Evaluation of trans-sphenoidal surgery in pituitary GH-secreting micro- and macroadenomas: a comparison between microsurgical and endoscopic approach.

AIM: Acromegaly is caused by a GH-secreting pituitary adenoma, associated with many comorbidities and increased risk of mortality. Surgery is the first-line therapy. Success of therapy is measured by symptomatic improvement, preservation of pituitary function and biochemical control. Trans-sphenoidal surgery (TSS), endoscopic or microscopic, is the preferred treatment. To evaluate surgery effectiveness and individuate the technique associated with a higher remission rate, patients undergoing TSS were retrospectively selected. METHODS: Thirty-seven consecutive patients underwent surgery between 1996 and 2006. Tumors were classified into macroadenomas or microadenomas and into intrasellar, extrasellar and extrasellar with cavernous sinus invasion. Surgery was performed in 22 patients with endoscopic technique, in 15 patients with microsurgical approach. The hormonal assays were performed 6 months and yearly after surgery for an average of 5 years. RESULTS: Ten patients were affected by microadenoma, 27 by macroadenoma. In microadenomas remission rate was independent of the used technique. Within macroadenomas, remission percentage in endoscopic approach (68.75%) was significantly higher than in microscopic approach (18.18%) (P=0.018). Postsurgical biochemical remission was calculated combining the surgical technique and tumor extension: the endoscopic approach was associated with a significantly higher remission rate in extrasellar than both in intrasellar and extrasellar with cavernous sinus invasion. In the latter group, any technique had not reached biochemical remission. CONCLUSION: TSS is able to induce a long-term remission of acromegaly, with low risk of recurrence and complications. Endoscopic approach is more suitable than microscopic technique in macroadenomas and adenomas with suprasellar extension.

Combined treatment of odontogenic keratocysts: initial marsupialization and successive enucleation with peripheral ostectomy plus Carnoy's solution application. A five-year follow-up experience.

AIM: The odontogenic keratocyst (KCOT) is a locally aggressive, cystic jaw lesion with a high growth potential and a propensity for recurrence. Considering its neoplastic features, treatments of keratocysts are required and they are generally classified as conservative or aggressive. However, although in literature there are several studies, the choice of treatment strategies remains controversial. We report a two-stage protocol based on initial marsupialization and successive enucleation. METHODS: Three cases of large KCOTs have been treated by initial marsupialization and, after a mean period of six months, successive enucleation with peripheral ostectomy and application of Carnoy's solution was performed. RESULTS: All patients were instructed in daily irrigation using chlorhexidine 0.2% during the period of marsupialization. After enucleation, good healing was obtained in all cases and from two up to five years of follow-up, there is no evidence of recurrence. CONCLUSION: Two-stage surgical treatment protocol of keratocyst leads to complete healing, preservation of important anatomical structures and absence of recurrence.

Use of fresh frozen bone graft in rehabilitation of maxillar atrophy.

AIM: Fresh frozen bone (FFB) is homologous bone obtained from human donors, provided by Tissue Banks. It is a graft material in reconstructive surgery; it is currently and widely used in orthopedic surgery and lately it has been introduced in oral and maxillofacial surgery. The purpose of this work was to show the use of fresh frozen homologous bone for bony augmentation of the maxilla and mandible in preparation for dental reconstruction with endosseous implants, as an effective alternative to harvesting and grafting autogenous bone from intra- or extra-oral donor sites. METHODS: The case presented clinically demonstrates the use of FFB grafts in the vertical augmentation of a severe maxillary atrophy in general anesthesia, and the outpatient treatment with implants insertion and prosthetic restoration. Histologic evaluation of graft biopsy six months after surgery is added to clinical assessments. RESULTS: Clinical outcome is shown with good volumetric and morphological reconstruction of the alveolar ridge without the need of a donor site. Excellent graft integration and bleeding newly formed bone was seen at the second surgical step (six months after FFB grafting), when fixation screws were removed and implant placement procedure was performed. CONCLUSION: The use of FFB in major preprosthetic surgery may be an acceptable therapeutic alternative to the autogenous block graft (harvested from iliac crest or calvarium) for its success rate as graft material. Benefits include: surgical procedure with reduced discomfort and infection risk as a second operation field to harvest the graft is avoided; FFB is safe, cheap and available in programmed amounts, its use can significantly reduce operating time.

