Screening of hypercortisolism among patients with hypertension: an Italian nationwide survey.

PURPOSE: Screening of Cushing Syndrome (CS) and Mild Autonomous Cortisol Secretion (MACS) in hypertensive patients is crucial for proper treatment. The aim of the study was to investigate screening and management of hypercortisolism among patients with hypertension in Italy. METHODS: A 10 item-questionnaire was delivered to referral centres of European and Italian Society of Hypertension (ESH and SIIA) in a nationwide survey. Data were analyzed according to type of centre (excellence vs non-excellence), geographical area, and medical specialty. RESULTS: Within 14 Italian regions, 82 centres (30% excellence, 78.790 patients during the last year, average 600 patients/year) participated to the survey. Internal medicine (44%) and cardiology (31%) were the most prevalent medical specialty. CS and MACS were diagnosed in 313 and 490 patients during the previous 5 years. The highest number of diagnoses was reported by internal medicine and excellence centres. Screening for hypercortisolism was reported by 77% in the presence of specific features of CS, 61% in resistant hypertension, and 38% in patients with adrenal mass. Among screening tests, the 24 h urinary free cortisol was the most used (66%), followed by morning cortisol and ACTH (54%), 1 mg-dexamethasone suppression test (49%), adrenal CT or MRI scans (12%), and late night salivary cortisol (11%). Awareness of referral centres with expertise in management of CS was reported by 67% of the participants, which reduced to 44% among non-excellence centres. CONCLUSIONS: Current screening of hypercortisolism among hypertensive patients is unsatisfactory. Strategies tailored to different medical specialties and type of centres should be conceived.

Computerized tomography texture analysis of pheochromocytoma: relationship with hormonal and histopathological data.

OBJECTIVES: Pheochromocytomas are rare tumors which can present with heterogeneous secretion profiles, clinical manifestations, and radiologic appearance. Under a histopathological point of view, they can be characterized as more or less aggressive with the Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score. The aim of this study is to analyze the texture analysis characteristics of pheochromocytoma and identify whether the texture analysis can yield information aiding in the diagnosis and the characterization of those tumors. METHODS: Radiological, biochemical, and histopathological data regarding 30 consecutive patients with histologically confirmed pheochromocytoma were analyzed. Images obtained in the unenhanced, late arterial, venous, and delayed phases were used for the texture analysis. RESULTS: Urinary epinephrine and metanephrine levels showed a significant correlation (R2 = 0.946; R2 = 699) in the multivariate linear model with texture features, as well as Ki-67 (R2 = 0.397), PASS score (R2 = 0.182), GAPP score (R2 = 0.705), and cellularity showed a significant correlation (R2 = 0.389). The cluster analysis based on radiomic features resulted in 2 clusters, with significative differences in terms of systolic and diastolic blood pressure values at the time of diagnosis (p = 0.025), GAPP score (4 vs 6, p = 0.05), histological pattern (1-2, p = 0.039), and comedonecrosis (0% vs 50%, p = 0.013). CONCLUSION: In conclusion, our study provides the proof of concept for the use of texture analysis on contrast-enhanced CT images as a noninvasive, quantitative tool for helping in the characterization of the clinical, biochemical, and histopathological features of pheochromocytoma.

Radiologically defined lipid-poor adrenal adenomas: histopathological characteristics.

