In vitro evaluation of biomimetic chitosan-calcium phosphate scaffolds with potential application in bone tissue engineering.

This work reports on the physicochemical properties and in vitro cytotoxicity assessment of chitosan-calcium phosphate (Cs-CP) scaffolds for bone tissue engineering, which were synthesized by a novel biomimetic co-precipitation method. X-ray diffraction (XRD) along with scanning electron microscopy (SEM) analysis confirmed the porous morphology of the scaffolds and the amorphous nature of the inorganic phase with different crystallite sizes and the formation of various forms of calcium phosphate. Compressive mechanical testing revealed that the Young's modulus of the biomaterials is in the range of human trabecular bone. In vitro tests were performed on the biomaterials for up to 14 days to study the behavior of the osteoblast-like human cell line (MG63), primary human osteoblasts (HOS) and human dermal microvascular endothelial cells (HDMEC). The cytotoxicity was evaluated by the MTS assay for cell metabolism and the detection of membrane integrity (lactate dehydrogenase-LDH release). An expression of the vascular endothelial growth factor (VEGF) in the cell supernatants was quantified by ELISA. Cell viability gave values close to untreated controls for MG63 and HOS, while in the case of HDMEC the viability after 2 weeks in the cell culture was between 80-90%. The cytotoxicity induced by the Cs-CP scaffolds on MG63, HOS and HDMEC in vitro was evaluated by the amount of LDH released, which is a sensitive and accurate marker for cellular toxicity. The increased levels of VEGF obtained in the osteoblast culture highlights its important role in the regulation of vascularization and bone remodeling. The biological responses of the Cs-CP scaffolds demonstrate a similar proliferation and differentiation characteristics of the cells comparable to the controls. These results reveal that biomimetic Cs-CP composite scaffolds are promising biomaterials for bone tissue engineering; their in vivo response remains to be tested.

[In vitro trials with single and co-cultures of osteoblasts and endothelial cells : evaluation of new biomaterials for bone reconstruction and regeneration]. / Bewertung von neuartigen Biomaterialien zum Zweck der Knochenrekonstruktion und -regeneration : In-vitro-Versuche mit Mono- und Kokulturen von Osteoblasten und Endothelzellen.

Many different types of bone substitute biomaterials are being developed for different applications in the body. The current dogma is that if osteoblasts and endothelial cells grow and exhibit normal cell functions on these materials in vitro as single cultures or in co-cultures, then the biomaterials are suitable for implantation for bone reconstruction and regeneration. Generally, only in vivo animal studies will prove whether this is the case. However, in vitro studies offer a good pre-screening and selection basis to evaluate the biocompatibility of novel biomaterials prior to animal studies. Multicell type co-culture systems hold a great promise for the future.

Nasal cheek flap in ethmoidal and skull base tumour surgery: results and complications.

Surgery is the treatment of choice for the management of malignant nasal/ethmoidal tumours, followed, in most cases, by external radiotherapy. Two main procedures are adopted to resect these tumours depending upon stage and extension: ethmoidectomy and medial maxillectomy, via a transfacial approach, or craniofacial resection with a combined transcranial and transfacial approach. The nasal cheek flap technique allows complete nasal swing thus obtaining a wide access to both the nasal fossae and the ethmoidal labyrinth. Furthermore, this approach can also be used in the management of small intracranial tumours extended through the skull base to the nasal cavity, paranasal sinuses, upper and middle clivus. We have used the nasal cheek flap since 1992 with good aesthetic and functional results. Aim of the present study was to analyse personal experience, focusing on complications, aesthetic results and self-evaluation expressed by the patients.

Oropharyngeal carcinoma during pregnancy: clinical and psycho-oncological aspects.

Cancer is uncommon in pregnancy, occurring in approximately one out of 1000 pregnancies, although it has been noted that one out of 118 women diagnosed with cancer is pregnant at the time of diagnosis. In the last 10 years, two oropharyngeal carcinomas, (1 squamous cell carcinoma and 1 adenoid cystic carcinoma) which developed during pregnancy, have been diagnosed and treated in our Department. No cases of oropharyngeal cancer, during pregnancy, have so far been reported in the literature with the exception of one case of oral cancer. This report focuses not only on the clinical history but also the management of oropharyngeal carcinoma during pregnancy, in terms of choice and timing of treatment. A scrupulous psycho-oncological analysis was also carried out in order to throw further light on psychological repercussions of head and neck cancer in the pregnant woman.

