Carbon Ion Radiotherapy for sacral chordoma: a systematic review of the literature.

The aim of the present study is to describe the clinical outcomes and the incidence of complications related to Carbon Ion Radiotherapy (CIRT) in the treatment of sacral chordoma. Through a systematic review of published investigations on CIRT, we collected the local control rates (LC), the overall survival rates (OS) and the post-CIRT adverse effects. Afterwards, we calculated their weighted average, to have a broader perspective. PubMed/Medline and Google Scholar databases were searched to identify studies on Carbon Ion Radiotherapy as a treatment for sacral chordoma. We used Medical Subject Heading (MeSh) terms and keywords. We based our systematic review on the PRISMA guidelines. No data limitations were applied in the search on Pubmed/ Medline database; data limitation (from 2000 to 2019) was applied in the search on Google Scholar. Six studies were included in our review. Local control proportions reported in individual studies ranged between 77% and 96% (95% confidence interval), with respect to a 5-years follow-up. Overall survival rates ranged from 52% to 86% (95% confidence interval), with respect to a 5-years follow-up. Adverse CIRT-related events involving bone occurred in 7% of patients. Neurological and skin toxicities affected 20% and 5% of patients, respectively. Nowadays the gold standard of treatment for sacral chordoma is the surgical resection with wide margins. Whenever adequate oncological margins could not be achieved or could be achieved only by sacrificing neurological structures with consequent functional impairment, CIRT is an effective alternative which has been demonstrated to reach optimal local control and overall survival rate. The caregiver, anyway, should be aware of the potential adverse events and complications related to this kind of treatment.

The impact of SARS-CoV-2 pandemic on Oncologic and Degenerative Spine Surgery Department activity: the experience of Rizzoli Orthopaedic Institute under COVID-19 lockdown.

OBJECTIVE: Experience of Department of Oncologic and Degenerative Spine Surgery of Rizzoli Orthopaedic Institute during SARS-CoV-2 pandemic lockdown. PATIENTS AND METHODS: Retrospective observational study of surgically treated patients from 09th March 2020 to 04th May 2020. DATA COLLECTED: age, sex, type of disease, neurological status, days of hospitalization, complications and type of discharge. A comparison analysis with same period of the last year was performed in order to evaluate the impact of COVID-19 spreading on daily surgical activity. RESULTS: A total of 107 surgical procedures in 102 patients were performed from 09th March 2020 to 04th May 2020. Analysis showed a statistically significant difference in age, sex, ASIA class and type of treated disease compared to the same period of the last year (p=0.042, 0.006, 0.022 and 0.007, respectively). No statistically significant differences were observed in type of discharge, length of hospitalization and complications (p= 0.447, 0.261 and 0.127, respectively). 3 COVID-19 infections have been identified in hospitalized patients. 1 COVID-19 patient wad admitted from Emergency Department and was managed according to a dedicated path. CONCLUSIONS: Surgical activity was paradoxically increased during SARS-CoV-2 pandemic lockdown through the management of urgent and non-deferrable spinal disease with a low rate (3,9%) of COVID-19 infections.

Percutaneous vertebroplasty and balloon kyphoplasty in the treatment of osteoporotic vertebral fractures: a prospective randomized comparison.

PURPOSE: The purpose of this study is to compare the efficacy and safety of percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP) in the treatment of osteoporotic vertebral compression fractures. MATERIALS AND METHODS: Patients with osteoporotic vertebral body fractures (T4-L5) were randomized and not blinded to kyphoplasty (n = 69) or vertebroplasty (n = 70). The postoperative pain score (VAS) at 12 months was the primary end point. The radiographic results were evaluated in relation to the resolution of the fracture and the possible onset of further osteoporotic fractures during follow-up. RESULTS: A total of one hundred and thirty-nine patients were eligible for randomization (n = 70 for PVP group and n = 69 for BKP), and twenty-six patients (twenty in the BKP group and six in the PVP group) were excluded. The mean average age of patients was 73 years, and 82% of the patients were females. VAS pain score was significantly reduced after surgery in both groups, and there were no significant differences between the two groups in postoperative VAS score. There was a significant reduction in kyphotic wedge angle and improvement of the sagittal index in both groups, but there was no significant difference between the two groups. There was a significant higher risk incidence of adjacent level fractures in the vertebroplasty group. CONCLUSIONS: In terms of clinical outcomes, there were no differences between the two groups. Both showed a significant clinical improvement, vertebral body height restoration and reduction in the kyphotic angle. There was a significant higher risk of adjacent level fractures in the vertebroplasty group.

