Publications (51)200.25 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Background Autologous fat tissue grafting (AFTG) has been successfully used in the treatment of different sclerotic conditions, including scleroderma. Objectives We evaluated in patients with SSc who complained of a reduced mouth opening, the long-term efficacy of AFTG of the lips in improving mouth opening in comparison with hyaluronic acid (HA) filler. We also investigated whether these procedures may induce some changes in the microvascular architecture and dermal structure of the treated skin area. Methods We studied 30 patients with dcSSc, (median age 37±12 yrs, disease duration 11±8yrs): 15 were treated by topical perioral AFTG according to Coleman technique and 15 by HA filler. The filler was repeated after 3 months. Baseline and after treatment (at months 3, 6, and 12) mouth opening changes were assessed by measuring inter-incisal distance and oral perimeter. Pre- and post-treatment modifications of microvascular architecture were assessed by counting capillaries in the inferior lip videocapillaroscopy (VC) images. Similarly, histological sections of perioral skin biopsy were examined at baseline and 3 months to evaluate dermo-epidermic junction (DEJ), the collagen content (by Masson's Trichrome staining) and microvessel density (MVD) (by anti-CD34/CD31staining). Results 3 months after treatment both the inter-incisal distance and oral perimeter significantly increased (p<0.001). At the same time, a significant skin neovascularization became evident, both considering the VC images (p<0.001) and MVD scores in IH sections (p<0.0001). Finally, some skin histological aspects also improved, as shown by the significant changes in DEJ flattening scores (p<0.0001) and collagen content with less abnormal and denser collagen bundles. At 6 and 12 months, despite the disappearance of filling effect, both the functional improvement in mouth opening and the increased number of capillaries were maintained. No effect either on the mouth opening, VC images and skin histological aspects was observed in SSc patients treated by HA filler. Conclusions The present study shows that, in patients with SSc, AFTG can improve mouth opening, induce a neovascularization, and partially restore the skin structure. All these effects were confirmed in the long-term observation. The lack of functional and biological effects in the control group treated by HA filler, suggests that the observed therapeutic effect of lipostructure may be specifically ascribed to the on site transplantation of fat tissue. Our study may open new perspectives for the local and general therapeutic approach to SSc. Disclosure of Interest None declared
- [Show abstract] [Hide abstract] ABSTRACT: Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm of intermediate biologic potential, with uncertain etiology. This tumor occurs primarily in the lung, but the tumor may affect any organ system. A 75-year-old male was evaluated for voluminous palpable high abdominal mass with continuous and moderately abdominal pain, associated with abdominal distension for the last two months. Abdominal computed tomography showed a large ( 32 × 29 × 15 cm) heterogeneously enhanced mass with well-defined margins. At surgery, the mass originated from the greater omentum was completely excised. Histologically the tumor was a mesenchymal neoplasm in smooth muscle differentiation and was characterized by spindle-cell proliferation with lymphocytes, plasma cells, and rare eosinophils. Immunohistochemically, the tumor cells were positive for vimentin and smooth muscle actin and negative for anaplastic lymphoma kinase. Complete surgical resection of IMTs remains the mainstay of treatment associated with a low rate of recurrence. Final diagnosis should be based on histopathological and immunohistochemical findings. Appropriate awareness should be exercised by surgeons to abdominal IMTs in combination with constitutional symptoms, abnormal hematologic findings, and radiological definition, to avoid misdiagnosed.
