Surgery (RMH) - Theses
Permanent URI for this collection
Search Results
1 - 10 of 63
-
ItemThe use of robot-assisted surgery in reconstructive and functional urology( 2023-11)As surgical technology advances, bringing forth new devices and techniques, it becomes imperative for the medical profession to engage in rigorous due diligence to minimise potential harm to patients. Many countries have established robust processes for scrutinising medications, devices, and prostheses before their implementation in patient care. Both the general public and the medical community rely on these regulatory authorities to ensure safe access to medical devices and to safeguard patients from harm. Nevertheless, in recent years we have witnessed legal actions being taken against various medical device companies for their failure to adequately test products, resorting to shortcuts in the application process, which has subsequently led to permanent and debilitating harm. These failures emphasise the critical need for effective oversight by medical and public health authorities while also underscoring the individual responsibility of medical professionals and surgeons in upholding patient safety. A recent example of this failing is the incorrect use and insertion of pelvic mesh, which has been associated with complications from implantation. Whilst there were problems associated with implantation that ultimately became apparent, the complications associated with explantation are potentially much more severe. This low-volume, at-risk surgery, requires a different and more advanced skill set. The value of the credentialing process is intricately linked to the demonstration of thorough education and training, adherence to accreditation standards, compliance with reimbursement requirements, and alignment with state and federal laws. While the specifics of the credentialing processes may vary across healthcare institutions, it is imperative to consistently verify the authenticity of submitted documents to guard against fraudulent representations. A well-structured credentialing process serves as a robust defence against the admission of healthcare professionals with inadequate qualifications or training, thereby upholding the standard of patient care. Beyond the initial credentialing, ongoing audits of healthcare workers are essential. In the contemporary landscape of healthcare, characterised by an emphasis on quality, maintaining a detailed approach is crucial. This ongoing scrutiny ensures that the healthcare workforce remains in line with the highest standards, leaving minimal room for errors in the pursuit of delivering optimal patient care. The primary goal of this thesis is to develop credentialing guidelines on the use of robotic assistance surgery for reconstruction and functional urology. Underpinning this new field of surgical treatment, a critical review delves into the transferability of surgical skills, issues pertaining to training competency generally, credentialing of robotics-assisted surgery for related surgery and evaluation of other specialities robotic programmes. A Modified Delphi study was conducted to establish clinical consensus for the first guidelines on this topic. The second part of this project featured the introduction of a new robotic surgical procedure that implemented some of the ideas raised in Chapters 1 and 2. A critical review is included of the outcomes of this procedure as a multi-centre case series assessing the rate of successful removal of mesh, the functional outcomes at 12 months follow-up, recurrence of stress urinary incontinence and pelvic organ prolapse, and sexual function outcomes.
-
ItemDeconstructing the brain tumour microenvironment using multimodal analysis( 2023-06)Gliomas are a type of astrocytoma and are the most prevalent type of primary brain cancer, with the most aggressive form being glioblastoma (GBM), with a median survival of only 15 months. Rapid tumour cell invasion and progression is a significant challenge for patients and their oncologists and neurosurgeons, reducing treatment efficacy and inevitably leading to tumour recurrence. Cancer cells thrive by responding and adapting to cellular and non-cellular cues in the tumour microenvironment, including the extracellular matrix (ECM). However, little is known about ECM composition in brain tumours and how the ECM evolves during disease progression, and the impact of the ECM on immune cell localisation, cancer cell signalling and the functional activity of tumour cells. The PI3K and MAPK signalling pathways are typically dysregulated in GBM, and can activate the downstream transcription factor, CREB, which has been reported to regulate GBM malignancy. By integrating multiplex immunohistochemistry, histopathological staining, and spatial tissue analysis, as well as in vitro 3D GBM models, I investigated ECM composition in low- and high-grade glioma, and the spatial relationship between neoplastic cells, immune cells and the ECM in GBM tissue. My results demonstrated a grade-dependent increase in ECM deposition and an upregulation of type I and type IV collagen mRNA expression, which is associated with poor survival in patients with GBM. GBM cells and vascular cells were identified as key contributors of ECM protein deposition in GBM. Spatial analysis demonstrated that T-cells were predominantly located in perivascular niches in ECM-rich regions, while macrophages exhibited more efficient infiltration into tumour cell-rich regions. Extensive tissue remodelling contributes to cellular compartmentalisation in the tumour microenvironment and this compartmentalisation correlates with PI3K, MAPK and CREB activity, and histopathological hallmarks, including angiogenesis, tumour cell density and cell invasion. Inhibiting the PI3K and MAPK signalling pathways reduced 3D cell invasion and also facilitated a shift in the ECM composition, from a more fibrotic to a less fibrotic state. Taken together, the results suggest that the accumulation of ECM plays an important role in GBM progression, affecting both immune cell distribution and cancer cell signalling. These findings suggest that targeting the PI3K and MAPK pathways to ‘normalise’ the ECM could serve to enhance the efficacy of existing and novel therapies for GBM.
