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There is often a need to more precisely identify the extent of pathology and the fine elements of intracranial anatomic features during the diagnostic process and during many operations in the nose, sinus, orbit, and skull base region. In two case reports, we describe the methods used in the diagnostic workup and surgical therapy in the nose and paranasal sinus region. Besides baseline x-ray, multislice computed tomography, and magnetic resonance imaging, operative field imaging was performed via a rapid prototyping model, virtual endoscopy, and 3-D imaging. Different head tissues were visualized in different colors, showing their anatomic interrelations and the extent of pathologic tissue within the operative field. This approach has not yet been used as a standard preoperative or intraoperative procedure in otorhinolaryngology. In this way, we tried to understand the new, visualized "world of anatomic relations within the patient's head" by creating an impression of perception (virtual perception) of the given position of all elements in a particular anatomic region of the head, which does not exist in the real world (virtual world). This approach was aimed at upgrading the diagnostic workup and surgical therapy by ensuring a faster, safer and, above all, simpler operative procedure. In conclusion, any ENT specialist can provide virtual reality support in implementing surgical procedures, with additional control of risks and within the limits of normal tissue, without additional trauma to the surrounding tissue in the anatomic region. At the same time, the virtual reality support provides an impression of the virtual world as the specialist navigates through it and manipulates virtual objects.

In the paper we are introducing guidelines and suggestions for use of 3D image processing SW in head pathology diagnostic and procedures for obtaining physical medical model by additive manufacturing/rapid prototyping techniques, bearing in mind the improvement of surgery performance, its maximum security and faster postoperative recovery of patients. This approach has been verified in two case reports. In the treatment we used intelligent classifier-schemes for abnormal patterns using computer-based system for 3D-virtual and endoscopic assistance in rhinology, with appropriate visualization of anatomy and pathology within the nose, paranasal sinuses, and scull base area.

Frontal sinus fractures (FSF) are commonly caused by traffic accidents, assaults, industrial accidents and gunshot wounds. Classical roentgenography has high proportion of false negative findings in cases of FSF and is not particularly useful in examining the severity of damage to the frontal sinus posterior table and the nasofrontal duct region. High resolution computed tomography was inavoidable during the management of such patients but it may produce large quantity of 2D images. Postprocessing of datasets acquired by high resolution computer tomography from patients with severe head trauma may offer a valuable additional help in diagnostics and surgery planning. We performed virtual endoscopy (VE) and 3D volume rendering (3DVR) on high resolution CT data acquired from a 54-year-old man with with both anterior and posterior frontal sinus wall fracture in order to demonstrate advantages and disadvantages of these methods. Data acquisition was done by Siemens Somatom Emotion scanner and postprocessing was performed with Syngo 2006G software. VE and 3DVR were performed in a man who suffered blunt trauma to his forehead and nose in an traffic accident. Left frontal sinus anterior wall fracture without dislocation and fracture of tabula interna with dislocation were found. 3D position and orientation of fracture lines were shown in by 3D rendering software. We concluded that VE and 3DVR can clearly display the anatomic structure of the paranasal sinuses and nasopharyngeal cavity, revealing damage to the sinus wall caused by a fracture and its relationship to surrounding anatomical structures.

The main goal of our work was to evaluate advantages and disadvantages of virtual endoscopy (VE) techniques in routinely diagnostic and preoperative management of patients with various sinus diseases or head traumas in our practice. Fly-through algorithm was performed using an Xeon based workstation on data sets created from axial CT images acquired from 320 patients with various paranasal sinus disorders. Images were created using Siemens Somatom Emotion 16 continiously rotating helical CT scanner and archived in DICOM format. In comparison with real endoscopy, the VE has several advantages. It is completely non-invasive. It is possible to repeat the same procedure several times, therefore it may be a valuable tool for training. Interactive control of all virtual camera parameters, including the field-of-view is possible. Endoscopic viewing as opposed to real endoscopy is not restricted to the spaces defined by inner surfaces. The viewer may penetrate the walls and see the extent of lesions within and beyond the wall as well as the adjacent anatomic structures. Virtual endoscopy also has a potential to stage tumors by determining the location and the extent of transmural extension.