BACKGROUND: Adrenal lipid-poor adenomas (LPA) are defined by high unenhanced density (≥ 10 HU), and absolute and relative contrast medium washout > 60% and > 40%, respectively, at computerized tomography (CT). To date, no thorough histopathological characterization has been performed in those frequent lesions (one-third of adrenal adenomas). Our aim was to analyze the histopathological characteristics of adrenal LPA. METHODS: Patients with LPA (n = 57) were selected among consecutive subjects referred for an adrenal incidentaloma or ACTH-independent Cushing syndrome. FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) was performed in 37 patients. In patients treated by adrenalectomy (n = 17), Weiss score and Lin-Weiss-Bisceglia score (in tumors composed entirely or predominantly of oncocytes) were calculated. RESULTS: Radiological parameters did not differ among patients with ACTH-independent Cushing syndrome (n = 6) and those with adrenal incidentalomas associated with primary aldosteronism (n = 2), autonomous cortisol secretion (n = 14), or non-functioning (n = 35). Patients treated by adrenalectomy had larger tumors (28.9 ± 11.2 vs 17.3 ± 8.4 mm, P < 0.001), higher CT unenhanced density (29.1 ± 11.0 vs 23.1 ± 9.0 HU, P = 0.043), and FDG-PET adrenal uptake (9.0 ± 6.4 vs 4.4 ± 2.3 SUV, P = 0.003) than non-operated ones. Oncocytic features > 75% of the tumor were detected in 12/17 cases (70.6%). Five of those showed borderline-malignant histopathological characteristics by Lin-Weiss-Bisceglia score. Among remaining non-oncocytic tumors, 1/5 had a Weiss score ≥ 3. Overall, 6/17 tumors (35.3%) had borderline-malignant potential. Radiological parameters were similar between patients with benign and borderline-malignant tumors. CONCLUSIONS: Adrenal LPA are a heterogeneous group of tumors, mostly composed of oncocytomas. Up to 1/3 of those tumors may have a borderline-malignant potential at histopathology.

Traumatic spinal cord injuries: evidence from 30 years in a single centre.

STUDY DESIGN: Retrospective data analysis. OBJECTIVES: Traumatic spinal cord injury (TSCI) is a devastating injury that causes a lifelong disability, involving mostly young men. The aim of the study was to analyse some clinical and epidemiological features of TSCI patients admitted to the Spinal Unit of Florence, Italy, during 30 years, from 1981 to 2010. SETTING: Spinal Unit, Careggi University Hospital, Florence, Italy. METHODS: The medical files from the computerised database of the patients who sustained TSCI from 1 January 1981 to 31 December 2010 and received comprehensive care in the same centre were analysed. Information was collected with regard to demographic data, causes of injury, time of injury, associated injuries, treatment of the vertebral lesion and neurological condition at discharge. RESULTS: A total of 1479 patients were included. The number of two-wheeler road traffic accidents (RTAs) has increased over the years, whereas the percentage of falls and sports accidents has been quite constant. The lesions due to 4-wheeler RTAs tend to decrease. Lesions due to falls mainly affected older persons than those due to sports accidents, with a mean age at the time of injury of 52 and 25 years, respectively. Diving was the most common cause among sports and leisure accidents. Associated injuries were present in 56% of all the cases included. CONCLUSION: The cases of spinal cord injury due to two-wheeler RTAs have increased over the years probably because of the increasing diffusion of the use of such a vehicle, and such an eventuality has to be taken into consideration in future prevention strategies.

A case of spontaneous gastric rupture in a 5 years girl.

We describe a case of spontaneous gastric rupture in a child of 5 years old. The patient reached us in a serious condition; the anamnesis was negative for traumatic events or gastrointestinal disorders. An abdominal X-ray and CT scan revealed free air and fluid in the abdominal cavity, leading to the diagnosis of gastro-intestinal perforation. Submitted to urgent surgery, a rupture of the posterior wall of the stomach was found that was treated with gastrectomy "à la demande". The surgery follow-up was regular. Morphological and immunohistochemical study showed some muscular abnormalities of the muscular gastric wall.

Macroscopic and microscopic findings of the placenta in women with polycystic ovary syndrome.

