Nicola Papapietro

Expression pattern of receptor activator of NFκB (RANK) in a series of primary solid tumors and related bone metastases.

Receptor activator of NFκB ligand (RANKL), RANK, and osteoprotegerin (OPG) represent the key regulators of bone metabolism both in normal and pathological conditions, including bone metastases. To our knowledge, no previous studies investigated and compared RANK expression in primary tumors and in bone metastases from the same patient. We retrospectively examined RANK expression by immunohistochemistry in 74 bone metastases tissues from solid tumors, mostly breast, colorectal, renal, lung, and prostate cancer. For 40 cases, tissue from the corresponding primary tumor was also analyzed. Sixty‐six (89%) of the 74 bone metastases were RANK‐positive and, among these, 40 (59.5%) showed more than 50% of positive tumor cells. The median percentage of RANK‐positive cells was 60% in primary tumors and metastases, without any statistically significant difference between the two groups (P = 0.194). The same percentage was obtained by considering only cases with availability of samples both from primary and metastasis. Our study shows that RANK is expressed by solid tumors, with high concordance between bone metastasis and corresponding primary tumor. These data highlight the central role of RANK/RANKL/OPG pathway as potential therapeutic target not only in bone metastasis management, but also in the adjuvant setting. J. Cell. Physiol. 226: 780–784, 2011.

Epidemiology, genetics and biological factors of rotator cuff tears.

Rotator cuff disease is among the most common musculoskeletal disorders with high direct and indirect costs in industrialized countries. Not all rotator cuff tears are symptomatic. Genetics has recently been investigated as a factor involved in the pathogenesis of rotator cuff pathology. Genetic factors seem to be involved in symptom presentation and tear progression. As rotator cuff disease is multifactorial, no single gene is directly involved in the pathology. Phenotypic expression of genetic susceptibility manifests at the level of ultrastructure of the tendon. Predisposing genes may also operate through apoptosis and regenerative capacity. Studies on cellular and molecular biology are more numerous, but still incomplete, and recently have focussed on the role of apoptosis in tendinopathy, analyzing its key mediators and cellular changes. Oxidative stress is responsible for reduction of collagen synthesis. Biological investigations have identified recently new risk factors. Preliminary reports introduced the possible role of glucose as a risk factor for rotator cuff tear. Further studies are required to fully clarify the genetic and biological factors involved in rotator cuff tears.

Mesenchymal Stem Cell for Prevention and Management of Intervertebral Disc Degeneration

Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients with IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage IVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration.

Thoracoscopy for minimally invasive thoracic spine surgery.

Thoracoscopy has been used worldwide for many years by thoracic surgeons. Despite a long learning curve and technical demands of the procedure, thoracoscopy has several advantages, including better cosmesis, adequate exposure to all levels of the thoracic spine from T2 to L 1, better illumination and magnification at the site of surgery, less damage to the tissue adjacent to the surgical field, less morbidity when compared with standard thoracotomy in terms of respiratory problems, pain, blood loss, muscle and chest wall damages, consequent shorter recovery time, less postoperative pulmonary function impairment, and shorter hospitalization. Good results at short- and medium-term follow-up need to be confirmed at long-term follow-up.

Premetastatic niche: ready for new therapeutic interventions?

Introduction: Bone marrow-derived cells (BMDC) localize in premetastatic niche through chemokines and integrins signals and establish clusters that precede the arrival of even single metastatic tumor cell at distant site. CSCs demonstrate an increased metastatic propensity and would seem likely candidates for the acquisition of migratory capabilities and propagation of heterogeneous tumor cell populations to different target organs. Sonic Hedgehog (SHH), FOXM1 and Notch pathways and signaling molecules such as integrin and chemokine could dictate their fate. Areas covered: In this review, the molecular mechanisms of premetastatic niche onset are summarized. Expert opinion: Premetastatic niche is defined as a fertile microenvironment that forms in metastatic target organ and facilitates the invasion, survival and/or proliferation of metastatic tumor cells, providing a novel mechanism for the promotion of metastasis. Drugs targeting premetastatic niche could represent a new promising therapeutic approach in the treatment of bone metastases.

Spondylodiscitis: standards of current treatment.

Abstract Background: Spinal infections are an important clinical problem that often require aggressive medical therapy, and sometimes even surgery. Known risk factors are advanced age, diabetes mellitus, rheumatoid arthritis, immunosuppression, alcoholism, long-term steroid use, concomitant infections, poly-trauma, malignant tumor, and previous surgery or invasive procedures (discography, chemonucleolysis, and surgical procedures involving or adjacent to the intervertebral disc space). The most common level of involvement is at the lumbar spine, followed by the thoracic, cervical and sacral levels: lesions at the thoracic spine tend to lead more frequently to neurological symptoms. Objective: The aim of the current paper is to describe current evidence-based standards of therapy in the management of SD by emphasizing pharmacological therapy and principles and indications for bracing and surgery. Methods: A PubMed and Google Scholar search using various forms and combinations of the key words: spondylodiscitis, spine, infection, therapy, surgery, radiology, treatment. Reference citations from publications identified in the literature search were reviewed. Publications highlighted in this article were extracted based on relevancy to established, putative, and emerging diagnostic and therapeutic standards, either conservative (antibiotic therapy and bracing) or surgical. Findings: To date, conservative therapy, based on targeted antibiotic therapy plus bracing, represents the mainstay in the management of SD. Proper diagnosis and tailored therapy can improve clinical results and decrease the chance of failure. Surgery should be an option only for patients with complications of this disease, namely deformity, neural compression and neurological compromise. Current standards in the setting of SD are continuously evolving, as can be seen in the recent advances in the field of radiological diagnostics, and the use of growth factors and cell-therapy strategies to promote infection eradication and bone healing after surgery.

