Head and Neck squamocellular carcinomas: E-cadherin and Keratin 5 as biomolecular markers

E- Cadherin is a transmembranar protein that plays an important role in the cellular adhesion and insure the connection of the tissue cells; it is present in the epithelial cells and its aberrant expression is correlated with different kinds of head and neck squamocellular carcinoma. Keratin 5 (K5) is present in the basal layer of a stratified squamous keratinized and non keratinized epithe-lium. The purpose of the present study was to identify the expression particularities of E-cadherin and Keratin 5 in rapport with the localization and the differentiation of various head and neck squamocellular carcinomas (larynx, pharynx, hard palate, tongue, submandibular, lip, gingival sulcus, nasal pyramid, maxillary, zygomatic). Immunoreactions for E-cadherin in the tumoral cells were examined according to the this score: 0 (0% positive cells), 1 (30%). The presence of maximum score (value 3) of E-cadherin was found in well-differentiated squamocellular carcinomas of laryngeal, tongue, lip, nasal pyramid, zygomatic area origin. A lower value of the score was present in the less differentiated histopathological type. The role of E-cadherin in the squamocellular carcinomas is far from being clarified. It seems that the trials to estimate a prognosis in this clinical entity should include a combination between the molecular markers, the histopathological data and clinical parameters. K5 expression was observed in all squamocellular carcinomas included in the present study with scores between 1 and 3. For well and moderately differentiated histopathological types, a maximum score of 3 was recorded for all of the cases, not including the laryngeal area, which presented a score of 2. The following scores were identified in the regions of the poorly differentiated carcinomas: Jaw, 3; gingival sulcus, 2; and tongue and submandibular area, 1. The present study confirms the role of K5 in the definition of the differentiation of squamocellular carcinoma of head and neck revealing a differential expression depending on the anatomic site of the primary tumor. These observations may aid with an improved stratification of head and neck squamocellular carcinoma, thus improving the diagnosis and treatment strategies for this type of cancer

Heart failure with preserved systolic function: prevalence and clinical features in a cohort of patients admitted to internal medicine units. The study PRESYF-HF Tuscany.

Background. There is uncertainty about the prevalence and clinical characteristics of heart failure (HF) patients with preserved systolic function (PRESYF). Aim. To analyze the prevalence and clinical characteristics of patients with PRESYF in an unselected cohort of subjects consecutively hospitalized for HF. Methods. The study cohort included 338 patients consecutively admitted for HF at 24 Internal Medicine units homogeneously settled in Tuscany area (Italy). We did not have any criteria for exclusion. All patients had an echocardiographic measure of left ventricular ejection fraction (LVEF) within 72 hours from hospital admission. Patients with LVEF > 50% were considered to have PRESYF. Results. The patients with PRESYF were 112 (33,1%), those with depressed systolic function (DESYF) 226 (66,9%). In the group PRESYF were prevalent female sex, hypertensive etiology, and elevated BMI. The distribution for classes of age shows a great frequency of PRESYF in the elderly. Conclusion. About one third of patients admitted for HF have a PRESYF. They are different compared to those with DESYF. A correct identification of this form of HF may be important in clinical practice for more targeted therapeutic options and for prognostic implications

Aggressiveness pattern and second primary tumor risk associated with basaloid squamous cell carcinoma of the larynx

Basaloid squamous cell carcinoma (BSCC) is a rare, aggressive and distinct variant of squamous cell carcinoma (SCC) of the upper respiratory and digestive tract. We have evaluated disease specific survival (DSS) and overall survival (OS) through Kaplan-Meier method and mortality risk through univariate statistical analysis of Cox in 42 cases of BSCC and other 42 of laryngeal SCC (LSCC) matched for both age and sex. We demonstrated that laryngeal BSCC is a more aggressive tumor than LSCC as is associated to higher nodal recurrence of pathology (5 vs 2 patients, median survival, OR 2.7), a reduced survival (median survival 34 vs 40 months, OR 3.2 for mortality); in addition, basaloid patients have a higher risk to be affected by second primary tumors (13 vs 3 patients, OR 5.8) and a higher probability to die for this second tumor (Hazard Risk, HR 4.4). The analysis of survival shows an increased mortality risk concurrent with the parameters assessed by univariate analyses that assume a predictive and statistical significance in second tumor and grading in basaloid LSSC.Basaloid squamous cell carcinoma (BSCC) is a rare, aggressive and distinct variant of squamous cell carcinoma (SCC) of the upper respiratory and digestive tract. We have evaluated disease specific survival (DSS) and overall survival (OS) through Kaplan-Meier method and mortality risk through univariate statistical analysis of Cox in 42 cases of BSCC and other 42 of laryngeal SCC (LSCC) matched for both age and sex. We demonstrated that laryngeal BSCC is a more aggressive tumor than LSCC as is associated to higher nodal recurrence of pathology (5 vs 2 patients, median survival, OR 2.7), a reduced survival (median survival 34 vs 40 months, OR 3.2 for mortality); in addition, basaloid patients have a higher risk to be affected by second primary tumors (13 vs 3 patients, OR 5.8) and a higher probability to die for this second tumor (Hazard Risk, HR 4.4). The analysis of survival shows an increased mortality risk concurrent with the parameters assessed by univariate analyses that assume a predictive and statistical significance in second tumor and grading in basaloid LSSC

