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

Técnicas cirúrgicas para realização de craniotomias são descritas na literatura há mais de cinqüenta anos. Contudo, a sua realização ainda é limitada, muitas vezes pela ausência de diagnóstico conclusivo. Com o advento de métodos não invasivos como a tomografia computadorizada, a especificidade quanto ao tipo e localização da lesão tornou-se possível. As principais abordagens cranianas são as técnicas de craniotomia transfrontal que promovem acesso ao cérebro. Os principais pontos de referência para a realização da técnica são os seios venosos da dura mater. Este estudo visou analisar o acesso cirúrgico em relação ao seio venoso sagital dorsal, bem como compará-lo nos diferentes tipos de crânio: braquicefálico e mesaticefálico. Foram utilizados 16 crânios provenientes de 8 cães da raça boxer, 5 cães sem raça definida, 1 rotweiller, 1 labrador e 1 pinscher. O trajeto do seio venoso sagital superior foi estudado pelo método de injeção de solução de látex com pigmento colorido e sulfato de bário. A relação do SVSD foi estudada através de análise das imagens obtidas pela tomografia computadorizada. Os crânios braquicefálicos apresentaram índice cefálico médio igual à 91,24 e índice crânio fácil igual à 2,89; enquanto nos crânio mesaticefálicos obtivemos os valores médios de 79,77 e 1,92 para os índices cefálico e crânio facial respectivamente. O trajeto do seio venoso sagital dorsal foi delimitado, tendo início na porção média do arco zigomático e término ao nível do osso occipital nos dois grupos de crânios. Em relação às mensurações do seio venoso relativas à calota craniana obtivemos os valores médios da área = 7,35+-2,51; D1 = 6,65+-2,27; D2 = 16,17+-4,08; D3 = 15,75-+5,09; D4 = 18,33+-5,25 e D5 = 18,04+-5,87 no grupo mesaticefálico e os valores médios da área = 10,18+-4,69; D1 = 11,84+-2,35; D2 = 19,57+-2,61; D3 = 17,88+-2,31; D4 = 25,32+-5,68 e D5 = 24,84=-4,40 no grupo braquicefálico. Os valores referentes á área, D4 e D5 apresentaram diferença estatística (P<0,05), que denota diferença no formato da calota craniana entre os dois grupos, assim consequentemente diferença na medida citada como margem de segurança para a realização da abordagem cirúrgica do cérebro. / The surgical approaches for craniotomy are describe since the fifties. However, this realization is limited, many times for the absence conclusive diagnosis. The non invasive methods like computed tomography, the lesion locatization and type are easily made. The most important surgical approach is transfrontal craniotomy which promoves brain access. The principal landmarks to the surgery are the dura mater venous sinus. The objetive of this study was to analise the surgical access relation to the dorsal sagittal sinus and to compare with the different skull type: mesaticephalic and braquicephalic. Sixteen skulls from 8 Boxer dogs, 5 Mongrel dogs, 1 Rottweiler, 1 Labrador and 1 Pinscher. The sinus path was studied by solution of bario and látex whith coloured pigment injection. The dorsal sagittal sinus relation was studied by CT image analysis. The braquicephalic skulls showed cephalic index = 91,24 and cranio facial index = 2,89, and the mesaticephalic skulls presents 79,77 and 1,92 for cephalic and crânio facial index. The dorsal sagittal sinus path was delimited, and the medium of the zigomatic arc is this begging and the occipital bone the final, in both skull types. The venous sinus mensurations interface to the skull are: area = 7,35+/-2,51; D1 = 6,65+-2,27; D2 = 16,17+-4,08; D3 = 15,75-+5,09; D4 = 18,33+-5,25 e D5 = 18,04+-5,87 in mesaticephalic dogs and the medium mensurations da area = 10,18+-4,69; D1 = 11,84+-2,35; D2 = 19,57+-2,61; D3 = 17,88+-2,31; D4 = 25,32+-5,68 e D5 = 24,84=-4,40 in braquicephalic group. The área, D4 and D5 mensurations presents statistic difference (P<0,05), which show the skull form difference betwen the two groups, and the edge for the surgical approach to the brain.

Extant literature suggests that experiences of childhood adversity put individuals at increased risk for deleterious emotional-behavioral and metabolic outcomes. However, the precise mechanisms through which early adversity confers risk for such outcomes remains poorly understood. Therefore, this project sought to examine the extent to which Respiratory Sinus Arrhythmia reactivity (RSA-R), a metric of Parasympathetic Nervous System functioning, influences the relationship between adversity exposure and metrics of emotional-behavioral and metabolic health during childhood. Based on prior literature, we hypothesized that RSA-R would significantly moderate the association between exposure to childhood adversity and both emotional-behavioral and metabolic health. This hypothesis was partially supported. Indeed, RSA-R interacted with experiences of childhood adversity to predict internalizing symptoms and metabolic dysfunction. The implications of these findings and directions for future research will be discussed.