-
ItemExosomes mediate TGF-β signaling activity and promote breast cancer progression( 2023-03)Metastasis is the main cause of cancer-related deaths. Transforming growth factor-beta (TGF-beta) promotes metastasis by inducing epithelial-mesenchymal transition (EMT). Further, increased TGF-beta signaling is associated with reduced cancer patient survival. Nonetheless, the precise mechanisms underlying TGF-beta signaling activity amplification remain ill-characterized. Also, while on-target anti-TGF-beta inhibitors ameliorate metastasis in pre-clinical cancer models, cancer clinical trials show inconsistent results, highlighting a gap in the understanding of TGF-beta biology. Since our group has shown that cancer cell-exosomes (small extracellular vesicles/sEVs) increase TGF-beta signaling levels in vitro, sEV-induced TGF-beta signaling amplification could underlie metastasis. Analysis of breast cancer datasets revealed a neglectable mutation frequency in exosome-related genes, while their transcriptional levels were inversely associated with cancer patient survival and directly correlated with scores for TGF-beta signaling and EMT levels. In vitro, breast cancer cells were challenged with TGF-beta signaling inhibitors with out without recombinant human (rh)TGF-beta1 or cancer cell-sEVs to investigate alterations by immunofluorescence staining, western blot, scratch assay, and in transwell inserts. Compared with rhTGF-beta1-treated cell cultures, exosomes enhanced breast cancer cell EMT, migration and invasion, which was abrogated by TGF-beta signaling inhibitors. In vivo, exosomes amplified the TGF-beta signaling activity in breast cancer orthotopic xenografts, as quantified by In Vivo Imaging System (IVIS). Moreover, luciferase assay demonstrated that sEV-treatment increased the number of circulating tumor cells, multi-organ metastases, and tumor self-seeding. These results confirm previous findings from our group, further establishing a role for exosomes in driving TGF-beta signaling amplification and breast cancer progression. In addition to cancer cell-exosomes, cancer-associated fibroblast (CAF)-exosomes also contribute to cancer progression. Yet, CAFs are often overlooked in pre-clinical models. Here, we characterize human breast CAF-sEVs and compare their impact on breast cancer cells with that induced by rhTGF-beta1. Treatment with exogenous CAF-sEVs amplifies TGF-beta signaling activity in cancer cells in vitro and in vivo, as quantified by luciferase assay and IVIS, respectively. Accordingly, CAF-sEVs increase cancer cell aggressiveness in vitro and promote cancer progression in vivo. Likewise, CAFs induce TGF-beta signaling amplification in co-culture with poorly invasive MCF7 cells, promoting metastasis and tumor self-seeding. Conversely, genetically and pharmacologically targeting exosome trafficking and TGF-beta signaling reduce CAF-promoted effects. Thus, CAF-exosomes are critical for CAF-induced TGF-beta signaling amplification and breast cancer progression. Considering the role of exosomes, drugs targeting exosome trafficking could reduce TGF-beta-induced metastasis. In vitro, challenging with DMA to decrease exosome secretion reduces TGF-beta signaling levels in highly invasive MDA231 cells in a dose dependent manner. Further, combining DMA and SB431542 (TGF-beta type I receptor kinase inhibitor) at suboptimal doses potentiates this effect and inhibits MDA231 cell migration. Similar effects were observed in vivo where DMA reduces TGF-beta signaling levels and cancer progression, potentializing SB431542 activity when combined at suboptimal doses. In addition to characterizing the relevance of exosomes to TGF-beta signaling amplification, our study establishes a new approach to impair metastasis by simultaneously inhibiting exosome trafficking and TGF-beta signaling. We envision that future research may build on our findings, evaluating the translation of this therapeutic strategy for the treatment of cancer patients.