A Rationale for the Use of Clotted Vertebral Bone Marrow to Aid Tissue Regeneration Following Spinal Surgery.

Vertebral body bone marrow aspirate (V-BMA), easily accessible simultaneously with the preparation of the site for pedicle screw insertion during spinal procedures, is becoming an increasingly used cell therapy approach in spinal surgery. However, the main drawbacks for V-BMA use are the lack of a standardized procedure and of a structural texture with the possibility of diffusion away from the implant site. The aim of this study was to evaluate, characterize and compare the biological characteristics of MSCs from clotted V-BMA and MSCs from whole and concentrate V-BMAs. MSCs from clotted V-BMA showed the highest cell viability and growth factors expression (TGF-ß, VEGF-A, FGF2), the greatest colony forming unit (CFU) potency, cellular homogeneity, ability to differentiate towards the osteogenic (COL1AI, TNFRSF11B, BGLAP) and chondrogenic phenotype (SOX9) and the lowest ability to differentiate toward the adipogenic lineage (ADIPOQ) in comparison to all the other culture conditions. Additionally, results revealed that MSCs, differently isolated, expressed different level of HOX and TALE signatures and that PBX1 and MEIS3 were down-regulated in MSCs from clotted V-BMA in comparison to concentrated one. The study demonstrated for the first time that the cellular source inside the clotted V-BMA showed the best biological properties, representing an alternative and advanced cell therapy approach for patients undergoing spinal surgery.

Spinal tuberculosis: proposed spinal infection multidisciplinary management project (SIMP) flow chart revision.

OBJECTIVE: We propose a revised flow chart of spinal infection multidisciplinary management project (SIMP) aimed to standardize the diagnostic process and management of spinal tuberculosis (TB). MATERIALS AND METHODS: We reviewed data from all TB cases with osteoarticular involvement treated at a large tertiary teaching hospital in Bologna, Northern Italy, from January 2013 to December 2017. We cross-linked notified osteoarticular TB cases with SIMP database and we analysed clinical, diagnostic, and treatment data of all cases managed by SIMP. RESULTS: Osteoarticular TB accounted for the 7.8% (n=40) of all TB cases notified between 2013 and 2017 (N=513). Among the identified cases, 52% (n=21/40) had spine involvement: all were enrolled and evaluated by SIMP multidisciplinary group. Females accounted for 57% (12/21) of patients, the median age was 52 years (range 24-82). In the 67% (n=14/21) of cases, the major clinical symptom of spinal TB was back pain reported for a median of 4.5 months (range 1-12 months) before hospital admission. The interferon gamma release assay was positive in 75% (n=16/21) of patients. All patients performed MRI with gadolinium, which indicated spondylodiscitis in 90%. 18F-FDG-PET/CT revealed average maximum standardized uptake value (SUV max) of 12.54 (range 5.3-22) in 17/19 (89.5%). Bacteriological confirmation of TB was obtained in 86% of cases (n=18/21). One-third of patients (7/21) underwent surgery and 95% successfully completed the anti-TB treatment. CONCLUSIONS: Our data reveal that a multidisciplinary approach to spine tuberculosis facilitates early and accurate diagnosis and can improve medical and surgical management of this disease.

Carbon ions therapy as single treatment in chordoma of the sacrum. Histologic and metabolic outcome studies.

OBJECTIVE: Even though carbon ions treatment (CIRT) of sacral chordoma (SC) substantially reduces tumor mass, tumor remnants are observed in most patients. Differentiating tumor remnants from necrosis is challenging, expensive in terms of imaging and time-consuming. So far, there has not been a systematic histological and metabolic analysis of post-CIRT lesions. We designed a prospective study aiming to histologically a metabolically differentiate between viable tumor and foci of necrosis and of fibrosclerosis after CIRT and correlate these findings to clinical outcome in patients with SC. PATIENTS AND METHODS: Between January 2013 and December 2016 18 patients, 12 males and 6 females, with histological confirmation of sacral chordoma, underwent CIRT. The total dose was 70.4 GyE, with a daily fraction of 4.4 GyE, for 4 weeks. MRI was performed every three months after treatment. FDG PET-CT scan and CT-guided needle biopsy were performed 6-12 months after CIRT. The incidence of complications (intraoperative and postoperative), local control (LC), overall survival (OS) and progression-free survival (PFS), changes in neurological status, clinical outcomes and toxicity were considered. RESULTS: All histological analysis but 2 reported signs of necrosis and of fibrosclerosis after CIRT. One of these 2 patients turned into a dedifferentiated chordoma. Radiological partial response (PR) was observed in 10 patients (56.3%) and stable disease (SD) in 5 patients (28.3). Two patients (11%) had a local relapse. The overall survival rate was 100% at 24 months. FDG PET CT after CIRT showed uptake decreasing compared with the baseline exam in all but one patient. CONCLUSIONS: The histological presence of necrosis and of fibrosclerosis after CIRT at the histological analysis supports the previous clinical evidence on the efficacy of CIRT. Volumetric stability of the residual mass should be considered as a success of treatment. In cases of a volumetric increase of the mass, a CT needle biopsy should always be performed. In our series, during the follow-up, the FDG-PET was able to promptly detect an increased uptake in the case which later was histologically defined as dedifferentiated chordoma.

Isthmic spondylolisthesis and interspinous process device. Hype, hope, or contraindication?

OBJECTIVE: The aim of this study is to investigate, through the analysis of a case report and the literature review, indications and contraindications of Interspinous Process Device (IPD) in the surgical treatment of Lumbar Isthmic Spondylolisthesis (LIS). PATIENTS AND METHODS: A 37-years-old male with L5-S1 grade 2 LIS, treated with IPD at another center, referred to us eight months later with a worsening of back and leg pain. A revision surgery was performed with IPD removal and a L5-S1 TLIF. RESULTS: Clinical evaluation highlighted an improvement of pain, functionality, and quality of life scores at six months (VAS 4; ODI 30; EQ-5D 70) and twelve months follow-up (VAS 1; ODI 20; EQ-5D 90). CT scan was performed at six months and one-year follow-up to evaluate the fusion rate and stability of the implant. CONCLUSIONS: Given the pathologic anatomy and the biomechanics of LIS, IPD is ineffective in preventing further vertebral body slippage resulting in segmental kyphosis, because of the lack of connection between the posterior arch and the vertebral body due to the isthmic lesion.

Biomaterials as bone graft substitutes for spine surgery: from preclinical results to clinical study.

