Surgery - Christchurch
http://hdl.handle.net/10523/238
2024-03-29T10:54:07ZAdult Acute Appendicitis
http://hdl.handle.net/10523/15583
Adult Acute Appendicitis
2023
Lee, Mei sze
Acute appendicitis is a sudden onset of inflammation of the vermiform appendix and is one of
the most common general surgical conditions. Despite its prevalence and cost, there are gaps in our understanding of the aetiology and pathogenesis of acute appendicitis. This thesis had the opportunity to review the current evidence on the common aetiologies and potential pathogenesis of acute appendicitis, as summarised in the first chapter. The presence of faecolith and its impact on the pathogenesis of acute appendicitis was discussed in detail in the second chapter. With the advancement of technologies, our understanding of the human gut microbiome has evolved substantially. The third chapter in this thesis addressed the microbiome aspect of AA by using the 16S-rRNA sequencing technique to analyse the gut
microbiome of a cohort of adults with appendicitis. With longer life expectancy and an ageing population, the topic of AA in older adulthood, and its association with the early onset of colorectal cancer (CRC), is of current interest and was addressed in Chapter 4 of this thesis.
2023-07-18T03:09:15ZThe microbiota in inflammatory bowel disease- associated colorectal cancer
http://hdl.handle.net/10523/14176
The microbiota in inflammatory bowel disease- associated colorectal cancer
2022
Phan, Anh Thu Thi
Colorectal cancer (CRC) is the second leading cause of cancer death in New Zealand. Patients with inflammatory bowel disease (IBD) are at an elevated risk of developing CRC. Chronic inflammation in IBD is a critical predisposing factor in CRC progression. Aberrant immune response and chronic inflammation can emerge from changes in gut microbiota composition in genetically susceptible hosts. Microbial dysbiosis subverts intestinal homeostasis and impairs epithelial barrier function, thereby perpetuating inflammation and promoting carcinogenesis. High-throughput multi-omics analyses have discovered significant distinctions in microbial diversity and taxonomic and functional composition between healthy subjects and patients with IBD or CRC. However, it remains unknown if the microbial abundance and distribution differ between disease statuses and how that may influence the host responses. In addition, spatial information regarding bacterial distribution and abundance within the colonic tissue of IBD and IBD-CRC patients is currently unavailable.
The present study used RNAscope, a novel in situ RNA hybridisation assay, to characterise bacterial distribution in normal, inflamed and progressed (dysplastic/tumour) tissues in IBD and IBD-CRC patients. In silico quantification of 16S rRNA signal was performed using QuPath bioimage analysis platform to determine relative bacterial abundance. RNAscope results demonstrated extensive intra-tissue heterogeneity in bacterial distribution and interindividual variation in relative bacterial abundance. Bacterial 16S rRNA signals were primarily present in the mucus layer and colonic crypts. In addition, differences in mucus thickness and crypt morphology were observed across normal, inflamed and progressed tissue.
Contrary to our hypothesis, there was no evidence suggesting that the relative bacterial abundance drastically differed across normal, inflamed and progressed tissues in progressors and IBD controls. However, the presence of immune cells was significantly associated with local bacterial abundance. An attempt to correlate bacterial abundance and host expression of the lysozyme gene (LYZ) found no significant relationship between relative bacterial abundance and host expression of LYZ across all tissue types. RT-qPCR detected a low level of pan-bacterial 16S rRNA and Fusobacterium nucleatum RNA (Fn RNA) in CRC and IBD- CRC tumours. Relative 16S rRNA and Fn RNA level did not vary significantly between CRC and IBD-CRC tumours.
This preliminary study presents a unique picture of bacterial distribution and abundance in the colonic tissues of IBD and IBD-CRC patients at single-cell resolution. However, the small sample size (n =14) and high variability in the dataset may affect the reliability of statistical analyses. Future work should include larger cohorts to ascertain the findings from this study and to measure the impact of IBD subtypes, disease duration, extent of inflammation, and treatment history on bacterial abundance and host immune response, within the relevant spatial context.