The real-time requirement means that the simulation should be able to follow the actions of the user that may be moving in the virtual environment. The computer system should also store in its memory a three-dimensional (3D) model of the virtual environment. In that case a real-time virtual reality system will update the 3D graphic visualization as the user moves, so that up-to-date visualization is always shown on the computer screen. Upon completion of the tele-operation, the surgeon compares the preoperative and postoperative images and models of the operative field, and studies video records of the procedure itself Using intraoperative records, animated images of the real tele-procedure performed can be designed. Virtual surgery offers the possibility of preoperative planning in rhinology. The intraoperative use of computer in real time requires development of appropriate hardware and software to connect medical instrumentarium with the computer and to operate the computer by thus connected instrumentarium and sophisticated multimedia interfaces.

Conduction of tele-3D-computer assisted operations as well as other telemedicine procedures often requires highest possible quality of transmitted medical images and video. Unfortunately, those data types are always associated with high telecommunication and storage costs that sometimes prevent more frequent usage of such procedures. We present a novel algorithm for lossless compression of medical images that is extremely helpful in reducing the telecommunication and storage costs. The algorithm models the image properties around the current, unknown pixel and adjusts itself to the local image region. The main contribution of this work is the enhancement of the well known approach of predictor blends through highly adaptive determination of blending context on a pixel-by-pixel basis using classification technique. We show that this approach is well suited for medical image data compression. Results obtained with the proposed compression method on medical images are very encouraging, beating several well known lossless compression methods. The predictor proposed can also be used in other image processing applications such as segmentation and extraction of image regions.

Surgical preparation is enhanced by the availability of computer-generated three-dimensional models that allow surgeons to explore the surgical field in various projections prior to an actual operation. In fact, with adequate computed tomography images, an entire operation can be simulated beforehand so that surgeons can plan the safest and most effective approach and be prepared to avoid or overcome obstacles during the actual procedure. Also, computer technology allows surgeons to conduct remote consultations and to even perform telesurgery--that is, to operate on a patient from a great distance. In this article, we describe our experience with computer-assisted local and remote endoscopic sinus surgery in Croatia.

Objective: Reinke's space (RS) is a highly specific structure in which the majority of vocal fold pathology occurs. The vibratory equivalents of structurally normal RS are regular vocal fold vibrations and normal glottic mucosal waves. Recently, RS has been considered to be composed not only of fibres but also of extracellular matrix (ECM), which is an extremely important component of a normal mucosal wave. As Reinke's oedema (RO) is characterized by excessive ECM in RS, we investigated the cell activity in RO tissue which is possibly responsible for excessive ECM production., Material and Methods: Tissue samples were obtained from 20 RO patients during microlaryngeal surgery. Tissue was analysed histochemically using the AgNOR method and the proliferation activity was assessed immunohistochemically using Ki67 monoclonal antibodies., Results: AgNOR activity was detected in prominent stromal cells in 16 patients. Also, more pronounced activity, compared to the surrounding control tissue, was demonstrated in the epithelial cells of 17 patients using a Ki67 proliferation marker. Electron microscopy showed thickening and decomposition of the basement membrane in all RO tissue samples., Conclusions: Vocal fold mucosa that has been damaged by smoking and phonotrauma may react by producing excessive ECM, resulting in RO. Both epithelial and stromal cells are in a state of higher metabolic activity, indicating their role in this production.

The level of Ki-67 antigen expression has been proven to correlate with cellular proliferation. The aim of the study was to show correlation of Ki-67 expression with the clinical stage and its predictive value for the prognosis of laryngeal carcinoma. The study included 48 patients with surgically removed carcinoma of the larynx. Study results pointed to a significant difference in the mean value of Ki-67 reactivity between the study and control group consisting of cadaveric laryngeal tissue free from the disease. Correlation was found between the TNM stage of carcinoma and percentage of Ki-67-labeled cells. A significant correlation was also observed between Ki-67 reactivity at the time of laryngeal surgery and 2-year clinical outcome of the disease. Ki-67 reactivity was significantly higher in the group of patients with disease remission compared with the control group but was significantly lower as compared with the group of patients with poor outcome.

