Postoperative pain is still poorly managed among surgical patients despite evidence-based approaches to its treatment being well established. Prompted by the persistence of this problem, many researchers have studied factors influencing postoperative pain management. Empirical clinical research has dominated this area and has presented a set of factors which, albeit important, have not taken into account the influence of contextual factors on the individual’s practices in pain management. This study is designed to examine the role of context on the practices and interactions of professionals and patients during postoperative pain management. Informed by the insights of post-structuralism, it uses nonparticipant observation, informal and semi-structured interviews with participants of both genders (29 staff nurses, 13 surgeons, 38 patients, and 20 patients’ family members), and a document review to construct a case study of four surgical patients’ wards in two Jordanian hospitals. Also included is a descriptive analysis of pain and distress scores, and a thematic analysis of the raw data The findings reveal both a significant problem with pain among Jordanian surgical patients, and limited engagement by nurses in postoperative pain management. It is found that a series of socio-cultural and organizational factors limit participants’ practices in respect of pain management. Influential socio-cultural factors include: sexual surveillance, an inferior public view of nurses, patriarchal ideas, and use of personal influence (wasta). Organisational factors include: hierarchical observations, fear of punishment, the subordination of nursing staff, perceptions of low staffing and high workload, and social hierarchies, such as rank. In combination these contextual factors operate as a set of disciplinary and power mechanisms that limit the ability of nurses to become involved in patients’ pain management; impede nursing professionalism by restricting autonomy and self-regulation; reduce some of the patients’ willingness to communicate pain and lead to a reluctance to be cared for by professionals of a different gender. It is concluded that in this area organisational policies are subservient to nurses’ culturally constructed approaches to pain management. As such, socio-cultural factors appeared to have a greater effect than organizational factors. Recommendations are made to address the situation and provide for appropriate pain relief after surgery.

Background: The present study aimed to explore if risk factors associated with loading at knee were associated with degenerative changes in ACL injured groups. Methods: Part 1: Biomechanics were investigated for gait, jogging and single legged squatting (SLS) in Anterior Crucitate Ligament Reconstructed (ACLR) (n=30), Anterior Cruciate Ligament Deficient (ACLD) (n=28) and controls (n=30). Analysis of biomechanics was also undertaken on a subgroup of ACLR (ACLR2) (n=10) 12.9±1.8 months after their first assessment. From the ACLR2 those with MRi (ACLM) were recruited (n=8). Part 2: Comparison between the ACLM groups NHS diagnostic scans and a follow up scan was undertaken 27±11.7 months apart. Quantitative measurement of cartilage thickness and a semi-quantitative analysis developed from the Whole-Organ Magnetic Resonance Imaging Score (WORMS) was undertaken. Part 3: Used a case series analysis incorporating individual participants’ outcomes from the first two parts of the study. Statistical analysis: Differences between ACLR, ACLD and control groups was performed using ANOVA. Longitudinal analysis was performed using a paired t-test and changes in MRi using a Wilcoxen signed-rank test. Results: Biomechanics: No significant differences between groups existed for gait. For jogging ACLD and ACLR demonstrated reductions in peak knee extensor moment. The SLS showed a reduction in sagittal plane knee range of motion in the ACLD. The ACLD group had lower self-reported measures of function compared to the ACLR group. Quantitative MRi: No significant differences in regional cartilage thickness between diagnostic and follow up scans was observed. Semi-quantitative MRi: Significant improvement in total knee score was observed in ACLM. Discussion: Despite increased loading being associated with the development of OA, the ACLD and ACLR groups maintained or decreased knee moments. Interestingly, the one ACLM participant with worsening of total semi-quantitative score had evidence of decreased extensor moment. However, reductions in net moment caused by a stiffening strategy may still lead to increased compression forces that may have implications for knee health in the full ACLR and ACLD. Conclusion: No evidence of degenerative changes was found in ACLM. However, individual’s demonstrated degenerative changes in some features; this may suggest that OA is an end point but initiated and developed through different mechanisms.