2022-11-23T01:03:26ZThe pathogenesis of acute diverticulitis and the role of the intestinal microbiome
http://hdl.handle.net/10523/13633
The pathogenesis of acute diverticulitis and the role of the intestinal microbiome
2022
O'Grady, Michael
Aim
This thesis has four aims:
1. To provide a contemporary overview of the pathogenesis of acute diverticulitis.
2. To examine the health care burden of acute diverticulitis, including with long term
follow up.
3. To examine the association between statin use and risk of acute diverticulitis.
4. To examine the role of the colonic microbiome in the pathogenesis of acute
diverticulitis.
Method
A literature review was undertaken. A retrospective study of patients admitted to Christchurch Hospital with acute diverticulitis was performed to estimate the financial burden of acute diverticulitis, including with long term follow up. A retrospective study of patients admitted to Christchurch Hospital with acute diverticulitis, linked to PHARMAC data was performed to assess statins as a risk reducing agent. A prospective case control study was performed to assess the colonic microbiome of patients admitted to Christchurch Hospital with acute diverticulitis.
Results
Acute diverticulitis is a common condition with rising incidence. The understanding of its pathophysiology has evolved, and is now considered to arise through a process of dysregulated immune response to intestinal microbiota in a genetically susceptible individual.
In a cohort of 170 patients the health care cost associated with acute diverticulitis was NZD4814 per patient, and there is a significant proportion of expense incurred subsequent to the initial presentation. Cost was distributed disproportionately – high cost of care was associated with complicated disease, surgical intervention and length of stay.
In a population based case-control study statin use was not found to be associated with reduced risk acute diverticulitis.
Distinct microbiome changes were found in patients with acute diverticulitis in a prospective case control study. Individuals with acute diverticulitis showed lower diversity compared with controls, and had lower abundance of healthy commensal bacterial genera and higher abundance of several known pathogenic bacterial genera.
Conclusion
This thesis provides a contemporary overview of the pathogenesis of acute diverticulitis, outlining a multifactorial process. Environmental risk factors are hypothesised to influence the colonic microbiome, which in turn interacts with the host immune system, thereby influencing local and systemic inflammation. New evidence from this thesis supports this hypothesis with distinct microbiome compositional changes demonstrated in patients with acute diverticulitis. This opens up several areas for further research in prognostication and in risk reduction. One such class of risk reducing agents, statins, was not found to alter risk. The economic burden of this disease was found to be significant and long term, further emphasising the need for ongoing research in order to reduce this burden to our health system, and to individuals and their family.
2022-09-14T23:01:37ZStudies on the Aetiology and Management of Acute Diverticulitis
http://hdl.handle.net/10523/12855
Studies on the Aetiology and Management of Acute Diverticulitis
2022
Turner, Gregory Andrew
Diverticulosis of the colon is a common condition, affecting more than 70% of 70-80-year-olds. However, only a small proportion will go on to develop acute diverticulitis (AD). The reason why certain individuals with diverticulosis develop complications while the majority remain asymptomatic is unclear.
It is hypothesised that the microbiome of the colon plays an important role in the aetiology of AD. This thesis aims to evaluate this theory, as well as review the published literature in special scenarios of diverticular disease sometimes encountered in clinical practise.
Chapter one provides an overview of what is already known about the human microbiome - the natural history, evaluation, and current understanding of its role in human health and disease.
The ideal specimen for assessing the colonic microbiome has yet to be established, therefore chapter two reports a feasibility study validating rectal swabs compared to stool specimens undergoing 16S rRNA gene sequencing.
Having introduced important concepts in study of the microbiome, chapter three will focus on the colonic microbiome in acute diverticulitis, aiming to establish whether microbiome profiles from individuals with AD correlate with clinical presentation, specifically focussing on complicated, or recurrent episodes of AD.
Acute diverticulitis most commonly affects older patients, therefore contemporary clinical practise guidelines for the management of AD are predominantly based on evidence derived from AD affecting the sigmoid colon in older patients – the typical presentation of AD seen in Western countries. However, AD can affect any location of the colon, at any age. Whether such “atypical” presentations represent the same entity has been debated, with implications for clinical management.
Chapter four will therefore review aspects of diverticular disease of the right-sided colon and its clinical management. The prevalence of right-sided diverticulosis in a New Zealand population has not previously been reported, this will be defined in chapter five.