Vibrationally Resolved Absorption and Emission Spectra of Dithiophene in the Gas Phase and in Solution by First-Principle Quantum Mechanical Calculations.

The absorption and emission spectra of dithiophene have been computed in different environments (gas phase, apolar, and polar solvents) and at different temperatures, including Duschinsky, temperature and solvent effects at full ab initio level, and considering the anharmonicity of the double well potential associated with the inter-ring torsional mode. The computed spectra are in very good agreement with the experimental ones, allowing for a complete assignment of the main vibrational features. Five different density functionals (BLYP, B3LYP, CAM-B3LYP, BHLYP, and PBE0) have been tested, and CAM-B3LYP and PBE0 are the most accurate.

Four-year clinical and neuroradiological follow-up of a papillary tumor of the pineal region.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

The self-association coiled-coil domain of PML is sufficient for the oncogenic conversion of the retinoic acid receptor (RAR) alpha.

In acute promyelocytic leukemia (APL) the retinoic acid receptor alpha (RARα) becomes an oncogene through the fusion with several partners, mostly with promyelocytic leukemia protein (PML), all of which have in common the presence of a self-association domain. The new fusion proteins, therefore, differently from the wild-type RARα, which forms only heterodimers with retinoic X receptor alpha, are also able to homo-oligomerize. The presence of such a domain has been suggested to be crucial for the leukemogenic potential of the chimeric proteins found in APL blasts. Whether or not any self-association domain is sufficient to bestow a leukemogenic activity on RARα is still under investigation. In this work, we address this question using two different X-RARα chimeras, where X represents the coiled-coil domain of PML (CC-RARα) or the oligomerization portion of the yeast transcription factor GCN4 (GCN4-RARα). We demonstrate that in vitro both proteins have transforming potential, and recapitulate the main PML-RARα biological properties, but CC-RARα is uniquely able to disrupt PML nuclear bodies. Indeed, in vivo only the CC-RARα chimera induces efficiently APL in a murine transplantation model. Thus, the PML CC domain represents the minimal structural determinant indispensable to transform RARα into an oncogenic protein.

TGF-beta1 and VEGF after fresh frozen bone allograft insertion in oral-maxillo-facial surgery.

Bone regeneration technique using allografts is widely used in oral surgery to repair alveolar defects and to increase alveolar volume for endosseous implant insertions. Bone allografts promote the reabsorption and neo-synthesis of bone tissue, which are regulated by numerous cytokines, proteins and growth factors. In this study, six patients with insufficient alveolar volume for endosseous implant insertions, were treated with bone regeneration technique using Fresh Frozen Bone (FFB) allografts collected from the femoral head or the hip. Samples of bone graft collected during graft insertion surgery and biopsies collected six months later during implantology were fixed, decalcified and analyzed histomorphologically and morphometrically by haematoxylin-eosin staining. In addition, TGF-beta1 and VEGF were analyzed by immunohistochemistry. The histological analysis of FFBs showed wide areas of calcified bone organized in osteons intermingled with areas of non-calcified matrix containing osteoblasts. However, the regenerated alveolar bone, collected six months after the graft insertion surgery, showed wide areas of non-calcified matrix. TGF-beta1 and VEGF were less expressed in FFB than in regenerated alveolar bone.

Type-3 metabotropic glutamate receptors negatively modulate bone morphogenetic protein receptor signaling and support the tumourigenic potential of glioma-initiating cells.

Targeted-therapies enhancing differentiation of glioma-initiating cells (GICs) are potential innovative approaches to the treatment of malignant gliomas. These cells support tumour growth and recurrence and are resistant to radiotherapy and chemotherapy. We have found that GICs express mGlu3 metabotropic glutamate receptors. Activation of these receptors sustained the undifferentiated state of GICs in culture by negatively modulating the action of bone morphogenetic proteins, which physiologically signal through the phosphorylation of the transcription factors, Smads. The cross-talk between mGlu3 receptors and BMP receptors was mediated by the activation of the mitogen-activated protein kinase pathway. Remarkably, pharmacological blockade of mGlu3 receptors stimulated the differentiation of cultured GICs into astrocytes, an effect that appeared to be long lasting, independent of the growth conditions, and irreversible. In in vivo experiments, a 3-month treatment with the brain-permeant mGlu receptor antagonist, LY341495 limited the growth of infiltrating brain tumours originating from GICs implanted into the brain parenchyma of nude mice. While clusters of tumour cells were consistently found in the brain of control mice, they were virtually absent in a large proportion of mice treated with LY341495. These findings pave the way to a new non-cytotoxic treatment of malignant gliomas based on the use of mGlu3 receptor antagonists.

Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet.

Skeletal demineralization and mineral metabolism derangement are well-recognized features of untreated celiac disease (CD). Although treatment with a gluten-free diet appears to prevent bone loss while correcting skeletal demineralization in childhood, there is evidence that bone mineral density does not return to normal in celiacs diagnosed in adulthood. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, and ligand of receptor activator of NFkB (RANKL) are involved in the process of bone turnover and have been implicated in the pathogenesis of osteoporosis and other metabolic bone diseases. We measured OPG, RANKL, bone mineral density (BMD), and biochemical markers of bone turnover in 32 adult female premenopausal celiac patients on a gluten-free diet, and thirty age-matched healthy women. We correlated the OPG/RANKL ratio with the severity of bone loss. Celiac patients had a mean BMD lower than controls in lumbar spine and in the femoral neck. Serum levels of bone alkaline phosphatase (BAP, marker of bone formation), and urinary excretion of telopeptides of type I collagen (a marker of bone resorption) were significantly higher than in controls. Serum OPG and RANKL levels were significantly higher in CD patients than in controls, while the OPG/RANKL ratio was significantly lower in CD patients than in controls and was positively correlated with BMD at the spine. The role of elevated OPG in CD patients is unclear, but it might represent a compensatory mechanism against other factors that promote bone damage. Further studies are required to assess a possible therapeutic potential of osteoprotegerin in optimally treated celiacs with persistent osteopenia.

Sub-neurotoxic neonatal anoxia induces subtle behavioural changes and specific abnormalities in brain group-I metabotropic glutamate receptors in rats.

Anoxia in the first week of life can induce neuronal death in vulnerable brain regions usually associated with an impairment of cognitive function that can be detected later in life. We set-up a model of subneurotoxic anoxia based on repeated exposures to 100% nitrogen during the first 7 days of post-natal life. This mild post-natal exposure to anoxia specifically modified the behaviour of the male adult rats, which showed an attention deficit and an increase in anxiety, without any impairment in spatial learning and any detectable brain damage (magnetic resonance imaging and histological analysis). Post-anoxic rats showed a reduction in the expression of group-I metabotropic glutamate receptors (i.e. mGlu1 and mGlu5 receptors) in the hippocampus and cerebral cortex, whereas expression of the mGlu 2/3 receptors, the NR1 subunit of NMDA receptors, and the GluR1 subunit of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors was unchanged. mGlu1 and mGlu5 receptor signalling was also impaired in postanoxic rats, as revealed by a reduced efficacy of the agonist (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) to stimulate polyphosphoinositide hydrolysis in hippocampal slices. We conclude that rats subjected to subneurotoxic doses of anoxia during the early post-natal life develop behavioural symptoms that are frequently encountered in the inattentive subtype of the attention deficit hyperactivity disorder, and that group-I mGlu receptors may be involved in the pathophysiology of these symptoms.

Hepatitis C-associated osteosclerosis (HCAO): report of a new case with involvement of the OPG/RANKL system.

We report a new case of hepatitis C-associated osteosclerosis (HCAO). The clinical presentation of the patient was an acquired deep severe bone pain with increased serum bone alkaline phosphatase activity (up to 12 times the upper limit of normal), and generalized bone sclerosis, temporally related to the hepatitis C-virus (HCV) infection. We documented in this patient an increase of circulating osteoprotegerin (OPG), and a concentration of circulating receptor activator for nuclear factor-kB ligand (RANKL) below the lower limit of the reference range. The observed abnormalities of the OPG/RANKL system may contribute to the maintenance of the positive balance of bone remodeling that characterizes patients with HCAO.

A Theoretical Study on the Factors Influencing Cyanine Photoisomerization: The Case of Thiacyanine in Gas Phase and in Methanol.