Colorectal cancer is the second most common cause of cancer death in the Western World. Although staging and prognosis is presently based on pathological assessment of primary tumour invasion and the presence of lymph node and distant metastases, it is increasingly recognised that other factors pertaining to both the tumour and host may similarly affect outcome. The local and systemic environment, encompassing host inflammatory responses and the tumour microenvironment, are examples of such. However, how such measures may compliment present TNM-based staging are not clear. Furthermore, tumour and host factors, both modifiable and non-modifiable, which may determine the local and systemic environment, remain to be fully determined. The present thesis examined the clinical and prognostic utility of assessment of the local and systemic environment, and potential tumour and host factors which may determine these responses. The following conclusions were drawn: Examining patients from the United Kingdom and Japan, Chapter 2 and 3 concluded that assessment of the systemic inflammatory response, utilising the modified Glasgow Prognostic Score, provides further prognostic stratification in addition to TNM stage. Although the proportion of patients exhibiting an elevated systemic inflammatory response differed between populations, the prognostic value was comparable. Chapter 4 validated assessment of the tumour stroma percentage as a prognostic factor independent of TNM stage and the local inflammatory cell infiltrate (cancer-specific survival HR 1.84, 95% CI 1.17-2.92, P=0.009). Chapter 7 further confirmed the prognostic value of a combined tumour microenvironment score, based on assessment of the generalised inflammatory cell infiltrate and tumour stroma percentage, in patients with primary operable colorectal cancer. This score, termed the Glasgow Microenvironment Score, was able to stratify patients into a good prognostic group, with five-year survival of 89%, an intermediate group with a two-fold increased risk of death and five-year survival of 75%, and a poor prognostic group, with a four-fold increased risk of death and five-year survival of 51%. Chapters 5 and 6 identified the presence of mismatch repair deficiency and activation of the JAK/STAT3 as two potential mechanisms which may determine host local and systemic inflammatory responses. However, the prognostic value of such candidate mechanisms was weak, suggesting that other pathways and tumour characteristics are implicated, and that molecular heterogeneity is likely to play an important role in determining not only the local and systemic environment, but also outcome. Chapter 9 concluded that the Immunoscore, an immunohistochemistry-based assessment of T-lymphocyte density within the tumour microenvironment, held greater prognostic value than assessment of the generalised inflammatory cell infiltrate using the Klintrup-Mäkinen grade. However, assessment of tumour stroma percentage provided additional prognostic value irrespective of the methodology employed to examine the local inflammatory cell infiltrate. Furthermore, the results of Chapters 7, 8 and 9 together suggested that loss of the local, anti-tumour immune infiltrate was the primary event which allows continued tumour growth, development of a tumour-supportive microenvironment and propagation of a systemic inflammatory response. Chapter 10 concluded that pre-diagnosis use of aspirin but not statins was associated with a lower modified Glasgow Prognostic Score, despite strong associations with comorbidity and BMI. This did not translate into an improvement in survival, potentially reflecting the underlying indication for use of these drugs primarily as cardiovascular secondary prevention medications. Finally, Chapter 11 examined the clinical utility of assessment of the tumour microenvironment using colonoscopic biopsy specimens, concluding that the use of biopsy-derived specimens was feasible. Furthermore, in addition to identifying patients who may benefit from therapies targeting the tumour microenvironment, assessment of a biopsy-derived Glasgow Microenvironment Score had comparable prognostic value to full section assessment of the tumour microenvironment.

Femoroacetabular impingement syndrome is a disorder of the hip joint in which irregular contact occurs between the joint surfaces during motion, typically because certain hip shapes (cam or pincer morphology). In this thesis a systematic review demonstrated that the point prevalence of cam and pincer morphology was not known. This systematic review identified that there were no established diagnostic criteria for cam and pincer morphology. A consensus development conference was used to define FAI syndrome and how it should be diagnosed. This consensus conference was unable to establish the radiographic criteria to define cam and pincer morphology. A case control diagnostic study was undertaken to identify the optimal measures to identify cam and pincer morphology, using cross sectional imaging. These definitions were applied to a sample representative of the general population in order to determine the point prevalence of cam and pincer morphology. The same diagnostic criteria were applied to a group of professional golfers, in this population, asymmetry between left and right hips, and cam and pincer morphology were found to be associated with reduced hip related quality of life. A systematic review identified there was evidence to show that cam morphology caused hip osteoarthritis. However, the evidence to show that pincer morphology and FAI syndrome caused OA was presently lacking. No experimental studies were identified assessing whether treating cam and pincer morphology or FAI syndrome altered the risk of developing OA. A feasibility randomised controlled trial was conducted to determine whether proxy markers of osteoarthritis, measured on magnetic resonance imaging, could be used in a trial to determine whether surgery alters the natural history of FAI syndrome.