STUDY QUESTION: Do patients with polycystic ovary syndrome (PCOS) have macroscopic and/or microscopic placental alterations? SUMMARY ANSWER: The placental structure in patients with PCOS, even in those with uncomplicated pregnancy, is altered. WHAT IS KNOWN ALREADY: The spectrum of pregnancy complications seems to have a common denominator: a defective trophoblast invasion and placentation. In women with PCOS, alterations in endovascular trophoblast invasion related to insulin resistance and hyperandrogenism have been observed. STUDY DESIGN, SIZE, DURATION: For this prospective case-control study, 30 pregnant patients with PCOS (cases) and 60 healthy pregnant women without PCOS features (controls) were enrolled and studied until delivery. Clinical, biochemical, ultrasonographic and obstetric data were recorded. The baseline clinical and biochemical data for screening for PCOS and for inclusion/exclusion were obtained before the seventh week of gestation. At delivery, placentas were collected and detailed macroscopic and microscopic analyses were performed. PARTICIPANTS, SETTING, METHODS: Cases and controls were matched for age and BMI (all <30 kg/m(2)). The matching procedure was one-to-two. Only subjects with spontaneous conception and uncomplicated pregnancies were included in the final analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Placental weight (P = 0.04), thickness (P = 0.02), density (P = 0.02) and volume (P = 0.01) were significantly inferior in women with, compared with those without PCOS. The placentas from patients with PCOS more frequently had an irregular shape (P = 0.03) and a higher cord coiling index (P = 0.02). Differences between cases and controls also concerned the extent of villous (P = 0.04) and intervillous (P = 0.01) spaces, the extent of fibrosis (P = 0.03), endovascular trophoblast (depth, extension and morphometry) (P < 0.05) and mitotic activity (P = 0.01). The percentage of patients with lesions [22/30 (73.3%) versus 25/60 (41.7%), respectively; P = 0.01] and the mean number of placental lesions (3.5 ± 2.1 versus 1.4 ± 1.1, respectively; P = 0.02) were higher in the PCOS than the control group. The odds ratio for placental alterations, adjusted for weight gain, was 2.8 (95% confidence interval 1.3-9.9). LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study was the selection of a specific PCOS sample, which is probably not representative of the PCOS phenotype as a whole. In fact, we excluded patients with PCOS who were obese and who achieved a pregnancy following the use of ovulation inductors or assisted reproduction techniques. WIDER IMPLICATIONS OF THE FINDINGS: The present study is the first to demonstrate that the morphology and microscopic structure of placenta in patients with PCOS with an uncomplicated pregnancy are altered. Further studies are needed to assess a correlation of these changes with the increased risk of obstetric complications observed in some pregnancies of women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no conflict of interest and no financial support for the research. TRIAL REGISTRATION NUMBER: N/A.

25 years or more after spinal cord injury: clinical conditions of individuals in the Florence and Stockholm areas.

SETTING: Retrospective analysis and retrospective follow-up. INTRODUCTION: Spinal cord injury (SCI) patients have today a nearly normal lifespan. Avoidance of medical complications is key to this end. The aim of the study was to analyse health in individuals surviving 25 years or more after traumatic SCI in Stockholm and Florence, and compare medical complications. METHODS: Data from the databases of the Spinal Unit of Florence and from the Spinalis, Stockholm were analysed. Patients included were C2-L 2, American Spinal Cord Association (ASIA) Impairment Scale (AIS) A-C, and ≥25 years post traumatic SCI. Patients underwent a thorough neurological and general examination, and were interviewed about medical events during those years. Analysed data include: gender, age at injury, current age, neurological level, AIS, cause of injury, presence of neuropathic pain (NP), and spasticity and medical complications. RESULTS: A total of 66 Italian patients and 74 Swedish patients were included. The only statistical difference between the groups was cause of injury due to falls was higher in the Florence group (P<0.01). Male/female ratio was 4:1. Traffic accidents were the most common cause of injury. In all, 60% were paraplegics. Pressure ulcers (PU) occurred in nearly 60% and 32% experienced NP. Respiratory complications (RC) occurred in 25% among tetraplegics. Neurological deterioration occurred in 14%. CONCLUSION: PU, bony fractures, spasticity and NP are important problems after SCI. RC are of clinical importance in the tetraplegics. Complications occur during all periods after injury. Many patients are otherwise healthy 25 years or more after SCI.

Multiple oral and cerebral relapses of a Granular cell tumor (Abrikossoff Tumor) in a young girl affected by congenital dyserythropoietic anemia type II.

