Giovanni Guerra

Clinical outcome of central conventional chondrosarcoma

Aim of this study was to analyze (1) survival, local recurrence (LR), and metastasis rates between the three histological tumor grades; (2) whether type of treatment and tumor site influenced prognosis for each histologic grade.

Specific antibodies reacting with simian virus 40 capsid protein mimotopes in serum samples from healthy blood donors

Simian virus 40 (SV40), a small DNA tumor virus, was inadvertently administered to human populations with the use of contaminated vaccines. SV40 sequences have mainly been detected in healthy individuals and cancer patients using polymerase chain reaction techniques. However, some studies have failed to reveal the presence of SV40 in human specimens. These conflicting results indicate the need for new research to verify whether SV40 is circulating in humans. Mimotopes from SV40 structural peptides were tested to investigate for specific reactions to human sera antibodies. An indirect enzyme-linked immunosorbent assay with synthetic peptides from SV40 viral capsid proteins 1-2-3 (VPs 1-2-3) was set up and employed to test 855 serum samples from healthy blood donors. Data from immunologic assays indicate that serum antibodies against SV40 VP mimotopes are detectable, although with a low titer, in blood donors 18 to 65 years old. The overall prevalence of serum samples that reacted with the 2 SV40 VP peptides was 18%. The strong points for this novel method include the simplicity of its approach and the potential to discriminate between SV40-specific antibody responses and to draw correlations between responses to the 2 independent SV40 peptides. These data suggest that SV40, or a yet undetected closely related polyomavirus, is circulating in human populations, but with lower prevalence than that of the ubiquitous BK and JC human polyomaviruses.

Serological Evidence of an Early Seroconversion to Simian Virus 40 in Healthy Children and Adolescents

At present Simian virus 40 (SV40) infection in humans appears to be transmitted independently from early contaminated vaccines. In order to test the spread of SV40 infection in children, an immunologic assay employing specific SV40 synthetic peptides corresponding to its viral protein (VP) antigens was employed to estimate the seroprevalence of this polyomavirus in Italian infants and adolescents. Serum samples from 328 children and adolescents, up to 17 years, were investigated. Serum antibodies against SV40 VPs were detected by indirect enzyme-linked immunosorbent assays. The seroprevalence of this polyomavirus was calculated after stratifying the subjects by age. Anti-viral capsid protein 1-2-3 SV40 IgG antibodies were detected in 16% of the study participants. The prevalence of antibodies against SV40 VPs tended to increase with age in children, up to 10 year old (21%). Then, in the cohort of individuals aged 11–17 years, the prevalence decreased (16%). A higher prevalence rate (23%) of SV40 VP antibodies was detected in the cohorts of 1–3 year and 7–10 year old children, than in children and adolescents of the other age groups. This age corresponds to children starting nursery and primary school, respectively, in Italy. IgM antibodies against SV40 VP mimotopes were detected in 6–8 month old children suggesting that SV40 seroconversion can occur early in life. SV40 VP antibodies are present at low prevalence in Italian children (16%), suggesting that SV40 infection, although acquired early in life, probably through different routes, is not widespread. The low SV40 seroprevalence suggests that SV40 is less transmissible than other common polyomaviruses, such as BKV and JCV. Alternatively, our immunologic data could be due to another, as yet undiscovered, human polyomavirus closely related to SV40.

Post-Radiation Sarcomas. Clinical Outcome of 52 Patients

Previous studies reported on post‐radiation sarcomas. However, the incidence, latency from radiation therapy, treatment, and survival has been difficult to evaluate. We performed a retrospective, single‐institutional study to determine these factors for post‐radiation sarcomas.

Seroprevalence of Human Malawi Polyomavirus

ABSTRACT The seroprevalence of the recently discovered human Malawi polyomavirus (MWPyV) was determined by virus-like particle-based enzyme-linked immunosorbent assay (ELISA) in age-stratified Italian subjects. The findings indicated that MWPyV infection occurs early in life, and seroprevalence was shown to reach 42% in adulthood.

Fractures and fracture-dislocations of the proximal humerus: A retrospective analysis of 82 cases treated with the Philos(®) locking plate.

OBJECTIVE To present the experience in a single institution of the management of 82 consecutive fractures and fracture-dislocations of the proximal humerus treated with the Proximal Humeral Internal Locking System (Philos(®)) plate. MATERIALS AND METHODS A total of 81 patients with 82 proximal humerus fractures (one patient had bilateral fracture) were treated at our institution with open reduction and internal fixation with Philos(®) plate from January 2008 to December 2012 and the clinico-radiological outcome was analysed. Twelve of these patients also had a dislocation of the proximal humerus. According to the Neer classification, there were seven two-part fractures, 40 three-part fractures and 35 four-part fractures. All patients received a similar physical therapy programme following internal fixation. Mean final follow-up was 32 months. Functional outcome was evaluated for each patient using the Constant-Murley score; radiographic evaluation was also conducted and complications were recorded. RESULTS At the end of the follow-up period, the mean Constant-Murley score for the injured side was 75 points (range 42-92); results were graded as excellent for eight patients, good for 52, moderate for 17 and poor for five. Twenty-three patients (28%) had complications during the follow-up period. Reoperation was required in 12 patients. Complications included avascular necrosis of the humeral head in 10 patients (12%), varus positioning of the head in four patients (4.8%), impingement syndrome in three patients (3.6%), secondary screw perforation in three patients (3.6%), non-union of the fracture in two patients (2.4%) and infection in one patient (1.2%). CONCLUSIONS Open reduction and internal fixation of proximal humeral fractures with the Philos(®) plate was associated with good clinical outcomes provided the correct surgical technique was used. To better evaluate the real incidence of complications, it is important to follow patients for more than one year after surgery as some complications may arise after this time.

