Silvia Terzi

Major bone defect treatment with an osteoconductive bone substitute

A bone defect can be provoked by several pathological conditions (e.g. bone tumours, infections, major trauma with bone stock loss) or by surgical procedures, required for the appropriate treatment. Surgical techniques currently used for treating bone defects may count on different alternatives, including autologous vascularized bone grafts, homologous bone graft provided by musculoskeletal tissue bank, heterologous bone graft (xenograft), or prostheses, each one of them dealing with both specific advantages and complications and drawbacks. The main concerns related to these techniques respectively are: donor site morbidity and limited available amount; possible immune response and viral transmission; possible animal-derived pathogen transmission and risk of immunogenic rejection; high invasiveness and surgery-related systemic risks, long post-operative. physical recovery and prostheses revision need. Nowadays, an ideal alternative is the use of osteoconductive synthetic bone substitutes. Many synthetic substitutes are available, used either alone or in combination with other bone graft. Synthetic bone graft materials available as alternatives to autogeneous bone include calcium sulphates, special glass ceramics (bioactive glasses) and calcium phosphates (calcium hydroxyapatite, HA; tricalcium phosphate, TCP; and biphasic calcium phosphate, BCP). These materials differ in composition and physical properties fro each other and from bone (De Groot in Bioceramics of calcium phosphate, pp 100–114, 1983; Hench in J Am Ceram Soc 74:1487–1510, 1994; Jarcho in Clin Orthop 157:259–278, 1981; Daculsi et al. in Int Rev Cytol 172:129–191, 1996). Both stoichiometric and non-stoichiometric HA-based substitutes represent the current first choice in orthopedic surgery, in that they provide an osteoconductive scaffold to which chemotactic, circulating proteins and cells (e.g. mesenchymal stem cells, osteoinductive growth factors) can migrate and adhere, and within which progenitor cells can differentiate into functioning osteoblasts (Szpalski and Gunzburg in Orthopedics 25S:601–609, 2002). Indeed, HA may be extemporarily combined either with whole autologous bone marrow or PRP (platelet rich plasma) gel inside surgical theatre in order to favour and accelerate bone regeneration. A case of bifocal ulnar bone defect treated with stoichiometric HA-based bone substitute combined with PRP is reported in here, with a 12-month-radiographic follow-up.

Efficacy Evaluation of a New Treatment Algorithm for Spinal Metastases

Study Design. A semiprospective clinical study was conducted. Objective. To evaluate the efficacy of a new treatment algorithm for spinal metastases. Summary of Background Data. The surgical treatments in spinal metastatic have been progressing in recent years, while the surgical indications have been controversial. A new treatment algorithm for spinal metastases was developed and prospectively applied clinically in our department since 2002. Methods. This study included 202 patients with 206 lesions treated in January 1997 to December 2006 and continuously followed-up for more than 6 months or dead within this period. A total of 124 patients with 124 lesions were operated before 2002 were allocated to the control group and 78 patients with 82 lesions prospectively treated after 2002 were allocated to the prospective study group. The primary managements were nonsurgical treatment, palliative surgery, debulking, and en bloc resection. Neurologic evolvement, postoperative survival time, and local recurrence/development rates were statistically compared as the indexes of treatment outcome. Results. Although there was no significant difference of neurologic evolvement immediately after operation (P = 0.24), the prospective study group achieved significantly better neurologic function than the control group long time after operation (P = 0.03). No significant difference (P = 0.26) was shown in local recurrence/development rate comparison. The mean postoperative survival time comparison showed significant difference (P < 0.01). Conclusion. The efficacy of the algorithm has been validated preliminarily by the significantly longer survival time and better long-time neurologic function evolvement in the prospectively study group. But the algorithm should continuously be in development and be updated with the latest improvement in metastatic treatment.

Mesenchymal stem cells derived from vertebrae (vMSCs) show best biological properties

PurposeDue to their properties and characteristics human mesenchymal stem cells (MSCs) appear to have great therapeutic potential. Many different populations of MSCs have been described and to understand whether they have equivalent biological properties is a critical issue for their therapeutic application.MethodsWe proposed to analyze the in vitro growth kinetics of MSCs derived from different body sites (iliac crest bone marrow, vertebrae bone marrow, colon mucosa, dental pulp).ResultsMesenchymal stem cells derived from vertebrae can be maintained in culture for a greater number of steps and they also generate mature cells of all mesenchymal lineages with greater efficiency, when induced into osteogenic, adipogenic and chondrogenic differentiation.ConclusionsThe ability of vertebrae-derived MSCs in terms of expansion and differentiation is very interesting at the light of a clinical application for bone fusion in spine surgery.