CASE REPORT: A 14-year-old girl presented with 1 cm large whitened lesion on the ventral surface of the tongue, appeared from 1 month. Past history showed congenital dyserythropoietic anemia type II. The lesion was excised and microscopic and immunohistochemical analyses were compatible with benign Abrikossoff tumor. Total body MRI was negative. After six months the patient presented a second tongue lesion and four months later another large painful lesion in the soft palate, with the same istological diagnosis. In addition, she had other multiple lesions: two apperead at pharyngeal level (not biopsied) that remain stable over time, and one at the pituitary gland. CONCLUSION: Granular cell tumors, with or without multiple lesions, are rare in children. About 50% of cases involve the head and neck region, with the tongue being the most affected site. Therapy is based on the surgical excision of the lesions; however some tumor forms, although their histological aspect of benignity, often have an important infiltrative power, making the therapeutic approach difficult, as in our case.

Atrial fibrillation ablation induces reverse remodelling and impacts cardiac function.

AIM: Atrio-ventricular anatomo-functional response to successful surgical atrial fibrillation (AF) ablation has been poorly investigated. Determinants of AF recurrence following surgical ablation are still debated. METHODS: Sixty-nine patients underwent AF ablation during major cardiac surgery. Main outcomes were clinical and echocardiographic results after monopolar and/or bipolar ablation were recorded. Secondary outcomes were freedom from AF, rehospitalization and congestive heart failure (CHF) at follow-up. Predictors of AF-recurrence were evaluated. RESULTS: Fifty-three patients (76.8%) were in sinus rhythm (SR) at 31.4±10.6 months of mean follow-up. Overall freedom from AF-recurrence was 61.4±6.6%, from hospital readmission 89.9±3.6%, from CHF 91.9±5.05%. Compared to AF-patients, SR-patients demonstrated better freedom from re-hospitalization (98.1±1.9% vs. 62.5±12.1%; P=0.0001) and CHF (94.7±5.1% vs. 77.8±13.9%; P=0.006). At follow-up SR-patients demonstrated atrial (preoperative 5.9±1.2 cm vs. follow-up 5.2±1.0; P=0.01) and ventricular reverse remodelling (preoperative LVDd 5.8±1.6cm vs. follow-up 5.0±1.3 cm; P=0.002 - preoperative LVDs 4.2±1.8 cm vs. follow-up 3.8±1.2 cm; P=0.045). E/A ratio was normal in 90.6% of SR-patients (69.6% of the total population of the study). TDI at the level of the left lateral annulus showed an improved left ventricular systole (Sm), and diastole (Em, E/Em) for SR-patients compared to AF-patients (Sm 9.30±1.66 vs. 7.81±1.41, P=0.001; Em: 10.55±1.87 vs. 7.44±0.40, P=0.001; E/Em: 0.06±0.02 vs. 0.11±0.05, P=0.0001). Preoperative atrial diameter (OR=23.9; P=0.002) and tricuspid insufficiency at follow-up (OR=3.5; P=0.008) were independent predictors of AF-recurrence. Neither etiology, nor duration of AF, nor even ablation technique influenced SR recovery (P=NS for all measurement). CONCLUSION: Radiofrequency AF ablation achieves 76.8% of SR recovery at follow-up. Maintenance of SR improves clinical, haemodynamic and echocardiographic results.

[Algorithm for assessment of exposure to asbestos]. / Proposta di algoritmo per la valutazione stimata dell'esposizione lavorativa ad amianto.