Finally, the incidence of AD in patients under 50-years old has been increasing in recent years. Chapter six describes the changing epidemiology, attempts to explain the increasing incidence, and discusses aspects of clinical management that may differ in the younger cohort affected by AD.
2022-04-27T22:46:04ZClinical Implications of Unplanned Readmissions in Colorectal Surgery
http://hdl.handle.net/10523/12783
Clinical Implications of Unplanned Readmissions in Colorectal Surgery
2022
D'Souza, Joel
Aim: To define the 30-day unplanned readmission (UR) rate after colorectal surgery at Christchurch Public Hospital and to evaluate its use as a key performance indicator (KPI) of surgical care.
Methods: A systematic review and meta-analysis of the literature was undertaken. A retrospective study of patients who underwent curative colorectal cancer surgery between 2012 and 2017 was performed to derive and validate a prediction model for UR. A prospective study of patients who underwent colorectal surgery between 2018 and 2019 was performed to investigate frailty and social support as risk factors for UR.
Results: International UR rates ranged from 6% to 29% after colorectal surgery. Despite limitations from significant heterogeneity in the literature, increased comorbidity, stoma formation and postoperative complications were identified as potential predictors of UR. The retrospective analysis demonstrated that rectal cancer, stoma formation and postoperative complications were statistically significant predictors of UR after colorectal cancer surgery in New Zealand. A simple bivariable prediction model comprised of rectal cancer and postoperative complications predicted UR with an AUC of 0.62 on external validation. Frailty and Social support were not found to be significant risk factors for UR.
Conclusions: URs after colorectal cancer are common, predictable, and occur within two weeks of index discharge. The UR rate is a valid KPI indicator of elective colorectal surgery.
2022-03-20T19:37:46ZNutritional Immunity: Butyrate and Colon Carcinogenesis
http://hdl.handle.net/10523/12424
Nutritional Immunity: Butyrate and Colon Carcinogenesis
2021
Phang, Ruth
Early-onset of colorectal cancer (EOCRC) is increasing amongst younger populations. A
main contributing factor is modern-day diets. Clinical studies indicate that high fibre nutrition
regimens may be protective against the EOCRC. An abundant metabolite of fibre is butyrate,
which has been observed to mitigate the loss of intestinal mucus and E-cadherin in human
colorectal adenocarcinoma cell lines. E-cadherin facilitates intercellular signalling, which is
essential for the suppression of tumorigenesis and metastasis progression. Bacteroides
fragilis toxin (BFT) is a metalloprotease virulence factor of enterotoxigenic B. fragilis
(ETBF) that induces the cleavage and degradation of E-cadherin. ETBF is commonly found
colonised in the intestinal mucus of patients who were susceptible to developing colorectal
neoplasia and pre-cancerous lesions. Associations between butyrate’s potential level of
protection against BFT is yet to be explored in current literature. Thus, in this study, ETBF
was used as a bacterial model to test the hypothesis that butyrate acts to upregulate E-cadherin
and/or mucus production, which protects against B. fragilis-mediated cellular
responses in colonic adenocarcinoma cells.
The cellular effects of butyrate are conventionally investigated in the undifferentiated HT29
cell line. However, the mucus secreting HT29-MTX cells are postulated to be more
physiologically representative of the colonic epithelia. Both HT29 and HT29-MTX cell lines
were used to model BFT-mediated loss of E-cadherin. These cells were treated with 5 mM of
butyrate and/or B. fragilis for 24-hours. Trypan blue exclusion was applied to quantify cell
proliferation and viability. RT-qPCR was utilized to quantify CDH1 and MUC2 gene
expression, which encodes for E-cadherin and mucin 2 (intestinal mucus) respectively.
Alcian blue staining was implemented to assess acidic mucin expression. Immunofluorescent
microscopy was used to evaluate E-cadherin and mucin 2 protein levels.
