Thesis (Ph. D.)--University of Chicago, Dept. of Anatomy. / Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Thesis (doctoral)--Albert-Ludwigs-Universität, Freiburg. / Description based on print version record. Includes bibliographical references.

The equine paranasal sinuses are a frequent site of disease. They are anatomically complex structures encased in bone that are difficult to visualize. Because of their complexity and location, accurate diagnosis and treatment of the affected sinus(es) is difficult without a good understanding of their anatomy. Use of 3-D computer models in anatomy education has increased in recent years and shows promise in teaching anatomy of complex structures. The goal of this thesis was to develop a computer program illustrating a 3-D model of the equine paranasal sinuses to aid teaching the anatomy of the paranasal sinuses. A CT scan of a horse’s head was performed and a 3-D reconstruction was generated. The paranasal sinuses were illustrated in the reconstructed images using Adobe Photoshop 6.0. Adobe Flash Professional CS5 was used to create an interactive computer program from the images. The resulting computer program depicts the sinuses and features of the skull at five key points plus or minus nine degrees of rotation.

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Medical Sciences, Temporomandibular Disorders/Orofacial Pain. Title from pdf file main screen (viewed on April 23, 2010). Includes bibliographical references.

Introduction: Forensic pathologists may be asked to identify the race group or sex of a cranium of unknown origin. Race group refers to geographic ancestry and sex is biological sex. An analysis of the volumes and measurements of human paranasal sinuses, namely maxillary, ethmoid, sphenoid and frontal sinuses, in dried crania of different race and sex groups (European and Zulu male and female) was undertaken to search for a new improved approach of classifying crania according to race and sex. This anatomical assessment of the human paranasal sinuses identifies race and sex variations in the paranasal sinuses. Variations in paranasal sinus volumes and measurements may mean a variation in anatomical landmarks. The best combination of sinus measurements was selected to classify a cranium according to race group and sex making this research relevant to the field of forensic medicine. Objectives: To compare the paranasal sinus volumes and measurements of dried crania of European and Zulu descent with respect to race group and sex and to develop a method of classifying a cranium according to race group or sex by using dimensions of the paranasal sinuses. Methodology: Documented, cadaver derived, dried crania were obtained from the Raymond A. Dart Collection of Human Skeletons, housed at the School of Anatomical Sciences at the University of the Witwatersrand, Johannesburg, South Africa. Age, race and sex were recorded for each cranium within the collection and hence within the study sample. 26 Adult European crania; 13 male, 13 female. Age range 19-75yrs (mean 49.42yrs) and 27 Adult Zulu crania: 13 male, 14 female. Age range 16-90yrs (mean 40.16yrs) was selected for this study. An additional cranium of unknown origin was also analysed in the research. European crania were from descendants of Europe living in South Africa and Zulu crania were obtained from Zulu patients who were part of the Zulu tribe of South Africa. 53 crania with intact paranasal sinuses (106 individual sinuses for each of the maxillary, ethmoid, sphenoid and frontal sinuses) were studied. In addition, 2 sinuses from the unknown cranium were analysed. The dried crania of European and Zulu origin were assessed by helical, multislice computed tomography using 1mm coronal slices. The area for each slice was obtained by tracing the outline of each slice. A volume was calculated by the CT machine that totaled the slices for each sinus. Measurements of width, length and height were also assessed, as were other craniometrical measurements. Statistical analysis was performed for all European and Zulu male and female sinuses in respect of volumes and measurements. Further statistical analysis searched for classification patterns. In addition, forty patients' scans from the European and Zulu male and female groups in Southern Africa were also assessed. CT scans of 10 adult European males, 10 adult European females, 10 adult Zulu males and 10 adult Zulu females provided 40 pairs of maxillary, ethmoid, sphenoid and frontal sinuses for analysis. Europeans were South African persons of European descent and Zulus were from the Zulu tribe of Kwa Zulu Natal in South Africa. Results: The aim of identifying race and sex differences in this anatomical region is achieved. Significant race and sex variations were found in the European and Zulu, male and female groups when analysing the volumes and measurements of the paranasal sinuses. The very best combinations of classifiable measurements were described and are being put forward as a new tool in human forensic identification studies. The significant sex classification figure of 91.8% by combining ethmoid, sphenoid and frontal paranasal sinus measurements, is a new discovery for using a combination of the sinuses. The significant race classification figure of 95.9 % is an excellent classification figure for classification according to race. This was done using the measurements of maxillary, ethmoid and total distance across the sinuses. All this was achieved by using the measurements of the paranasal sinuses in a European and Zulu, male and female population. Conclusion: Forensic race and sex identification of crania is now possible using a combination of measurements from the paranasal sinuses. A new approach to classifying a cranium into an race or sex group is revealed by way of using a new combination of paranasal sinus measurements. This discovery is of importance to forensic medicine in the realm of identification as it provides a measurable way of assigning race or sex to a cranium within a particular region. Other studies based on other race groups may add further value. What is clear is that the paranasal sinuses are now of established value when assessing race or sex group of a unknown cranium. A new tool for forensic race and sex identification is provided to the armamentarium of the forensic pathologist and associated disciplines.

