Claudio Parrilla

Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models.

Local gene transfer of the human Lim mineralization protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. To develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP-3 and seeded on a hydroxyapatite/collagen matrix prior to autologous implantation. Here, we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing, as determined by X-rays, histology and three-dimensional microcomputed tomography (3DμCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3 in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation.

Multidisciplinary Approach in the Treatment of T1 Glottic Cancer The Role of Patient Preference in a Homogenous Patient Population

AbstractBackground and Purpose:To compare oncological outcome and voice quality among a uniform and well-defined subset of patients with T1 glottic carcinoma.Patients and Methods:Patients, affected by laryngeal glottic carcinoma, treated by laser CO2 surgery or radiotherapy, have been analyzed. Overall survival and disease-free survival were calculated. In order to verify differences in functional outcomes and voice quality, all patients were interviewed during their last follow-up visit during 2009 using the VHI (Voice Handicap Index) questionnaire. The data were analyzed using the MedCalc software.Results:A total of 143 patients were analyzed: 73 underwent surgery and 70 underwent radiotherapy. No statistically significant differences were found between the two groups in terms of overall survival and disease-free survival; dividing patients into stages T1a and T1b also made no difference. In order to evaluate the differences in outcomes for surgery and radiotherapy, patients were interviewed using the VHI questionnaire. Better scores for each category in the VHI were found for patients receiving radiotherapy compared to surgery (physical: p = 0.0023; functional: p < 0.0001; environmental: p < 0.001). The median VHI score for radiotherapy patients was 4, while for surgical patients it was 18 (p < 0.0001).Conclusion:This study confirms the well-known knowledge that results from radiotherapy and surgery in early glottic cancer treatment are equivalent. Furthermore, the role of patient preference in the treatment modality choice and the value of a multidisciplinary approach for a detailed and multi-oriented discussion with the patient are outlined.ZusammenfassungHintergrund und Zielsetzung:Es sollen das onkologische Ergebnis und die Sprachqualität in einer homogenen und gut definierten Gruppe von Patienten mit T1-Stimmbandkarzinomen verglichen werden.Patienten und Methoden:Patienten mit einem Glottiskarzinom, die sich einer CO2-Laser-Operation oder einer Radiotherapie unterzogen hatten, wurden analysiert. Das Gesamtüberleben und die krankheitsfreie Zeit wurden errechnet. Um Unterschiede im funktionellen Ergebnis und bezüglich der Sprachqualität zu quantifizieren, wurden alle Patienten während der letzten Nachsorge im Jahre 2009 dazu angehalten den VHI-(Voice Handicap Index-)Fragebogen auszufüllen. Diese Daten wurden mittels der MedCalc-Software bearbeitet.Ergebnisse:Insgesamt wurden 143 Patienten untersucht: 73 wurden operiert und 70 erhielten eine Strahelentherapie. Es konnte kein statistisch signifikanter Unterschied zwischen den zwei Gruppen bezüglich der Gesamtüberlebenszeit und der krankheitsfreien Zeit festgestellt werden; dies gelang auch nicht, wenn die Gruppen in Stadium T1a und T1b getrennt betrachtet wurden. Um die Unteschiede zwischen Operation und Radiotherapie zu evaluieren, wurde der VHI-Fragebogen verwendet. Es ließ sich zeigen, dass in jeder Kategorie des VHI-Fragebogens die Patienten, die strahlentherapiert wurden, bessere Ergebnisse erzielten als jene, die operiert wurden („physikalisch“: p = 0,0023; „funktionell“: p < 0,0001). Der durchschnittliche VHI-Score für strahlentherapierte Patienten ist 4, im Gegensatz zu 18 für operierte Patienten (p < 0,0001).Zusammenfassung:Diese Studie bestätigt die Erkenntnis, dass Radiotherapie und Operation beim Stimmbandkarzinom im frühen Stadium zu äquivalenten Ergebnissen führen. Weiterhin wird die Bedeutung des Patientenwunsches im Hinblick auf die Therapieoptionen und die Bedeutung eines multidiszplinären Therapieansatzes belegt.

ENDOSCOPIC HORIZONTAL PARTIAL LARYNGECTOMY BY CO2 LASER IN THE MANAGEMENT OF SUPRAGLOTTIC SQUAMOUS CELL CARCINOMA

The objective of this study was to evaluate the results of endoscopic horizontal supraglottic laryngectomy (EHSL) by CO2 laser.

Undifferentiated Human Adipose Tissue-Derived Stromal Cells Induce Mandibular Bone Healing in Rats

OBJECTIVE To test the osteo-regenerative potential of adipose tissue-derived stromal cells (ATSCs), an attractive human source for tissue engineering, in a rat model of mandibular defect. Human dermal fibroblasts (HDFs) were used as a differentiated cellular control in the study. DESIGN The ATSCs and HDFs were isolated from human lipoaspirate and skin biopsy specimens, respectively. Cells were characterized in vitro and then adsorbed on an osteo-conductive scaffold to be transplanted in a mandibular defect of immunosuppressed rats. Naked unseeded scaffold was used as a negative control. MAIN OUTCOME MEASURES Bone healing was studied by computerized tomography and histologic analysis after 4, 8, and 12 weeks. RESULTS Computed tomography showed that undifferentiated ATSCs induced successful bone healing of the mandible defect when transplanted in animals, compared with HDFs and negative controls. Histologic analysis demonstrated that the newly formed tissue in the surgical defect retained the features of compact bone. CONCLUSION Undifferentiated human ATSCs are suitable for cell-based treatment of mandibular defects, even in the absence of previous osteogenic induction in vitro.