[Hyperbaric oxygen therapy application in otorhinolaryngology and head and neck surgery: state of the art and review of literature]. / Applicazioni dell'ossigenoterapia iperbarica in otorinolaringoiatria e in chirurgia cervico-facciale: stato dell'arte e revisione della letteratura.

Hyperbaric Oxygen Therapy (HOT) encompasses an extensive research area in which new indications, some of which are now well-codified, have emerged both in the fields of medical and surgical pathology. Its utilization in carefully targeted clinical situations, in which its true efficacy can be demonstrated, is first of all connected with medicolegal responsibility, in suspected iatrogenic accidents; its application must furthermore be subordinated to a favourable cost/benefit ratio for the health service employing it. In otorhinolaryngology and head and neck surgery, HOT is a strategic therapeutic weapon in several applications. Its most widely recognized indications are radiation lesions, chronic osteomyelitis of the mandible, head and neck infections, malignant external otitis, sudden hypoacusia, chronic tinnitus, encephalitis, treatment of the gasseous embolus, skin grafts, vascularized flaps, cervicoencephalic traumas. HOT indications as a radiosensitizing and/or chemiosensitizing factor are still being studied. Both a review of the literature and our experience appear, beyond any doubt, to confirm that HOT promotes faster recovery and reduces hospital stays, thus qualifying as a new therapeutic aid that complements the usual well-established methods.

[Endoscopic follow-up of translaryngeal Fantoni tracheostomy]. / Follow-up endoscopico di tracheotomie translaringee sec. Fantoni.

Dilatational tracheotomy techniques are widely used in the long-term management of the respiratory tract in patients in intensive care units (ICU). The translaryngeal tracheotomy technique (TLT) was first described by Fantoni in 1993 and rapidly asserted itself, especially in Europe. This technique basically differs from the other percutaneous techniques in that it involves a progressive, retrograde, dilatation of the trachea in a single session conducted from inside the trachea, working outward, simultaneously exerting a counter-pressure on the pre-tracheal soft tissues with the fingers. The present study involves an endoscopy follow-up of 130 patients who had undergone TLT at the Intensive Care Unit of our Hospital between November 2000 and May 2001. The pre-operative oro-tracheal intubation time varied from 1 to 42 days. All patients filled out a brief questionnaire containing validated questions on their general health and quality of life with particular attention focused on respiratory conditions. Then, after receiving informed consent, the patients underwent laryngo-tracheoscopy with local anesthetic using a flexible tracheobronchoscope. All tests were recorded and viewed later by two operators in order to identify and divide the patients according to the level of execution of the tracheotomy and the presence of sequelae. The results obtained have shown that, like other percutaneous tracheotomy techniques, TLT provides some benefits including the fact that procedure can be performed at the bedside in a short time, with few post-operative complications, simpler nursing and fewer sequelae in time. Analysis of data concerning time of tracheostomy execution, tracheal level of stomia and nursing times has revealed three factors that determine severe sequelae: delay in tracheostomy execution, high level of execution with cricoid involvement and onset of problems during first tracheal cannula change.

[Complications of tracheostomy in critically ill patients: comparison of dilation and surgical techniques]. / Confronto sulle complicanze di varie tecniche tracheotomiche in area critica.