-
ItemInvestigation of colorectal cancer outcomes through the use of state-wide administrative data and data linkage( 2023)Background Healthcare administrative data are data that are collected at each encounter with the healthcare system, as part of routine process. Although primarily not for research purposes, administrative data can be utilised as a low-cost source of information for clinical outcomes research, with broader population coverage compared to clinical databases. The use of population-based data linkage to combine various data sources into a linked record has also become an increasingly valuable epidemiology research tool to attempt to address the deficiencies in a single dataset. The current evidence for the effect of socioeconomic disadvantage (SED) on stage at presentation and survival for colorectal cancer in Australia is conflicting, with varying definitions of advanced stage at presentation. The main aim of this thesis was to evaluate the impact of SED (based on area-level measurements) on stage at presentation and survival in patients who had undergone resections for colorectal cancer. Methods The main methodology underpinning the projects in this thesis utilised administrative data and data linkage to construct a more detailed dataset to report on clinical outcomes, and to allow for more adjustments for potentially confounding co-variables. Data linkage services were provided by the Centre for Victorian Data Linkage (CVDL). The Victorian Admitted Episodes Dataset (VAED) was used to identify all patients who had undergone a colorectal cancer resection in Victoria in 2010-2020, and then linked to the Victorian Cancer Registry (VCR) and the Victorian Death Index (VDI) to provide further sociodemographic, pathology, and survival data. SED was measured using the Index of Relative Socioeconomic Disadvantage (IRSD) in quintiles, an area-level composite measure utilising data from the Australian Bureau of Statistics, available from the VCR. Stage at presentation was grouped into specific Tumour Node Metastasis (TNM) stage groupings that were more or less likely to be symptomatic. Multivariable regression analysis was performed to adjust for potentially confounding covariables. Overall survival was analysed using Cox proportional hazards multivariable regression and odds of presenting with an advanced stage tumour were analysed with multivariable logistic regression. Results These studies found that in patients who had undergone resection for colorectal cancer (8,189 patients over a 10-year period in Victoria), there was no evidence of effect of area-level SED on the odds of presenting with a locally advanced stage tumour, which was more likely to be symptomatic (OR=1.08, CI: 0.92 - 1.28; OR=1.09, CI: 0.92 - 1.29; OR=1.00, CI: 0.84 - 1.19; OR=1.11, CI: 0.92 - 1.35 (SED quintiles 2-5 v. SED quintile 1 (most disadvantaged))). Similarly, there was no evidence of effect of SED on the odds of presenting with an early-stage tumour, which was more likely to be asymptomatic. There was no evidence of association between SED and odds of presenting with a more advanced overall stage (Stage III-IV versus Stage I-II). There was no evidence of difference in overall survival comparing patients from different quintiles of SED (HR = 0.96, CI: 0.86 - 1.07; HR = 0.99, CI: 0.88 - 1.11; HR=0.94, CI: 0.84 - 1.06; HR=1.04; CI: 0.91 - 1.18 for SED 2-5 respectively compared to SED 1 (most disadvantaged)). Conclusion The large, detailed studies in this thesis found no evidence that area-level SED was associated with differences in stage at presentation or with poorer overall survival on colorectal cancer resection patients in Victoria. While data regarding symptomatic versus asymptomatic presentations is lacking in registries, these results provide indirect evidence that presentation with less likely symptomatic and more likely symptomatic colorectal cancer may be similar across SED groups in patients undergoing CRC resections.