Tumours of the atlas and axis: a 37-year experience with diagnosis and management

PurposeThis paper presents a single institution’s longterm experience regarding the incidence and management of tumours of the atlas and axis and discusses clinical and imaging findings and treatment options.Materials and methodsWe searched the registry of the Istituto Ortopedico Rizzoli for patients admitted and treated for tumours of the upper cervical spine. We identified 62 patients over 37 years, from July 1973 to October 2010. There were 39 male and 23 female patients, with a mean age of 39.5 (range 5–77) years. For each patient, we collected data on clinical presentation, imaging and treatment. Mean follow-up was 10 years.ResultsBenign bone tumours were diagnosed in 24 (39%) and malignant tumours in 38 (61%) patients. The most common tumours were bone metastases, followed by osteoid osteomas and chordomas. The atlas was involved in six and the axis in 52 patients; in four patients, both the atlas and axis were involved. The most common clinical presentation was pain, torticollis, dysphagia and neurological deficits. Surgical treatment was performed in 35 patients and conservative treatment, including intralesional methylprednisolone injections and halo-vest immobilisation with or without radiation therapy, chemotherapy or embolisation, in the remaining patients. One patient with osteoblastoma of the atlas had local recurrence. All patients with metastatic bone disease had local recurrence; four of the eight patients with plasmacytoma progressed to multiple myeloma within 1–4 years. All patients with chordomas had two to four local recurrences. Patients with osteosarcomas and chondrosarcoma died owing to local and distant disease progression.ConclusionsBone tumours of the cervical spine are rare. However, they should be kept in mind when examining patients with neck pain or neurological symptoms at the extremities. In most cases, only intralesional surgery can be administered. Combined radiation therapy and chemotherapy is indicated for certain tumour histologies.RiassuntoObiettivoVogliamo riportare l’esperienza raccolta presso un unico istituto in un lungo arco di tempo sull’incidenza e la gestione delle neoplasie dell’atlante e dell’epistrofeo, analizzandone riscontri clinici e radiologici, e le opzioni terapeutiche.Materiali e metodiRicercando nell’archivio dell’Istituto Ortopedico Rizzoli tutta la documentazione relativa ai pazienti trattati per neoplasie del rachide cervicale superiore, sono stati individuati 62 pazienti in un arco di tempo di 37 anni (da luglio 1973 ad ottobre 2010), 39 uomini e 23 donne, con età media di 39,5 anni (5–77 anni). Di ogni paziente sono stati raccolti i dati circa le manifestazioni cliniche al momento del ricovero, la documentazione radiologica ed il trattamento eseguito. Il tempo di controllo medio è stato di 10 anni.RisultatiIn 24 casi (39%) è stata diagnosticata una neoplasia benigna, in 38 (61%) una neoplasia maligna. Metastasi ossee, osteomi osteoidi e cordomi sono stati rispettivamente gli istotipi più frequenti. In 6 pazienti la neoplasia interessava l’atlante e in 52 l’epistrofeo; in 4 pazienti la neoplasia interessava sia l’atlante che l’epistrofeo. Le manifestazioni cliniche più frequenti comprendevano dolore, torcicollo, disfagia e deficit neurologici. Il trattamento chirurgico è stato eseguito in 35 casi, mentre nei rimanenti casi è stato eseguito trattamento conservativo mediante infiltrazioni intralesionali di metilprednisolone ed immobilizzazione con halo vest, associato o meno a chemioterapia, radioterapia o embolizzazione. Un paziente con osteoblastoma dell’atlante ha avuto recidiva locale; tutti i pazienti con metastasi hanno sviluppato recidive locali. Degli 8 pazienti con diagnosi di plasmocitoma solitario, per 4 c’è stata la progressione a mieloma multiplo in un tempo compreso tra 1 e 4 anni. I pazienti con diagnosi di cordoma hanno sviluppato dalle 2 alle 4 recidive locali. I pazienti con diagnosi di osteosarcoma e condrosarcoma sono deceduti per la progressione locale e a distanza della malattia.ConclusioniI tumori ossei del rachide cervicale sono rari. Non possono tuttavia essere esclusi nei casi di cervicalgia e sintomatologia neurologica periferica. In molti casi il trattamento chirurgico può essere soltanto a margini intralesionali. Per determinati istotipi è indicata l’associazione con chemio e radioterapia.