The tracheotomy, one of the oldest surgical procedures, has in recent years been the focus of particular attention given the undoubted, and not always justified, increase in indications, and by the introduction of dilatational tracheotomy techniques, particularly in critically patients. The present work compares the standard surgical tracheotomy with the more recent percutaneous techniques (Ciaglia dilatational tracheotomy and Fantoni translaryngeal tracheotomy). In particular, the relationship between the technique adopted, timing and complications were analyzed for 215 tracheotomies performed at different Intensive Care Units at our Hospital between 1993 and 1998 (106 performed using the standard surgical technique, 51 with the Ciaglia technique and 58 with the Fantoni technique). The pre-operative oro-tracheal intubation time ranged between 4-54 days (17 tracheotomies performed before oro-tracheal intubation). The results of this study showed that percutaneous techniques present fewer early post-operative complications (severe bleeding, erosive stomitis, dislocation of the cannula) and above all fewer sequelae in time (tracheal stenosis, tracheomalacia). The surgical procedures are shorter and nursing is limited to a few days which certainly results in a savings in health care resources. After decannulation, the esthetic result in patients that underwent the dilatational tracheotomy can be considered excellent. Among the disadvantages one must recall the possible dislocation of the cannula immediately after surgery: forced reinsertion of the cannula exposes the patient to the risk of creating a dangerous false route. The results obtained are statistically significant and in line with those found in the literature. The conclusion is drawn that, when performed by skilled surgeons and aided by endoscopy, the percutaneous tracheotomy techniques are the method of choice for patients in critical areas.

Is pressure dressing necessary after ear surgery?

Compressive bandages carry intrinsic risks and complications. The purpose of this study was to assess whether compressive head bandages are necessary after ear surgery to prevent complications such as hematoma or wound infection. A prospective, randomized, controlled study was conducted from August 1, 1993, to June 1, 1999. We randomly assigned 420 consecutive middle ear or mastoid operations to either a pressure bandage group or to a no-pressure bandage group. A careful follow-up was planned, and complications were recorded. In the pressure bandage group, 3 patients had bruising over the pinna and 70 patients had minor skin erythema when the dressing was removed. No patient had bruising or erythema in the no-pressure bandage group. No patient had hematoma, wound infection, or any other wound complication in either group. As a result of this study, we have decided to abandon the use of compression bandages after uncomplicated ear surgery.

Enlarged approach to the anterior cervical spine.

In this report a new enlarged approach to the anterior cervical spine is presented. A 66-year-old female, having a large C3-C4-C5 chordoma, recurrent after surgery and following radiotherapy, underwent a surgical resection. The approach allows a wide retraction of the nasopharynx, oropharynx and larynx from the midline, only sacrificing the superior laryngeal nerve on one side. Its continuity can be re-established later by adopting the stent in tube technique. The approach we used presents all the risks of infection common in trans-oral approaches. For this reason, closure of the pharynx in two layers must be meticulous and watertight and reinforced by using a myofascial sternocleidomastoid flap, according to the tracheoesophageal fistula closure technique. A correct alignment of the tongue, the pre-plating of the mandible and the correct suture of the vermillion border guarantee excellent cosmetic and functional results.

Pectoralis major myocutaneous flap: analysis of complications in difficult patients.

The purpose of this study was to assess and discuss the effects of old age and systemic diseases on complications related to the use of a pectoralis major myocutaneous flap (PMMF) for reconstruction in head and neck surgery. Eighty-four consecutive patients, operated on between January 1992 and December 1998, were included in the study. Of these patients, 47 were in relatively good condition, while 37were old and frail or affected by systemic diseases. Patients were monitored for complications during a follow-up of 2 years. All patients included in the study had very advanced squamous cell carcinomas (T3-T4) and reconstruction with PMMF was performed after a commando procedure, a total laryngectomy with partial pharyngectomy, or a composite resection. Necrosis of skin island was the most frequently encountered complication, but no surgical intervention was needed. Overall, complications occurred more frequently in patients with underlying pathologies, the risk ratio adjusted for age and sex being 2.94, but 95% confidence intervals were 0.99-8.65 and all complications were minor. In summary, we recommend the use of PMMF for immediate repair in difficult patients who have large oropharyngo-laryngeal excisions and radical neck dissections and who suffer concomitantly with various medical problems known to increase complication rates. PMMF proved to be suitable to give these patients good chances of a quick recovery with satisfactory aesthetic and functional results.

New options for aerodigestive tract replacement after extended pharyngolaryngectomy.