One of the main objectives of our 3-dimensional (3D) computer-assisted functional endoscopic sinus surgery was to design a computer-assisted 3D approach to the presurgical planning, intraoperative guidance, and postoperative analysis of the anatomic regions of the nose and paranasal sinuses. Such an extremely powerful approach should allow better insight into the operating field, thereby significantly increasing the safety of the procedure. The last step to implementing the technology in the operating room was to connect the computer workstations and video equipment to remote locations by using a high-speed, wide-bandwidth computer network. During patient preparation, the surgeon in the operating room consulted remote experienced and skillful surgeons by viewing CT images and 3D models on computer workstations. The surgeon and consultants used software for CT image previews and 3D model manipulations on top of collaboration tools to define the pathosis, produce an optimal path to the pathosis, and decide how to perform the real surgical procedure. With tele-flythrough or tele-virtual endoscopy rendered through the use of 3D models, both surgeons can preview all the characteristics of the region (ie, anatomy, pathosis) and so predict and determine the next steps of the operation. This ensures greater safety thanks to the operation guidance and reduces the possibility of intraoperative error. The duration of the teleconsultation is thus shortened, which may prove the greatest benefit of tele-3D computer-assisted surgery. If this method were used, clinical institutions would spend less money for telesurgical consultation.

Foreign bodies in paranasal sinuses are found quite infrequently. They are usually detected after various types of head trauma and most commonly occur as a consequence of improper handling of firearms or explosives. In countries at war, eg, during the war in Croatia, adults and children were almost equally exposed to these injuries. The diagnosis should be based on results from precise computer tomography (CT) scanning in axial and coronal sections, and, using these data, tissues of different densities at these anatomical locations can be differentiated. The possibility of exact preoperative, noninvasive visualization of the spatial relationships of anatomic and pathologic structures with 3-dimensional (3D) computer-assisted diagnosis and intraoperative navigational techniques allows the surgeon to achieve a considerable advantage in the preoperative examination of the patient and to reduce the risk of intraoperative complications, all by the use of virtual surgery (VS) or virtual diagnosis. The expected contribution of the mentioned computer-assisted surgical technique manifests itself in defining the most appropriate mode of CT scanning of the head to design the 3D operating field model, and the possibility of active and dynamic 3D visualization of the desired anatomical regions is realized. 3D reconstruction of anatomic units becomes a routine preoperative procedure, providing a highly useful and informative visualization of the regions of interest, and, thus, advancing the definition of geometric information on anatomical contours of the 3D model by the transfer of so-called image pixel to contour pixel.

The main goal of our dynamic 3D computer-assisted reconstruction of a metallic retrobulbar foreign body following orbital injury with ethmoid bone involvement was to use 3D-information obtained from standard computed tomography (CT) data to explore and evaluate the nasal cavity, ethmoidal sinuses, retrobulbar region, and the foreign body itself by simulated dynamic computed visualization of the human head. A foreign body, 10 x 30 mm in size, partially protruded into the posterior ethmoidal cells and partially into the orbit, causing dislocation and compression of the medial rectus muscle and inferior rectus muscle. The other muscles and the optic nerve were intact. Various steps were taken to further the ultimate diagnosis and surgery. Thin CT sections of the nasal cavity, orbit and paranasal sinuses were made on a conventional CT device at a regional medical center, CT scans were transmitted via a computer network to different locations, and special views very similar to those seen on standard endoscopy were created. Special software for 3D modeling, specially designed and modified for 3D C-FESS purposes, was used, as well as a 3D-digitizer connected to the computer and multimedia navigation through the computer during 3D C-FESS. Our approach achieves the visualization of very delicate anatomical structures within the orbit in unconventional (non-standard) sections and angles of viewing, which cannot be obtained by standard endoscopy or 2D CT scanning. Finally, virtual endoscopy (VE) or a 'computed journey' through the anatomical spaces of the paranasal sinuses and orbit substantially improves the 3D C-FESS procedure by simulating the surgical procedure prior to real surgery.