The effects influencing cyanine photoisomerization on the S1 surface in the condensed phase have been investigated by an integrated quantum mechanical approach, focused mainly on 3,3'-diEt-2,2'-thiacyanine. After excitation, a barrierless motion, involving the torsion coupled to bond skeletal deformation, leads to a slightly nonplanar local C2 minimum, which we propose to be the fluorescent state. Crossed a barrier of ≈120 cm(-)(1), a steeper path drives to a more stable C1 minimum S1-Min, corresponding to a pseudoperpendicular twisted intramolecular charge transfer (TICT) state. CAS(6,6) optimization allows for locating the lowest energy S1/S0 conical intersection in the isomerization path which is reached from S1-Min by an increased asymmetry of the two rings and a marked pyramidalization at one N center. The S1 surface is rather flat in the Franck-Condon region and suggests that other paths can be competitive with the minimum energy one. The comparison among different cyanines shows how variation of the molecular scaffold and/or of its substituents modulate the dynamics of the photoisomerization. All the indications coming from our computations are in line with and provide an explanation to the available experimental results.

Evaluation of the use of iliac cancellous bone and anorganic bovine bone in the reconstruction of the atrophic maxilla with titanium mesh: a clinical and histologic investigation.

The present article describes a titanium mesh procedure used for bone augmentation in the treatment of severe maxillary atrophy. A mix of iliac cancellous bone and anorganic bovine bone in a 1:1 ratio is proposed for achieving the best bone quality at the time of implant placement, which is performed 5 to 6 months after the augmentation surgery. This procedure provides for 3-stage surgery using a titanium mesh (which is removed 4 to 5 months later) to retain the cancellous bone/Bio-Oss mixture. Bone specimens taken 5 to 6 months after the augmentation procedure showed bone regeneration and the presence of vessels, indicating bone vitality.

Three-dimensional facial morphometric assessment of soft tissue changes after orthognathic surgery.

OBJECTIVE: In this study, a 3-dimensional system with landmark representation of the soft tissue facial surface was applied for the evaluation of facial changes occurring after orthognathic surgery in 5 patients. STUDY DESIGN: Standardized facial landmark acquisitions were performed before and 1 year after surgery (combined maxillary Le Fort I and sagittal mandibular osteotomies). The 3-dimensional coordinates of 22 facial soft tissue points were collected on each subject through use of a computerized noninvasive method and used to calculate a set of selected parameters. RESULTS: Three-dimensional soft tissue analysis of patients was in general agreement with the type of surgery performed, with volumetric contraction of the lower facial third and expansion of the middle facial third. Moreover, negative effects of surgery were quantified (eg, an increase in alar base dimensions); the global asymmetry of facial soft tissues was increased by intervention, but asymmetry in the lower facial third was reduced. CONCLUSIONS: The method used in this study proved useful as a complementary diagnostic aid, enabling quantitative evaluation of the final soft tissue results of surgery, which were proportional to those expected on the basis of the type of treatment and skeletal data.

Long-term results with autogenous onlay grafts in maxillary and mandibular atrophy.

This paper describes onlay graft procedures and discusses the technical considerations involved in one- or two-stage implant placement. The results of a 5-year clinical experience with such procedures are reported. Intra- and extraoral donor sites were used to harvest cortico-cancellous grafts: 25 patients were treated with chin monocortical grafts, 8 patients with monocortical hip grafts, and 18 patients with bicortical hip grafts, depending on the size of the defect and the location of the graft. The monocortical grafts were used in the maxilla, and the bicortical grafts in the mandible. Four months after the surgery, a reentry procedure was performed to place implants in the patients with monocortical grafts, while the implants in the mandibular onlays were placed simultaneously with bone augmentation. CT (computer tomography) and Panorax comparisons were made 24 hours postoperatively; after 4 months for the monocortical grafts only; and after 1, 3, and 5 years to evaluate the bone resorption. The results obtained with the onlay grafts suggest that this is the method of choice for solving different kinds of alveolar and basal jaw bone reabsorption. Either a monocortical bone or a bicortical graft (type 1 or type 2 bone atrophy, respectively) with the osseointegrated fixtures-bone graft combination were found to guarantee acceptable reabsorption of a graft during 5 years and prevented failure of the prosthetic rehabilitation. In monocortical grafts, delayed fixture placement by 4-6 months is the most predictable; the one-stage procedure is preferred for the bicortical hip graft in the mandible.