There is no universally approved method in the scientific literature to identify subjects exposed to asbestos and divide them in classes according to intensity of exposure. The aim of our work is to study and develope an algorithm based on the findings of occupational anamnestical information provided by a large group of workers. The algorithm allows to discriminate, in a probabilistic way, the risk of exposure by the attribution of a code for each worker (ELSA Code--work estimated exposure to asbestos). The ELSA code has been obtained through a synthesis of information that the international scientific literature identifies as the most predictive for the onset of asbestos-related abnormalities. Four dimensions are analyzed and described: 1) present and/or past occupation; 2) type of materials and equipment used in performing working activity; 3) environment where these activities are carried out; 4) period of time when activities are performed. Although it is possible to have informations in a subjective manner, the decisional procedure is objective and is based on the systematic evaluation of asbestos exposure. From the combination of the four identified dimensions it is possible to have 108 ELSA codes divided in three typological profiles of estimated risk of exposure. The application of the algorithm offers some advantages compared to other methods used for identifying individuals exposed to asbestos: 1) it can be computed both in case of present and past exposure to asbestos; 2) the classification of workers exposed to asbestos using ELSA code is more detailed than the one we have obtained with Job Exposure Matrix (JEM) because the ELSA Code takes in account other indicators of risk besides those considered in the JEM. This algorithm was developed for a project sponsored by the Italian Armed Forces and is also adaptable to other work conditions for in which it could be necessary to assess risk for asbestos exposure.

Analysis of UbcH10 expression represents a useful tool for the diagnosis and therapy of astrocytic tumors.

Previous studies suggest the expression of UbcH10 gene, that codes for a protein belonging to the ubiquitin-conjugating enzyme family, as a valid indicator of the proliferative and aggressive status of tumors of different origin. Therefore, to look for possible tools to be used as diagnostic markers in astrocytic neoplasias, we investigated UbcH10 expression in normal brain, gliosis and low-grade and high-grade astrocytic tumors by immunohistochemistry. UbcH10 expression was observed in low-grade astrocytoma and in glioblastoma. Our data indicate a clear correlation between UbcH10 expression and the histological grade of the astrocytic tumors. Moreover, the analysis of UbcH10 expression allows the differentiation between gliotic and malignant tissues. Finally, since proteasome inhibitors have recently been considered as possible drugs in the chemotherapy of various tumors, our results would suggest new perspectives for the treatment of brain malignancies based on the suppression of the UbcH10 function.

Granulocytic sarcoma (chloroma) in HIV patient: a report.

Isolated chloromas (granulocytic sarcomas) are rare tumours. Chloromas are masses composed of immature granulocytic cells. Granulocytic sarcoma occurs primarily in patients with acute myelogenous leukaemia, but can also arise in patients with other myeloproliferative disorders. We present an adult case of chloroma in HIV patient, which occurred as sudden death. Skin examination of right thigh showed dyschromia. Longitudinal incision of muscle revealed a "dark green" infiltration. Pathology showed in muscle fragments a infiltrate of granulocytes. The histologic sections of the excised tumour confirmed the cytologic diagnosis of chloroma.

Combined use of interferon alpha-2, chlorambucil and prednisone in previously treated patients with low-grade non-Hodgkin's lymphomas. Results of a phase II study.

AIMS AND BACKGROUND: To investigate therapeutic activity and safety of alpha-interferon (alpha-IFN) in combination with chlorambucil (CLB) and prednisone (PDN), we treated 9 low-grade non-Hodgkin lymphoma patients with clinical evidence of relapsed (5 cases) or resistant (4 cases) disease with such an association. METHODS: In all instances, treatment consisted of alpha-2a IFN administered by subcutaneous route thrice weekly for 3 weeks, CLB, 5 mg/day for 21 days, and PDN, 30 mg three times a week for 3 weeks. Cycles were repeated every 28 days. RESULTS: A well-documented clinical response was observed in 6 (4 CRs+2 PRs) of 9 patients. Interestingly, 3 of 4 CRs were achieved in patients with histologically proven bone marrow involvement. Median duration of response was 18.5 months (range, 4-29 months). Myelosuppression was a common side effect. Two patients experienced grade 3 hematologic toxicity which did not preclude continuation of therapy. CONCLUSIONS: As new purine analogues are not currently available, the combination of alpha-IFN, CLB, and PDN may represent, in our opinion, a valid therapy for patients not eligible for aggressive therapy such as autologous bone marrow transplantation.

Ovarian masses in the pediatric patient.