Purpose: To compare the efficacy and tolerability of a 3-day course of azithromycin with a 10-day course of amoxicillin/clavulanic acid in the treatment of acute sinusitis in adults., Patients and Methods: One hundred adult patients with acute sinusitis were included in an open, randomized study. Clinical diagnosis of sinusitis was confirmed by nasal endoscopy, sinus radiography, and (when possible) by culture of sinus aspirate. Patients were randomized to receive azithromycin (500 mg once daily for 3 days) or amoxicillin/clavulanate (625 mg every 8 hours for 10 days)., Results: A significantly faster resolution of signs and symptoms of sinusitis was observed in the azithromycin-treated patients. By the end of therapy (days 10-12), 95% of the patients in the azithromycin group and 74% in the amoxicillin/clavulanate group were cured. The remaining patients' conditions were improved. By the follow-up visit, cure was achieved in 98% of the azithromycin-treated patients, and 91% of the amoxicillin/clavulanate-treated patients. Treatment failure was observed in three patients from the amoxicillin/clavulanate group, and relapse occurred in one patient from each group. Bacteriologic eradication was achieved in 23 of 23 and 21 of 24 patients treated with azithromycin and amoxicillin/clavulanate, respectively. Both drugs were well tolerated. Two patients (4%) from the azithromycin group and five patients (10%) from the amoxicillin/clavulanate group reported mild gastrointestinal disturbances., Conclusions: In adults with acute sinusitis, a 3-day course of azithromycin was as effective and well tolerated as a 10-day course of amoxicillin/clavulanic acid. A significantly simpler dosage regimen and faster clinical effect were the advantages of azithromycin.

Aim: To assess the diagnostic accuracy of ultrasonography in comparison to radiographic and sinusoscopic techniques of maxillary sinuses examinations in acute and chronic sinus inflammations., Methods: Ninety diseased sinuses in 50 patients (32 male and 18 female) were examined radiographically, ultrasonographically, and sinusoscopically. Ultrasonography was performed with Sinuscan 102 Sinusprint with 3.0 MHz transducer frequency, with A-mode curve display and Bulk-display. Radiography was performed in occipitonasofrontal and occipitonasomental projection, and sinusoscopy by local anesthesia using an optic instrument under 0 degrees, 30 degrees, and 70 degrees. Statistical assessment of ultrasonography sensitivity and specificity in relation to radiographic and sinusoscopic techniques was carried out. The data were compared using McNemar's test for paired data., Results: Negative ultrasonographic agreed with negative radiographic findings in 18 of 20 sinuses. When ultrasonographic findings revealed mucosal thickening, complete filling, polyp or cyst, the agreements with radiographic findings were 24/30, 21/25, and 11/15, respectively. Negative ultrasonography agreed with negative sinusoscopic findings in 17/20 sinuses. When ultrasonographic findings revealed mucosal thickening, complete filling, polyp or cyst of the maxillary sinuses, the agreements with sinusoscopic findings were 26/30, 23/25, and 13/15, respectively. In comparison to radiological findings, the sensitivity of ultrasonography was 0.93 and specificity 0.60, and in comparison to sinusoscopic examination, sensitivity of ultrasonography was 0.93 and specificity 0.74., Conclusions: Ultrasonography can be used as a diagnostic method in the early diagnosis of sinus diseases. Compared to radiographic and sinusoscopic findings, it shows a high agreement in negative and positive findings, i.e., a high sensitivity and specificity.