Findings of this study indicated 2-8 mM of butyrate had no significant effect on B. fragilis growth or viability. In uninfected HT29 cells, butyrate increased CDH1 (3.30-fold, P<0.05) and plasma membrane-associated E-cadherin expression. This effect was not concentration dependent. Butyrate (5 mM) also increased CDH1 (1.99-fold, P<0.01) and E-cadherin protein levels in ETBF-infected HT29 cells. Similarly, butyrate increased CDH1 expression in uninfected (7.32-fold, P<0.01) and infected (6.11-fold, P<0.05) HT29-MTX cells. Butyrate also upregulated acidic mucin expression in mucin granulae and reduced MUC2 expression. Further investigation is needed to determine the effect of butyrate on E-cadherin and mucin 2 protein expression in HT29-MTX cells. This study provides insight into further investigation of butyrate as a potential chemo-preventative therapy against BFT-mediated colorectal carcinogenesis.
2021-11-08T03:48:20ZProbiotics and Acute Otitis Media (AOM)
http://hdl.handle.net/10523/12359
Probiotics and Acute Otitis Media (AOM)
2021
Chen, Tzu-Yu
Introduction:
Acute otitis media (AOM) is the most common bacterial infection in children for which parents seek medical advice (1). Acute otitis media commonly presents with fever, ear pain, and hearing impairment. Common otopathogens include Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis (2,3). Colonisation with these organisms at a young age is associated with an increased risk of developing AOM in young children (1). Despite vaccination against strains of S. pneumoniae and NTHi, there has been little impact on the overall prevalence of otitis media. The lack of vaccine impact is primarily due to an increase in disease attributable to non-vaccinated strains (2,4). Management of non-resolving AOM involves the use of broad-spectrum antibiotics. However, frequent and inappropriate use of antibiotics is associated with increasing antimicrobial resistance and facilitates colonisation with resistant strains of pathogenic species (5,6). Thus, in light of the high prevalence and the considerable burden of AOM in the community, new strategies for preventing recurrent AOM are needed.
Aims:
1. To review the literature on the use of probiotics in the prevention of AOM.
2. To determine the efficacy of probiotics against otopathogens.
3. To assess the ability of probiotics to colonise the nasopharynx.
Methods:
A literature review was carried out across databases, Medline, EMBASE, PubMed and Cochrane, using keywords related to probiotics, otitis media and ear infection. The search phrases were searched as medical subject headings (MeSH), and as a subject, terms with possible endings were denoted with “*” to expand the search. The literature title and the abstract were then screened and related articles were obtained and critically analysed. Meta-analysis was then conducted on homogenous data to determine the overall benefit of probiotics on AOM.
To determine the efficacy of Streptococcus salivarius K 12 on the inhibition of otopathogens. Isolates of otopathogens from otitis-media prone children were cultured and plated against S. salivarius K12.
To determine the ability to colonise the nasopharynx, fifty healthy adult volunteers were recruited and randomised to S. salivarius given orally and nasally. Pre-colonisation swabs were taken followed by a course of oral antibiotics. A two-week course of probiotics was provided to the volunteers. One week after the completion of probiotics, the individuals were swabbed again. Both swabs were analysed with real-time quantitative polymerase chain reaction. (RT-qPCR).
Results:
From the literature review, thirteen studies were identified. Overall, the study designs were heterogeneous and were of moderate quality. Five of the studies had enough similarity in population selection, methodology and outcome measure for meta-analysis. The conglomerate data from these five studies showed no demonstrable prophylactic effect for the use of probiotics on AOM. Probiotics species varied widely in the literature and also in the route of administration. The evidence for the use of probiotics in AOM was therefore conflicting and insufficient to support their clinical use in the prevention of AOM.
In the trial of probiotics versus otopathogens isolates, 107 known otopathogens isolates from a previous study lead by Mills et al. were culturable and identifiable. When tested against the bacteriocin-like inhibitory substance (BLIS) from S. salivarius K12, 48% had demonstrable inhibition. Overall, complete inhibition of all S. pneumoniae was witnessed with partial to no inhibition of other known otopathogens.
The colonisation trial did not yield sufficient data to suggest or refute the ability of the S. salivarius to colonise the nasopharynx or alter its microflora. However, it has been demonstrated that the tolerability of the nasal route of probiotics administration was not as good as previously thought.