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Humans make a wide variety of decisions every day - from which route to take to the store to which job offer to accept. It has recently been proposed that two different systems, one affective and intuitive (System 1), the other logical and deliberative (System 2) interact to guide decision making. Neuroimaging research has supported this hypothesis, but other physiological indices of emotion regulation have been largely unexplored in the context of decision making. Respiratory Sinus Arrhythmia (RSA) is an index of cardiac vagal control, and has been shown to mediate emotion regulation, and vary under stress. Both impaired sleep and the phase of the sleep/wake circadian schedule also influence the expression and regulation of emotion. Sleep deprivation has been shown to lead to poor decision-making, but the relationship between sleep/wake circadian rhythms and decision making has been largely unexplored. Physiological indicators of emotion regulation (such as RSA) are likely to interact with sleep/wake circadian rhythms to influence the strategies used in decision making. The present study found that while time of day did not have an independent influence on decision making or risk taking, these functions appear to fluctuate with body temperature, a physiological index of circadian phase, with optimal performance occurring at higher body temperatures. Furthermore, while RSA appears to be unrelated to decision making and risk taking, circadian phase may influence physiological responses to stress (as measured by RSA) at different times of the day. In particular, morning-types may be more reactive to stress in the evening than during the day. Further research is needed to validate and clarify these findings.

This study characterized maxillary sinus mucositis (SIMS) adjacent to teeth with apical periodontitis (AP), and assessed its resolution three months after endodontic treatment. 29 subjects who maxillary posterior teeth with AP were imaged with cone-beam computed tomography (CBCT). Resolution of SIMS was assessed with CBCT three months after treatment, and periapical healing was assessed using the PAI after six months. Four non-compliant subjects were discontinued and SIMS was identified in 14/25 subjects (56%). Three months post-treatment, SIMS was resolved fully in 3/10 subjects (30%), and partially in 3/10 subjects (30%). Six months post-treatment, 6/10 subjects (60%) were classified as healed or healing. CBCT revealed a lower-than-expected prevalence of SIMS adjacent to teeth with AP. In specific cases SIMS might linger beyond three months after the elimination of the endodontic infection. Due to the low statistical power, association between the resolution of SIMS and periapical healing could not be explored.

This study characterized maxillary sinus mucositis (SIMS) adjacent to teeth with apical periodontitis (AP), and assessed its resolution three months after endodontic treatment. 29 subjects who maxillary posterior teeth with AP were imaged with cone-beam computed tomography (CBCT). Resolution of SIMS was assessed with CBCT three months after treatment, and periapical healing was assessed using the PAI after six months. Four non-compliant subjects were discontinued and SIMS was identified in 14/25 subjects (56%). Three months post-treatment, SIMS was resolved fully in 3/10 subjects (30%), and partially in 3/10 subjects (30%). Six months post-treatment, 6/10 subjects (60%) were classified as healed or healing. CBCT revealed a lower-than-expected prevalence of SIMS adjacent to teeth with AP. In specific cases SIMS might linger beyond three months after the elimination of the endodontic infection. Due to the low statistical power, association between the resolution of SIMS and periapical healing could not be explored.

Ecogeographic patterns of modern human craniofacial diversity suggest external nasal structures reflect climatic adaptations for respiratory and thermoregulatory functions. Regarding internal structures, the maxillary sinus supposedly varies as a function of the nasal cavity while not contributing in respiratory function. Owing to conflicting results, this study reinvestigates that claim by evaluating maxillary sinus variation in a larger sample (n=200) spanning 11 ecogeographic regions. The surface-area-to-volume (SA:V) ratio (i.e., relative mucosal area) was collected in addition to sinus volume and linear dimensions. Pearson correlations show nasal cavity breadth and maxillary sinus volume are not significantly correlated, and individuals from cold, versus hot, climates exhibit larger volumes with lower surface-area-to-volume (SA:V) ratios. Individuals from high altitudes display a unique configuration with high SA:V ratios and large maxillary sinus volumes. Analyses of variance largely fail to find significant differences among the 11 samples. However, a canonical variate analysis of nasal and sinus dimensions indicates clear separations between the heat- and cold-adapted populations, as well as among the cold-adapted populations. Specifically, Arctic populations display smaller sinus volumes and lower SA:V ratios. Mantel tests indicate certain sinus dimensions depart from isolation-by-distance models. Results indicate that maxillary sinus form does not simply follow isolation-by-distance models and cannot simply be explained in terms of nasal cavity breadth or craniofacial architecture— suggesting that environmental pressures are directly acting on the sinus. Functional possibilities for the sinus include thermoregulatory functions among Arctic populations and/or nitric oxide production for high-altitude populations. Additional considerations and future lines of research are presented.

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