- [Show abstract] [Hide abstract] ABSTRACT: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterised by the clonal proliferation of the haematopoietic precursors together with the progressive development of bone marrow fibrosis. This stromal alteration is an important clinical issue and specific prognostic markers are not currently available. In bone marrow biopsies from 58 PMF patients, we explored the methylation pattern of genes encoding cytokines involved in the stromal reaction, namely platelet-derived growth factor-beta (PDGFB), transforming growth factor-beta (TGFB) and basic fibroblast growth factor (FGF2). We also evaluated the methylation profile of the Long Interspersed Nucleotide Element 1 (LINE-1). PDGFB, FGF2 and LINE-1, but not TGFB, were significantly differently methylated in PMF compared to controls. Significantly, PDGFB hypomethylation (<16%) was correlated with a favourable PMF prognosis (grade of marrow fibrosis, p=0.03; International Prognostic Scoring Systems p=0.01 and Dynamic International Prognostic Scoring Systems, p=0.02). Although the basis of the association of PDGFB hypomethylation with favourable prognosis remains to be clarified, we speculate that hypomethylation in PMF could represent the effect of acquired somatic mutations in genes involved in epigenetic regulation of the genome. Copyright © 2014 Elsevier Ltd. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: Tenosynovial giant cell tumour/pigmented villonodular synovitis (TGCT/PVNS) is a benign neoplasm of synovium and tendon sheath. We conducted a retrospective pooled analysis in three major referral centers. Patients treated between 1998 and 2008 were examined. Only patients presenting with primary disease or first relapse were included. 5-year local failure free survival (5-year-LFFS) was analysed. 294 patients were included: 254 with new diagnosis and 40 in 1st local recurrence (171 F/123 M; median age: 36years; tumour size ⩽2cm in 27% of patients, >2 to ⩽5cm in 41%, and >5cm in 32%). A diffuse pattern was reported in 69%, localised in 31%. No metastases were documented. Local failure (LF) was reported in 28% of patients: 36% in diffuse pattern, 14% in localised (p=0.002); median time to LF: 16months. With a median follow-up of 4.4years, 5-year-LFFS was 66%, with multiple (up to five) local recurrences in 40% of relapsed patients. Size <2cm, macroscopically complete resection, female gender and new diagnosis were associated with a better local control. After multivariate analysis, a previous relapse was independently associated with local failure. This study underlines the propensity of TGCT/PVNS to multiple local recurrences. In absence of clinical factors, biological studies are needed to identify prognostic factors of local failure. After a first local recurrence, surgery does not seem to have a curative potential. In these high risk patients, studies addressing the role of target therapies are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.
- [Show abstract] [Hide abstract] ABSTRACT: Background: To identify the best surgical approach to atypical lipomatous tumors we reviewed 171 patients who underwent surgery at two sarcoma referral centers with different surgical policies. Methods: Of the 151 patients (88 %) with primary tumors, 95 were treated at Institution A and 76 were treated at Institution B. At Institution A, a wide surgical resection, including a slight cuff of soft tissue around the mass, was adopted, which was defined as marginal resection (MR) according to the Enneking classification. At Institution B, a simple tumor resection (SR), according to the Enneking classification, was employed. En bloc surgical resection was the goal in both centers. The primary outcomes of the study were local recurrence-free survival (LRFS), incidence of secondary dedifferentiation at recurrence, and presence of residual tumor after re-excision. Results: Sixteen patients (9 %) had local recurrence. The 10-year LRFS was 82 %. No cases of secondary dedifferentiation were observed. Residual tumor after re-excision was found in 46 % of cases. In univariate analysis, sclerosing subtype, tumor rupture, and SR were unfavorable prognostic factors for LRFS. Sclerosing subtype and tumor rupture were independent prognostic factors for LRFS in multivariate analysis. SR was significantly associated with tumor rupture. Conclusions: Sclerosing subtype and tumor rupture are unfavorable prognostic factors for local recurrence. MR is associated with a lower risk of tumor rupture than SR. Neurovascular and major muscle resections are not necessary in principle. Re-excision after unplanned surgery is not always mandatory. A preoperative core needle biopsy could be useful in identifying the sclerosing subtype.
