Thesis (doctoral)--Rijksuniversiteit te Utrecht.

Thesis (doctoral)--Rijksuniversiteit te Utrecht.

Thesis--Wisconsin. / Includes bibliographical references (leaves 80-84).

Thesis (Ph. D.)--University of Nebraska, 1931. / "Contribution from the Zoological laboratories, University of Nebraska, no. 179." Includes bibliographical references (p. 70-72).

Thesis (M.S.)--University of Michigan, 1969.

Thesis (M.S.)--University of Michigan, 1969.

Thèse d'exercice : Médecine. Oncologie option radiothérapie : Université de Nantes : 2005. / Bibliogr. f. 79-82 [49 réf.].

Despite the advance in modern oncology, there was limited improvement over the survival outcome of head and neck cancers. Until the discovery of the etiological association between Human Papillomavirus (HPV) and oropharyngeal cancer, an accelerated evolution in the field of head and neck oncology began. This viral-related tumor has ignited tremendous effort in American and European countries to explore the optimal treatment approaches. In contrast, the paucity of comprehensive and robust studies commonly exists in many Chinese and Asian countries. Little is known about the current situation of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) in Hong Kong. This retrospective local multi-institutional study attempted to explore the HPV-associated OPSCC in Hong Kong from various aspects, including demographics, risk factors, clinical and histological features, molecular profile, as well as clinical outcomes. Finally, attempts were made to determine any predictive factors to stratify high-risk patients in this distinct disease entity and explore the most appropriate detection algorithm of the biologically active HPV infection in our locality. With the support from the Hong Kong Cancer Registry and nine public hospitals, 141 (43.3%) of 326 newly diagnosed OPSCC in the whole population of Hong Kong between 2005 and 2009 were recruited. Inclusion criteria were histologically proven OPSCC with tumor specimens available for prospective laboratory tests. Those with non-SCC, non-oropharyngeal in origin and incomplete clinical records were excluded. Prospective HPV PCR and genotyping, and immunohistochemical staining with p16, p53, cyclin D1 and HER-2 were performed. Univariate and multivariate analyses were performed to assess the correlations between various parameters and HPV-associated OPSCC. Epidemiologically, based on the combined positivity in HPV PCR and p16, the prevalence of HPV-associated OPSCC was 22%. Thirty (96.8%) of thirty one were HPV-16, the remaining one was HPV-18. In the univariate analysis, this cancer directly correlated with female gender (p=0.014), younger age (p=0.012), non-smoker (p=0.02), non-drinker (p=0.06) and early primary tumor (p=0.001). Histologically, basaloid differentiation (p<0.001), non-keratinization (p=0.007) and high tumor infiltrating lymphocyte (TIL) level (p<0.001) showed significant correlations. A distinct molecular profile was identified, with p16 positivity noted in all cases (p<0.001), few of p53 (p<0.001) and cyclin D1 positivity (p<0.001) and absence of HER2 over-expression. Significantly superior prognosis was demonstrated in HPV-associated OPSCC. The 5-year overall and disease specific survivals were 67.0% and 88.6% compared with 27.8% (p<0.001) and 41.3% (p<0.001) in the non-viral counterpart respectively. Other good prognostic factors identified for OS and DSS included early primary disease (T1/T2) (p=0.02; p=0.001), absence of distant metastasis (both p<0.001), high TIL level (both p<0.001), p16-positivity (p=0.002; p=0.003), non-smoker (p=0.021; p=0.014). In the multivariate analysis, the HPV-associated tumor (HR: 0.28; 95% CI: 0.08 – 0.93; p=0.038), early primary tumor (HR: 0.52; 95% CI 0.30 – 0.89; p=0.017) and absence of distant metastasis (HR=0.15 95% CI: 0.07 – 0.3; p<0.001) were associated with lower risk of death from any causes after controlling other confounding factors. Most importantly, high TIL level in HPV-associated OPSCC patients was associated with 89% (HR: 0.11; 95% CI: 0.02 – 0.61; p=0.012) lower risk of death from any causes than those with low TIL level, but not present in non-HPV counterpart. In addition, either HPV PCR complemented with typical high-risk genotyping results or p16 IHC positivity complemented with HPC PCR positivity using specific designed primers were two reasonably sensitive and specific detection algorithms based on the local genotypic distribution of this disease. In summary, this is the first most comprehensive and robust local study indicating the importance of HPV-associated OPSCC in Hong Kong. It successfully illustrated various distinctive characteristics of this viral-related cancer. Additionally, it has suggested a potential predictor to identify the minority with more aggressive diseases and the most effective laboratory detection algorithms in this locality. It definitely facilitates the next step in exploring this disease via larger and prospective trials in coming future. / published_or_final_version / Surgery / Master / Master of Medical Sciences