-
ItemNo Preview AvailableReSET Robotics Remodelling Surgical Education and Training in Robotics( 2022)Introduction & Objectives We aimed to develop a urology robotics curriculum that meets the training needs of robotic surgery novices without using live animals. We aimed to design and assess the feasibility of a digital and synthetic organ model curriculum capable of training learners to a level of competency in robotics prior to live surgery. Methods A review of robotic simulation education literature was performed. An online course was designed using Kern’s method for the development of surgical curricula. Learners then progressed to virtual reality simulation training prior to surgeries on a robot assisted radical prostatectomy model fabricated from polyvinyl alcohol, a low-cost hydrogel. Results A complete curriculum was designed and assessed by participants at each stage. This included: A an 11 module online teaching the foundations of robotics. 3 hours of 3D stereoscopic live surgical video. Psychomotor training using virtual reality robotic simulators. Synthetic organ procedural simulation training with objective performance metrics for operative time, blood loss, positive margins, nerve strain, anastomotic leak tests and neurovascular bundle preservation. A system to score live proctored robot assisted radical prostatectomy cases with GEARS and RACE scores which are validated robotic performance scoring systems. Conclusions We have demonstrated the feasibility and preliminary educational validity of a digital training program that includes realistic synthetic human organ models for urological robotic surgery. These surgical models are scalable and offer a viable alternative to live animal surgery without the cost, ethical and accessibility draw backs associated with animal training.
-
ItemThe role of IL-11 signaling in glioblastoma progression( 2022)Glioblastoma is the most common and lethal brain tumour in adults with a mean survival rate of only 12-15 months with current treatment. The microenvironment of a tumour is becoming increasingly more important to current research, with many findings suggesting that the transcription factors driving oncogenic processes are more often due to cytokine stimulation than gene mutation. There have been multiple signalling molecules and corresponding receptors identified as key role-players in the development of glioblastoma, its severity and ability to evade treatment. Cytokines are molecules that initiate and mediate a range of cellular activities essential to the homeostasis of a heathy person but also to tumour growth, invasion and survival. This includes the critical growth factors and cytokines that activate signalling pathways controlling many pro-oncogenic cellular functions. The interleukin-11 (IL-11) cytokine has become increasingly recognised as a driver of the pathogenesis of a wide range of cancers, however, very little is known regarding its role in glioblastoma. Considering this, we hypothesized that IL-11 would contribute to glioblastoma cell viability, migration, invasion and overall tumour progression. We initially identified that IL-11 and its receptor (IL-11RA) inversely correlate with tumour grade and glioblastoma survival. To study the role of IL-11 in glioblastoma, we next determined the expression of endogenous IL-11RA in a range of cell lines and transfected those expressing very little of the gene with the IL-11RA (cell lines #20 and #28). Proteomic analysis was conducted to reveal changes in protein expression after transfection. A large number of proteins involved in proliferation, migration and invasion were seen to be upregulated in the IL-11RA transfected cells. Indeed, the IL-11RA transfected cells displayed significantly greater growth, migration and invasion in proliferation, wound healing, transwell and spheroid invasion assays. This was reversed with IL-11RA knockdown. The proteomic analysis also highlighted the upregulation of proteins involved in metabolism, particularly glutaminolysis and inhibition of apoptosis. Metabolomic analysis revealed the IL-11RA transfected cells displayed increased levels of glutamine oxidation, as well as increased proliferation and survival of these cells in conditions of depleted glucose or glutamine. Similarly, IL-11RA transfected cells displayed no significant difference in invasion rate in the presence or absence of glucose, when glutamine was available. Alternatively, blocking both glucose and glutamine metabolism with a number of drugs significantly reduced the proliferation, migration and invasion of these cells. Our findings suggest that the IL-11RA transfected cells are able to utilise alternative metabolites such as glutamine, in the absence of glucose, in order to proliferate, migrate and survive. Overall, the results of this thesis suggest that the IL-11RA plays an important role in proliferation, migration, invasion, survival and metabolism in glioblastoma.
