Anterolateral thigh free flap in reconstruction of lateral skull base defects after oncological resection.

PURPOSE: Evaluation of the utility of the free anterolateral thigh flap reconstruction of the defects resulting from radical temporal bone resection in the management of lateral skull base malignancies in a single institution. METHODS: An analysis of 17 en bloc subtotal petrosectomies for removal of malignant tumours was performed. There were 12 squamous cell carcinomas, 4 basal cell carcinomas and 1 adenoid cystic carcinoma. The tumours were staged with the University of Pittsburgh TNM system. In all patients, the lateral temporal bone with the preservation of the petrous apex and carotid artery was performed. All patients had parotid gland resection. The post-resection defect was reconstructed with an ALT free flap. RESULTS: Tumour radical resection and defect reconstruction with an ALT flap was achieved in all patients without intraoperative complications. The transplants were harvested as fasciocutaneous flaps, 11 perfused by musculocutaneous and 6 by septocutaneous perforators. The ALT flaps had a mean pedicle length of 8 cm (6-12 cm), and the flap size ranged between 6 × 15 cm and 15 × 30 cm. The flaps were supplied by nine facial, five occipital and three maxillary arteries. Recipient-site veins included eight internal jugular, seven facial, one retromandibular and one external jugular vein. All arterial pedicles were anastomosed in an end-to-end manner. The veins were anastomosed with interrupted sutures and in 11 cases with Synovis-Coupler® devices. All the flap transfers were performed successfully. Three patients experienced postoperative complications. CONCLUSIONS: The ALT flap proved to be effective for covering large temporal skull base defects resulting from the radical removal of temporal bone malignancies. The functional and cosmetic results were acceptable with a low complication rate.

Management of Radiation Induced Carotid Stenosis in Head and Neck Cancer.

OBJECTIVES: Presentation of radiation-induced lesions in carotid arteries of patients with head and neck squamous cell carcinoma (HNSCC) and the evaluation of the effectiveness of endovascular treatment of symptomatic stenoses. MATERIALS AND METHODS: We retrospectively analyzed 26 patients who underwent surgery and subsequently cervical radiotherapy (RT) for HNSCC, focusing on radiation-induced vascular disease in neck arteries-from the latency period to the occurrence of neurological events-and the endovascular treatment of the internal carotid artery (ICA) and/or of common carotid artery (CCA) stenoses. The vascular lesions were diagnosed with Doppler ultrasonography and selective digital angiography. Patients with >70% stenoses of ICA and/or CCA were scheduled for carotid artery stenting (CAS). They were followed-up with neurological examinations and Doppler ultrasonography at 6, 12, and 24 months after stenting. RESULTS: Radiation-induced vascular diseases occurred in the ICA in 22 patients (85%), CCA in 15 (58%), and in ECA in 15 (58%). The stents were implanted in 25 ICA and 17 CCA. Thirteen patients (50%) had one stent, eight (30%) had two stents, four (15%) had three stents, and one patient had five stents. Overall, 46 stents were implanted. Technical success was achieved in all patients. No cerebrovascular events occurred in the 24-months follow-up. CONCLUSION: RT in patients with HNSCC holds a significant risk factor of developing carotid artery stenosis and cerebrovascular events. Carotid stenting is preferable mode of treatment for radiation-induced stenosis. A screening program with doppler ultrasonography enables pre-stroke detection of carotid stenosis.

Osteopetrosis of the Temporal Bone Treated with Cochlear Implant.

Osteopetrosis is a heterogeneous group of skeletal disorders. It is a rare genetic disease caused by osteoclast dysfunction, leading to invalid bone desorption and remodeling and an increase in skeletal mass and density. We present the case of a 52-year-old female with osteopetrosis of the temporal bone. She reported loss of hearing in her left ear 14 years ago because of a head trauma. Four months ago, she was conservatively treated because of sudden sensorineural hearing loss in her right ear with no improvement. Her pure tone average audiogram was bilaterally 90 dB with 10% speech recognition. The patient was implanted with a cochlear implant. Except for the extremely thick and dense cortical bone of the mastoid, surgery was uneventful. Speech recognition 6 months after the surgery showed 75%. The results were stable for 3 years follow-up. Patients with profound hearing loss caused by osteopetrosis may benefit from cochlear implantation.