Diagnosis and treatment of benign notochordal cell tumors of the spine: report of 3 cases and literature review.

Study Design. Clinical case series. Objective. To describe the clinical, radiological, and histological presentation of a series of patients presenting with benign notochordal tumors, and review the existing literature on the topic. Summary of Background Data. During the past decade, several authors have reported a spine tumor with benign clinical characteristics and histological resemblance to notochordal tissue. The prognosis and appropriate management remain controversial. Methods. Description of clinical, radiological, and histological findings in 3 patients with benign notochordal tumors of the spine. Results. All cases presented with subacute mild pain, without neurological deficit. Tumors developed at L3, S1, and S4, without canal involvement or apparent instability. The first 2 patients presented with classic imagenological findings were treated conservatively, showing no progression on follow-up. The last patient presented an atypical lytic pattern and contrast enhancement on magnetic resonance imaging, and underwent en bloc resection, with significant associated morbidity. Histopathology of the specimen revealed coexistent foci of incipient chordoma. Conclusion. Benign notochordal cell tumors represent a clinical entity derived from notochordal tissue, with characteristics distinct but closely related to the classic chordoma. Some radiological features may suggest the presence of chordoma precursors. Because its true potential for aggressiveness is still undetermined, a careful decision making must weigh the morbidity of en bloc procedures in the spine with uncertain natural history.

Efficacy and Safety of Selective Arterial Embolization in the Treatment of Aneurysmal Bone Cyst of the Mobile Spine. A Retrospective Observational Study.

Study Design. A retrospective observational study. Objective. Our aim is to define the efficacy and safety of serial selective arterial embolization (SAE) in the treatment of aneurysmal bone cysts (ABCs), to explore potential treatment alternatives, and to define a therapeutic algorithm. Summary of Background Data. ABC is a benign lesion with an unpredictable behavior. Its treatment is challenging especially in poorly accessible surgical areas, such as spine and pelvis. Currently, the first-line treatment of ABC is repeated SAE until healing. Other options have been used with variable success rates. Methods. From January 2004 to September 2015, 23 patients affected by ABC of the mobile spine have been treated with SAE and prospectively followed up by computed tomographic scan and magnetic resonance imaging. Signs of neurological deficit, complications, healing of the lesion, and clinical outcomes were registered. Signs of healing are defined as peripheral sclerotic bone rim formation, decrease of the ABC mass, disappearance of the double content image, and bone formation inside the ABC mass, associated with remission of pain. Results. Twenty-three patients underwent SAE according to the protocol. Seventeen patients have healed. The number of procedures necessary to obtain healing (clinical and radiographic) varied from 1 to 10. No complication occurred during the procedure. Follow-up time ranged from 5 to 120 months after the last angiographic procedure. All 17 patients had complete relief of pain symptoms. Six patients did not respond to SAE, presenting a progressive clinical and radiographic worsening, and underwent other medical or minimally invasive treatments. Conclusion. Our study confirms the safety of SAE. The efficacy of the treatment was however lower than expected. SAE is indicated when pathological fracture or signs of cord damage are not detected. Infiltration with autologous bone marrow concentrate or administration of Denosumab is under investigation as alternative choices of treatment. Level of Evidence: 4

Management of Metastases to the Spine and Sacrum

The incidence of bone metastatic deposit from carcinoma is second only to pulmonary and hepatic metastases. The most frequently affected segment of the skeleton is the vertebral column. Refinement of the protocols for treating tumour patients has led to a progressive improvement in the prognosis for many tumour histotypes in terms of increase of life expectancy. The choice of the most appropriate treatment is of crucial importance for the patient who may be severely disabled by the presence of untreated spinal metastases. It is commonly accepted that bone metastases are an expression of a systemic disease, and therefore require multi-disciplinary treatment, integrating radiotherapy (RT), chemotherapy (CHT) and surgery. The most appropriate treatment for patients with metastatic disease of the vertebral column is controversial. Appropriate surgical treatment of bone metastases and tumours in general has now become an integral part of the correct approach to the tumour patient. The evolution of anaesthetic techniques now allows more aggressive treatment of some patients with spinal and sacral metastases. These procedures can dramatically improve the patient’s quality of life and may prolong the patient’s life expectancy by preventing complications related to paralysis.

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

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.

