Perfusion analysis of benign parotid gland tumors by contrast-enhanced ultrasonography (CEUS).

BACKGROUND: Diagnosis of parotid gland tumors is sometimes challenging due to their diversity and pleomorphic histological appearance. B-scan sonography along with color-coded duplex sonography is the gold standard in the diagnostic workup of these lesions, whereas histopathology is to date the gold standard for the final diagnosis. To date no single imaging technique provides the chance for an art-diagnosis with highly diagnostic accuracy. Contrast enhanced ultrasonography (CEUS) on the other hand provides information of the perfusion down to the capillary level. Currently there are only a few papers published with systematical examination of the perfusion in benign parotid gland tumors and its diagnostic significance. PATIENTS AND METHODS: One hundred patients with a parotid gland tumor were examined. The examinations included conventional B-scan sonography, color-coded duplexsonography along with contrast enhanced ultrasonography (CEUS). B-scan sonographic parameters, i.e. echogenicity, shape, size, demarcation, and borders of a lesion along with vascularization estimated by color-coded-duplexsonography were analyzed. Analysis of quantitative CEUS parameters was performed using 8 regions of interest (ROI), which were standardized located throughout the entire tumors. The perfusion parameters were analyzed for particular tumor entities. Qualitative CEUS analysis with estimating the perfusion pattern was additionally performed. RESULTS: Histological examination revealed benign tumors in 92 cases, with pleomorphic adenomas and Warthin´s tumors were the most frequent entities. Malignant conditions were found in 8 cases. CEUS revealed a centripetal perfusion pattern in malignant tumors significantly more frequently than in benign tumors. CEUS showed a significant heterogenic perfusion in all tumors, with a higher perfusion in the medial parts of the tumors and in some cases also in the center. Perfusion patterns of PA and WT were different. WT displayed centrifugal, centripetal, and central diffuse perfusion more often than PA, whereas in PA perfusion often was limited to the capsule or periphery. Oncocytoma had the highest perfusion values. Intraglandular cysts showed no intralesional perfusion. CONCLUSIONS: CEUS analysis in different parts of benign tumors revealed a significant heterogeneity in tumor perfusion. Some perfusion pattern could be identified which might be characteristic for particular lesions. Based on this, the diagnostic accuracy of CEUS in the differential diagnosis of parotid gland tumors can be increased. In particular, the perfusion analysis within the tumors using ROIs located standardized throughout the entire tumor provides additional information which are important for the art diagnosis and in differentiation of tumor entity.

Clinical parameters influencing the results of anterior rhinomanometry in children.

BACKGROUND: Nasal obstruction is a frequent symptom in both adults and children and it is a common reason to see an otorhinolaryngologist. Endoscopy of the nasal cavity and the epipharyngeal space along with anterior rhinomanometry is regarded the gold standard since many years to estimate the severity of nasal obstruction in the particular patient. Endoscopy shows anatomical reasons for an obstruction, whereas the nasal flow volume and nasal resistance can be determined using anterior rhinomanometry. Currently, there are only few data available for rhinomanometry results in children. The purpose of the present study was to evaluate the application of this technique in the pediatric population for objective evaluation of nasal flow. Whether it achieves reproducible results and which clinical parameters have some influence on the results were studied. PATIENTS AND METHODS: 427 children (average age of 8.5 years, range 7 months through 17 years) who were admitted to evaluate nasal patency or for allergy testing were examined. After clinical examination and endoscopy of the nasal cavity and epipharyngeal space, anterior rhinomanometry was performed before and after application of decongestant nose drops separately for each nose side in 334 children. The nasal flow with a pressure of 150 Pasc was measured and served for statistical evaluation. Flow values were correlated to clinical and endoscopic parameters along with results of allergy tests (prick tests). RESULTS: Reproducible rhinomanometric measurements were possible in children age 3 years and older. However, the standard deviation and variation of measurements were significant in this cohort of patients. Statistically highest significant correlations were found between flow measurements and body height along with the age of the children (p < 0.01) and status following adenoidectomy (p < 0.05). No statistically significant correlations were found between rhinomanometry and results of prick tests. CONCLUSIONS: The study demonstrates that rhinomanometry can be applied in the pediatric population for objective evaluation of nasal obstruction and for determining the effects of decongestant nose drops. The highest correlation was found between nasal flow and children's body height, children's age and status following adenoidectomy. The correlation between nasal flow and clinically/endoscopically determined degree of nasal obstruction was lower. However, definition of normal flow values for particular age groups is challenging since the results showed high variation and standard deviation. Yet with regard to individual patient, the technique achieves reliable results in nasal provocation tests, which are widely used for allergy testing in children. When performed in children it should always be considered that there are age-specific requirements for the examination and interpretation of results in this patient cohort.