[Transmyocardial laser revascularization in patients with peripheral coronary atherosclerosis. Indications and preliminary results]. / Rivascolarizzazione transmiocardica laser in pazienti con coronarosclerosi periferica. Indicazioni e risultati preliminari.

BACKGROUND: Surgical intervention for coronary artery disease (CAD) is determined by the viability of coronary artery branches. When peripheral coronary artery disease is present, conventional bypass grafting is not suitable. Research has recently been done on alternative methods such as transmyocardial laser revascularization (TMLR). TMLR works through the vascular connections that are present between the cardiac chambers and the myocardial muscle in the human heart. The creation of 1-mm transmural cardiotomies through a CO2 laser should improve myocardial perfusion. METHODS: From February to June of 1996, twelve patients (9 males and 3 females with a mean age of 67.8 +/- 4.6) with CAD (mean n0 of diseased vessels 2.7), angina (mean CCS class 3.5 +/- 0.5), mean ejection fraction 47.8% and viable ischemic myocardium on scintiscan in segments without graftable coronary branches, underwent TMLR at our institute. Nine of the 12 patients also underwent associated CABG (mean number of anastomoses per patient: 2.5). Cardiopulmonary bypass was never used, since coronary anastomoses and laser cardiotomies were performed on the beating heart. RESULTS: Perioperative mortality was 2/12 (16.6%). Postoperative inotropic support and diuretic therapy was required in most cases. At a mean follow-up period of 4.2 months, all remaining patients are still alive: 5/10 are angina-free (CCS 0), 4/10 are in CCS class 1 and 1/10 is in CCS class 2 (mean 0.6 +/- 0.7). CONCLUSIONS: We believe that TMLR could be considered an effective mean to treat symptomatic myocardial ischemic disease in which coronary bypass grafting is not suitable. During the immediate postoperative period, contractile myocardial dysfunction occurs in a high percentage of patients treated using TMLR and consequently it would be worthwhile to invest in further research.

Bidirectional inferior vena cava-pulmonary artery shunt.

BACKGROUND: Bidirectional superior vena cava-pulmonary shunt is widely used as an interim palliation for patients with univentricular hearts. Bidirectional inferior vena cava-pulmonary artery shunt, as an alternative approach of partial Fontan circulation, may offer the advantage of performing the complete Fontan circulation more easily due to the already constructed inferior vena cava lateral tunnel. METHODS: We used bidirectional inferior vena cava-pulmonary artery shunt in 2 patients. Contraindications to a complete Fontan circulation were due to, respectively, a volume-overloaded systemic ventricle and an irregular pulmonary arterial tree. RESULTS: Postoperative courses were uneventful. There were no significant pleural effusions. Transcutaneous oxygen saturations were 77% and 78%. Pulmonary-to-systemic blood flow ratios were 0.57 and 0.63. A complete Fontan circulation was safely performed 8 and 12 months later, without any "Fontan-related" complications. CONCLUSIONS: Bidirectional inferior vena cava-pulmonary artery shunt can be useful in selected patients with univentricular hearts, although its place in the field of "partial Fontan operations" cannot be determined as yet.

Primary cardiac malignancy presenting as left atrial myxoma. Clinical and surgical considerations.

Primary heart neoplasms occur in 0.002-0.3% of autopsies: 30% are myxomas and 20-30% are malignancies, almost always sarcomas. Cardiac metastases are 10 to 40 times more frequent than primary heart cancer. We describe a case of a left atrial sarcoma erroneously diagnosed as myxomas preoperatively. Standard surgical indication for resection of cardiac myxomas is based on echocardiography. Because of the severity of cardiac malignant lesions than can mimic atrial myxomas at echocardiography, through preoperative investigation should be accomplished, best by magnetic resonance imaging. In case of suspected malignancy, total body computed tomography should be performed to avoid unnecessary cardiac operations in case of disseminated cancer. To date the only good medium and long-term results in the therapeutic management of heart sarcomas have been achieved by transplantation: the probable explanation is that criteria of surgical radicality should be those followed for soft tissue tumors located elsewhere in the organism.