Evaluation of effectiveness of endovascular embolisation for the treatment of pelvic congestion syndrome--preliminary study.

OBJECTIVES: The Aim: The aim of the study was to evaluate the effectiveness, safety and clinical outcomes of endovascular embolisation of pelvic congestion syndrome (PCS). MATERIAL AND METHODS: This prospective, observational study carried out between January and May of 2014 encompassed 24 female patients aged 22-44 years (average - 31 years) diagnosed with PCS. Diagnosis of PCS was established by medical history physical examination, transvaginal Doppler ultrasound examination and confirmed by MRI. The patients were qualified for phlebography and ovarian vein embolization with 0.035" detachable coils and/or microcoils. Pelvic pain scores were assessed before and 3 months after the procedure with the visual analog scale (VAS; 0 - no pain, 10 - unbearable pain). RESULTS: Embolisation procedures were performed in 23 out of 24 patients. Nineteen patients underwent unilateral and 4 patients bilateral embolisation of the ovarian vein. In one case, safe and selective vessel catheterization was not possible due to the anatomical variant of venous flow. Nineteen patients underwent unilateral embolisation of the left ovarian vein. Four patients had the left and right ovarian veins embolized; in one of them, the internal iliac vein was additionally closed (the two-stage procedure). The technical success rate was 96%. Procedures lasted 23-78 minutes (32 minutes on average). An average of 40 ml of contrast was administered during the procedures. The total mean radiation dose at the reference point was 389 mGy (from 127 mGy to 1112 mGy). A decrease in pelvic pain intensity according to VAS was considered a clinical success. The median VAS pelvic pain score before the procedure was 8. Three months after the procedure median pelvic pain score decreased to 1 (p < 0.001). In two cases, the ovarian vein was injured and the contrast medium extravasated, which was clinically insignificant. In one case, a small injection site haematoma developed. CONCLUSION: Embolisation is a minimally invasive, effective and safe method of treatment for PCS. The cooperation between gynaecologists and interventional radiologists is essential for successful outcomes.

[Importance of donor site vascular imaging in free fibula flap reconstruction]. / Znaczenie diagnostyki obrazowej unaczynienia miejsca pobrania w planowaniu rekonstrukcji wolnym platem strzalkowym.

INTRODUCTION: Free fibula flap is widely used in head and neck reconstruction. Imaging studies of the donor site can reveal vascular abnormalities and therefore prevent acute leg ischemia. AIM: Evaluation of the role of donor site vascular imaging studies for free fibula flap planing. MATERIAL AND METHODS: Out of 35 free flap reconstructions performed in Otolaryngology Head and Neck Surgery Department in Medical University in Lublin in 2011-2012, there were 10 fibula flaps. Each patient had preoperative lower leg subtraction angiography performed. RESULTS: Lower leg angiography revealed vascular abnormalities in two out of 10 patients scheduled for free fibula flap transfer. One had dominant peroneal artery and second occlusion of anterior tibial artery. In both cases fibula was harvested from the other leg. CONCLUSIONS: Imaging studies reveal lower leg vascular abnormalities in 20% of cases thus facilitate surgical plans alternations and prevent serious complications in free fibula flap patients.

[The use of MRI DWI-imaging in assessment of cholesteatoma recurrences after canal wall up technique]. / Zastosowanie badania rezonansu magnetycznego w sekwencjach dyfuzyjnych do oceny chorych po operacji zamknietej z powodu perlaka.

INTRODUCTION: The use of closed technique in cholesteatoma treatment carries a significant risk of development of residual disease thus requires a second look operation in a proportion of patients. In those with no residual cholesteatoma the second surgery could be avoided. THE AIM OF THE STUDY: was to evaluate the use of non-echo planar HASTE diffusion-weighted MR imaging in the detection of cholesteatoma in patients after canal wall up surgery due to cholesteatoma. MATERIAL AND METHODS: We evaluate the results of half-Fourier-acquisition single-shot turbo-spin-echo (HASTE) diffusion-weighted magnetic resonance imaging in 18 patients after canal wall up surgery performed 6 to 20 months after primary surgery. 16 patients were operated in our center and 2 elsewhere. All the patients underwent second look surgery that verified the result of MRI scanning. RESULTS: MRI DWI detected 2 cholesteatomas in patients operated elsewhere and none in patients operated in our center. Four cholesteatomas were found during second look operations. Two false negatives were in 1 patient with cholesteatoma pearl of less than 2mm in diameter and in 1 patient with mural cholesteatoma. There were no false positive results. CONCLUSION: Non EPI MRI DWI can be used as a screening tool to detect residual or recurrent cholesteatoma and may substitute the need of second look surgery.