Denosumab in patients with aneurysmal bone systs: A case series with preliminary results

Abstract PURPOSE:: Aneurysmal bone cyst (ABC) is a rare skeletal tumor usually treated with surgery/embolization. We hypothesized that owing to similarities with giant cell tumor of bone (GCTB), denosumab was active also in ABC. METHODS:: In this observational study, a retrospective analysis of ABC patients treated with denosumab was performed. Patients underwent radiologic disease assessment every 3 months. Symptoms and adverse events were noted. RESULTS:: Nine patients were identified (6 male, 3 female), with a median age of 17 years (range 14-42 years). Primary sites were 6 spine-pelvis, 1 ulna, 1 tibia, and 1 humerus. Patients were followed for a median time of 23 months (range 3-55 months). Patients received a median of 8 denosumab administrations (range 3-61). All symptomatic patients had pain relief and 1 had paresthesia improvement. Signs of denosumab activity were observed after 3 to 6 months of administration: bone formation by computed tomography scan was demonstrated in all patients and magnetic resonance imaging gadolinium contrast media decrease was observed in 7/9 patients. Adverse events were negligible. At last follow-up, all patients were progression-free: 5 still on denosumab treatment, 2 off denosumab were disease-free 11 and 17 months after surgery, and the last 2 patients reported no progression 12 and 24 months after denosumab interruption and no surgery. CONCLUSIONS:: Denosumab has substantial activity in ABCs, with favorable toxicity profile. We strongly support the use of surgery and/or embolization for the treatment of ABC, but denosumab could have a role as a therapeutic option in patients with uncontrollable, locally destructive, or recurrent disease

IsoBED: a tool for automatic calculation of biologically equivalent fractionation schedules in radiotherapy using IMRT with a simultaneous integrated boost (SIB) technique

<p>Abstract</p> <p>Background</p> <p>An advantage of the Intensity Modulated Radiotherapy (IMRT) technique is the feasibility to deliver different therapeutic dose levels to PTVs in a single treatment session using the Simultaneous Integrated Boost (SIB) technique. The paper aims to describe an automated tool to calculate the dose to be delivered with the SIB-IMRT technique in different anatomical regions that have the same Biological Equivalent Dose (BED), i.e. IsoBED, compared to the standard fractionation.</p> <p>Methods</p> <p>Based on the Linear Quadratic Model (LQM), we developed software that allows treatment schedules, biologically equivalent to standard fractionations, to be calculated. The main radiobiological parameters from literature are included in a database inside the software, which can be updated according to the clinical experience of each Institute. In particular, the BED to each target volume will be computed based on the alpha/beta ratio, total dose and the dose per fraction (generally 2 Gy for a standard fractionation). Then, after selecting the reference target, i.e. the PTV that controls the fractionation, a new total dose and dose per fraction providing the same isoBED will be calculated for each target volume.</p> <p>Results</p> <p>The IsoBED Software developed allows: 1) the calculation of new IsoBED treatment schedules derived from standard prescriptions and based on LQM, 2) the conversion of the dose-volume histograms (DVHs) for each Target and OAR to a nominal standard dose at 2Gy per fraction in order to be shown together with the DV-constraints from literature, based on the LQM and radiobiological parameters, and 3) the calculation of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) curve versus the prescribed dose to the reference target.</p

Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study

SIMPLE SUMMARY: The lung is the most frequent site of metastasis in Ewing sarcoma, the second most common bone cancer affecting children, adolescents and young adults. The five-year overall survival of patients with isolated lung metastasis is approximately 50% after multimodal treatments including chemotherapy, surgery and radiotherapy. This retrospective study aimed to investigate the feasibility and the predictors of survival in 68 Ewing sarcoma patients with lung metastases who received high-dose chemotherapy with busulfan and melphalan, followed by reduced dose whole-lung irradiation, as part of two prospective and consecutive treatment protocols. This combined treatment strategy is feasible and might contribute to the disease control in lung metastatic Ewing sarcoma with responsive disease. Furthermore, the results of this study provide support to explore the treatment stratification for lung metastatic Ewing sarcoma based on the histological response of the primary tumor. ABSTRACT: Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor