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.

Is minimally-invasive spinal surgery a reliable treatment option in symptomatic spinal metastasis?

OBJECTIVE: Up to 70% of patients with cancer are likely to develop spine metastasis. Radiation therapy is the standard of care for painful spinal metastases in absence of unstable or impending fractures. More frequently these patients require open palliative surgery for pain, vertebral collapse and neurological deficits. Minimally Invasive Spine Surgery (MISS) techniques using percutaneous pedicle screw fixation may be considered as an alternative to open surgery in selected cases. MISS techniques are thought to be associated with fewer tissues damages resulting in early pain relief,  they also allow for early mobilization and optimization of function. PATIENTS AND METHODS: From 2011 to 2018, 52 patients affected by spinal metastasis were treated with MISS techniques in Rizzoli Orthopaedic Institute of Bologna and in Cisanello Hospital of Pisa, Italy. All patients underwent percutaneous pedicle screw fixations (PPSF) coupled with mini-decompressions in case it was required by spinal cord compressions. All patients were evaluated pre and post-operatively by Frenkel classification and VAS scores. RESULTS: Mean follow-up time was 19,4 months. Preoperatively, Frankel scores were E in 37 patients, D3 in 6 patients, D2 in 3 cases, D1 in 3 patients, B in one patient and C in two. The Frankel score improved in 10 patients, remained stable in 40 patients and worsened in two patients. Preoperatively, the mean VAS score in 29 patients treated with PPSF procedure with spinal decompression was 7, while postoperatively, it became 5. In 23 patients who underwent only PPSF procedure without spinal decompression mean VAS score was 5, postoperatively it became 3. CONCLUSIONS: In selected cases, MISS surgeries may be considered as a valid alternative to open surgery. Although the efficacy of PPSF has been well documented in trauma or degenerative spine surgery, there is not sufficient literature about MISS techniques in spinal metastasis and further studies are needed to elucidate the most appropriate patient in which this approach could represent the gold standard of treatment.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

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.

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.

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.

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.

MitomiRs delineating the intracellular localization of microRNAs at mitochondria.

Mitochondria play a crucial role in energetic metabolism, signaling pathways, and overall cell viability. Mitochondrial dysfunctions are known to cause a wide range of human diseases that affect tissues especially those with high energetic requirements, such as skeletal muscle, heart, kidney, and central nervous system, while being involved in cancer, aging, and metabolic processes. At the same time, the microRNA (miRNA) gene family has been demonstrated to be involved in most cellular processes through modulation of proteins critical for cellular homeostasis. Given the broad scope of reactivity profiles and the ability of miRNAs to modify numerous proteomic and genomic processes, new emphasis is being placed on the influence of miRNAs at the mitochondrial level. Recently, the localization of miRNAs in mitochondria was characterized in different species. This raises the idea that those miRNAs, noted "mitomiRs," could act as "vectors" that sense and respond dynamically to the changing microenvironment of mitochondria at the cellular level. Reciprocally, we present the involvement of mitochondria in small RNA biogenesis. With the aim of deciphering the significance of this localization, we discuss the putative mechanism of import of miRNAs at mitochondria, their origin, and their hypothetical roles within the organelle.

Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage.

Our group recently described recurrent somatic mutations of the miRNA processing gene DICER1 in non-epithelial ovarian cancer. Mutations appeared to be clustered around each of four critical metal-binding residues in the RNase IIIB domain of DICER1. This domain is responsible for cleavage of the 3' end of the 5p miRNA strand of a pre-mRNA hairpin. To investigate the effects of these cancer-associated 'hotspot' mutations, we engineered mouse DICER1-deficient ES cells to express wild-type and an allelic series of the mutant DICER1 variants. Global miRNA and mRNA profiles from cells carrying the metal-binding site mutations were compared to each other and to wild-type DICER1. The miRNA and mRNA profiles generated through the expression of the hotspot mutations were virtually identical, and the DICER1 hotspot mutation-carrying cells were distinct from both wild-type and DICER1-deficient cells. Further, miRNA profiles showed that mutant DICER1 results in a dramatic loss in processing of mature 5p miRNA strands but were still able to create 3p strand miRNAs. Messenger RNA (mRNA) profile changes were consistent with the loss of 5p strand miRNAs and showed enriched expression for predicted targets of the lost 5p-derived miRNAs. We therefore conclude that cancer-associated somatic hotspot mutations of DICER1, affecting any one of four metal-binding residues in the RNase IIIB domain, are functionally equivalent with respect to miRNA processing and are hypomorphic alleles, yielding a global loss in processing of mature 5p strand miRNA. We further propose that this resulting 3p strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations.

Aneurysmal bone cyst of the mobile spine: the therapeutic role of embolization.

PURPOSE: Our aim is to define the role of embolization in the treatment of aneurysmal bone cyst of the spine in order to include this option in the decision making process. METHODS: From April 2004 to November 2009, seven patients with primary aneurysmal bone cyst of the mobile spine treated by embolization have been prospectively followed-up. All clinical presentations and imagings were recorded. There are many options of embolic agent and techniques used, but all aim to devascularize the tumor. The therapeutic protocol includes: embolization repeated every 8 weeks until the appearance of radiographic signs of healing. Complications, rate of healing and clinical outcome were analyzed. RESULTS: The number of embolizations varied from one to a maximum of seven without related intra- or post-operative complications. One patient, after four selective arterial embolizations, underwent direct percutaneous injection of embolic agents into the cyst. A clinical and radiographical response was achieved in all patients who were found alive and completely free of disease at mean follow-up of 46 months after last treatment and nobody crossed to surgical option. CONCLUSION: Embolization seems to be the first option for spinal aneurysmal bone cyst treatment because of the best cost-to-benefit ratio. It is indicated in intact aneurysmal bone cyst, when diagnosis is certain, when technically feasible and safe and when no pathologic fracture or neurologic involvements are found. If embolization fails, other options for treatment would still be available.

Staging and treatment of osteoblastoma in the mobile spine: a review of 51 cases.

PURPOSE: To define the role of Enneking staging system and of the consequent different treatment options on the outcome of osteoblastoma (OBL) of the spine. METHODS: A retrospective review of 51 patients with OBL of the mobile spine conducted to compare the outcomes among the different types of treatments at long term follow-up (25-229 months, av.90). These 51 patients were previously staged according to Enneking staging system and treatment selected accordingly. 10 stage two (st.2) OBLs were treated with intralesional excision and 41 stage three (st.3) OBLs were treated either by intralesional excision or en bloc resection. The intralesional excision group was divided considering the use or not of radiation therapy after surgery. The recurrence rate was compared among these groups and also considering previous open surgery ("non intact" vs. "intact"). The statistical significance was defined using the Fisher Exact test. RESULTS: No local recurrence occurred in the st.2 patients treated by intralesional excision. Considering the st.3 patients, 2 local recurrences out of 13 patients occurred in the en bloc resection (15.4 %) group. All occurred in "non intact" cases (67 %). In the intralesional group, 5 local recurrences out of 27 patients occurred (18 %) being none in the group that received radiation therapy after surgery. Two occurred in the "intact" (7 %) and three in the "non intact" group (75 %). Considering all patients, the difference between the recurrence rate between "intact" and "non intact" groups was statistically significant (p < 0.002). CONCLUSIONS: Intralesional excision proved to be effective in st.2 lesions and en bloc resection in st.3. Radiotherapy seems to be an effective adjuvant treatment when en bloc resection is not feasible or requires unacceptable functional sacrifices. The first treatment significantly affects the prognosis as previously treated patients have worse prognosis.

Ewing's sarcoma of the mobile spine.

OBJECTIVES: To evaluate the role of enbloc resection on the oncological outcome of patients with Ewing's sarcoma of the mobile spine treated with systemic multiagent chemotherapy combined with radiation therapy. While the role of chemotherapy and radiation therapy is well known and accepted in the treatment of Ewing sarcoma, there is no consensus on the role of enbloc resection in those tumors occurring in the mobile spine and, therefore, it can be difficult to conclude the decision making process, particularly if to achieve a tumor-free margin resection functionally relevant structures should be sacrificed. The study design of this work was the retrospective analysis of a series of 27 cases of Ewing sarcoma of the mobile spine homogeneously treated. METHODS: Twenty-seven patients with primary ES of the mobile spine were treated from 1979 to 2008 by the same multidisciplinary team. All the patients presented with pain. Motor deficits were present in 6 patients. All the patients were submitted to multiagent protocols of chemotherapy (always) and radiotherapy (alternative to surgery or associated to). Surgery was performed in 17 cases both for functional purpose (7 cases: intralesional piecemeal excision) both for curative purpose (10 cases: enbloc resection, resulting characterized by marginal/wide or intralesional margins). Patients were observed for a minimum of 2 years or until death. The mean follow-up time was 65 months (median 28 months; ranging 2 to 218 months). Neurological function, local recurrence, distant relapse, and treatment-related complications were evaluated. RESULTS: Three periods were considered according to the evolution of therapeutic strategies. Four patients were treated in the period 1979 to 1982. All were submitted to chemotherapy (REA-2) and radiation therapy (RT). Two of them were submitted to intralesional excision. All these patients died 2 to 29 months later without significant difference in the two groups. In the period 1983 to 1990 all patients were treated with chemotherapy (REN-1/2) and RT. Two were submitted to intralesional excision and had a worse evolution as died of the disease at 2 and 11 months follow up, while the patients who did not received surgery evolved more favourably: 1 died of the disease 57 months after the end of the treatment, 3 are continuously disease free at 130, 190, 290 months. The sixteen patients treated in the period 1991 to 2008 received chemotherapy (REN-3 and ISG-SSG) and RT, combined with intralesional excision in 3, with enbloc with intralesional margins in 4, enbloc with tumor-free margins (wide or marginal) in 6. Only one patient submitted to tumor-free margin enbloc resection had local recurrence and died 29 months after the treatment (biopsy was performed by open approach), the other surviving continuously disease free at 17 to 193 months follow-up (av. 76 months). All the patients submitted to intralesional excision and to enbloc resection resulting in margin violation had the same prognosis, as died of the disease 10 to 63 months after the treatment. Only one of the 3 patients who had no surgery died of the disease 8 months after the treatment, the other surviving 9 and 49 months follow-up. Among the seven patients who had neurological symptoms at the occurrence, just those with no metastasis and who underwent enbloc resection are alive. CONCLUSIONS: The current study seems to demonstrate that tumor-free margin enbloc resection provides better local control and longer survival, while the results after intralesional margin resection or piecemeal excision combined with chemotherapy and RT is less effective than chemotherapy and RT alone.

Germline mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers.

BACKGROUND: Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer; lobular breast cancer also occurs excessively in families with such condition. METHOD: To determine if CDH1 is a susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45 years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2. Cases were ascertained through breast cancer registries and high-risk cancer genetic clinics (Breast Cancer Family Registry, the kConFab and a consortium of breast cancer genetics clinics in the United States and Spain). Additionally, Multiplex Ligation-dependent Probe Amplification was performed for 134 cases to detect large deletions. RESULTS: No truncating mutations and no large deletions were detected. Six non-synonymous variants were found in seven families. Four (4/318 or 1.3%) are considered to be potentially pathogenic through in vitro and in silico analysis. CONCLUSION: Potentially pathogenic germline CDH1 mutations in women with early-onset or familial lobular breast cancer are at most infrequent.

Osteoporotic vertebral fractures: a disabling and expensive disease of our century. A minimally invasive surgical technique to reduce the pain, the hospitalization, and restore the function.

BACKGROUND AND OBJECTIVES: Minimally invasive spine surgery has gained a great consent in the treatment of vertebral osteoporotic fractures. We perform a retrospective clinical and radiographic review on 32 consecutive patients (22 female and 10 male) surgically treated for a thoracolumbar osteoporotic fracture (type A) by a minimally invasive system. By this study, we propose to determine the safety and efficacy of an expandable, percutaneous, minimally invasive technique to reduce the disability caused by vertebral osteoporotic fractures. MATERIAL AND METHODS: We retrospectively reviewed 32 patients who were operated on between 2003 and 2004 by means of an innovative technique which employs an expandable system inserted by a minimally invasive approach into the vertebral body. Average age at surgery was 64.8 years (range, 27-82). All patients were mobilized in first post-operative day with no external immobilization and discharged from the Hospital in the second post-operative day. RESULTS AND CONCLUSIONS: This innovative technique which employs an expandable system inserted by a minimally-invasive approach into the vertebral body permits to obtain a double mechanical support for the vertebral plate, to partially reduce the fracture, to mobilize the patient immediately, reducing disability and costs related to the vertebral osteoporotic fractures.

Management of bone metastases.

Bone metastases are only apparently similar lesions, considering the large varieties of istotypes and the spread of the primary tumour. Although these metastases develop early and are not terminal events, they have to be considered as severe complications. 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 anesthesiological techniques permits surgical treatments that once were considered prohibitive. The application of new adjuvant therapies increases the effectiveness for surgical treatment. Controversy exists over the most appropriate treatment for patients with bone metastatic disease. The purpose 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. As the number of treatment options for metastatic bone disease has grown, it has become clear that effective implementation of these treatments can only be achieved by a multidisciplinary approach.

CYP1B1 expression in rat testis and Leydig cells is not inducible by aryl hydrocarbon receptor agonists.

1. Cytochrome P450 1B1 (CYP1B1) is highly expressed in testis, but there is conflicting information regarding the inducibility of testicular CYP1B1 by aryl hydrocarbon receptor (AhR) agonists. 2. To assess AhR-mediated regulation, testicular CYP1B1 expression was measured following treatment of adult rats with 3-methylcholanthrene and various dosages of benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The effect of TCDD on CYP1B1 expression in R2C rat Leydig and MA-10 mouse Leydig cells in culture was also determined. 3. Immunoblot analysis showed that treatment with benzo[a]pyrene at dosages up to 200 mg/kg/day and 3-methylcholanthrene at 25 mg/kg/day did not induce testicular CYP1B1 expression. Treatment with TCDD at dosages of 1, 5 or 100 microg/kg had no effect, but testicular CYP1B1 protein levels were increased by approximately 50% at dosages of 10 and 50 microg/kg. 4. CYP1B1 mRNA levels in MA-10 and CYP1B1 protein levels in R2C cells were not induced by exposure to TCDD (10-1000 nM). 5. Overall, the results indicate that rodent testicular CYP1B1 is not inducible by AhR agonists.

Spinal metastasis: a retrospective study validating the treatment algorithm.

A retrospective clinical study was conducted to validating the treatment algorithm in patients with spinal metastasis. The study participants were 43 patients with spinal metastasis from carcinoma. Since most interventions are palliative we had to seek for clear definitions to describe the results, aiming to increase the quality of life. To this purpose, we would introduce the concept of "target achievement". We presume that the target is achieved when all the following findings are present: a survival rate which is not inferior to the average, improvement or the maintenance of the neurological condition and achievement of local control. The results of this study demonstrate that performing the treatment suggested by the algorithm, the majority of the patients have a good residual quality of life. Worse results are obtained when a more aggressive treatment is selected.