Introduction: Sinonasal inverted papilloma (SNIP) is an uncommon benign tumor with a high recurrence rate, significant malignant potential and unknown etiology. The population in Hong Kong is unique in its high population density and having a majority of Chinese people who are ethnically and geographically predisposed to certain cancers. Research on the etiology, pathogenesis, diagnosis and treatment of the neoplasm and comparison with reported findings from other parts of the world may contribute to management of the condition in terms of prevention, staging and treatment. / Aims: The aim of the thesis is to describe the common and unique clinico-pathological characteristics of SNIP in Hong Kong and compare these with reported characteristics in populations from other geographical areas and in other races with the expectation of attaining new insights into the diagnosis and management of SNIP in Hong Kong patients. / Methods: Four studies designed to evaluate the risk factors, viral associations, cell-cycle protein expression, radiological features, clinical features, treatment approaches and treatment outcomes were conducted. The findings of these studies were compared with those reported from different geographical areas of the world. Study 1: Evaluation of the risk factors associated with SNIP by a case-controlled epidemiological study of 50 patients with SNIP and 150 matched control patients. Study 2: Evaluation of the prevalence of human papillomavirus (HPV), Epstein-Barr virus (EBV), p21 and p53 expression in SNIP and comparison with reports from the literature. In a case-control study, 73 SNIP, 48 nasal polyps (NP) and 85 hypertrophied turbinates (HT) specimens were examined by polymerase chain reaction (PCR) for HPV. Seventy-three SNIP, 30 NP and 32 HT specimens were examined by in-situ hybridization (ISH) for EBV and by immunohistochemistry (IHC) for p21 and p53. SNIP results were compared with those of NP and HT (as controls). Study 3: Evaluation of the radiological signs, accuracy of prediction of tumor origin and extent, and accuracy of preoperative staging of SNIP of plain computed tomography by an observational study of plain CT scans and operative findings from 30 patients with SNIP. Study 4: Evaluation of the clinico-pathological features and treatment outcomes of SNIP in 56 patients seen between 1990 and 2008 with follow-up of more than 2 years and comparison with the results of the literature. / Results and conclusions: There are certain unique clinico-pathological features of sinonasal inverted papilloma (SNIP) in Hong Kong which are related to its predominantly Chinese population, high population density, heavy pollution and, accessible and efficient specialist services. Concordant with the results of another case-control study in the literature, the study described herein demonstrated that occupational chemical exposure, but not smoking, is a risk factor for SNIP. This is the first case-control study demonstrating that alcohol intake, allergic rhinitis, nasal polyposis, sinusitis, non-sinonasal papilloma and non-sinonasal malignancy are not risk factors for SNIP. The low prevalence of HPV in non-malignant sinonasal inverted papillomas (NMIPs) in Hong Kong suggests that it does not play a significant pathogenic role. The absence of EBV in SNIPs in Hong Kong concurs with most reports that EBV is not a causative agent. The high p21 and low p53 expression in SNIPs compared with the average values reported from other studies further support the presence of a non-p53-dependent p21 regulatory pathway. The higher prevalence of both HPV and p53 in malignant sinonasal inverted papilloma (MIP) than in NMIP agrees with other reports that both could be markers of malignant transformation. However, their inverse relation suggests they are independent factors. Although most plain CT signs are the same as those previously reported and not pathognomonic for SNIP, the high predictive value of the “pedunculation sign and absence of intra-tumor calcification are unique to Hong Kong patients. Concordant with other reports, “bony strut or focal hyperostosis is highly accurate in predicting the site of SNIP origin. This is the first report on the accuracy of preoperative CT staging, which is slightly lower than that of preoperative MRI staging (80% versus 86%). The estimated incidence of SNIP (2.4/1,000,000/year) is low but may be an underestimation as the number from the private sector is undetermined. The male:female ratio of SNIP patients in both Hong Kong and Asia is low, suggesting a geographic or racial influence on sex predilection. The absence of extrasinonasal extension, low rates of cellular atypia, dysplasia and synchronous malignancy in the Hong Kong SNIPs may reflect less aggressive tumor behavior as well as accessibility to efficient specialist services. The distribution of tumor origins, presenting symptoms and presenting stages of the Hong Kong SNIPs are similar to those reported elsewhere. The higher recurrence rate in the Hong Kong series is related to inadequate treatment of the tumor origin and inadequate conversion to combined external approaches in the early cases. Contrary to previously reported statistics, combined extranasal approaches were used more often in secondary cases than in primary cases. As in previously reported series, the recurrence rate in secondary cases tended to be higher than that in primary cases. Concordant with previous reports from the endoscopic era, most recurrences in Hong Kong occurred at the original tumor site and were discovered within the first 2 years after surgery. The average time of diagnosis of the first recurrence was much shorter than that of the pre-endoscopic era (1.2 years vs. 4.3 years). As reported elsewhere, about one-third of recurrences required combined external approaches for salvage. This is the first report comparing 2-, 5- and 10-year-follow-up results, and suggesting a minimum of 2 years’ follow-up before reporting results to avoid underestimation of recurrences. / Sham, Cheuk-lun. / Thesis (M.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 215-237). / CHAPTER 1 / Introduction / Chapter 1.1 --- Sinonasal inverted papilloma --- p.1 / Chapter 1.1.1 --- Nomenclature and classification --- p.1 / Chapter 1.1.2 --- Etiology and pathogenesis --- p.4 / Chapter 1.1.3 --- Gross and histological pathology --- p.9 / Chapter 1.1.4 --- Site of tumor attachment and extension --- p.10 / Chapter 1.1.5 --- Association with malignancy --- p.11 / Chapter 1.1.6 --- Incidence and demographics --- p.11 / Chapter 1.1.7 --- Clinical features --- p.12 / Chapter 1.1.8 --- Radiological features --- p.13 / Chapter 1.1.9 --- Staging --- p.14 / Chapter 1.1.10 --- Treatment modalities --- p.16 / Chapter 1.1.11 --- Treatment outcomes, recurrence and residual disease --- p.17 / Chapter 1.2 --- Unique characteristics of the Hong Kong population --- p.19 / Chapter 1.3 --- Research aims, areas and hypotheses --- p.22 / Chapter 1.3.1 --- Research aims --- p.22 / Chapter 1.3.2 --- Research areas and hypotheses --- p.23 / Chapter 1.4 --- Research plan and methodology --- p.25 / Chapter 1.5 --- Summary of Chapter 1 --- p.28 / CHAPTER 2 / Risk factors associated with SNIP / Chapter 2.1 --- Background --- p.29 / Chapter 2.2 --- Hypothesis --- p.29 / Chapter 2.3 --- Patients and methods --- p.30 / Chapter 2.4 --- Results --- p.35 / Chapter 2.5 --- Discussion --- p.39 / Chapter 2.6 --- Summary of Chapter 2 --- p.45 / CHAPTER 3 / Evaluation of the prevalence of HPV, EBV, p21 and p53 expression in SNIP in Hong Kong and comparison with results reported in the literature / Chapter 3.1 --- Background --- p.46 / Chapter 3.2 --- Hypothesis --- p.48 / Chapter 3.3 --- Patients and methods --- p.48 / Chapter 3.4 --- Results --- p.55 / Chapter 3.4.1 --- Overall results --- p.55 / Chapter 3.4.2 --- Comparison of the results of HPV studies --- p.57 / Chapter 3.4.3 --- Comparison of the results of EBV studies --- p.68 / Chapter 3.4.4 --- Comparison of the results of p21 studies --- p.71 / Chapter 3.4.5 --- Comparison of the results of p53 studies --- p.74 / Chapter 3.5 --- Discussion --- p.79 / Chapter 3.5.1 --- HPV and SNIP --- p.79 / Chapter 3.5.2 --- EBV and SNIP --- p.95 / Chapter 3.5.3 --- p21 and SNIP --- p.98 / Chapter 3.5.4 --- p53 and SNIP --- p.103 / Chapter 3.6 --- Summary of Chapter 3 --- p.115 / CHAPTER 4 / Evaluation of the radiological signs, accuracy of prediction of tumor origin and extent, and accuracy of preoperative staging of SNIP by plain computed tomography / Chapter 4.1 --- Background --- p.117 / Chapter 4.2 --- Hypothesis --- p.118 / Chapter 4.3 --- Patients and methods --- p.118 / Chapter 4.4 --- Results --- p.120 / Chapter 4.5 --- Discussion --- p.135 / Chapter 4.6 --- Summary of Chapter 4 --- p.142 / CHAPTER 5 / Evaluation of the clinico-pathological features and treatment outcomes of SNIP and comparison with results reported in the literature / Chapter 5.1 --- Background --- p.143 / Chapter 5.2 --- Hypothesis --- p.144 / Chapter 5.3 --- Patients and methods --- p.144 / Chapter 5.4 --- Results --- p.148 / Chapter 5.4.1 --- Incidence --- p.148 / Chapter 5.4.2 --- Demographics --- p.150 / Chapter 5.4.3 --- Presenting symptoms --- p.154 / Chapter 5.4.4 --- Site of tumor origin --- p.156 / Chapter 5.4.5 --- Rate of association with malignancy --- p.158 / Chapter 5.4.6 --- Staging of disease (Krouse system) and recurrence rate --- p.163 / Chapter 5.4.7 --- Treatment approaches and recurrence rates --- p.165 / Chapter 5.4.8 --- Comparison between patients with and without previous surgery --- p.167 / Chapter 5.4.9 --- Time and site of recurrence --- p.170 / Chapter 5.4.10 --- Surgical approaches used in salvage surgery --- p.175 / Chapter 5.4.11 --- Complication rate --- p.176 / Chapter 5.5 --- Discussion --- p.178 / Chapter 5.5.1 --- Incidence --- p.178 / Chapter 5.5.2 --- Demographics --- p.179 / Chapter 5.5.3 --- Present symptoms and duration --- p.180 / Chapter 5.5.4 --- Sites of tumor origin --- p.181 / Chapter 5.5.5 --- Association with malignancy --- p.182 / Chapter 5.5.6 --- Disease stages (Krouse system) and recurrence rate --- p.184 / Chapter 5.5.7 --- Treatment approaches and recurrence rates --- p.186 / Chapter 5.5.8 --- Comparison between patients with and without previous surgery --- p.187 / Chapter 5.5.9 --- Time and site of recurrence --- p.189 / Chapter 5.5.10 --- Surgical approaches used in salvage surgery --- p.191 / Chapter 5.5.11 --- Complication rate --- p.192 / Chapter 5.5.12 --- Management principles based on clinico-pathological features --- p.193 / Chapter 5.6 --- Summary of Chapter 5 --- p.197 / CHAPTER 6 / Summary of thesis and future perspective --- p.201 / REFERENCES --- p.215 / APPENDIX / Questionnaire for study of risk factors of SNIP --- p.238

Chronic rhinosinusitis is a common disorder of chronic inflammation of the upper respiratory tract. It is associated with significant symptoms and impairment of the quality of life of sufferers. Despite recent advances in the medical and surgical management of chronic rhinosinusitis, there remains a population of patients who fail to obtain relief from their symptoms. Chronic inflammation of the mucosa of the nasal cavity and paranasal sinuses is one of the hallmarks of chronic rhinosinusitis. This inflammation is demonstrated by an increased number of chronic inflammatory cells, elevated levels of pro-inflammatory cytokines, increased expression of adhesion molecules and metaplastic changes in the epithelium. The current medical treatments for chronic sinusitis aim to reduce this inflammation and consequently improve symptoms. In recent years, evidence has emerged that macrolide antibiotics have an anti-inflammatory effect that is separate from their anti-bacterial effect. This effect was first described in the treatment of diffuse panbronchiolitis, a disorder of chronic inflammation of the lower respiratory tract. Following the success of macrolides in treating this condition it was trialed in chronic rhinosinusitis. Several open-label trials have subsequently demonstrated a beneficial effect. Laboratory studies have investigated the mechanism of the anti-inflammatory effect of macrolides. These have shown that macrolides effect cytokine production, inflammatory cell apoptosis, expression of adhesion molecules, neutrophil oxidative burst, bacterial virulence and mucociliary function. In this thesis we report a series of experiments designed to further investigate the mechanism of action and clinical effect of macrolides. In vitro studies using whole sections of chronic rhinosinusitis mucosa cultured for 24 hours in macrolide, prednisolone or control showed that macrolide and prednisolone produced significant reductions in the production of interleukin-5, interleukin-8 and granulocyte-macrophage colony stimulating factor. The same cultured specimens also showed a reduction in expression of transforming growth factor-?. No reduction was seen in the expression of the key pro-inflammatory nuclear transcription factor Nuclear factor-?B. In our in vivo experiments, biopsies were taken from chronic rhinosinusitis patients who had received a 3-month course of macrolide. These biopsies showed a reduction in the number of neutrophils present following treatment. There was no reduction in the number of other inflammatory cells or in the expression of TGF-? and NK-?B. We have performed the first ever double-blinded, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis. Patients receiving macrolide showed significant improvements in saccharine transit time, nasal endoscopic scoring and symptom scores following a 12 week course. Patients with low levels of serum immunoglobulin E showed significantly improved outcomes compared to those with high levels. Interleukin-8 levels in nasal lavage fluid were significantly reduced in the patients with low levels of IgE following macrolide treatment. No improvements in any of the objective or subjective outcome measures were seen in the placebo-treated patients. We have performed a series of experiments investigating the anti-inflammatory effect of macrolide antibiotics from 'the bench to the bedside'. These experiments have provided insight into the mechanism of action of macrolides in the laboratory setting and evidence of a beneficial effect in the treatment of chronic rhinosinusitis patients.

Purpose: Cancers of the sinonasal tract are rare, comprise a diverse group of histologies and are known for their poor prognostic outcomes. The primary aim of this study was to evaluate the 2- and 5-year overall survival (OS) rates in patients treated with radical and palliative intent for sinonasal squamous cell carcinoma (SNSCC). Methods: A retrospective review of medical records of all patients presenting to Cape Town's Groote Schuur Hospital between January 2003 and December 2013 was carried out. All patients with histologically proven squamous cell carcinoma (SCC) of the maxillary sinus and nasoethmoidal complex who underwent treatment at Groote Schuur Hospital and/or iThemba LABS (Laboratory for Accelerator Based Sciences) were included. Fifty-five patients with cancers of the sinonasal tract were identified from the electronic patient system; 23 were excluded either because of different histologies, lack of histology or having initiated treatment outside of Groote Schuur Hospital. The medical records of 32 patients were utilised for final analysis. 2- and 5-year OS was calculated using Kaplan-Meier analysis. Results: The majority (75%) of patients had an ECOG performance status of 1 with facial asymmetry secondary to tumour mass or swelling being the most common presenting symptom (present in 68,75% of cases). 62,50% of cases originated within the maxillary antrum and 56,25% of cases were classified as keratinizing SCC. Twenty-six (81,25%) patients presented with stage IV disease; nodal disease was seen in 13 (40,63%) patients and distant metastasis in 4 (12,50%) patients. Most patients underwent palliative intent treatment with only 11 (34,38%) having radical treatment. The cumulative 2- and 5-year OS from the date of treatment initiation was 26% and 19% respectively. Median OS for the entire cohort was 7,7 months and was statistically significant between intent groups at 5,19 months (95% CI:3.43– 6.95) for palliative compared to 35,45 months (95% CI: 0.00–138.52) for radical patients (c2 = 7.80, p = 0.005). Conclusion: Despite a decline in incidence of disease over the last 30 years and the improved diagnostic and therapeutic modalities available today, the prognosis and survival outcomes for SNSCC remains poor.

No description available.