- [Show abstract] [Hide abstract] ABSTRACT: Background Indoleamine 2,3 dioxygenase 1 and 2 (IDO1-IDO2) enzymes catabolise tryptophan (TR) to its metabolite kyurenine (KNR), and are competitively inhibited by 1-Methyl-TR (1M-TR). IDO1-IDO2, once activated in dendritic cells (DCs) by IFN-type 1, may induce immune-tolerance by suppressing antigen-specific T-cell response directly or by activating T-reg cells . The role of IDO in autoimmune diseases has not been completely elucidated. In collagen-induced arthritis of DBA/1 mice, IDO1 limits the arthritis phenotype, as shown by the detrimental effect of 1M-TR treatment. Conversely, in auto-reactive B-cell-mediated arthritis of K/BxN transgenic mice, IDO1 sustains the autoimmune aggression, as demonstrated by arthritis improvement and auto-reactive B-cell reduction in draining lymph nodes after 1M-TR treatment . Finally, significantly increased plasma KNR levels and KNR/TR ratio have been reported in patients with systemic lupus and Sjogren's syndrome (SS) . Objectives To verify whether IDO1 is activated in SS focal sialoadenitis (FS), and investigate the relationships between IDO1 expression and the main cellular components in inflammatory foci. Methods Minor salivary gland biopsies from 22 patients (1 male, 21 females) with SS were examined for IDO1 expression using anti-IDO1 antibodies (Abs), and immuno-histochemistry (IHC). Prevalence of B-cells, T-cells, and plasmacytoid (p) DCs was investigated in FS infiltrates using monoclonal anti-CD20, -CD3, and -CD123 Abs, respectively. Immuno-fluorescence (IF) was used to evaluate the co-localization of IDO1+ cells with the immune cells within SS FS. Results Patients were aged 15-77 yrs. (mean 53.4 yrs), and their disease duration ranged from 1 to 16 yrs. (mean 8.9 yrs.). Anti-Ro/La Abs and extra-glandular features were recorded in 15 and 14 patients, respectively. IHC analysis demonstrated consistent expression of IDO1 within the focal infiltrates. A semi-quantitative IHC score showed significant correlation between IDO1 expression and FS scores (Spearman R=0.52, p<.02), prevalence of CD20+B-cells (R=0.79, p<.0005), and number of CD123+pDCs (R=0.64, p<.005), but not with the CD3+T-cells (R=0.14, p=ns). IF analysis of FS infiltrates characterized by germinal centre-like organization demonstrated presence of IDO1+ cells around the B-cell area and at the boundaries of the T cell rich zone. Conclusions IDO1 activity is present in SS FS, and appears to be related to the amount of pDCs and B-cells. Further investigations are needed to clarify the cell type(s) expressing IDO1 within the SS FS infiltrates and the immuno-regulatory role of this enzyme in SS. References Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3150
- [Show abstract] [Hide abstract] ABSTRACT: The survival of patients with axial skeletal or pelvic osteosarcoma (OS) remains poor, and the management of these patients is challenging. The object of this study is a cohort of unselected patients aged < 19 years with primary high-grade pelvic/axial OS. Patients were treated with high-dose methotrexate, doxorubicin, cisplatin, ifosfamide followed or preceded by local treatment (surgery and/or radiotherapy). Twenty patients aged 3-19 years were treated. Eight patients had pelvic OS, 8 axial OS and 4 mandible/maxilla OS. All patients received chemotherapy, after which necrosis was evaluable in 9 patients (≥90 % in 3). Sixteen patients underwent surgery. Radiotherapy was administered to 8 patients (total dose 34-60 Gy). The median follow-up was 35 months (8-276), and the 5-year disease-free survival and overall survival rates were 37 and 40 %, respectively. Six patients were alive at the time of this report: 2 with pelvic OS (both responded well to chemotherapy, one underwent hemipelvectomy and the other had non-radical surgery plus radiotherapy); 1 with axial and multicentric OS (with a good histological response and radical surgery); 3 with mandible/maxilla OS. Two patients died of secondary tumors (one bone and one breast cancer). It is worth noting that 4 patients had a p53 mutation: 1 is alive, 2 died of their OS, 1 of breast cancer. Adequacy of local treatment and pathological response influenced the prognosis for axial OS, which remained dismal. A high incidence of p53 mutation emerged in our series of patients.