Biomimetic 3D-printed custom-made prosthesis for anterior column reconstruction in the thoracolumbar spine: a tailored option following en bloc resection for spinal tumors

AbstractPurposeVarious techniques for anterior column reconstruction have been described after en bloc resection of spinal tumors. Limited evidence exists regarding one being superior to another. The purpose of this study is to evaluate 3D-printed vertebral bodies for spinal reconstruction after en bloc resection in the thoracolumbar spine. MethodsProspective observational study on custom-made 3D-printed titanium reconstruction of vertebral bodies after en bloc resection for spinal tumor was conducted between November 2015 and June 2017. 3D-printed vertebral bodies were monitored for mechanical complications such as (1) migration, (2) subsidence into the adjacent vertebral bodies, and/or (3) breakage. Complications and related details were recorded.ResultsThirteen patients (7 females and 6 males) were enrolled, and reconstruction of the anterior column was performed using custom-made 3D-printed titanium prosthesis after en bloc resection for spinal tumor (8 primary bone tumors and 5 solitary metastases). Subsidence into the adjacent vertebral bodies occurred in all patients at both proximal and distal bone–implant interfaces; however, it was clinically irrelevant (asymptomatic, and no consequences on posterior instrumentation), in 11 out of 12 patients (92%). In 1 patient (#4), severity of the subsidence led to revision of the construct. At an average 10-month follow-up (range 2–16), 1 implant was removed due to local recurrence of the disease and 1 was revisioned due to progressive distal junctional kyphosis.ConclusionPreliminary results from this series suggest that 3D printing can be effectively used to produce custom-made prosthesis for anterior column reconstruction.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

Systemic Amyloidosis with Predominant Spine Involvement: A Case Report

Purpose: Primary systemic amyloidosis with main bone involvement is a rare disease. Clinical symptoms and radiographic findings are usually nonspecific and may be confused with primary bone tumor, metastatic disease, metabolic disorders or infections. The occurrence of an amyloidoma in the spine is rare. Methods: We describe the case of a 57-year old man presenting with a pathological fracture of T7 in presence of a large, soft tissue mass narrowing the spinal canal, responsible for a worsening paraplegia. Diagnosis of systemic amyloidosis was made after surgical treatment. Pathological examination showed an amorphous eosinophilic material, positive staining with Congo red, birefringence under polarized light relating to amyloid, with the presence of rare plasma cells. Results: After surgical procedure patient’s symptoms improved but with incomplete neurological recovery. PET-CT scan revealed multiple bone locations without, at the beginning, extra-skeletal involvement. The patient underwent oncological and surgical treatment with progression of the disease and visceral involvement. He died two years after the diagnosis. Conclusions: Bone involvement during systemic amyloidosis is rare and often underestimated, it had predominantly visceral involvement (kidney, heart, liver, gastrointestinal tract, lung) and unfavorable clinical course if not treated. Appropriate histopathologic studies are an essential step to define diagnosis and treatment of these patients. Treatment consists of chemotherapy, steroids, autologous blood stem cell transplantation and biologic antiinflammatory drugs. Spine localization can bring to nerves compression or pathological fracture and, in these cases, surgical treatment has a role to improve patient’s quality of life.

Challenges in Spine: Management of Spinal Infections. A Flow-Chart to Guide Decision Making

Introduction Spinal infections are rare diseases, whose management highlights the importance of a multidisciplinary approach. Although treatment is based on antibiotics, always selected on coltural and antibiogram tests, surgery is required in case of development of spinal instability or deformity, progressive neurological deficits, drainage of abscesses, or failure of medical treatment. The first step of the algorithm is diagnosis, which is established on MRI with contrast, PET/CT scan, blood tests (CRP and ESR) and CT-guided needle biopsy. Evaluation of response to the specific antibiotic therapy is based on variations in Maximum Standardized Uptake Value (SUVmax) after 2 to 4 weeks of treatment. In selected cases, early minimally invasive surgery was proposed to provide immediate stability and avoid bed-rest. Material and Methods From 1997 to 2014, 182 patients affected by spinal infections have been treated at the same institution (Istituto Ortopedico Rizzoli – Bologna, Italy) according to the proposed algorithm. Mean age was 56 years (range 1 - 88). Male to female ratio was 1,46. Results Minimum follow-up was 1 year. Infections were mostly located in the lumbar spine (57%) followed by thoracic (37%) and cervical spine (6%). Conservative treatment based on antibiotics needed surgery (open and/or percuteneous minimally invasive) as an adjuvant in 83 patients out of 182 (46%). Conclusion Management of spinal infections still remains a challenge in spinal surgery and multisciplinary approach is mandatory. This algorithm represents the shared decision making process from diagnosis to the most appropriate treatment, led to successful outcomes with a low-complication rate.