Purpose: The etiology of sinonasal polyps is sometimes obscure. This study was undertaken to evaluate the potential role of arachidonic acid metabolites (AAm) on recurrent polyposis., Materials and Methods: Tissue production of prostaglandin E2 (PGE2), 6-keto-prostaglandin F1-alpha (PGI2), thromboxane A2 (TxA2), and leukotriene C4 (LTC4) by nasal mucosa was determined by radioimmunoassay in 27 patients with sinonasal polyposis (SNp) and in 10 volunteers., Results: The group of patients with SNp with the evidence of recurrences in postoperative period (Group 1) showed significantly lower PGE2 concentrations than group of patients with SNp recurrences (Group 2). The differences in concentrations of PGI2 in mentioned groups were insignificant. In comparison with other groups, a group of patients who underwent surgery several times for SNp (Group 4) had a higher mean TxA2 concentration. The LTC4 concentrations were the highest in groups of patients where SNp recurrences were observed. When the incidence of polyposis recurrences (within 18 months after surgery) was correlated with the level of LTC4 production at the time of surgery, the rate of recurrence was significantly higher in patients with increased LTC4 level than in those with normal LTC4 levels., Conclusions: LTC4 might have a prognostic value. The possible role of AAm in occurrence of SNp is apparent and suggests possible role for medical intervention.

Prostaglandin E2 has been identified as an immunosuppressive factor in patients with squamous cell carcinoma of the head and neck. Spontaneous prostaglandin E2 production by 21 cancer cell lines, which were obtained from 17 patients with squamous cell carcinoma of the head and neck, was determined by radioimmunoassay. In comparison with normal keratinocyte cultures, prostaglandin E2 production by cancer cell lines was significantly decreased (p < 0.0001). Prostaglandin E2 levels demonstrated no correlation to the site, stage, or histopathologic differentiation of the tumor. In a separate group of 17 patients with squamous cell carcinoma of the head and neck, tumor cells were isolated from fresh tumor specimens, and 24-hour PGE2 production in vitro was assayed. No correlation was found with tumor site, stage, or 2-year disease-free survival. Although prostaglandin E2 may have biologic significance in vivo in patients with squamous cell carcinoma of the head and neck, these findings suggest that measurements of tumor cell-derived prostaglandin E2 are not predictive of biologic behavior.

A prospective study was carried out to assess the possible biochemical background of the AAm production by HVF in accordance with selected histological types and voice disorders. The mass of new tissue forming HVF in different clinical cases led us to suspect, according to our previous results, that PGs, LTs and other AAm may be involved in the pathogenesis of HVF. The level of PGE2 in HFV was lower (0.7 ng/ml) than in control (1.09 ng/ml) but not significantly; the PGI2 level (0.01 ng/ml) in HVF was also nonsignificantly lower than in normals, while thromboxane A2 synthesis by HVF (0.42 ng/ml) was significantly less than in control (0.99 ng/ml). On the basis of these results the hypothesis of a possible role of AAm in the process of HVF could not be confirmed.

Spleen cells from mice bearing late-stage methylcholanthrene-induced tumor did not show any tumor activity when mixed with tumor cells in Winn's assay. Treatment of these mice with cyclophosphamide (CY) induced a tumor-inhibitory activity in spleen, occurring on day 7 after treatment, reaching its maximum on day 11 and disappearing by day 21. This antitumor activity could not be induced in control, tumor-free or T-deficient tumor-bearing mice. CY-induced tumor-inhibitory activity was immunologically specific, and mediated by Thy-1+, L3T4-, Ly-2+ cells. Contrary to spleen cells from untreated tumor-bearing mice, spleen cells from CY-treated tumor-bearing mice did not suppress the antitumor activity of immune spleen cells in Winn's assay. However, in contrast to immune spleen cells, CY-induced tumor-inhibitory cells did not manifest antitumor activity when transferred systemically (i.v.) into T-cell-deficient tumor-bearing mice. Even more, spleen cells from CY-pretreated mice, harvested 7-15 days after the drug administration, partially suppressed the antitumor activity of concomitantly transferred spleen cells from specifically immune mice. Nevertheless, CY-pretreated mice manifested concomitant immunity, i.e. these mice exhibited higher resistance to a second inoculum of the same tumor than did nontreated mice or even mice with excised primary tumor.