Endoscopic transsphenoidal approach versus microscopic approach in children

OBJECTIVES To confirm the efficacy and safeness of the endoscopic endonasal transsphenoidal (ETS) approach in the treatment of sellar and parasellar lesions in children compared with the conventional microscopic transsphenoidal approach (CTS). STUDY DESIGN Case series with chart review. SETTING A. Gemelli - University Hospital - Catholic University of Sacred Heart - Rome. SUBJECT AND METHODS We retrospectively evaluate 21 children (mean age 8.3 years) affected by sellar/parasellar lesions: 11 were treated via microscopic sublabial approach between 1995 and 2005 and 10 were treated with ETS approach between 2006 and 2009. RESULTS The past series (group A) comprised all sellar/suprasellar lesions and we observed: gross total surgical excision in 81.2% of cases, permanent morbidity in 1/11 patients, CSF fistula in 1/11 patients, mean hospitalization time of 5.8 days and PICU was required. The present series (group B) included 8 sellar/suprasellar and 2 clival lesions and we observed: GTS excision in 80% of the cases, no permanent morbidity, a mean hospitalization time of 4.1 days (P=0.01), CSF fistula in 2/10 patients and the PICU was not required. 10/11 patient of group A underwent to blood transfusion vs 4/10 of the group B (P=0.008). The mean pain score of group A was 5.8 ± 1.7 on the contrary in the group B it was 4.1 ± 1.5 (P=0.006). CONCLUSION The ETS approach to the sellar and parasellar region has proved its reliability and effectiveness in the adults. The minimal invasiveness makes it ideal for the treatment of pediatric lesion of this region, in which it is essential to preserve the integrity of the hypothalamic-pituitary axis and of the naso-facial structures to assure the correct growth of the child.

Oncologic outcomes in advanced laryngeal squamous cell carcinomas treated with different modalities in a single institution: A retrospective analysis of 65 cases

Treatment for laryngeal squamous cell carcinoma (SCC) has been predominantly surgical for decades, but in the last 20 years nonsurgical modalities (radiotherapy), with the aim of organ preservation, also became predominant among advanced stages. Retrospectively evaluating our series of stage III and stage IV laryngeal SCCs, we compared the 2 main therapeutic modalities.

Erbium: yttrium-aluminum-garnet laser stapedotomy—A safe technique

Objective To standardize the technical parameters of the erbium: yttrium-aluminum-garnet (Er:YAG) laser stapedotomy. Study Design Retrospective study of all patients with otosclerosis who underwent stapedotomy from January 2002 to January 2006. Subjects and Methods The charts of 152 consecutive patients who underwent stapedotomy were reviewed. The patients were stratified into two groups, according to the instrument used. Stapedotomies were performed in group A, with the OPMI®TwinEr: YAG laser; and in group B with manual microperforators. Results No statistically significant differences were found over all measured frequencies, between pre- and postoperative bone conduction thresholds, in each group. At the last postoperative follow-up, vertigo and nystagmus were not detected; two patients in group A and one patient in group B showed persistent tinnitus. Conclusion Er:YAG laser stapedotomy is a safe and effective procedure, with no damage of the inner ear when strict adherence to the safety parameters is observed. The Er:YAG laser is definitively suitable for stapes surgery, and represents a useful and safe tool in the armamentarium of otological microsurgery.

Early transcriptional events during osteogenic differentiation of human bone marrow stromal cells induced by Lim mineralization protein 3.

Lim mineralization protein-3 (LMP3) induces osteoblast differentiation by regulating the expression and activity of certain molecules involved in the osteogenic cascade, including those belonging to the bone morphogenetic protein (BMP) family. The complete network of molecular events involved in LMP3-mediated osteogenesis is still unknown. The aim of this study was to analyze the genome-wide gene expression profiles in human mesenchymal stem cells (hMSC) induced by exogenous LMP3 to mediate osteogenesis. For this purpose hMSC were transduced with a defective adenoviral vector expressing the human LMP3 gene and microarray analysis was performed 1 day post-adenoviral transduction. Cells transduced with the vector backbone and untransduced cells were used as independent controls in the experiments. Microarray data were independently validated by means of real-time PCR on selected transcripts. The statistical analysis of microarray data produced a list of 263 significantly (p < 0.01) differentially expressed transcripts. The biological interpretation of the results indicated, among the most noteworthy effects, the modulation of genes involved in the TGF-beta1 pathway: 88 genes coding for key regulators of the cell cycle regulatory machinery and 28 genes implicated in the regulation of cell proliferation along with the development of connective, muscular, and skeletal tissues. These results suggested that LMP3 could affect the fine balance between cell proliferation/differentiation of mesenchymal cells mostly by modulating the TGF-beta1 signaling pathway.

Oncologic results of the surgical salvage of recurrent laryngeal squamous cell carcinoma in a multicentric retrospective series: Emerging role of supracricoid partial laryngectomy

Several studies in the last decade evaluated conservative surgical procedures and, in particular, supracricoid operations as an alternative to total laryngectomy for the salvage of recurrences of laryngeal squamous cell carcinoma (SCC) after a first attempt of organ preservation.

Oncological results of the surgical salvage of recurrent laryngeal SCC in a multicentric retrospective series. The emerging role of supracricoid partial laryngectomy

Several studies in the last decade evaluated conservative surgical procedures and, in particular, supracricoid operations as an alternative to total laryngectomy for the salvage of recurrences of laryngeal squamous cell carcinoma (SCC) after a first attempt of organ preservation.