article presents the role of nutrition of both mothers and pre-term infants on nephron endowment, with final practical considerations.

[Risk assessment method for psychosocial factors at workplace: a North-West Tuscany area project]. / Metodologia di valutazione dei rischi psicosociali in ambiente di lavoro: un progetto toscano di area vasta.

The rising awareness of psychosocial risks at workplace means that it is ever more important to prepare methods to assess psychosocial factors in occupational environment. This project of north west tuscany area has the aim to realize an instrument for a gradual risk assessment for this kind of factors without the support of specialists. A decisional flow chart helps to approach the risk assessment step by step on the basis of company features, management and organization problems and company symptoms of stress. The final assessment combines the evaluation of perceived risks with job analysis realizing a matrix containing 5 risk levels, which suggests the priority of preventive measures. The intermediate level (level three) represents the activation level for the medical surveillance. This experience means a proposal for a quantitative assessment of psychosocial risks at workplace.

Antibiotic therapy in pregnancy and lactation.

When considering whether to administer drugs to women during pregnancy and lactation, we have to take into account that these substances may expose the fetus or neonate to multiple effects. This occurs because there is a unique situation where the maternal compartment is connected with the fetal or neonatal compartment through, respectively, the placental barrier or breast milk. The fetus in utero and the breast-fed neonate are to be considered as organisms exposed and sensitive to the effects of drugs that cross the placenta or enter the breast milk. This review focuses on the most frequently used antibiotics during pregnancy and lactation and presents useful suggestions for daily practice. Drugs that must be avoided are clearly underlined.

Evaluating alternative service contracts for medical equipment.

Managing medical equipments is a formidable task that has to be pursued maximizing the benefits within a highly regulated and cost-constrained environment. Clinical engineers are uniquely equipped to determine which policies are the most efficacious and cost effective for a health care institution to ensure that medical devices meet appropriate standards of safety, quality and performance. Part of this support is a strategy for preventive and corrective maintenance. This paper describes an alternative scheme of OEM (Original Equipment Manufacturer) service contract for medical equipment that combines manufacturers' technical support and in-house maintenance. An efficient and efficacious organization can reduce the high cost of medical equipment maintenance while raising reliability and quality. Methodology and results are discussed.

Flotation technique with coagulant and polymer application applied to the post-treatment of effluents from anaerobic reactor treating sewage.

This paper presents the results of a study performed with a lab-scale batch DAF unit fed with previously coagulated (with FeCl3 and/or cationic polymer) effluent from a pilot-scale expanded bed anaerobic reactor treating domestic sewage. The association between ferric chloride and polymers was studied, aimed at sludge reduction. Ferric chloride dosages ranging from 15 to 65 mg.l-1, and polymer dosages from 0.25 to 7.0 mg.l-1 were investigated. Flocculation conditions were kept constant: 20 min of time (Tf) and 80 s-1 of mean velocity gradient (Gf). Air requirement was kept to 19.0 g of air.m-3 wastewater, using 20% recycle ratio and saturation pressure at 450 kPa. When the anaerobic reactor was operating at steady state conditions, it was possible to reduce the FeCl3 dosage from 65 to 30 mg.l-1 after applying 0.4 mg.l-1 of non-ionic polymer, before the DAF process. For these dosages, 79% COD removal (residual of 23 mg.l-1), 86% total phosphate removal (residual of 0.9 mg.l-1) and 98% turbidity removal (residual of 2.6 NTU) were observed. Furthermore, the use of adequate polymer together with 30 mgFeCl3.l-1 leads to the production of high rising rate flocs.

Left ventricular diastolic function in systemic sclerosis.

OBJECTIVE: To assess left ventricular diastolic function in patients with systemic sclerosis (SSc) and to verify if a "primary" diastolic dysfunction might exist. METHODS: In total 124 patients and 41 healthy subjects underwent complete echocardiographic examination. The following pulsed wave Doppler variables were evaluated: peak velocity during early filling (E), peak velocity during late atrial filling (A), E/A ratio, and early filling deceleration time. RESULTS: Seventy-seven patients (62.1%) had conditions potentially affecting left ventricular diastolic function (Group A) and 47 patients (37.9%) formed a homogeneous group without cardiac involvement or other causes of abnormal diastolic function (i.e., systemic and/or pulmonary hypertension, ventricular hypertrophy, pericardial disease, systolic dysfunction, valvular heart disease, coronary artery disease) (Group B). The entire SSc population and Group A showed significant differences in the Doppler variables of diastolic function compared to the control group. No significant differences were found between Group B and controls. CONCLUSION: In patients with SSc, left ventricular diastolic dysfunction was found only in patients with conditions potentially affecting left ventricular diastolic function. In patients without conditions potentially affecting left ventricular diastolic function no differences were seen in comparison with controls. SSc does not seem to cause "primary" diastolic abnormalities.