OBJECTIVES: Assess the results of a new type of reconstruction of the aerodigestive tract after extended pharyngolaryngectomy. STUDY DESIGN: Follow-up of a total of eight patients who had surgery using ileocolic free graft. METHODS: The surgical technique is described. Five patients underwent pharyngolaryngectomy/cervical esophagectomy, and three patients had total laryngectomy with subtotal pharyngectomy. Patients were monitored to assess complications and recovery of satisfactory swallowing and speech. RESULTS: The technique, thanks to the use of material from the colon, proved to be extremely useful for the reconstruction of the digestive tract. At the same time, ileal anastomosis with the tracheal stump enabled aerodigestive crossing restoration, protected by the ileocecal valve. All patients recovered good swallowing capacity and phoniatric expression, which were obtained by digital occlusion of the tracheostomy, forcing the expiratory air through the ileum and ileocecal valve. Manometric tests also showed that after a while there was a gradual synchronization of swallowing between the transplanted colic segment and the residual esophagus. CONCLUSIONS: The technique described in the present study may be regarded, also in the light of possible further applications, as a new and interesting option for the reconstruction of the aerodigestive tract.

A multicenter trial of specific local nasal immunotherapy.

OBJECTIVE: To assess the efficacy and safety of specific local nasal immunotherapy (LNIT) in powder form in patients with allergic rhinitis, using subjective and objective parameters. STUDY DESIGN: A double-blind randomized multicenter trial of 102 patients with allergic rhinitis who were treated with specific LNIT for 8 consecutive months. METHODS: After identifying allergens with the skin prick test and sensitization threshold dose with the specific nasal provocation test, 102 patients were selected, of whom 55 were allergic to mites and 47 were allergic to Graminaceae or Parietaria pollen. The specific treatments were self-administered using an insufflator in two phases (phase 1: increasing doses; phase: 2, maintenance dose). Patients were evaluated before and after 32 weeks of treatment by subjective analysis of their self-reported symptoms and by objective analysis of nasal provocation test, nasal resistance by anterior rhinomanometry, and mucociliary clearance time. RESULTS: Clinical efficacy of LNIT for allergy to mites and pollens was confirmed by the differences in the symptoms score between the active group and the placebo group. The nasal provocation test results confirmed that this difference was statistically significant. The rhinomanometric analysis gave positive results for the treated group mainly in LNIT for mites. No differences in mucociliary clearance time were found. CONCLUSIONS: Specific LNIT is effective for allergic rhinitis and appears to offer considerable advantages over other hyposensitization methods. It can be done at home, patient compliance is good, and the treatment is safe.

[Equilibrium and orthognathodontic surgery: correlations in a group of patients undergoing treatment]. / Posturologia e chirurgia ortognatodontica. Correlazioni in un gruppo di pazienti trattati.

BACKGROUND: The aim of this study was to evaluate the main parameters provided by the static stabilometric test (mean X, mean Y, mean velocity, length of tracing, standard deviation of velocity, ellipse area) in the follow-up of patients suffering from skeletal occlusive pathology undergoing orthognathodontic surgery to confirm the re-establishment of postural equilibrium. METHODS: Fifteen patients with skeletal dysgnathia were correlated with a group of 10 healthy subjects. The same parameters were analysed in the dysgnathic subjects at 6 and 12 months after surgical correction. The patients enrolled in this study underwent surgery at the Division of Maxillofacial surgery of Turin University. Student's "t"-test and multivariate statistical analysis (Cox regression) were used for the statistical analysis of results. RESULTS: A significant variability was noted in some of the main parameters analysed (mean X, mean Y, tracing length) between the two populations (healthy and dysgnathic) compared to visual signs (eyes opened-closed). The change in stabilometric values within the group of dysgnathic patients was highly significant 6 and 12 months after surgery, not only in terms of visual signs but also the cervical component (retroflexion of the head), above all the value of mean Y (p = 0.001). CONCLUSIONS: An analysis of these results shows that static stabilometry can be a valuable aid both during the preoperative evaluation and during the follow-up in patients undergoing jaw surgery since it can quantify the improvement of body balance.

Reconstruction of the pharynx and cervical esophagus using ileocolic free autograft.

