Francesco Saverio De Ponte

Bisphosphonates Induce Apoptosis of Circulating Endothelial Cells in Multiple Myeloma Patients and in Subjects with Bisphosphonate-Induced Osteonecrosis of the Jaws

Bisphosphonates (BPs) are the current standard of care for bone lesions in patients with multiple myeloma (MM) but they are associated with a number of side effects such as osteonecrosis of the jaw. The exact mechanisms of osteonecrosis are not elucidated, and its physiopathology is based on several hypotheses such as a decrease in bone remodeling or an inhibitory effect on angiogenesis. The aim of our study was to investigate the mechanism involved in the pathogenesis of osteonecrosis. We examined the apoptosis of circulating endothelial progenitor cells in MM subjects before and after BP treatment and in osteonecrosis patients using a flow-cytometric analysis. Our data showed an increase in endothelial cell apoptosis in MM patients after BP administration and in osteonecrosis subjects. Our study seems in agreement with the hypothesis that BPs can inhibit angiogenesis interfering with endothelial cell proliferation and survival, leading to loss of blood vessels and avascular necrosis.

Sclerotherapy for cervical cystic lymphatic malformations in children. Our experience with computed tomography-guided 98% sterile ethanol insertion and a review of the literature

PURPOSE The treatment of cystic lymphatic malformations of the neck and mediastinum is controversial. Surgical management may be limited by the invasiveness of the procedure, the complex anatomy of this region, and the high recurrence rate. An alternative therapeutic method is sclerotherapy. We report our experience in the treatment of cystic lymphatic malformations of the neck by computed tomography (CT)-guided instillation of 98% sterile ethanol in children. METHODS Eight children with clinical suspicion of cervical cystic lymphatic malformation were assessed by ultrasonography (US) and magnetic resonance imaging (MRI) to define the location, size, and number of cystic cavities. The CT-guided instillation of 98% sterile ethanol was performed. Cystic fluid was analyzed by fine-needle aspiration cytology. Clinical and US or MRI follow-up was performed after 1 and 3 months and at 1 and 2 years. RESULTS The results were excellent with complete disappearance of the lesion in 7 (87.5%) of 8 patients. One patient (12.5%) with satisfactory results required a second alcohol injection with an excellent outcome. No allergic reactions or complications were observed. CONCLUSIONS The CT-guided 98% sterile ethanol sclerotherapy is a good alternative to surgical therapy. This procedure seems accurate, minimally invasive, safe, low cost, and reliable without untoward complications. Moreover, it does not exclude later surgical treatment.

Giant Olfactory Groove Meningiomas: Extent of Frontal Lobes Damage and Long-Term Outcome After the Pterional Approach

OBJECTIVE The treatment of giant olfactory groove meningiomas (OGMs; maximum diameter ≥ 6 cm) poses special problems and represents a surgical challenge. We discuss the long-term results in a series of 18 patients with giant OGMs and report our experience on a global strategy encompassing the pterional approach to manage the lesion and an extended transbasal approach to treat recurrences. METHODS Between February 1991 and December 2007, 18 patients with giant OGMs were surgically managed via a pterional craniotomy. Postoperative follow-up imaging was obtained at one, six, and 12 months and then yearly. In preoperative images, data from tumor volume were assessed. The volume of the residual right frontal porencephalic cave (ipsilateral to the operative side) was compared with the volume of the porencephalic cave measured in the left frontal lobe (internal control) in each case. Comparison between porencephalic cave and the original tumor volume for each side was also performed. RESULTS At the first operation in 17 of 18 patients (94.4%), the tumor resection was accomplished by a complete macroscopic lesion removal and coagulation of its dural attachment (Simpson grade II). In one patient, a Simpson grade V resection was obtained. The mean follow-up was 93.5 months, ranging from 12 to 214 months. Recurrences were observed in three patients (16.7%) at 103, 102, and 128 months, respectively, from the time of the first operation. These patients were operated on via an extended subfrontal transbasal approach accomplishing a complete (Simpson grade I) resection. No death occurred. The visual deficit improved in seven of 13 patients (53.8%), remained stable in five (38.5%), and worsened in one patient (7.7%). Overall, 17 of 18 patients (94.4%) had a good outcome and returned to their previous occupations. All the tumors presented with a symmetrical growth pattern. The mean meningioma volume was 23.51 ± 1.62 cm(3) for the right portion of the tumor and 23.04 ± 1.35 cm(3) for the left portion. The mean residual porencephalic volume was significantly smaller in the left frontal lobe (mean value 5.7 mL) than in the right frontal lobe (mean value 16.6 mL; P < 0.05). The mean residual porencephalic volume was significantly smaller than the tumor volume both in the left (P < 0.01) and in the right side (P < 0.05). CONCLUSION The pterional-transsylvian approach provides two major advantages: first, it minimizes morbidity and mortality through an early neurovascular control and by limiting parenchymal damage as demonstrated by a quantitative analysis; second it is associated with low recurrence rate at a long-term follow-up.

Patients with bisphosphonate-associated osteonecrosis of the jaw have unmodified levels of soluble vascular endothelial growth factor receptor 1.

In an article recently published in Leukemia and Lymphoma, Pozzi et al. reported 35 cases of bisphosphonate-associated osteonecrosis of the jaw (ONJ) in multiple myeloma patients [1]. In fact, sinc...

Intraosseous mandibular artero-venous malformations: case report.