Universal neonatal screening for sickle cell disease and other haemoglobinopathies in Ferrara, Italy

BACKGROUND Sickle cell disease is the commonest haemoglobinopathy in Africa, the Middle East and India. In recent years, its incidence has increased dramatically also in Europe and North America because of the high rate of migration of people from endemic areas. From January 2009 to January 2010 the number of foreign residents in the province of Ferrara (Italy) increased by 12.2%: most of the immigrants were from countries at high risk of sickle cell disease. Since neonatal screening and prophylactic penicillin in early childhood could reduce mortality by 10 years of age to less than 2%, the aim of this study was to establish a neonatal screening programme for haemoglobinopathies in Ferrara. MATERIALS AND METHODS First we assessed how many pregnant women underwent haemoglobin analysis by high performance liquid chromatography before or during pregnancy and how many of them were carriers of haemoglobinopathies. Subsequently, we verified the feasibility of neonatal screening for sickle cell disease and other haemoglobinopathies, analysing cord blood by high performance liquid chromatography. Neonates found to be positive were managed by a multidisciplinary team to implement all the appropriate prophylactic and therapeutic measures. RESULTS We found that 59% of women who delivered at the University Hospital of Ferrara, from 2007 to 2009, had undergone high performance liquid chromatography. Of the 41% who were not tested, many were from areas in which sickle cell disease is common. Between September 26th 2010 and January 31st 2012, 1992 neonatal tests were performed and 24 carriers of haemoglobinopathies were identified (16 with HbS, 4 with HbC, 2 with HbE, 1 with HbD Punjab and 1 with HbD-Ouled Rabah); 42.6% of the mothers of these 1,992 neonates had not undergone high performance liquid chromatography during pregnancy. DISCUSSION Currently prevention of haemoglobinopathies in Italy is provided during the pre-conception period but only to patients with abnormal blood counts. Neonatal screening is useful and cost-effective to ensure early diagnosis and appropriate treatment for infants with sickle cell disease or other haemoglobinopathies.

Tumors of the coracoid process: clinical evaluation of twenty-one patients

OBJECTIVE We present the incidence and management of bone tumors of the coracoid process and discuss the related clinical and imaging findings and treatment. MATERIALS AND METHODS We present 21 patients (7 males and 14 females; mean age, 39 years) treated for bone tumors of the coracoid process from 1900 to 2010. Mean follow-up was 44 months (range, 12-132 months). Clinical presentation, imaging, surgical treatment, complications, range of shoulder motion, and Musculoskeletal Tumor Society (MSTS) function were evaluated. RESULTS Bone tumors were benign in 7 (33%) and malignant in 14 (67%). The most common were chondrosarcomas, osteoblastomas, and chondroblastomas. The most common presentation was pain and palpable mass for a mean duration of 11 months. Limb salvage, with or without megaprosthetic reconstruction, was achieved in 20 patients. One patient required forequarter amputation. One patient with chondroblastoma and 2 with chondrosarcoma had local recurrence. The range of shoulder motion varied according to the type of resection: patients with curettage and limited resections without involvement of the abductor mechanism had better shoulder motion, and patients with scapulectomy and proximal humeral resections had significant limitations of motion. The mean MSTS score was 80% (range, 50%-100%). CONCLUSIONS Chondrosarcomas, osteoblastomas, and chondroblastomas are the most common bone tumors of the coracoid process. Limited resections are associated with nearly normal range of motion and excellent function; however, limited resections are acceptable in only in a small number of patients. In patients with malignant and recurrent lesions, wide resection is required, which is associated with significant limitations of shoulder function.

Simian virus 40 (SV40) antibodies in elderly subjects.

We read with interest the article of Wong et al. They described the prevalence and distribution among ethnic groups of polyomavirus SV40 antibodies in women in Houston, Texas. Their data were obtained using a plaquereduction neutralization assay, which is a high specific method to detect SV40 antibodies in human serum samples. However, this approach has significant disadvantages, such as: (i) time consuming, (ii) intensive labor, (iii) data are obtained in weeks, (iv) high cost. SV40-neutralization assay, because of these limitations, cannot be employed for large sample size. SV40 was recognized in the 1960 as contaminant of both inactivated (Salk) and live (Sabin) anti-poliomyelitis vaccines. After its isolation, SV40 was experimentally characterized as a transforming and oncogenic virus. Detection of SV40 antibodies has been attempted using different serologic methods, but the high protein homology among the three main polyomaviruses, SV40, BK virus (BKV) and JC virus (JCV), hampered the results, which were always affected by some cross-reactivity. Thus, it remains to be determined whether SV40 is also a human virus and the extend of its infection rate. The identification of SV40-seropositive healthy individuals and serum antibody reactivity to SV40 antigens are of paramount importance in revealing the prevalence of SV40 infection in humans. In particular, little information is available about SV40 infection in elderly subjects that are prove to develop tumors more often than individuals of younger age. We development a specific and sensitive indirect ELISA to detect SV40 antibodies in serum samples of normal subjects and patients affected by malignant pleural mesothelioma. In the present study, the same immunologic test