Significance:
The available literature on the use of probiotics for AOM is of low quality and quantity. Although S. salivarius is a potential probiotic choice for AOM prophylaxis, it only demonstrates inhibition in less than half of the otopathogen isolates. Therefore, it is unlikely to be effective, if used alone. The colonisation trial was unable to be completed as proposed due to unanticipated complications, but it did hint that the tolerability and safety of S. salivarius K12 need to be studied further.
2021-10-21T23:34:23ZComplication profiling and Evolution of pelvic exenteration surgery performed in high volume tertiary referral centres over thirty years
http://hdl.handle.net/10523/10919
Complication profiling and Evolution of pelvic exenteration surgery performed in high volume tertiary referral centres over thirty years
2021
McCormick, Jacob John
Objective: To examine the changes in exenterative surgery over three decades analysing oncological outcomes and whether changes in surgical approach have led to improved patient outcomes
Background: Advances in surgical technology, perioperative care and pattern of disease recurrence have coincided with an evolutionary change in exenterative surgery.
Methods: A review of prospectively maintained databases of pelvic exenteration surgery from 1988 – 2018 at two high volume specialised institutions. The total cohort was divided into three major time points (1988- 2004, 2005-2010 and 2011 to 2018) to allow comparative analysis. Primary endpoints were overall survival in primary and recurrent disease at each time point. Secondary endpoints included anastomotic leak, blood transfusion, ileus, wound infection rates and evolution of case complexity. Data were analysed using R with a p<0.05 considered significant.
Results: Six hundred and seventy patients underwent exenterative surgery. In 2011–2018 there was an increase in resection of recurrent malignancy with a continuous increase in gastro-intestinal malignancies resected over each time period(p<0.001,<0.01) and a reduction in gynaecological malignancy(p<0.001). A significant increase in sacrectomy, pelvic sidewall resection and ileal conduit reconstruction was observed (p<0.01,<0.001). In 2005–2010 patients had increased rates of ileus and anastomotic leak(p<0.05). Patients undergoing resection for primary disease had improved overall survival at time points 1998-2004 and 2011–2018 compared to those with recurrent disease(p=0.007,<0.001). Overall survival was significantly improved in patients with primary versus recurrent disease(p=0.022).
Conclusion: There has been a significant improvement in survival in patients undergoing pelvic exenteration surgery from primary disease. Case complexity has increased without significant morbidity.
BACKGROUND: The oncological role of pelvic exenteration for locally advanced and recurrent pelvic malignancies arising from the anorectum, gynaecological or urological systems is now well established. Despite this, the surgical community has been slow to accept pelvic exenteration, undoubtedly owing to concerns about high morbidity and mortality rates based on historical data. Therefore, the aims of this study were to assess the general major complications and predictors of morbidity following exenterative surgery for locally advanced and recurrent pelvic malignancies.
METHODS: Data were collected from prospective databases at two high-volume institutions specialising in beyond TME surgery for locally advanced and recurrent pelvic malignancies between 1990 and 2015. The primary outcome measures were major complications (Clavien-Dindo 3 or above) and predictors for morbidity.
RESULTS: A total of 646 consecutive patients requiring exenterative surgery for local advanced pelvic malignancies were identified. The median age was 63 years (range 19-89 years), and the majority were female patients (371; 57.4%). Five hundred and forty patients did not suffer a major complication (83.6%) following pelvic exenterative surgery. One or more major complications were observed in the remaining 106 patients (16.4%). The most common major complications were intra-abdominal collection (43.7%; n=59/135) and wound infection (14.1%; n=19/135). The overall inpatient mortality rate was 0.46% (n=3/646). Independent predictors for major morbidity following exenterative surgery for locally advanced or recurrent pelvic malignancies were squamous cell carcinoma of anus, sacrectomy, past history of peripheral vascular disease and requirement for blood transfusion.
CONCLUSION: Our series adds to the increasing evidence that good outcomes can be achieved for pelvic exenterative surgery in locally advanced and recurrent pelvic malignancies. A coordinated approach in specialist centres for beyond TME surgery demonstrates this is a safe and feasible procedure, offering low major complication rates.
2021-05-03T21:29:42Z