The role of serum autoantibodies, soluble adhesion molecules, plasma and mucosal cytokines were studied following surgery for ulcerative colitis (UC). A high prevalence of ANCA was found in UC but not in Crohn’s disease. ANCA positive UC sera were found to recognise a variety of antigens, namely lactoferrin, cathepsin G, enolase and elastase. Confocal microscopy revealed maximum immunofluorescence for P-ANCA to emanate from the intranuclear and not the extra-(peri) nuclear portion of the neutrophil, as currently believed. AECA, like ANCA, are also found in UC, suggesting immunological similarities with systemic vasculitis. Perhaps, UC represents a gut limited vasculitis. Persistance of ANCA, AECA, anti-EPI and antitropomyosin antibodies in the sera, several years following total colectomy, suggests that immunological mechanisms are not halted, by total colectomy. Soluble intercellular cell adhesion molecules, ICAM-1 and E-Selectin, but not VCAM-1, were found to be useful markers of disease activity in UC. Plasma levels of cytokines do not reflect disease activity, however, there is similar quantitative expression of pro-inflammatory cytokines by isolated mucosal mononuclear cells in both active UC and pouchitis, but not in nonspecific proctitis, which seems to suggest that pouchitis is not merely a complication of ileoanal pouch surgery but, that it represents reactivation of UC in ileal mucosa, which has undergone villous atrophy and colonic metaplasia.

This thesis reports a series of laboratory and clinical studies designed to investigate the acute effect of surgical palliation on ventricular function in children with functionally single ventricle anatomy. Ventricular volume and pressure were measured using a combined pressure-conductance catheter. Initial laboratory-based experiments were performed using a physical model of the left ventricle, which allowed examination of the measurement techniques used in the clinical studies but under controlled conditions. These experiments identified a non-linear conductance-absolute volume relationship and demonstrated for the first time that the calibration coefficient, \(\alpha_{SV}\) produced a significant, volume-dependent measurement error. These experiments also demonstrated that conductance volume measurements were adversely influenced by other electrical signals. The ventricular electrogram produced clinically important measurement error that has not previously been described. Two clinical studies were then undertaken to investigate the separate effects of the bidirectional cavo-pulmonary anastomosis (BCPA) and the completion total cavo-pulmonary connection (TCPC). These studies represent the core of the thesis. Both procedures were associated with significant changes in the pressure and volume conditions of the dominant ventricle. In addition, the BCPA was associated with a substantial and immediate improvement in ventricular systolic function but this was accompanied by an increase in diastolic chamber stiffness. By contrast, the TCPC was not associated with a significant change ventricular systolic or diastolic function in spite of the changes in ventricular load. Comparable changes were observed in patients with a dominant ventricle of either left or right ventricular morphology. These studies provide a more detailed understanding about the acute events that accompany surgical palliation in children with functionally single ventricle anatomy. These findings confirm the validity of staged surgical palliation in the management of these children.