Periprosthetic electrochemical corrosion of titanium and titanium-based alloys as a cause of spinal fusion failure.

Study Design. Posterior lumbar spine implants retrieved from patients affected by periprosthetic osteolysis were analyzed to identify corrosion and to investigate the electromagnetic fields (EMF) generated by corrosion currents and their effect on human osteoblasts proliferation. Objective. Analysis of retrieved instrumentation to better understand periprosthetic osteolysis and correlation of this information with clinical factors. Summary of Background Data. Recent studies have pointed out that mechanically assisted crevice corrosion represents the initial failure of spinal implants, resulting in the local decrease in pH, which leads to osteolysis. Methods. Electrochemical analysis was performed to characterize the corrosion currents and the EMF generated around the implants retrieved. Human primary osteoblasts cultures were used to determine the effect of continued EMF stimulation on cell growth. Cultures were exposed to the EMF stimulation for 48 hours, 72 hours, 7 days, and 14 days. Results. During the electrochemical corrosion tests both the screws and the bar showed a passivation current of 0312 and 0.05 &mgr;A/cm2, respectively. Osteoblasts exposed to an EMF of 12.1 × 10−6 T displayed a decreased proliferation rate. At each observation time, there were differences in cell numbers between the unexposed cells and the exposed cells. Conclusion. Aseptic periprosthetic bone loss can be due in part to the generation of electric and electromagnetic phenomena generated around metal devices, which inhibit osteoblasts growth and might hamper periprosthetic bone formation. This mechanism is of clinical significance and should be more deeply evaluated.

Cyclic sciatica related to an extrapelvic endometriosis of the sciatic nerve: new concepts in surgical therapy.

Sciatic pain caused by endometriosis of the sciatic nerve is an uncommon clinical finding and seems to have been verified histologically in only a few cases. Patients complain of typical signs and symptoms of common sciatica that are cyclic in nature. Suggested compression of lumbar root or sciatic nerve or its plexus could be confirmed by electromyography, computed tomography, or magnetic resonance imaging, and by prompt response to hormonal suppression of ovarian function with regression of the radiologic findings. Patients often have required radical surgery with total hysterectomy and bilateral salpingo-oophorectomy. However, conservative surgery with excision of the endometriosis from the nerve can be successful in selected patients who wish to preserve reproductive function. We report a case of sciatic nerve involvement explored by magnetic resonance imaging, with endometriosis in contact with the nerve in the right sciatic trunk.

Biomechanics of the Rotator Cuff: European Perspective

The rotator cuff has an important role in the stability and function of the glenohumeral joint. To understand the biomechanical proprieties of the rotator cuff, it is essential to understand the pathogenesis and effects of rotator cuff tears. The rotator cuff provides a stabilizing effect to the shoulder, because of compression of the humeral head against the glenoid cavity. The wide range of motion of the shoulder is allowed by the variety of rotational moments of the cuff muscles. Rotator cuff muscles action must be precisely coordinated to obtain the desired movement. Rotator cuff tendons are subjected to complex tension loads. The rotator cuff is also subjected to compressive loads. Upwardly directed humeral load squeezes the cuff between the humeral head and the coracoacromial arch. Extrinsic factors have always been considered among causes of cuff tears. However, evidence shows that acromial impingement is not the primary cause of rotator cuff tears. Tears of the rotator cuff change load distribution and determine a pattern that induces tear progression and extension. Progressive tears of the rotator cuff compromise glenohumeral stability and determine superior translation of the humeral head.

Static electromagnetic fields generated by corrosion currents inhibit human osteoblast differentiation.

Study Design. Human osteoblast cultures were exposed to a very low intensity static magnetic fields (SMF) to investigate its effects on osteoblast growth and differentiation. Objective. Analysis of the effects of periprosthetic SMF on the growth and differentiation of human osteoblast cell cultures in vitro. Summary of Background Data. The effects of pulsed electromagnetic fields (PEMF) on cell proliferation, especially in human osteoblast-like cells is well described, whereas few data are available on the effects of SMF on osteoblast cell culture. We previously demonstrated that the proliferation of human osteoblast cultures is reduced when cells are exposed to a continuous low intensity SMF comparable to the one that occurs around metal devices (Ti spinal implant) because of the generation of electric currents between the screw (Ti6Al4V) and the rod (Ti). Methods. Primary osteoblastic cells were isolated from a human femoral head. Osteoblast cultures were exposed to SMF and alkaline phosphatase activity was evaluated in the osteoblast cell cultures at different time points. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate mRNA expression levels of osteocalcin, Runx2, and collagen I genes. Results. The SMF-treated cells showed a progressive increase in the alkaline phosphatase activity which, however, remained always lower than the one observed in the control group at each observation time (72 hours, 7 and 14 days). RT-PCR demonstrated that Runx2 and collagen I mRNA were downregulated following SMF stimulation, whereas no change in osteocalcin mRNA was observed. Conclusion. Continuous low-intensity electromagnetic field comparable to the one that generates around metal devices because of the generation of corrosion currents inhibits osteoblasts differentiation pattern and might contribute at least in part to a decrease in periprosthetic bone formation occurring in vivo.