Vertebral fusion is performed in order to stabilize the spine in the presence of degenerative, traumatic or oncological pathologies that alter its stability. The autologous bone, harvested from the patient's iliac crest or from the lamina during surgery, is still considered the "gold standard" for spine fusion due to its osteogenic, osteoinductive and osteoconductive properties. However, several biological and synthetic bone substitutes have been introduced as alternatives for regenerating bone tissue. We have studied in particular the use of ceramic biomaterials prepared from hydroxypatite (HA), starting from in vitro analysis, through an in vivo study on ovine animal model and a post-market surveillance analysis, to finally design and perform a clinical study, which is ongoing in our Department. In the first step, HA-derived biomaterials were tested in vitro in the presence of bone marrow-derived human mesenchymal stem cells (hMSCs) and evaluated for their ability to activate precursor cells. In the second step, the biomimetic bone graft substitute SintLife® putty (MgHA) was evaluated in vivo. A posterolateral fusion procedure was applied on 18 sheep, where a fusion level was treated with MgHA, while the other level was treated with autologous bone. Microtomography and histological/histomorphometric analysis were performed six months of after surgery. In the third step, we reported the results of a post-market surveillance study conducted on 4 independent cohorts of patients (total 115 patients), in which HA-derived biomaterials were used as bone graft substitutes or extenders. Finally, a clinical study has been designed and approved by the Ethics Committee of our Institute and is currently ongoing. This study aims to evaluate the efficacy of the ceramic biomaterial SintLife® putty for bone replacement in patients treated by posterolateral fusion for degenerative spine disorders. HA biomaterials were effective in promoting the in vitro growth of hMSCs and their osteogenic differentiation. In the animal model, SintLife® putty has been effective in generating neo-formed bone tissue with morphological and structural features similar to those of the pre-existing bone. The post-market surveillance analysis has not reported any intra-operative nor early or late post-operative adverse events. Seven patients are currently recruited for the clinical trial designed to evaluate Sintlife efficacy for spine fusion (FU range: 1-7 months). No adverse events have been recorded. The first CT analysis performed at 6 months FU showed a good spine fusion. The study is ongoing. Our results, obtained from in vitro, preclinical and clinical studies, suggest that biomaterials derived from hydroxyapatite could be a valid alternative to autologous bone graft for vertebral fusion. This would potentially avoid or reduce the need of autologous bone harvesting and therefore, the risk of drawback-related side effects.

Iliac crest bone graft: a 23-years hystory of infection at donor site in vertebral arthrodesis and a review of current bone substitutes.

OBJECTIVE: This is an exemplary case report underlining a relevant morbidity which could be associated to the use of autologous iliac crest bone graft (ICBG) for spine fusion. CASE REPORT: Starting from 1990, a 25-years-old woman underwent two subsequent surgical treatments for non-Hodgkin lymphoma vertebral localizations. In the second surgery, arthrodesis was obtained with autograft through right posterior iliac crest osteotomy. During the chemotherapy treatment following the surgery, the patient suffered from infection at posterior iliac crest scar, the site of previous graft, caused by methicillin-resistant Staphylococcus aureus. She was subjected to surgical debridement and specific antibiotic treatment with local healing and phlogosis index reduction. Chemotherapy protocol was concluded and the patient healed with definitive lymphoma remission. After 22 years the patient had a relapse of donor site infection, requiring a new antibiotic therapy and a new surgical debridement. RESULTS: The relapsed infection at donor site lasted for a long period, more than one year, despite of specific care. It finally healed after another accurate surgical debridement and postoperative antibiotic therapy. CONCLUSIONS: This case report underlines the possible consequences on the patient's quality of life of a long-term disease affecting the iliac crest bone graft donor site. Literature concerning alternatives to autograft for spine fusion is also reviewed.

A post-market surveillance analysis of the safety of hydroxyapatite-derived products as bone graft extenders or substitutes for spine fusion.

OBJECTIVE: Iliac crest bone graft (ICBG) is considered the gold standard for spine surgical procedures to achieve a successful fusion, because of its known osteoinductive and osteoconductive properties. Considering its autogenous origin, the use of ICBG has not been associated to an increase of intraoperative or postoperative complications directly related to the surgery. However, complications related to the harvesting procedure and to the donor site morbidity have been largely reported in the literature, favoring the development of a wide range of alternative products to be used as bone graft extenders or substitutes for spine fusion. The family of ceramic-based bone grafts has been widely used and studied during the last years for spine surgical procedures in order to reduce the need for iliac crest bone grafting and the consequent morbidity associated to the harvesting procedures. PATIENTS AND METHODS: We report here the results of a post-market surveillance analysis performed on four independent cohorts of patients (115 patients) to evaluate the safety of three different formulations of hydroxyapatite-derived products used as bone graft extenders/substitutes for lumbar arthrodesis. RESULTS: No intraoperative or post-operative complications related to the use of hydroxyapatite-derived products were detected, during medium and long follow up period (minimum 12 months-maximum 5 years). CONCLUSIONS: This post-market surveillance analysis evidenced the safety of ceramic products as bone graft extenders or substitutes for spine fusion. Moreover, the evidence of the safety of hydroxyapatite-derived products allows to perform clinical studies aimed at evaluating the fusion rates and the clinical outcomes of these materials as bone graft extenders/substitutes, in order to support their use as an alternative to ICBG for spine fusion.

Spina bifida occulta in high grade spondylolisthesis.

A 14-year-old boy presented with symptomatic high-grade dysplastic type spondylolisthesis, with a presence of spina bifida occulta, not diagnosed by plain radiographs, but confirmed on preoperative CT and MR. Circumferential fusion with partial reduction of L5/S1 was performed. Awareness of the coexistence of spondylolisthesis and spina bifida by an accurate preoperative planning is paramount to avoid iatrogenic damage to neural elements during surgery.

Less invasive surgery in idiopathic scoliosis: a case report.

BACKGROUND: Minimally invasive spine surgery (MISS) has become popular during the last decade due to continuous evidence in favor of lesser soft tissue damage, faster recovery, higher patient satisfaction and reduced health costs. During the last years, surgical ambition for better results as well as most detailed knowledge of spinal anatomy, have resulted in the continuous and successful expansion of indications of MISS, covering already successfully a wide range of degenerative spinal pathologies as well as adult spinal deformities. AIM: We describe here a case report of a patient with adolescent idiopathic scoliosis (AIS) treated by minimally invasive posterior pedicle screw instrumentation. MATERIALS AND METHODS: We report the case of an 18 years old female patient affected by AIS, Lenke type 1AN, with a 65 degree right thoracic curve and severe rib hump. Posterior pedicle screw instrumentation as well as corrective manoeuvres were performed exclusively by minimally invasive procedure, through three small midline skin incisions. RESULTS: We obtained a good clinical and radiographical correction of scoliosis, which was maintained during the follow-up period. We also observed a limited intra-operative blood loss, a limited operative time, limited pain, earlier mobilization and limited hospital stay. CONCLUSIONS: A minimally invasive technique can be used for the surgical treatment of AIS, showing satisfying deformity correction and multiple perceived advantages, although long-term data are needed before this kind of surgery can be recommended for routine use.

Is lumbar drainage of postoperative cerebrospinal fluid fistula after spine surgery effective?

AIM: This study is a retrospective consecutive case series analysis of 198 patients who underwent spine surgery between 2009 and 2010. The aim of this paper was to assess the efficacy and safeness of bed rest and lumbar drainage in treating postoperative CSF fistula. Postoperative cerebrospinal fluid (CSF) fistula is a well-known complication in spine surgery which lead to a significant change in length of hospitalization and possible postoperative complications. Management of CSF leaks has changed little over the past 20 years with no golden standard advocated from literature. METHODS: Postoperative CSF fistulas were described in 16 of 198 patients (8%) who underwent spine surgery between 2009 and 2010. The choice of the therapeutic strategy was based on the clinical condition of the patients, taking into account the possibility to maintain the prone position continuously and the risk of morbidity due to prolonged bed rest. Six patients were treated conservatively (position prone for three weeks), ten patients were treated by positioning an external CSF lumbar drainage for ten days. The mean follow-up period was ten months. RESULTS: All patients healed their wound properly and no adverse events were recorded. Patients treated conservatively were cured in a mean period of 30 days, while patients treated with CSF drainage were cured in a mean period of 10 days. CONCLUSION: Lumbar drainage seems to be effective and safe both in preventing CSF fistula in cases of large dural tears and debilitated/irradiated patients and in treating CSF leaks.

Navigation-assisted surgery for tumors of the spine.

PURPOSE: Computer-assisted navigation systems are largely used for pedicle screws positioning in degenerative and traumatic spine surgery. In oncologic spine surgery its use is still developing and could be extended for tumor identification and excision. Aim of this paper is to present our experience. METHODS: Seven selected patients (5 females, 2 males), mean age 44 years (min 17-max 62) affected by primary benign or malignant tumors of the spine or spine metastases were surgically treated with the use of computer-assisted navigation system from March to October 2011. RESULTS: At 18 months mean F.U. (min 15-max 23), no LR were observed. Revision surgery was necessary only in one case for C1 pedicle screw malpositioning. CONCLUSIONS: Navigation system can improve surgical accuracy in screws placement and tumor localization and excision. Learning curve and technical aspects must be considered to avoid potential serious mistakes.

Mesenchymal stem cells from patients to assay bone graft substitutes.

Bio-engineered scaffolds used in orthopedic clinical applications induce different tissue responses after implantation. In this study, non-stoichiometric Mg(2+) ions and stoichiometric apatites, which are used in orthopedic surgery as bone substitutes, have been assayed in vitro with human adult mesenchymal stem cells (hMSC) to evaluate cytocompatibility and osteoconductivity. hMSCs from the bone marrow aspirates of orthopedic patients were isolated and analyzed by flow cytometry for the surface markers Stro1, CD29, CD44, CD71, CD73, CD90, CD105 (positive) and CD45, CD235 (negative). The hMSC were analyzed for self-renewal capacity and for differentiation potential. The hMSC, which were grown on different biomaterials, were analyzed for (i) cytotoxicity by AlamarBlue metabolic assay, (ii) osteoconductivity by ELISA for activated focal adhesion kinase, (iii) cytoskeleton organization by fluorescence microscopy, and (iv) cell morphology which was investigated by scan electron microscopy (SEM). Results indicate that isolated cell populations agree with minimal criteria for defining hMSC cultures. Non-stoichiometric Mg(2+) and stoichiometric apatites, in granular form, represent a more favorable environment for mesenchymal stem cell adhesion and growth compared to the non-stoichiometric Mg(2+) apatite, in nano-structured paste form. This study indicates that different forms of biomaterials modulate osteoconductivity and cellular growth by differential activation focal adhesion kinase.

Human mesenchymal stem cells and biomaterials interaction: a promising synergy to improve spine fusion.

PURPOSE: Spine fusion is the gold standard treatment in degenerative and traumatic spine diseases. The bone regenerative medicine needs (i) in vitro functionally active osteoblasts, and/or (ii) the in vivo induction of the tissue. The bone tissue engineering seems to be a very promising approach for the effectiveness of orthopedic surgical procedures, clinical applications are often hampered by the limited availability of bone allograft or substitutes. New biomaterials have been recently developed for the orthopedic applications. The main characteristics of these scaffolds are the ability to induce the bone tissue formation by generating an appropriate environment for (i) the cell growth and (ii) recruiting precursor bone cells for the proliferation and differentiation. A new prototype of biomaterials known as "bioceramics" may own these features. Bioceramics are bone substitutes mainly composed of calcium and phosphate complex salt derivatives. METHODS: In this study, the characteristics bioceramics bone substitutes have been tested with human mesenchymal stem cells obtained from the bone marrow of adult orthopedic patients. RESULTS: These cellular models can be employed to characterize in vitro the behavior of different biomaterials, which are used as bone void fillers or three-dimensional scaffolds. CONCLUSIONS: Human mesenchymal stem cells in combination with biomaterials seem to be good alternative to the autologous or allogenic bone fusion in spine surgery. The cellular model used in our study is a useful tool for investigating cytocompatibility and biological features of HA-derived scaffolds.

Clinical features, diagnostic and therapeutic approaches to haematogenous vertebral osteomyelitis.

This article review the clinical features and the diagnostic approach to haematogenous vertebral osteomyelitis in order to optimise treatment strategies and follow-up assessment. Haematogenous spread is considered to be the most important route: the lumbar spine is the most common site of involvement for pyogenic infection and the thoracic spine for tuberculosis infection. The risk factors for developing haematogenous vertebral osteomyelitis are different among old people, adults and children: the literature reports that the incidence seems to be increasing in older patients. The source of infection in the elderly has been related to the use of intravenous access devices and the asymptomatic urinary infections. In young patients the increase has been correlated with the growing number of intravenous drug abusers, with endocarditis and with immigrants from areas where tuberculosis is still endemic. The onset of symptoms is typically insidious with neck or back pain often underestimated by the patient. Fever is present in 10-45% of patients. Spinal infections may cause severe neurological compromise in few cases, but mild neurological deficit, limited to one or two nerve roots, was detected in 28-35% of patients. The diagnosis of haematogenous vertebral osteomyelitis may be very difficult, as the symptoms can be sometimes not specific, vague or almost absent. The usual delay in diagnosis has been reported to be two to four months, despite the use of imaging techniques: in the early diagnosis of vertebral ostemyelitis is important the role of bone scintigraphy. The general principles for the management of spine infections are non operative, consisting of external immobilization and intravenous antibiotics, followed by oral antibiotics. Indications for surgery should be given in case of absence of clinical improvement after 2-3 weeks of intravenous antibiotics, persistent back pain and systemic effects of chronic infection and with presence or progression of neurological deficit in elderly or in cervical infection. Chronic ostemyelitis may require surgery in case of a development of biomechanical instability and/or a vertebral collapse with progressive deformity.

Prevalence of liver tumours in HIV-1 tat-transgenic mice treated with urethane.

The human immunodeficiency virus type 1 (HIV-1) Tat protein stimulates cell proliferation, inhibits apoptosis, displays angiogenic functions and is believed to be involved in the pathogenesis of Kaposi's sarcoma (KS) and other tumours arising in AIDS patients. Tat-transgenic (TT) mice, which constitutively express Tat in all tissues and organs, may therefore be predisposed to tumorigenesis. To test this hypothesis, we treated TT mice with urethane, a general carcinogen inducing tumours of various organs. The results indicate that, after injection of urethane, the incidence of lung tumours and lymphomas is not significantly different in the TT and control (CC) mice, whereas liver preneoplastic lesions and tumours show a significantly greater incidence in TT than in CC mice. This remarkable carcinogenic effect of urethane for the liver may be due to a tat-induced predisposition, manifested as a liver cell dysplasia (LCD), spontaneously affecting most of the TT mice. LCD may exert a promoting effect by stimulating proliferation of cell clones initiated by the mutagenic effect of urethane. In addition, LCD, which is associated with aneuploidy and chromosome instability, may enhance the progression to malignancy of the preneoplastic lesions induced by urethane. Interestingly, a significantly greater incidence of vascular ectasias and haemangiomas was detected in the liver of urethane-treated TT mice, most likely due to the marked angiogenic properties of Tat. This study suggests a role for Tat in the promotion and progression of tumours initiated by exogenous and endogenous carcinogens in HIV-1-infected patients, thereby contributing to the tumorigenesis in the course of AIDS.

Spinal metastases: treatment evaluation algorithm.

Spinal metastases are only apparently similar lesions, considering the large varieties of istotypes and the spread of the primary tumor. These metastases develop early and are not terminal events, they have to be considered as severe complications because, when possible, surgical treatment can improve the history of the patient in terms of life expectancy and quality of life. The approach to these lesions should be multidisciplinary in collaboration with oncologists and radiotherapists, in fact the average of survival of these patients has increased in recent years. The evolution of anesthaesiological techniques that permit surgical treatments that were once considered prohibitive. The application of new adjuvant therapy increases the effectiveness for surgical treatment. Controversy exist over the most appropriate treatment for patients with metastatic disease of the vertebral column. The purpose of this article was to determine the best sequential process to arrive at the most appropriate treatment considering the individual general conditions and the parameters of the metastases. We review 269 cases in 182 patients suffering from spinal metastases from a solid tumour treated between 1996 and 2002. As the number of treatment options for metastatic spinal disease has grown, it has become clear that effective implementation of these treatments can only be achieved by multidisciplinary approach.