Sinogenic Orbital Complications.

BACKGROUND: The term "orbital complication" does not designate an independent nosological entity, but is rather a collective designation for diseases or disease effects that involve the orbit and its internal structures by extension from outside. In general, their most prominent manifestation is swelling of the orbital soft tissues, usually unilaterally. The incidence of sinogenic orbital complications is approximately 1.6 per 100 000 children and 0.1 per 100 000 adults per year. METHODS: This review is based on publications retrieved by a selective search of the literature on the epidemiology, diagnosis, and treatment of sinogenic orbital complications. RESULTS: Acute sinusitis is the most common cause of orbital complications. These are diseases of the orbit with potentially serious consequences for the eye and the risk of intracranial complications such as cavernous sinus thrombosis, meningitis, or brain abscess. Aside from acute sinusitis, many other infectious and non-infectious diseases can extend to and involve the orbit. Because of the complexity and severity of the condition, its diagnosis and treatment are always an interdisciplinary matter. The treatment is primarily conservative, under observation in a hospital, and generally consists of the treatment of acute sinusitis with measures to combat edema along with the administration of broad-spectrum antibiotics. Surgical intervention is needed in severe cases or if there is an abscess. An endonasal approach is usually used for drainage. CONCLUSION: In 95-98% of cases in stages I-IV, healing is complete and without further sequelae. Even if vision is affected preoperatively, it usually recovers fully when therapy is appropriate. Approximately 15% of the patients who undergo surgery need more than one operative procedure.

Impact of human papillomaviruses (HPV) on recurrence rate and malignant progression of sinonasal papillomas.

Sinonasal papillomas are characterized by their potential for frequent recurrences and malignant progression. Currently, the role of human papillomavirus (HPV) infection in sinonasal papillomas is unclear. A study was conducted to elucidate the impact of HPV infection on recurrence and malignant progression of sinonasal papillomas. One hundred and seven patients with 151 tumors could be examined. One hundred and one patients suffered from benign papilloma, mostly inverted papillomas (IP); six patients suffered from carcinomas in situ and squamous cell carcinomas (SCC) ex-IP. Recurrent IP were more often HPV-positive than non-recurrent tumors (38.8% vs. 60%-65%). Low-risk (LR) HPV infection (especially HPV 6) increased the risk of tumor recurrences (p = 0.0385 and p = 0.0556, respectively). IP and oncocytic papillomas (both lesions are known for their malignant potential) were more often high-risk (HR) HPV-positive (15.5% and 16.7%) than fungiform papilloma (which usually does not progress to carcinoma). CIS and SCC ex-IP displayed higher HPV rates than benign IP (83.3% vs. 38.8%), especially higher rates of HR-HPV (66.7% vs. 23.8%, p = 0.0415). Data from this study endorse the hypothesis that recurrence of sinonasal papillomas is promoted by LR-HPV infection and that malignant progression of IP is promoted by HR-HPV infection.

Orbital complications in children: differential diagnosis of a challenging disease.

Orbital swelling in children presents diagnostic and therapeutic challenges. Most are associated with acute sinusitis with complicating factors possibly including: amaurosis, meningitis, intracranial abscess or even cavernous sinus thrombosis. However not all acute orbital swelling is associated with acute sinusitis. A careful evaluation is critical prior to initiating therapy. Clinical records of 49 children (27 girls, 22 boys, with an average age of 11.8 years) were retrospectively reviewed. Historical data evaluated included all available information from parents and previous treating physicians. All patients underwent intensive pediatric, ophthalmologic, and otorhinolaryngologic examinations. Computed tomography (CT scans) were additionally performed in 40 % of children. The results of any examinations were also evaluated. Eighteen of the 49 patients had an orbital complication due to acute sinusitis. All 18 had elevated body temperature, C-Reactive Protein (CRP) values and white blood cell counts. Endoscopy of the nose revealed pus in the middle meatus in each case. According to Chandlers' classification, ten children presented with a preseptal, and eight children had a postseptal orbital cellulitis. All patients were admitted to the hospital and treated with intravenous antibiotics. CT scans further demonstrated signs of subperiostal abscess in four children. Functional endoscopic sinus surgery (FESS) was required in six children, including all patients with subperiostal abscess. Twenty children experienced orbital swelling unrelated to acute sinusitis, i.e. atheroma, inflammed insect stings, dental related abscess, conjunctivitis, and Herpes simplex associated superinfection. In three children, acute orbital swelling was caused by an orbital tumor. Orbital complications of an acute sinusitis occur often in the pediatric patient group, and most of these patients can be treated conservative with intravenous antibiotics. Indications for FESS include failure to improve or worsening of clinical symptoms during 24 h of therapy, signs for subperiostal abscess in CT scan, and/or vision loss. Patients with infectous orbital complications had fever, elevated CRP and white blood cell counts. This symptom complex is key in making the correct diagnosis. Interestingly, 61 % of patients in this study demonstrated non-sinusitis related diseases leading to acute orbital swelling, which also required prompt recognition and appropriate therapy.

Microscopic examination of iatrogenic subglottic tracheal stenosis: observations that may elucidate its histopathologic origin.

OBJECTIVES: The histopathologic origin of iatrogenic subglottic tracheal stenosis (ISTS) remains unclear. The purpose of this study was to use detailed operative microscopy to systematically examine the operative en bloc specimens of patients with ISTS and to observe the histologic and morphological changes in the hopes that these observations will provide insight into the histopathologic origin of these devastating injuries. METHODS: The operative specimens of 18 patients who underwent open tracheal or laryngotracheal resection for ISTS were examined. Precise morphological characteristics were investigated for each tissue layer, including the adventitia, the outer surface of the perichondrium, the cartilage, the inner surface of the perichondrium, the submucosa, and the mucosa. Each tissue layer was evaluated independently and in relationship to the other layers. The cartilaginous airway was further evaluated relative to the pars membranacea. RESULTS: The most common morphological finding in the epithelium was squamous metaplasia with occasional intense inflammation visible in the underlying mucosa, including cicatrization. The underlying cartilage demonstrated ossific metaplasia with sequestration in many cases. By far the most pronounced changes were found in the outer perichondrium and overlying adventitia and included diffuse paucicellular or hyperplastic fibrosis with intense hyperplastic scar formation or hyaline cicatrization. In the pars membranacea, severe scar formation and hyperplastic fibrosis were predominant. Ossific metaplasia was particularly severe in the lateral or outer parts of the tracheal ring, particularly in the vicinity of the adventitia and outer perichondrium. These changes were much more pronounced than the relatively minor changes observed in the submucosa and mucosa. CONCLUSIONS: The most severe pathologic observations occurred in the lateral tissue layers, ie, the outer perichondrium and adventia. Given that an injury occurs from the tracheal lumen, these tissue layers have the greatest distance from the site of injury. As only minor changes occurred in the inner tissue layers, we hypothesize that these tissues have a greater regenerative capacity than the outer layers. This study supports the theory that the depth of the airway injury is more critical to the development of ISTS than is the extent or length of the injury.

Reconstruction of large pharyngeal defects with microvascular free flaps and myocutaneous pedicled flaps.

PURPOSE OF REVIEW: The current review will focus on the therapeutic options for reconstruction of large and complex defects of the oropharynx and hypopharynx, and the cervical esophagus following surgery for squamous cell carcinoma. The advantages and disadvantages of pedicled flaps, including the pectoralis major myocutaneous flap (PMMF) and supraclavicular artery flap (SAF), as well as the fasciocutaneous free flaps, including the radial forearm free flap (RFFF), the anterolateral thigh flap (ALT), and the jejunum free flap, are reviewed with particular emphasis on the literature from the past 2 years. RECENT FINDINGS: For partial pharyngeal defects, several reconstructive options, that is, PMMF, RFFF, SAF, and ALT might all be appropriate. When large mucosal surfaces need reconstruction, RFFF seems to be the most utilized. Nevertheless in reviewing the literature, no specific pedicled or free flap seems superior over other options. In cases of tongue reconstruction ALT or RFFF may be appropriate. After circumferential resections of the hypopharynx and cervical esophagus, free flaps achieve a significantly lower fistula and stricture rate compared to pedicled flaps with ALT and free jejunal flaps being used most commonly. However, donor-site morbidity and the complications of jejunal harvesting can be significant. Due to its great versatility, good reported functional and oncological outcomes, and reduced overall complication rate, the ALT flap warrants consideration. Finally, transoral robotic surgery (TORS) may provide future options for reconstruction. SUMMARY: Currently the head and neck surgeon has a diverse armamentarium available to reconstruct even large and complex pharyngeal defects. Selecting the best reconstructive option must be individualized. Fasciocutaneous free flaps, that is, RFFF and especially ALT, are assuming a greater progressive role in pharyngeal reconstruction. TORS may eventually lead to new options for reconstructive surgery.

Ultrasound usage in the head and neck surgeon's office.

PURPOSE OF REVIEW: To review the essential developments in neck sonography published in the past 12 months and to elucidate their influence on the indications and diagnostic accuracy of office-based ultrasonography. RECENT FINDINGS: In the screening of the neck in patients with squamous cell carcinoma, sonographic and duplex sonographic characteristics have been described to identify lymph node metastases, that is, size, shape, echogenicity, homogeneity, absence of hilar sign and hilar vessel, surface irregularity, necrotic areas, evidence of extracapsular spread, peripheral perfusion pattern, focal vascularization defects, and high pulsatility index. The combination of conventional ultrasound, duplex sonography, and ultrasound-guided fine-needle aspiration biopsies (USgFNAB) achieves an overall accuracy of nearly 100%. Ultrasound has been found to be most accurate in the diagnosis and differential diagnosis of thyroid and parathyroid disorders, the localization of parathyroid adenomas and the differential diagnosis of thyroid gland disorder. Sonographic characteristics, however, are mostly unspecific. Sonography provides the chance to obtain cytologic material under direct view by USgFNAB. SUMMARY: Office-based ultrasonography is a simple and rewarding technique that is enhanced by the experience of the investigator. The neck surgeon who is caring for the patient might use this information for diagnostic and therapeutic management. Due to high accuracy, noninvasiveness, and lack of radiation exposure, ultrasonography is required in the diagnosis and differential diagnosis of any pathologic masses in the entire neck and prior to any surgical procedure. Future developments, that is, elastography, might lead to further improvement in the diagnostic accuracy to differentiate benign and malignant masses.

Expression of bcl-2 is associated with microvessel density in olfactory neuroblastoma.

Erythropoietin (Epo) expression is regulated via hypoxia-inducible factor (HIF)-1alpha-directed gene transcription. Activation of the erythropoietin receptor (EpoR) by Epo leads to elevated expression of the anti-apoptotic protein, bcl-2, which has recently been shown to promote angiogenesis in malignant tumors. Expression of HIF-1alpha, Epo, EpoR, and bcl-2 was studied by immunohistochemistry in a series of 20 olfactory neuroblastoma (ONB) samples. Data were correlated with microvessel density, proliferative activity, and apoptosis in the specimens and survival analysis was performed to investigate the prognostic value of the examined factors. Immunohistochemical analysis revealed robust expression of HIF-1alpha, Epo, EpoR, and bcl-2 in ONB. Ninety percent of the samples showed HIF-1alpha immunoreactivity and in 60% of the cases, bcl-2 immunoreactivity was observed. A significant positive correlation between the expression levels of HIF-1alpha and bcl-2 and the microvessel density was found. Survival analysis did not reveal any prognostic significance for the tested factors. Expression of HIF-1alpha, Epo, Epo-R, and bcl-2 may play a functional role in ONB pathogenesis. Our data suggest that bcl-2 may act as a stimulator of angiogenesis in ONB, and thus represents a novel target for anti-angiogenic treatment strategies in the therapy of ONB.

Comparative analysis of the epithelium stroma interaction of acquired middle ear cholesteatoma in children and adults.

In the clinical setting, pediatric cholesteatomas frequently behave more aggressively than similar lesions in adults. The reason for the difference in behavior is still unclear. The purpose of the present study was to investigate the cell to cell and epithelial-stroma interaction of acquired cholesteatoma in adults and children and search for differences on the cellular level, which might explain the different behavior of these lesions. Operative specimens of 54 patients [40 adults (average age of 39.7 years), 14 children (average age of 8.3 years)] who underwent primary surgery for an acquired cholesteatoma of the middle ear were examined by histopathology and DNA-image cytometry (DNA-ICM). Immunohistochemical investigations included expression of proliferation markers (proliferation cell nuclear antigen and MIB-1) along with cell surface markers reflecting the cell-to-cell interaction (i.e. alpha1beta6-integrin, E-cadherin, I-CAM = CD54), and the epithelial to stroma interaction (i.e. alphav and beta3 intergin chains, V-CAM = CD106, CD44v6 and fibronectin). Pediatric cholesteatomas demonstrated higher incidence of acute inflammation and more extensive disease relative to those from the adults. Indices of DNA-ICM, however, revealed normal diploid DNA content in both groups. Higher proliferation scores occurred in the pediatric group compared to adult cholesteatoma. Cell surface markers and cell adhesion molecules were equally expressed in both groups except alpha1beta6-integrin and fibronectin, which were over expressed in pediatric cholesteatomas. Statistically, however, these differences showed only a trend towards significance. According to the results of the present study, pediatric and adult cholesteatomas do not show any marked differences on the cellular level. Thus the observed clinical more aggressive behavior of pediatric cholesteatoma is likely due to other secondary factors such as more intense inflammation, disturbed middle ear ventilation or the diminished calcium salt content of pediatric bone.

Molecular biologic characteristics of seven new cell lines of squamous cell carcinomas of the head and neck and comparison to fresh tumor tissue.

BACKGROUND: Squamous cell carcinoma (SCC) is the most frequent malignant tumor of the upper aerodigestive tract. Cell lines of these tumors facilitate the investigation of various tumor biological parameters. This study was conducted to compare molecular biologic characteristics between cell lines and fresh tumor tissue. METHODS: In seven SCC-derived cell lines, cytokeratin 5/6 and cytokeratin 19 expression, DNA content, chromosome aberrations and tumorigenicity were assessed in nude rats. Unbalanced numerical and structural chromosomal aberrations were investigated by comparative genomic hybridization (CGH), and results were compared to those obtained in fresh tumor tissues of the same patients. RESULTS: All cell lines expressed cytokeratins 5/6 and 19, indicating their epidermoid origin. Tumor growth after transplantation into nude rats occurred in five of seven cell lines. Routine histology and immunohistochemical examinations confirmed SCC. Aneuploidy was detected in all cell lines, with a 2c deviation index ranging from 1.9 through 9.5 and a 5c exceeding rate ranging from 2.6 through 36.7%. The most frequent chromosomal aberrations in cell lines were overrepresentations of chromosomal material on chromosomes 15q, 7p (5 cases each), 3q, 5p (4 cases each), and 11q and 17q (3 cases each) and losses of chromosomal material on chromosomes 3p, 18q (3 cases each), and 19p and 7q (2 cases each). Comparing these results to CGH analysis of fresh tumor tissue from the same patients, overrepresentations of chromosomal material on 10q, 20q and 21q, along with loss of chromosomal material on 4q was detected more frequently in primary tumors, whereas overrepresentations on 7p and loss of chromosomal material on 7q were more frequently detected in cell lines. Nevertheless, there was a high degree of similarity of chromosomal alterations in cell lines and corresponding fresh tumor tissue. CONCLUSION: The data suggest a high degree of genetic similarity between tumor cells of cell lines and the tumors from which they were derived. Therefore, these cell lines can serve as an accurate model to investigate cell biology of SCC in vitro.