Recent literature suggests that 84% of lower extremity amputations (LEAs) are due to peripheral arterial occlusive disease (PAOD), and half of those will have diabetes. Only 40% will go on to rehabilitate with a prosthetic limb and the remainder will be wheelchair dependent. Until now, the majority of research has focused on the short-term clinical outcomes in this population e.g. prosthetic fitting, morbidity and mortality rates. There is a dearth of research into the long-term impact of a LEA on the individual’s quality of life (QoL), especially in those with PAOD with or without diabetes. Aim This thesis aims to determine which factors influence QoL after an LEA due to PAOD in the presence or absence of diabetes. Methods A prospective review of medical case notes and other relevant documentation was conducted on all patients who underwent a major lower extremity amputation for PAOD in NHS Greater Glasgow and Clyde in Scotland, between 1st March 2014 and 28th February 2015. Patients who consented to follow-up completed the EQ-5D-5L QoL measure, Reintegration into Normal Living (RNLI) and the Prosthetic Limb Users Survey of Mobility (PLUS-M), 6 and 12 months after LEA. Semi-structured interviews were conducted on 15 participants who completed follow up questionnaires to explore their views and experiences of living with a LEA and to understand which factors influence their QoL. Results There were 171 participants with a LEA in one year and their mean age was 66.2 years, 75% were males and 53% had diabetes. Over two thirds of the cohort lived in the two most deprived areas in Glasgow. From the follow up questionnaires (n=101) participation, measured by the RNLI had the greatest influence on QoL six and twelve months after LEA. Limb fitting positively influenced QoL, however, level of mobility was poor for all levels of LEA and there was a positive association between mobility (PLUS-M) and QoL. Mortality was seven times greater in those who were not limb fitted. Face-to-face interviews identified five broad themes that influenced QoL: the prosthesis; experience of pain; social support/isolation; sense of self/identity and interactions with others with an amputation. Conclusion Quality of Life was influenced by several factors, primarily participation, which was improved if limb-fitted. Those of male gender, younger age and diagnosed with diabetes were more likely to have a prosthesis fitted. While having a prosthesis did not determine QoL per se, those with greater levels of mobility were more likely to be able to participate, feel less isolated and require less social support which afforded them greater levels of QoL. Conversely, those who were wheelchair dependent or had poorer levels of prosthetic mobility reported lower levels of QoL; which was associated with dependence on social support, feelings of isolation and changes in the way they felt about themselves.

This thesis details my contribution to the literature on military surgery, based on both front-line surgical experiences as well as research carried out on causes of death and disability, particularly in relation to limb injuries, the most common site of wounding in conflict. Injury analysis (6 papers). Injury prevention/mitigation (5 papers). Management (8 papers). Outcome (13 papers). Education (9 papers).

Improving the survival of patients with pancreatic ductal adenocarcinoma (PDAC) remains an oncological and surgical challenge. PDAC pathogenesis is underlined by numerous molecular aberrations occurring at a genetic and epigenetic level, however their spectrum of occurrence and clinical impact has not yet been fully elucidated. The majority of patients present with locally advanced or metastatic disease and even the 15-20% of patients who undergo resection for cure have a median survival limited to 18-24 months. Surgical treatment carries a high morbidity and identification of patients expected to have a poor prognosis could assist in the decision making process. The present thesis examines the prognostic importance of pathological and molecular factors in PDAC, specifically: 1. An examination of the frequency, the prognostic impact of resection margin involvement, and furthermore the prognostic influence of tumour involvement at individual margins. 2. Determination of the prognostic impact of peripancreatic fat invasion following resection of PDAC. 3. The investigation of the relationship of candidate protein biomarker expression with overall survival in a large PDAC tissue microarray cohort using immunohistochemistry. 4. Determining gene expression profiles associated with pancreatic cancer compared to normal tissue using gene expression microarray analysis with subsequent development and validation of a prognostic gene signature. 5. microRNAs were identified that associated with pancreatic cancer clinicopathological factors including survival. 6. Copy number aberrations were identified using array comparative genomic hybridisation that correlated with clinicopathological factors following resection for PDAC. 7. Finally the identification of potentially important regulator genes contributing to pancreatic tumourigenesis, was made by integrating the gene expression, microRNA expression and copy number data from previous sections using a bioinformatic approach. In this work a combination of enhanced pathological staging criteria along with the correlation of molecular marker expression and genomic profiling signatures with clinical outcome data has yielded interesting results in patients undergoing resection for pancreatic cancer that allowed detailed disease characterisation and subsequent clinically relevant outcome stratification.

Researchers have indicated the need for consideration of emotional distress prior to surgery. Measures of pre-operative anxiety have been developed and include the Pre-operative Intrusive Thoughts Inventory (PITI). The aim of the present study is to evaluate the application of the PITI in a mid- to older-adult population awaiting elective hernia repair. A cross-sectional design was employed to examine whether anxiety, depression, previous surgical history and personality characteristics modified intrusive thoughts. Twenty-one participants were recruited and assessed in hospital before surgery. Measures of state anxiety, neuroticism, psychoticism and negative surgical history correlated with the PITI or its subscales. However, lower levels of pre-operative distress as assessed by the PITI were found in the present sample when compared to mean scores in the original study and reasons for these findings are proposed. Results indicate the importance of assessment of pre-operative functioning and the association of psychological and personality characteristics in responses to surgery.