- [Show abstract] [Hide abstract] ABSTRACT: Background Autologous fat grafts (AFG) for restoring soft tissue defects have been used for many decades and has many clinical applications. Recent studies have shown the efficacy of the AFG in the treatment of localized scleroderma. Besides mechanical lipofilling, AFG seems to produce trophic effects on both vascular and stromal cells. However, the exact mechanisms underlying the clinical results are far to be completely understood. Objectives A prospective pilot study has been carried out aimed at evaluating whether the perioral AFG in SSc patients may improve the mouth functional impairment related to the sclerotic changes. In addition, we tried to clarify whether the perioral fat filling might induce local trophic changes in the stromal and vascular structures. Methods Twenty-five patients with diffuse SSc (dcSSc) (mean age + SD 36.5+16 yrs, disease duration of 12±9 yrs) and perioral skin fibrotic changes with limited mouth opening were treated by topical perioral administration of AFG. Lipofilling was performed according to the Coleman tecnique. Follow-up was performed at 1 and 3 months postoperatively by evaluating measure of inter-incisal distance and mouth perimeter; skin hardness was measured by a digital durometer. A baseline and 3 months post-treatment evaluation of microcirculatory abnormalities was made using labial video capillaroscopy and skin biopsy. Results: Results. All patients made good postoperative recovery without complications showing an immediate subjective improvement of their skin stiffness. One and 3 months after lipofilling, the median measure of inter-incisal distance was significantly increased in comparison with the score before treatment (p=0.02); the same results, with overtime significant improvement from baseline to 1 and 3 months, were confirmed by measuring mouth perimeter (p=0.004 and 0.003). Durometer evaluations showed that skin hardness resulted significantly lower after treatment (p=0.014 and 0.019). Labial capillaroscopy of treated patients showed significant improvement in microvascular patterns after AFG in term of increase in capillary density (p=0.001) with more regular organization of microcirculation, increased length and reduced diameter shapes. Pathological studies confirmed the improvement in capillary density in the areas of treated skin with a significant upregulation of CD31 and CD34 expression (p<0.001); a significant increase in the number of dermal papillas was also observed after lipostructure. Conclusions Our study suggest that AFG of SSc fibrotic perioral changes can provide immediate and long-lasting benefits in terms of both aesthetic and functional improvement. Itis a safe, relatively non-invasive, and rapid procedure. In addition we provide evidences that AFG has the potential to favour neovascularization in SSc and revert SSc fibrotic features. The overtime increase of treatment benefits suggests that other mechanisms different from the simple fat filling may be involved. The cellular and/or tissue mechanisms underlying these changes need further investigation. Disclosure of Interest None Declared
- [Show abstract] [Hide abstract] ABSTRACT: Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H + -rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma. MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin. Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients. This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy.
- [Show abstract] [Hide abstract] ABSTRACT: Autologous fat tissue grafting (AFTG) has been successfully used in the treatment of different sclerotic conditions, including localised scleroderma. Patients with advanced systemic sclerosis (SSc)?related perioral thickening and mouth opening limitation are candidates to this therapeutic approach. Aim of the study. AFTG of the lips was performed to improve mouth opening in patients with SSc. We enrolled in the study 20 patients with diffuse SSc, (median age 35 +15 years and 11+10 years of disease duration). Two?ml?fractions of autologous fat drawn from trochanteric or peri?umbelical areas were injected in 8 different sites around the mouth. Baseline and after treatment mouth opening changes were assessed by measuring inter?incisal distance and oral perimeter, while skin hardness was tested by digital durometer. Pre? and post?treatment modifications of microvascular architecture were assessed by counting capillaries in the inferior lip videocapillaroscopy (VC) images, and by scoring the microvascular density (MVD) in anti?CD34/CD31 immuno?histochemical (IH) stained perioral skin biopsy sections. Similarly, histological sections were examined to evaluate dermo?epidermic junction (DEJ) modifications. Three months after treatment, both the inter?incisal distance and oral perimeter significantly increased (p <0.001). At the same time, a significant skin neovascularization became evident, both considering the VC images (p <0.001) and MVD scores in IH sections (p <0.0001). Finally, some skin histological aspects also improved, as shown by the significant changes in DEJ flattening scores (p <0.0001). The present study suggests that, in patients with SSc, AFTG can improve mouth opening and function, induce a neovascularization, and partially restore the skin structure.