Ovarian masses in the pediatric patient are uncommon. Children with ovarian tumors, however, pose diagnostic and therapeutic challenges because their presentation can mimic other more common intraabdominal disorders and their tumor histology varies widely. The refinement of surgical techniques and the advent of more effective chemotherapy in the past 25 years has increased overall survival rates from approximately 20% to 70%, thus improving the outcome for girls with malignant tumors. This article summarizes the current evaluation and management of ovarian masses in childhood and reviews pertinent pathology.

[Cytopathology in the diagnosis of benign breast lesions]. / La citopatologia nella diagnostica delle lesioni mammarie benigne.

In this review dealing with cytologic features of non-malignant diseases of the breast, authors try to correlate cytopathologic findings with clinical condition. Five different clinical presentations are recognized: cystic nodule, solid nodule, not palpable lesions, spontaneous secretion, mastitis. An overview of literature data is provided by authors who emphasize either reliability or specificity of cytopathological methodologies. Furthermore, they conclude that along with clinico-radiologic diagnostic procedures, cytology represents a mainstay for prognostic assessment and presurgical evaluation of breast lesions.

Effects of simvastatin and rosuvastatin on RAS protein, matrix metalloproteinases and NF-κB in lung cancer and in normal pulmonary tissues.

OBJECTIVES: In this study, we have evaluated effects of 24-hour treatments with simvastatin or rosuvastatin on RAS protein, NF-κB and MMP expression in LC tissues obtained from 12 patients undergoing thoracic surgery. MATERIALS AND METHODS: Normal and lung tumour tissues obtained from each sample were exposed to simvastatin (2.5-30 µm) or rosuvastatin (1.25-30 µm) and western blot analysis was then performed. RESULTS: We documented increased expression of proteins, MMP-2, MMP-9 and NF-κB-p65 in LC tissues, with respect to normal tissues (P < 0.01). In the malignant tissues, simvastatin and rosuvastatin significantly (P < 0.01) and dose-dependently reduced RAS protein, MMP-2/9 and NF-κB-p65 expression. CONCLUSIONS: In conclusion, our results suggest that simvastatin and rosuvastatin could play a role in LC treatment by modulation of RAS protein, MMP-2/9 and NF-κB-p65.

Clinical and prognostic evaluation of bone marrow infiltration (biopsy versus aspirate) in early chronic lymphocytic leukemia. A single center study.

BACKGROUND AND OBJECTIVE: Recently published studies dealing with chronic lymphocytic leukemia (CLL) patients in early clinical stage reported that bone marrow (BM) biopsies and aspirates can be considered complementary methods of evaluating the extent of BM involvement. Consequently, we designed the present study to investigate the clinical and prognostic implications of BM biopsies and aspirates in a series of stage A CLL patients followed-up in a single center. PATIENTS AND METHODS: BM biopsy sections and aspirate smears obtained at the time of diagnosis from 102 CLL stage A patients were retrospectively evaluated. Results were correlated with clinical and hematological features as well as with survival and disease-progression risk. RESULTS: Diffuse (D) BM histology was detected in 10 patients (9.8%) while 21 (20.5%) displayed lymphocyte infiltration (LI) > 80%. Twenty-six patients (25.4%) died with a 5- and 10-year survival probability of 85% and 50%, respectively. The survival of patients with D-BM histology was significantly shorter than that of patients with non-diffuse (non-D) histology (p < 0.05). Interestingly, when considering only CLL-related deaths (i.e. leukemia progression, infections) were considered, there was an increase in the statistical significance of BM histology (p = 0.01). There was no difference in life expectancy in cases with LI either using different cut-off levels (i.e. 70% and 80%) or excluding non-CLL related deaths. According to our experience, disease progression could only be predicted by BM histology (p = 0.008), while LI was not useful for forecasting progression to more advanced stages (p = NS). INTERPRETATION AND CONCLUSIONS: In patients with early CLL, BM histology provides more reliable information regarding the clinical outcome of the disease than LI.