The work presented in this thesis concerns neurophysiology and pharmacology of the oesophageal afferent pathways involved in oesophago-pharyngeal reflexes and oesophageal nociception. Disturbances of reflexes governing contractile and relaxation responses of the upper oesophageal sphincter (DOS) are likely to be implicated in the pathophysiology of conditions involving excessive oesophago-pharyngeal regurgitation, impaired oesophageal clearance, and an abnormal belch reflex. Visceral hypersensitivity, a heightened perception of gastrointestinal sensation is frequently observed in functional gastrointestinal disorders and provides compelling evidence that it plays an important role in the pathogenesis of functional heartburn and non-erosive reflux disease. The work in this thesis explores the neurophysiology, pharmacology and pathophysiology of oesophago-DOS reflexes in humans by experimentally inducing DOS relaxations in healthy controls and patients with reflux laryngitis, and by recording DOS motor responses during spontaneous oesophago-pharyngeal regurgitation. Nociception was assessed by measuring oesophageal sensitivity to electrical stimulation and oesophageal acid perfusion in healthy controls, which was then compared with several heartburn populations (functional heartburn, erosive and non-erosive reflux disease). Additional studies were performed to evaluate the potential role of intraluminal impedance in defining antegrade bolus flow through the pharyngo-oesophageal segment during swallowing as a prelude to the adaptation of the technique to find a more accurate method for the detection of oesophago-pharyngeal regurgitation. The main findings from this work are as follows. 1) Mucosal lignocaine-sensitive afferents mediate the distension-induced oesophago-DOS relaxation reflex and lignocaine insensitive, presumably muscular mechanoceptors, mediate the distension-induced oesophago-DOS contractile reflex. The latter reflex is also upregulated by oesophageal acidification indicative of a possible protective mechanism. 2) Prolonged studies in patients with proven oesophago-pharyngeal regurgitation demonstrated that the most common mechanism of oesophago-pharyngeal regurgitation is a transient, non-swallow related, relaxation of the DOS. 3) Experimental evaluation of the oesophago-DOS relaxation reflex revealed that it is upregulated in patients with reflux laryngitis, suggesting that the aberrant afferent signalling in the oesophagus may be a contributory factor mediating oesophago-pharyngeal regurgitation. 4) Measurement of oesophageal sensory thresholds in response to electrical stimulation and acid perfusion revealed that all patients, irrespective of the presence or absence of mucosal injury, exhibit acid-induced hypersensitisation. 5) The viscro-somatic referral pattern of acid- and electrically-induced chest pain is increased in patients with functional heartburn and non-erosive reflux disease. These findings support the hypothesis that central sensitisation of nociceptive pathways may contribute to symptom reporting in these heartburn populations.

Thesis (Ph. D.)--Cornell University, 1927. / Descriptive letterpress on versos facing the plates. "Reprinted from the American journal of anatomy, vol. 44, no. 2, September, 1929." The fate of the ultimobranchial body in the white rat (Mus norvegicus albinus)" (p. 349-377) is reprinted from the American journal of anatomy, v. 38, no. 3, Jan., 1927. "Literature cited": p. 315-317, 366-368.