- [Show abstract] [Hide abstract] ABSTRACT: Ewing sarcoma (ES) is the second most common type of primary bone malignancy, and retains a high propensity to metastasize; the prognosis of patients with disseminated disease is very poor, with an event-free survival rate of <20%. Current multimodality treatment for ES consists of combined chemotherapy before and concurrent with surgery and local radiotherapy for the involved bone. Cisplatin is one of the most widely used drugs for the treatment of bone tumors in children, but is not currently used in ES. We describe a child with multifocal ES, treated with a phase II trial including a single-drug window therapy, which displayed a dramatic response to 2 courses of cisplatin and had a favorable outcome.
- [Show abstract] [Hide abstract] ABSTRACT: We compared two chemotherapy regimens that included methotrexate (MTX), cisplatin (CDP), and doxorubicin (ADM) with or without ifosfamide (IFO) in patients with nonmetastatic osteosarcoma of the extremity. Patients age ≤ 40 years randomly received regimens with the same cumulative doses of drugs (ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), and IFO 30 g/m(2)) but with different durations (arm A, 44 weeks; arm B, 34 weeks). IFO was given postoperatively when pathologic response to MTX-CDP-ADM was poor (arm A) or given in the primary phase of chemotherapy with MTX-CDP-ADM (arm B). End points of the study included pathologic response to preoperative chemotherapy, toxicity, and survival. Given the feasibility of accrual, the statistical plan only permitted detection of a 15% difference in 5-year overall survival (OS). From April 2001 to December 2006, 246 patients were enrolled. Two hundred thirty patients (94%) underwent limb salvage surgery (arm A, 92%; arm B, 96%; P = .5). Chemotherapy-induced necrosis was good in 45% of patients (48% in arm A, 42% in arm B; P = .3). Four patients died of treatment-related toxicity (arm A, n = 1; arm B, n = 3). A significantly higher incidence of hematologic toxicity was reported in arm B. With a median follow-up of 66 months (range, 1 to 104 months), 5-year OS and event-free survival (EFS) rates were not significantly different between arm A and arm B, with OS being 73% (95% CI, 65% to 81%) in arm A and 74% (95% CI, 66% to 82%) in arm B and EFS being 64% (95% CI, 56% to 73%) in arm A and 55% (95% CI, 46% to 64%) in arm B. IFO added to MTX, CDP, and ADM from the preoperative phase does not improve the good responder rate and increases hematologic toxicity. IFO should only be considered in patients who have a poor histologic response to MTX, CDP, and ADM.
- [Show abstract] [Hide abstract] ABSTRACT: The authors report a clinical case of a primary sternal chondrosarcoma, presented as a mass in the anterior mediastinum. The patient was treated with subtotal sternectomy and sternal transplantation followed by radiotherapy. Twelve months after surgery, the patient is in good clinical condition, without any sign of tumor relapse and with normal respiratory mechanics. Primary malignant tumors of the sternum are uncommon and a presentation mimicking thymoma is rare and unreported. The stermal replacement with a cryopreserved allograft sternum is an innovative technique that overcomes the problems related to the prosthetic biocompatibility or to the bone autograft.