External and middle ear diseases: radiological diagnosis based on clinical signs and symptoms.

OBJECTIVE: Pathology of the external and middle ear is the most frequent reason to prescribe antibiotics and perform surgery in children and young adults. In the majority of cases imaging studies are not performed; the need for imaging comes when complications are suspected or when treatment is not effective. This paper discusses indications for temporal bone imaging studies and presents the most frequent pathological conditions, together with differential diagnosis, clinical symptoms and methods of treatment. METHODS AND RESULTS: This pictorial review describes major external and middle ear diseases, with special regard to clinical findings and appropriate reporting. CONCLUSIONS: Apprehension of the complete clinical picture, together with imaging clues, narrows differential diagnosis and helps avoid mistakes. Evaluation of temporal bone pathologies requires close cooperation between the clinician and radiologist.

Head and neck cancer: value of perfusion CT in depicting primary tumor spread.

BACKGROUND: The aim of this study was to assess head and neck squamous cell cancer and surrounding tissue in computed tomography contrast enhanced and perfusion studies, and to examine the role of perfusion imaging in depiction of tissue infiltration. MATERIAL/METHODS: We prospectively evaluated 43 primary malignant head and neck tumors, using standard CT followed by perfusion. Blood flow, blood volume, mean transit time, and permeability values were obtained using regions of interest (ROIs) over lesions and surrounding tissue. Results were compared with histological analysis of resected tissue. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for both methods. RESULTS: We found significant differences between infiltrated and non-infiltrated tissue, especially with regard to muscles. In case of bone and salivary gland infiltration, change in perfusion parameters did not allow proper diagnosis. CONCLUSIONS: CTP shows promise in depicting malignant infiltration. The combined use of CECT plus CTP results in correct staging of the majority of head and neck tumors.

Epistaxis in patients with hereditary hemorrhagic telangiectasia treated with selective arterial embolization.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare systemic fibrovascular dysplasia also known as Rendu-Osler-Weber disease. Epistaxis is often the first and foremost symptom of the disease and recurrent epistaxis is the main complaint. PURPOSE: Evaluation of effectiveness and safety of endovascular treatment of epistaxis in HHT patients. MATERIAL AND METHODS: Between June 2004 and January 2008, 14 patients with HHT underwent embolization of external carotid artery (ECA) branches due to severe epistaxis. There were eight men and six women aged 27-42 years. Patients were referred for endovascular treatment when primary management with electrocautery and nasal packing was ineffective. Arteries suspected of bleeding were catheterized super-selectively with micro-catheters to perform embolization. Polyvinyl alcohol particles (PVA) or embospheres in diameter of 500-700-µm were used as an embolic material. RESULTS: Embolization was technically successful in 11 (78.5%) patients. Immediate, complete control of bleeding was achieved in 12 (85%) patients. During long-term follow-up recurrent nasal bleeding occurred in six (43%) patients 6-24 months after treatment. There were no severe complications after embolization. Nine patients experienced mild facial pain which resolved within three days after the treatment. Three patients in whom arterial spasm was observed, suffered from facial paraesthesia lasting for 3-5 days after embolization. Out of 14 patients, 12 were available for 24-month follow-up evaluation. All except one claimed reduction in frequency and severity of epistaxis which had a positive impact on their quality of life. CONCLUSION: Endovascular embolization of epistaxis in patients with HHT is an effective and safe procedure although it cannot provide a long-term cure in most cases. Embolization reduces the frequency, severity and duration of nasal bleeding in patients with HHT, improving patients' quality of life.

Evaluation of tracheal stenosis: comparison between computed tomography virtual tracheobronchoscopy with multiplanar reformatting, flexible tracheofiberoscopy and intra-operative findings.

The aim of the study was to evaluate and compare various helical CT display modes [virtual endoscopy (VE)] and multiplanar reformations (MPR), conventional flexible tracheobronchoscopy (FT) and intra-operative (IO) findings in patients with tracheal stenosis and to analyze the advantage of MPR and VE in diagnosis and treatment planning and in postoperative follow-up. Thirty-seven patients with tracheal stenosis underwent standard neck and chest CT followed by MPR and VE. Results were correlated with the results of FT and IO findings. Thirty-three of the 37 stenoses were correctly graded and measured adequately using VE. Complete correlation among CT, fiberoptic tracheoscopy, and surgery of stenosis grading, stenosis length and length of planned resection segment of the trachea was noted between 33 of 37 patients with tracheal stenosis. Correlation between VE and IO was noted in 35 of 37 patients and between FT and VE was noted in 33 of 37 patients with tracheal stenosis. The sensitivity of VE was 94-97%, specificity was 100% with comparison to IO findings. The sensitivity and accuracy of MPR was 86-89% and specificity was 100% with comparison to FT findings. The results of the study indicate that VE is an excellent, consistent, and objective technique. VE with MPR is very useful in diagnostic evaluation and treatment planning in patients with tracheal stenosis.

The content of cadmium, cobalt and nickel in laryngeal carcinoma.

INTRODUCTION: The aim of the study was to determine the content of cadmium (Cd), cobalt (Co) and nickel (Ni) in the samples from laryngeal carcinoma in comparison with the level of these elements in the samples of healthy mucous membrane from the same larynx. MATERIAL AND METHODS: The study was conducted on 43 patients with laryngeal carcinoma. The levels of Cd, Co, and Ni in carcinoma and healthy control tissues was determined by inductively coupled plasma optical emission spectrometry (ICP - OES) using sequential spectrometer. RESULTS: No significant differences were found between the levels of the Cd, Co, and Ni in laryngeal carcinoma vs tissues without carcinoma. However, it was noted that the concentration of Cd in tumors of patients with metastases to cervical lymph nodes was significantly higher than in tumors without metastases. The content of Co was significantly higher in more advanced laryngeal tumors: in stage-T4 than in stage T3. It is of interest that the levels of Cd, Co and Ni were significantly higher in tumors in patients from rural than urban areas. CONCLUSIONS: The imbalance in the level of nickel, cadmium and cobalt in laryngeal cancer may be due to a changed cellular metabolism in the cancer process. However, the results of our study reveal the significant differences in the concentration of these metals between patients from urban and rural areas which suggests that this fact may be related to environmental or occupational factors and therefore it requires further study.

Evaluation of cervical lymph nodes with CT perfusion in patients with hypopharyngeal and laryngeal squamous cell cancer.

BACKGROUND: In patients with head and neck squamous cell cancer, metastases in cervical lymph nodes still remain the single most important negative predicting factor. Their presence reduces overall 5-year survival by 50%. The aim of the study was to evaluate the role of computed tomography perfusion (CTP) for differentiation between metastatic and non-metastatic cervical lymph nodes in patients with squamous cell cancer of hypopharynx and larynx. MATERIAL/METHODS: This was a prospective single center study of 18 consecutive patients. Eleven patients with squamous cell cancer of the hypopharynx and seven patients with laryngeal cancer underwent CT examination of the neck followed by CTP. Group II, III, and V of lymph nodes were evaluated. Perfusion maps of basic parameters (blood flow [BF], blood volume [BV], mean transit time [MTT] and permeability surface [PS]) were reconstructed for all patients. In all patients resection of primary tumour along with neck dissection was performed. Lymph nodes underwent histopathological examinations for presence of metastases. CTP parameters were related with histological analysis of resected nodes. RESULTS: CTP and histological findings of 65 nodes were correlated. 24 of them were metastatic and 41 were non-metastatic. Metastatic nodes showed significant hyperperfusion, comparing to non-metastatic ones. An average value of BF in metastatic nodes was 136.4 ml/100 g/min, BV was 7.7 ml/100 g, MTT was 4.4 s and PS was 19.4 ml/100 g/min. The average values for non-metastatic nodes were: BF was 80.7 ml/100 g/min, BV was 4.7 ml/100 g, MTT was 5.6 s and PS was 12.8 ml/100 g/min. The differences were significantly higher for BF, BV and PS values (p<0.05). CONCLUSIONS: CTP may be useful in differentiation between metastatic and non-metastatic lymph nodes, based on evaluation of the value of BF, BV and PS.

Computed tomography perfusion examination is helpful in evaluating the extent of oropharyngeal and oral cavity cancer.

BACKGROUND: Squamous cell cancer (SCC) of the head and neck, like other malignancies, should be reported with regard to TNM classification and treated accordingly. Sole anatomic imaging has its drawbacks, as early lesion detection often remains challenging, non-neoplastic processes can mimic malignancies and there are doubts concerning the extent of tumour. The purpose of this study was to perform assessment of head and neck squamous cell cancer and surrounding tissue, in order to examine the relationship between perfusion measurements derived from CT perfusion imaging (CTP) and histologic evaluation of resected tissue. MATERIAL/METHODS: We prospectively evaluated 21 primary SCC of the oral cavity and oropharynx, using contrast enhanced CT of the head and neck followed by CTP examination at the level of tumour. Blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability (PS) values were calculated with use of manually drawn regions of interest (ROIs) over the lesions and on the contralateral side. Results were compared with histologic analysis of resected tissue. RESULTS: CTP was possible in all twenty one patients, but one did not undergo surgery. Of the remaining twenty, four had retromolar trigone cancer, nine had tongue cancer and seven had tonsil cancer. We found significant differences between infiltrated and healthy tissue. Differentiation was most reliable by using blood flow (BF), permeability surface (PS) and blood volume (BV). CONCLUSIONS: CTP shows promise in distinguishing benign and malignant processes, primarily by means of BF, BV and PS.

Squamous cell carcinoma of the head and neck-The role of diffusion and perfusion imaging in tumor recurrence and follow-up.

Computed tomography and magnetic resonance imaging-based techniques of functional imaging are proven to be sensitive and reliable tools for detection and staging of head and neck cancer. These new techniques enable to visualize and differentiate subtle pathologic changes before they become evident on standard cross-sectional images. However, it is their role in evaluating possible recurrence and estimation of treatment response that holds the biggest promise. This article describes the role and usefulness of diffusion and perfusion in detecting recurrence and follow-up in patients with head and neck squamous cell carcinoma.

Measurement of glycine in a brain and brain tumors by means of 1H MRS.

AIM: Evaluation of a peak at 3.55 ppm in a long echo time (TE) recognized as glycine (Gly) in the WHO grade II gliomas and central neurocytomas by means of 1H MRS. MATERIAL AND METHODS: Retrospective analysis of 19 patients with histopathologically confirmed WHO grade II glioma and 2 patients with central neurocytoma was conducted. 1H MRS (TE = 135 ms and TE = 144 ms) was performed with 1.5 T and 3.0 T scanners. Gly/Cr, Gly/Cho and Gly/NAA ratios were compared between the analysed groups. Additional analysis of a brain of 61 healthy volunteers was conducted. RESULTS: Glycine was distinguished in 12 out of 19 (63%) WHO grade II gliomas. Among those 12 WHO grade II gliomas only in 26% of a spectra Gly was recognized. In both central neurocytomas Gly was distinguished and in 43% of the spectra Gly was recognized. The ratio of Gly/Cr in central neurocytomas was higher than in WHO grade II gliomas (mean(CNC) 0.62 ± 0.18 vs. mean(WHO II) 0.37 ± 0.10; p < 0.001) but the ratio of Gly/Cho was lower (mean(CNC) 0.18 ± 0.04 vs. mean(WHO II) 0.24 ± 0.07; p < 0.001). There was no difference between analysed groups in terms of Gly/NAA ratio (mean(CNC) 0.36 ± 0.09 vs. mean(WHO II) 0.36 ± 0.14; p = NS). Only in 0.3% of the spectra of normal brain Gly was distinguished. CONCLUSIONS: Glycine is found in WHO II grade gliomas as well as in central neurocytomas, but only in a part of a tumor volume. It is necessary to perform 1H MRS of the whole tumor volume to confirm/exclude the presence of glycine. Glycine in a normal brain can not be identified by means of conventional 1H MRS performed by means of 1.5 T or 3.0 T scanners.

Langerhans cell histiocytosis of the parietal bone with epidural and extracranial expansion - case report and a review of the literature.

Langerhans cell histiocytosis is a rare neoplasm that belongs to the histiocytic and dendritic cell neoplasm group according to the 2008 WHO classification. It has been defined as neoplastic proliferation of Langerhans cells that express CD1a and S-100 proteins and have Birbeck granules on the ultrastructural examination. Clinical presentation and behaviour are heterogeneous and can range from a solitary lytic bone lesion with a favourable course to a fatal disseminated leukaemia-like form, with a wide spectrum of intermediate clinical presentations between these two extremes. Here, we present a case report of a solitary calvarial lesion in an adolescent boy along with a review of the literature. Presenting features, initial diagnostic evaluation and treatment protocol of a unifocal monosystemic calvarial location of LCH are presented.

Widening of coronary sinus in CT pulmonary angiography indicates right ventricular dysfunction in patients with acute pulmonary embolism.

OBJECTIVES: Right ventricular dysfunction (RVD) may occur in the course of acute pulmonary embolism (PE). Patients with RVD need more intensive treatment, and the prognosis is more severe. The aim of this study was to evaluate the usefulness of the measurement of the coronary sinus in the assessment of RVD in patients with acute PE and to compare it with other indicators of RVD. METHODS: Retrospective assessment of 55 CT pulmonary angiography examinations with signs of acute PE was performed. Pulmonary artery systolic pressure (PASP) was echocardiographically assessed in all patients, and RVD was defined as PASP values greater than 30 mmHg. CT measurements included the size of the heart ventricles, mediastinal vessels and the width of the coronary sinus. RESULTS: Median width of the coronary sinus was 16 mm (range 12-24 mm) in patients with increased PASP and 10 mm (range 7-22 mm) in patients with normal PASP (p = 0.001). Best cut-off value was assessed to be 12.5 mm, with sensitivity 94% and specificity 75%. It was characterised by the largest area under ROC curve (0.82) among analysed parameters. CONCLUSION: Width of the coronary sinus seems to be a promising parameter for identification of RVD in patients with acute PE. A prospective study should be undertaken to further assess its clinical and prognostic applicability.

[Diagnostic evaluation of temporal paragangliomas]. / Diagnostyka przyzwojaków kosci skroniowej.

Paragangliomas are rare tumours deriving from paraganglia--small bodies of neuroendocrine tissue. Approximately 3% of paragangliomas occur in the head and neck area accounting for about 0,6% of all tumours of this region. Head and neck paragangliomas are divided into two groups: neck tumours (carotid body tumor and vagal paraganglioma) and temporal paragangliomas (jugular bulb tumor and tympanic paraganglioma). Temporal paragangliomas arise from paraganglia located in the petrous part of the temporal bone. Radiological evaluation of these lesions is essential for confirming the diagnosis and surgery planning. Most useful methods are magnetic resonance imaging and computed tomography. These modalities deliver important information about tumour location, extension and the state of the surrounding structures. Carotid angiography is a second step diagnostic method, performed in patients with jugular bulb paraganglioma. It has a diagnostic value and allows palliative or preoperative embolization of the tumor. Ultrasonographic evaluation and scintigraphy also provide advantages in diagnostic management.

The modern methods of gastric imaging.

The major aim of the review is presenting contemporary diagnostic methods applied in gastric imaging as well as their place in clinical treatment. The authors discuss both conventional and modern methods. Although the method of double contrast barium meal is still the most important in stomach diagnostics, the modern methods such as EUSG, CT and MRI are becoming more and more meaningful not only in evaluating gastric neoplastic pathological changes. All applied diagnostic procedures should not be competitive but complementary and constitute an excellent means in hands of an experienced clinicist and radiologist.

Indirect CT venography of the abdominal cavity and lower limbs in patients with the suspicion of pulmonary embolism--indications, technique, diagnostic possibilities.

Multi-slice computed tomography has become the main method to diagnose and evaluate the intensity of acute pulmonary embolism (PE). The most common cause of PE is thrombosis of veins of the lower limbs and pelvis. The paper presents various aspects of the use of combined pulmonary artery arteriography and indirect venography performed using multi-slice tomography in relation to other methods imaging the venous system used so far. The authors presented the techniques of CT examination of venous vessels of the lower limbs, abdominal cavity and pelvis in patients with the suspicion of PE, typical images of lesions, results of studies concerning these issues conducted to date and their own experience based on clinical practice.