Intraosseous mandibular artero-venous malformations (AVMs) are rare (5% of all vascular malformations) but of great clinical importance. They can lead to dental emergencies and may cause disfigurement, morbidity, and even death. We describe the radiological appearance and the endovascular treatment of a rare high-flow vascular malformation of the mandibular body resembling a dental cyst, embolized by Guglielmis detachable coils (GDC).

Tongue schwannoma: clinicopathological findings.

Schwannomas are peripheral nerve sheath tumors. Approximately 25% of extracranial schwannomas are located in the head and neck district, but only 1% shows an intraoral origin. We report a case of a 28-year-old patient with a tongue schwannoma. Morphologic analysis and immunohistochemical findings strongly support the diagnosis. Surgical treatment is discussed.

Frameless stereotactic radiosurgery for the treatment of multiple sclerosis-related trigeminal neuralgia

BACKGROUND Trigeminal neuralgia (TN) affects 7% of patients with multiple sclerosis (MS). In such patients, TN is difficult to manage either pharmacologically and surgically. Radiosurgical rhizotomy is an effective treatment option. The nonisocentric geometry of radiation beams of CyberKnife introduces new concepts in the treatment of TN. Its efficacy for MS-related TN has not yet been demonstrated. METHODS Twenty-seven patients with refractory TN and MS were treated. A nonisocentric beams distribution was chosen; the maximal target dose was 72.5 Gy. The maximal dose to the brainstem was <12 Gy. Effects on pain, medications, sensory disturbance, rate, and time of pain recurrence were analyzed. RESULTS Median follow-up was 37 (18-72) months. Barrow Neurological Institute pain scale score I-III was achieved in 23/27 patients (85%) within 45 days. Prescription isodose line (80%) accounting for a dose of 58 Gy incorporated an average of 4.85 mm (4-6 mm) of the nerve and mean nerve volume of 26.4 mm3 (range 20-38 mm3). Seven out of 27 patients (26%) had mild, not bothersome, facial numbness (Barrow Neurological Institute numbness score II). The rate of pain control decreased progressively after the first year, and only 44% of patients retained pain control 4 years later. CONCLUSIONS Frameless radiosurgery can be effectively used to perform retrogasserian rhizotomy. Pain relief was satisfactory and, with our dose/volume constraints, no sensory complications were recorded. Nonetheless, long-term pain control was possible in less than half of the patients. This is a limitation that CyberKnife radiosurgery shares with other techniques in MS patients.

Complex Craniofacial Trauma Resulting From Fireworks Blast

The authors report the case of a patient who sustained a complex craniofacial trauma secondary to a recreational fireworks blast. Initial assessment and management were performed with a multidisciplinary approach to achieve control of cerebral hemorrhage, debridement of wounds and brain, isolation of the brain from the external environment, reconstruction of the cranial base floor, and orbital and facial reconstruction. Modification of multiple conventional approaches, along with a multispecialty surgical team, were used to deal effectively with this unusual patient who was treated by single-stage immediate management. Reconstruction of both the intracranial and extracranial compartments was considered successful with a satisfactory cosmetic result.

Effect of bisphosphonates on the mandibular bone and gingival epithelium of rats without tooth extraction

Osteonecrosis of the jaw (ONJ) is an adverse effect of bisphosphonate treatment that has become the subject of increasing investigations, in particular due to its poorly understood pathogenesis. Several experimental studies on animal models have been conducted; however, the majority of these replicate human ONJ following tooth extraction, and describe alterations in the bone and gingival epithelium when necrosis is manifested. The aim of the present study was to analyze the rat mandibular bone and gingival epithelium during 45 days of zoledronate treatment (which is a bisphosphonate agent), without tooth extraction. Intraperitoneal injections of zoledronate acid (0.1 mg/kg) were performed three times a week in normal male Wistar rats (n=20), while a control group of rats (n=20) was treated with saline solution for 45 days. After 7, 15, 30 and 45 days of drug treatment, all rats were sacrificed and hematoxilin and eosin staining, immunofluorescence and scanning electron microscopy analyses were performed. The results of the analyses after 7 and 15 days of treatment were similar in the treatment and control group. After 30 and 45 days of treatment, structural alterations were observed in the bone. No structural alterations to the gingival epithelium were observed. Based on these results, it was hypothesized that low doses of zoledronate act directly on the bone tissues to induce morphological alterations from bone to necrotic tissue following surgical procedures, although no cytotoxic effects were detected in the gingival epithelium.

Histomorhological and clinical evaluation of maxillary alveolar ridge reconstruction after craniofacial trauma by applying combination of allogeneic and autogenous bone graft

A variety of techniques and materials for the rehabilitation and reconstruction of traumatized maxillary ridges prior to dental implants placement have been described in literature. Autogenous bone grafting is considered ideal by many researchers and it still remains the most predictable and documented method. The aim of this report is to underline the effectiveness of using allogeneic bone graft for managing maxillofacial trauma. A case of a 30-year-old male with severely atrophic maxillary ridge as a consequence of complex craniofacial injury is presented here. Augmentation procedure in two stages was performed using allogeneic and autogenous bone grafts in different areas of the osseous defect. Four months after grafting, during the implants placement surgery, samples of both sectors were withdrawn and submitted to histological evaluation. On the examination of the specimens, treated by hematoxylin and eosin staining, the morphology of integrated allogeneic bone grafts was revealed to be similar to the autologous bone. Our clinical experience shows how the allogeneic bone graft presented normal bone tissue architecture and is highly vascularized, and it can be used for reconstruction of severe trauma of the maxilla.