-
ItemCirculating Biomarkers in Glioma( 2022)The identification of accurate circulating biomarkers, otherwise termed “liquid biopsy,” is a major goal in oncology research due to the potential clinical applications in population screening, tumour monitoring and delivery of individualised treatments resulting from tumour genotyping. Recently, large datasets have been made available due to advances in genome sequencing and mass spectrometry, however the difficulty remains in translating these findings to clinically meaningful applications. Gliomas are the most common primary brain cancer and its most aggressive form, glioblastoma (GBM), is rapidly and uniformly lethal.1 Circulating biomarkers have the potential to aid in a number of challenges that are faced in managing these patients. Despite increased efforts in biomarker discovery, currently there is no validated liquid biopsy for glioma. In this thesis, three candidate biomarkers are investigated for use in several clinical applications. Firstly, the small non-coding RNA sequence microRNA, is shown to be able to monitor for glioma progression, assess tumour burden and improve prognostic predictions. Following this, reliable detection of circulating tumour DNA (ctDNA) in plasma of patients is demonstrated using highly sensitive next generation sequencing and PCR techniques. The potential of ctDNA as a diagnostic adjunct for complete molecular tumour characterisation is shown, as well as the ability of ctDNA to monitor an individual tumour’s genomic evolution including identifying early in the blood key gene mutations associated with chemoresistance. Finally, a pilot study is presented using spiral microfluidics, confirming the presence of circulating tumour cells in the blood of glioma patients as a method to increase tumour DNA concentration.
-
ItemIdentifying the Risks and Drivers of Aggression in Prostate Cancer( 2022)Prostate cancer is the most commonly diagnosed cancer and the second commonest cause of death in Australian men. The natural history of localised prostate cancer is markedly variable. Most individuals will lead a biologically indolent course where it may never be clinically significant while an unpredictable minority of individuals, approximately 10%, will rapidly progress to metastases and eventually succumb to the disease. Currently there are no adequate methods in determining the difference between an indolent or aggressive course of the disease at an early stage; therefore, leading to significant over-treatment of indolent disease as well as under-treatment of aggressive disease. The identification of potential drivers of aggression in prostate cancer are explored through the compilation of published papers in an integrated thesis by investigating the impacts of obesity, velocity of biochemical recurrence, aggressive ductal adenocarcinoma variant, as well as the molecular comparison between primary and matched metastatic tumours. Obesity is linked with more aggressive prostate cancer and higher rates of disease recurrence post treatment. It is unclear if this is due to specific tumour-promoting effects of obesity or diagnostic bias. The effect of obesity on the accuracy of pre-treatment risk categorisation was determined, and mediation analysis was used to identify the contribution of biologic versus non-biologic mechanisms to the observed increased risk of biochemical recurrence. The analysis included 1587 patients. Despite similar rates of adverse pathological features at prostatectomy, biochemical recurrence rates were significantly higher in very obese patients, which persisted after adjustment for stage, grade and PSA. Tumour volume however correlated significantly with BMI (p = 0.004), and the difference in predicted and observed ‘tumour attributable’ PSA (Delta-PSA) in very obese patients was greater than three times higher than that of healthy patients (p = 0.0067). Regression analysis indicated that the effect of BMI on tumour volume was fully mediated indirectly by its effect on PSA. Inclusion of this diagnostic error as a covariate in the survival analysis attenuated the effect of BMI on recurrence. Being very obese suppresses tumour-associated PSA resulting in a diagnostic bias that is responsible for errors in risk classification, and potentially contributes to a delay in initial presentation. Radical prostatectomy is one of the preferred treatment modalities for localised prostate cancer. Although the majority of patients experience long term disease control, depending on the pre-treatment clinical characteristics of the cohort under study, up to a third of men will develop disease recurrence. The most common manifestation of disease recurrence is a detectable serum PSA in the postoperative period. This thesis characterises the pattern of late disease recurrence in the largest contemporary cohort of localised prostate cancer patients treated with radical prostatectomies in the active surveillance era. Total of 2312 patients were included in the final analysis with up to 12 years of follow up data. The average patient had clinically localised prostate cancer, an elevated PSA, and ISUP grade group 2 on biopsy. 