BACKGROUND: Advanced stage hypopharyngeal cancer is commonly treated by surgery and radiotherapy. This report presents a technique using ileocolic free autograft as a single-stage procedure for voice and swallowing rehabilitation after pharyngolaryngoesophagectomy. METHODS: Digestive tract restoration is obtained by using the cecum and ascending colon, while the last ileal loop, protected by the ileocecal valve for food and liquid inhalation, is anastomized to the cervical trachea. After abdominal harvesting, the ileocolic complex is transected, transposed, and then revascularized in the cervical field. RESULTS: Six patients underwent this operation successfully with recovery of swallowing function and vocal performance within a short period of time, varying from 18 to 38 days. CONCLUSION: On the basis of achieved results, the ileocolic free autograft can be considered a good option for pharyngoesophageal reconstruction, offering as it does an immediate restoration of swallowing and voice function.

[Tinnitus during headache: clinical-instrumental evaluation]. / Acufeni associati a cefalea: valutazioni clinico-strumentali.

During the five years running from December 1993 to January 1998, 112 patients who had come to our University Clinic suffering from headache were examined. From this group 71 complaining of tinnitus during headache were recruited for the study: 19 patients suffered from migraine without aura, 8 migraine with aura, 15 tension headache, 21 mixed headache, 3 basic migraine and 5 cluster headache. The purpose of this work was to determine the incidence and to identify the frequency of the various types of tinnitus in the study sample. Once cardiovascular and metabolic pathologies, previous cranial or cervical traumas, barotrauma, chronic on-the-job noise exposure, cervical arthritis, ATM malocclusion, use of drugs that damage the hearing apparatus, morbose processes of the external and middle ear, otosclerosis, jugular tympanum paraganglioma, Meniere's disease, acoustic neurinoma were all ruled out, the patients underwent the following battery of instrumental tests: tonal audiometry, impedance measurement, vestibular examination, electronystagmography, ABR, simplified tinnitometry. Only those patients with normal hearing underwent the tinnitometry and, therefore, the type of tinnitus was established only for this group of 53 patients. Tinnitometry showed that 37% of these subjects had tinnitus at the higher frequency tones, 11% at the middle frequencies, 29% complained of tinnitus at the lower frequencies while 23% complained that the bothersome buzzing was a compound noise. In addition, the subjective intensity of the tinnitus was analyzed. The authors devised a tinnitus irritation scale covering a range from 0 (not irritating) to 10 (intolerable). The tinnitus was bilateral in 66% of the cases while it was limited to only one ear in the remaining 34%. In 15% of the cases tinnitus was present even when there was no headache. In the literature, the etiopathogenesis of tinnitus associated with migraine headache has been attributed to vascular and neuropeptide mechanisms. Even the psychological component appears to play a role in triggering the event. These hypotheses deserve more in depth study.

[Ileocolic free autograft in advanced cervical oncology]. / La trasposizione ileo-colica nella patologia oncologica cervicale avanzata.

In head and neck oncology, cancer of the hypopharynx and esophagus still proves difficult to interpret because all treatments give poor results. In order to improve the quality of life for these patients as quickly as possible, one-step reconstructive methods such as the gastric pull-up and free autografts of revascularized intestinal segments are increasingly being used. This work presents a method for a free autograft of the ileocolic segment. After cervical pharyngolaryngoesophagectomy, this method provides a continent aerodigestive carrefour, protected by the ileocolic valve. Three patients successfully underwent this procedure. Deglutition and phonation were recovered quite quickly: between 18 and 38 days. On the basis of the results and after further, more in-depth experience--including adequate follow-up and post-radiotherapy coloesophageal electromanometry to determine the presence and type of motor propulsion exerted by the distal esophagus--the authors conclude that this method is one of the most interesting options available for the surgical reconstruction of pharyngoesophageal circular defects.

Twenty years of experience with Marullo's supraglottic laryngectomy.