- [Show abstract] [Hide abstract] ABSTRACT: The aim of this study is the review of our data obtained from 1960 to 2010 in the Oncological Orthopaedics Unit of G. Pini Institute, evaluating appearance, anatomic site, complications, recurrences and different kinds of treatment of 126 paediatric patients affected by aneurysmal bone cyst. All cases were controlled and confirmed by clinical, histologic and radiographic examination. The average age was 11.8 years. Biopsy was made in every case. The treatment of choice was surgical: simple curettage, curettage and bone grafting, simple resection in expendable bones. Selective embolization was used in difficult or hazardous sites. The recurrence rate was 21% for the cases treated until 1976 and 8.9% for those treated from 1976 to 2010. A literature review about other methods of treatment is presented.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to determine the efficacy of platelet-rich plasma (PRP) 1-injection during an Achilles tendon rat tear model. 80 male adult imbreded rats (Wistar Kyoto), underwent under surgical tendon rupture. 40 Animal (PRP group rats) were given a local injection with 0,25 mL of PRP, and 40 animal (control group) were given the same quantity of control solution. The rats were sacrified at 1, 2, 4 and 6 weeks (each time point, 20 rats of the each group) after surgical tear and tendon tissue was analysed by macroscopic aspect, histology, immunostaining and Real Time (RT)-PCR to evaluate tissue repair. PRP improved tendon remodelling by better coordination of the reconstructive process with earlier formation of tendon-like continuity only in the first week after surgery. However, after 2,4 and 6 weeks, Achilles tendons in the PRP group had no difference compared to the control group. Immunostaining and RT-PCR did not show any difference between PRP treated and untreated group. Based on these findings a single injection of PRP appear not useful for Achilles rat tendon tear.
- [Show abstract] [Hide abstract] ABSTRACT: Ectodermal dysplasia (ED) comprises a large heterogeneous group of inherited disorders that are characterized by primary defects in the skin, hair, nails, eccrine glands and teeth. The most characteristic findings are the reduced number of teeth. All rehabilitative programmes involve proper evaluation of skeletal relationships. Prosthetic-implantological treatment at the end of bony growth can be used. In this article a case of ED treated with Le Fort I for maxillary advancement, femur homografts, implants' insertion and immediate loading is described. In December 2007, a 38-year-old female was referred to the Maxillofacial Department of Galeazzi Hospital (Milan, Italy) who had a diagnosis of ED. Twelve implants were inserted in one-step surgical procedure. No implant was lost and all are stable. The occlusion is stable after 15 months of follow-up. The results indicate that the one-step oral rehabilitation can be performed in adults who are affected by ED. Also, this significantly reduces the time of oral and facial rehabilitation.
- [Show abstract] [Hide abstract] ABSTRACT: The osteoid osteoma is a benign bone lesion that accounts for 12.1% of benign tumors and 2.9% of all primary bone tumors. The third of the proximal femur is the most frequent location, followed by the tibia, the posterior elements of the spine and the humerus. The tumor, however, may be found in all parts of the skeleton. It affects more often males than females (2:1); 75% of patients are between 10 and 30 years of age. It is uncommon in children younger than 5 years and adults over 40 years. The authors discuss the case of a 33-year-old man who undegoes arthroscopy of the ankle for a partial synoviectomy due to chronic synovitis. Two years ago the patient underwent a surgical open intervention of reconstruction of the anterior talofibular ligament of the ankle, for an anterolateral instability of II degree following an ankle strain. After that intervention, the patient has complained about the persistence of articular swelling with marked functional limitation, without benefit from conservative therapies. During arthroscopy a large amount of hypertrofic synovial tissue is found, located in the anterior portion of the ankle. This tissue is removed and a biopsy is performed. The bioptic sample is composed by synovial membrane with chronic flogosis and emosiderinic pigments and a “nidus” of osteoblastic benign proliferation related to an osteoid osteoma. This patient therefore had a reactive chronic sinovitis secondary to a rare localization of osteoid osteoma.
Azienda Ospedaliera Istituto Ortopedico Gaetano PiniMilano, Lombardy, Italy