Plasma prostaglandin E (PGE) levels were determined by radioimmunoassay in 53 patients with various stages (II, III, and IV) of hypopharyngeal and laryngeal squamous cell carcinoma, in 12 non-cancer patients and in 10 healthy volunteers. The mean PGE concentration was somewhat higher in non-cancer patients (mean +/- SD = 34.6 +/- 5.37 pg/ml) than in healthy subjects (28.1 +/- 4.96 pg/ml). In spite of a high data variability, the mean preoperative PGE levels in cancer patients were proportional to the stage of the disease and higher than in non-cancer patients (41.2 +/- 19.7 pg/ml, 52.8 +/- 26.7 pg/ml and 82.0 +/- 34.9 pg/ml in stages II, III and IV respectively). The mean plasma PGE concentration significantly decreased for all tumour stages 15-30 days after surgical removal of the tumour, but rose again in some patients within 6-18 months after surgery. The incidence of tumour recurrences 6 and 18 months after surgery was significantly higher in patients with an increased preoperative PGE level (greater than 43.3 pg/ml) than in those patients with a PGE level within the normal range (less than 43.3 pg/ml). The mortality was also higher in the former group, but the difference did not reach the level of significance. Similarly, the mean preoperative and most postoperative concentrations of PGE were significantly higher in patients in whom tumour recurred within 18 months than in tumour-free patients.

Arachidonic acid metabolites (AAm) have important regulatory functions within several areas of otorhinolaryngology: modulation of immune and allergic responses, inflammation, allergy, etc. The aetiology of vocal fold polyps is still obscure as are the possible mechanisms responsible for their forming and developing. The aim of this study was therefore to investigate the relationship between release of prostaglandins (PGE2, PGI2) and tromboxans (TxA2) from vocal fold polyps ex vivo in 21 patients, in comparison to normal airway mucosa. The production of PGE2 by vocal fold polyps was less than in the controls (ng/ml) (0.5 +/- 0.54; n = 21 vs. 1.09 +/- 0.78; n = 21) (p less than 0.05) but higher than in nasal polyps (0.14 +/- 0.11; n = 16) (p less than 0.01). Prostacyclin production by vocal fold polyps (0.99 +/- 0.92) was less than in control mucosa (2.24 +/- 1.93) (p less than 0.01), but higher than by nasal polyps (0.26 +/- 0.14) and less than in controls (0.99 +/- 0.73) (p less than 0.01) or nasal polyps (0.52 +/- 0.04) (p less than 0.01).

A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly.

Evaluation of total serum proteins and RIST immunoelectrophoresis of immunoglobulins IgG, IgA and IgM were carried out on a group of 35 children of both sexes suffering from secretory otitis. The transudate aspirated from the middle ear was examined only by immunoelectrophoresis. The values for albumin and gammaglobulins were decreased for all the patients. The values for RIST were significantly lower than those where an allergic cause was present. The values for immunoglobulins in transudate were also significantly lower than normal.

40 children of both sexes, aged 5-12, with deviations or fractures of the nasal septum were tested. These children were selected for septoplasty on the basis of anamnestic data, ENT examination and anterior rhinomanometry with and without anamnestic data. The control group consisted of 15 children, of approx. the same age and sex distribution, with normal nose breathing and rhinomanometrical findings. The operated group underwent clinical and rhinomanometrical examination 3 and 12 months after surgery, and the control group 12 months after the initial examination. Septoplasty was performed under general anaesthesia with locally applied vasoconstrictors. The results showed that rhinomanometrical resistances prior to surgery were significantly higher in all the subjects in the operated group than those in the control group. Rhinomanometrical resistances were lower in 29 operated cases 3 months after septoplasty than before septoplasty, and significantly lower in 32 operated cases 12 months after septoplasty. Rhinomanometrical resistances in the operated group 12 months after surgery were a little higher than those in the control group 12 months after the initial examination. Failures and complications after septoplasty are commented upon, as is their influence on rhinomanometrical resistances.