Investigations for fine mapping of amplifications in chromosome 3q26.3-28 frequently occurring in squamous cell carcinomas of the head and neck.

OBJECTIVE: Overrepresentations of chromosomal material on the long arm of chromosome 3 frequently occur in squamous cell carcinoma of the head and neck. This experimental study was conducted for further fine mapping of these overrepresentations by interphase fluorescence in situ hybridization (FISH) of tumor cells in cell lines. METHODS: Seven cell lines derived from squamous cell carcinomas of the head and neck were investigated by comparative genomic hybridization to analyze unbalanced chromosomal aberrations. Overrepresentations of chromosomal material on the telomeric part of the long arm of chromosome 3 were further analyzed by interphase FISH using YAC contig clones. RESULTS: Chromosomal aberrations which frequently occurred were overrepresentations on 5p (n = 4), 7p (n = 5), 11q13 (n = 3), 15q (n = 5), 17q (n = 3), 19q (n = 2), 20q (n = 2) and 22q (n = 3). Reoccurring losses of chromosomal material were found in 3p (n = 3), 7q (n = 2), 18q (n = 3) and 19p (n = 2). Gains of chromosomal material on chromosome 3q were found in 4 out of 7 cell lines, with a high copy number of amplifications occurring in the chromosomal region of 3q26.3-28. Further experiments revealed a physical mapping of this amplification to a narrow band of 13.8 Mbp on chromosome 3q, whose amplification borders were represented by the YAC clones 754_f_3 centomeric and 955_b_2 telomeric. CONCLUSIONS: By FISH, the amplification of chromosomal material on 3q could be fine mapped on a narrow band on 3q26.3-27. This aberration can be considered as a breakpoint in tumorigenesis. Putative candidate oncogenes and tumor suppressor genes located in this region might be a target for mutations leading to tumor progression.

Analysis of cytogenetic aberrations in esthesioneuroblastomas by comparative genomic hybridization.

Esthesioneuroblastoma (ENB) are rare tumors originating from the olfactory epithelium of the superior nasal cavity. This lesion is morphologically closely related to Ewing sarcoma and other peripheral primitive neuroectodermal tumors (pPNET). The affiliation of ENB to the pPNET family is still under discussion. Only very limited and contradictory cytogenetic data are available on ENB and only one patient has been analyzed by comparative genomic hybridization (CGH), so far. In the present study, genomic imbalances of three ENB were analyzed by CGH to evaluate (1) a recurrent pattern of imbalances, and (2) its relation to the pPNET family. The CGH analysis of three ENB revealed multiple recurrent aberrations including DNA overrepresentations of chromosomal material of the entire chromosome 19, partial gains of the long arms of chromosomes 8, 15, and 22, and deletions of the entire long arm of chromosome 4. Beside these common aberrations, several single gains and losses occurred, that is, gains on 6p, 10q, 1p, 9q, and 13q. We confirmed the former observation of amplified genetic material on chromosome 8 and found several new, currently not described recurrent genetic aberrations distinct from those described for pPNET. Our findings give evidence that ENB is not part of the pPNET family. We suggest that the combined gain of genetic material on 15q, 22q, and chromosome 8 might be indicative for ENB. To verify our findings and to define prognosis-related aberrations, a larger number of cases needs to be studied.