We present a follow-up study of 142 patients on whom we performed supraglottic laryngectomy (SL) with an anterior subperichondral approach using Marullo's technique, which was described in 1975. Between January 1976 and December 1992, 142 patients (age range, 35-73 years) with squamous cell carcinoma of the supraglottic larynx were treated with SL or extended SL (ESL) and ipsilateral or bilateral neck dissections with or without postoperative radiotherapy. All cases were staged according to the 1997 UICC TNM classification. Survival was defined by the Kaplan-Meyer method and showed an overall survival of 77% and a local control rate of 78%. Regarding functional rehabilitation, the mean nasogastric tube-removal time was 16 days (range, 10-39 days) for SL and 23 days (range, 11-102 days) for ESL. Voice quality was very satisfactory after SL, while the voice was often harsh or breathy after ESL with postoperative radiotherapy. The overall oncologic and functional results obtained with Marullo's SL were very similar to those obtained with the classic Alonso's operation and demonstrated that this technique makes it possible to reach "en bloc" supraglottic sites and the hyothyroepiglottic space. We consider the operation to be safe and simple to perform, provided the sub-perichondral plane is correctly identified. This approach allows the surgeon easily to reach the correct transverse level above the anterior commissure of the vocal cords. Inferiorly, the resection cuts through the floor of the ventricle and is considered to be the safe oncologic plane for pure supraglottic lesions. This technique has also been used successfully in extended resections to treat tumors involving the base of the tongue, pyriform sinus and one arytenoid.

Angiogenesis: prognostic significance in laryngeal cancer.

The aim of this study was to evaluate the role of angiogenesis in the progression of laryngeal squamous cell carcinoma (LSCC). We correlated disease-free survival with microvessel count (MC) in the hot spot areas of 97 randomly selected caucasian males with LSCC followed for 60 to 90 months after surgery with or without radiotherapy. The results obtained indicate that: a) MC higher than 130 microvessels/mm2 is a cut-off value that distinguished patients who relapsed during the follow up period; b) multivariated analysis indicates that MC (p < 0.00001) is an independent predictor of disease free-survival; c) multivariated analysis selectively done on cases with relapse demonstrates that MC correlates with the presence of metastasis (or/and M) with local relapse (T). We suggest that MC is useful in the assessment of prognosis in LSCC and probably will permit selection of patients that could benefit from anti-angiogenic therapy associated with chemotherapy and/or radiotherapy.

[Reconstructive strategies in head and neck cancer: case history review from 1992 to 1997 (154 cases)]. / Strategie ricostruttive in oncologia cervico-cefalica: revisione della casistica (154 casi) degli anni 1992-97.

Technological progress in reconstructive surgery, in particular the use of pedunculated or free flaps, has given new impetus to head and neck dissection. This stems from the fact that such techniques provide greater oncological radicality, reduce the number of severe post-operative complications and give better quality of life. The present study examines 154 patients suffering from upper aero-digestive tract neoplasms (131 males and 23 females; age range 23-82 years) who had undergone radical surgery. Reconstruction was performed with flaps in 154 cases: 119 pedunculated flaps (102 large myocutaneous pectoral and 17 temporal muscle flaps) and 35 free flaps (18 radial osteofasciocutaneous, 13 radial fasciocutaneous and 4 omentum flaps). Analysis of the individual districts showed that the flap of choice was the temporal muscle flap when surgery involved the soft parts of the orbital-maxilly-zigomatic area and the rhinopharynx. This is because it is highly moldable and reliable. In surgery of the oral cavity and oropharynx the grand pectoral flap is most frequently used as it provides enough tissue for the reconstruction, adequately protects the vascular-nerve axis in the neck and it is quick and easy. However, the functional results are not the best and there is some alteration in the initial phases of deglutition. To reduce these problems, the authors encourage the use of free flaps which provide good results from both the functional and esthetic points of view. They are, however, more difficult to perform and this leads the authors to conclude that they should only be selected for certain patients (long life expectancy, female, young, etc.). In the center where the authors work the flap of choice is the radial fasciocutaneous or osteofasciocutaneous flap. In surgery of the hypopharynx and larynx reconstruction is normally performed with a grand pectoral myocutaneous flap, sculpted as needed for the individual case. In this region, reconstruction proves functionally satisfactory even when there is a minimum of residual mucosa. Finally, for reconstructive surgery of the apex, the omentum free flap was used as it is malleable and can be used to reconstruct broad areas of dissection. The esthetic and functional results, the low incidence of complications and the greater quality of life suggest that this type of flap be extended to the surgery of locally advanced tumors in combination with an accurate, valid reconstructive solution.