88.7% of patients had ISUP grade group 2 or higher at prostatectomy. A subgroup of 446 patients had undetectable PSA levels at 5 years after prostatectomy; 11.7% of them progressed to experience biochemical recurrence. In this subgroup, late recurrers had significantly higher-grade tumours on ISUP and Gleason sum (p < 0.001 and p = 0.001, respectively), higher rates of extraprostatic extension (p = 0.022), and larger tumour volumes (p = 0.032). Logistic regression demonstrated that prostatectomy ISUP grade group was a significant predictor (OR 2.14, 95% CI 1.43-3.20, p < 0.001). Additionally, the timing of recurrence resides on a continuum of risk and that the potential concept of dormant micrometastatic involvement requires further research and evaluation. Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. Prostatectomy patients with ductal variant histology from two institutional databases were identified and compared to an independent acinar adenocarcinoma cohort. A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Deep whole exome sequencing was performed in selected cases (n = 8). Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 vs 22.0 months, p = 0.03) and metastasis-free survival (6.7 vs 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH. The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to the initiation of salvage therapies and the onset of metastatic disease. The exploration of the impacts of obesity, velocity of biochemical recurrence, aggressive ductal adenocarcinoma variant, as well as the molecular comparison between primary and matched metastatic tumours to provide insights into potential drivers of aggression in prostate cancer.
-
ItemImpact of polyacrylamide hydrogel (Bulkamid®) in the management of stress urinary incontinence in women( 2021)Stress urinary incontinence (SUI) is a highly prevalent condition among women, with a significant impact on quality of life. Although mid-urethral sling (MUS) is widely considered the reference standard treatment following failure of conservative measures, increasing concern over the risk of mesh morbidity has resulted in it falling out of favour. Instead, more women are choosing to undergo urethral bulking agent treatment as a minimally invasive alternative, despite a lower efficacy rate to open surgery. Despite urethral bulking agents being a well-established treatment in women with SUI, there is a paucity of data to guide its use in clinical practice. Currently marketed urethral bulking agents include polyacrylamide hydrogel (Bulkamid) polydimethylsiloxane (Macroplastique), carbon-coated zirconium oxide (Durasphere), calcium hydroxylapatite (Coaptite) and polymerising polydimethylsiloxane silicone gel (Urolastic). Clinical data comparing the outcomes of these agents are limited. This thesis assesses and compares all available urethral bulking agents used in the treatment of SUI in women. Variable mean success rates of 30%-80% are reported in the short-term. Better long-term success rates were found with Bulkamid, Coaptite and Macroplastique on qualitative review. The majority of urethral bulking agents are reported to be safe, with less frequent adverse events such as urinary tract infection, temporary acute urinary retention and de novo urgency reported. More significant complications such as migration into lymph nodes and erosion have also been reported yet are rare. Despite the common use of polyacrylamide hydrogel urethral bulking agent injections since its introduction in 2006, long-term clinical data are limited. This thesis demonstrates the long-term outcomes of polyacrylamide hydrogel (Bulkamid) transurethral injections in an Australian cohort of women with SUI performed by a single surgeon. 21% of women did not respond to primary polyacrylamide hydrogel (Bulkamid) treatment and proceeded to alternative anti-incontinence surgery. As opposed to the common perception of urethral bulking agents being a short-term therapy, requiring frequent repeat injection, 53% of women at 7-8 years post initial injection self-reported a successful outcome. Polyacrylamide hydrogel (Bulkamid) injection was associated with benefits on other important patient-reported outcomes such as urinary incontinence-related symptom distress and life impact. Short-term adverse events were infrequent and mild and there was no serious long term adverse event. Knowledge of factors associated with superior outcomes in women treated with urethral bulking agents for stress urinary incontinence remains limited yet could help clinicians better select and counsel patients on expected outcomes. This thesis explores factors associated with polyacrylamide hydrogel (Bulkamid) treatment success in women with SUI, and demonstrates that women with type 3 urethral hypermobility, a well-supported urethra, were more likely to report treatment success than women with non-type 3 urethral hypermobility before treatment. Poor bladder compliance before treatment was associated with higher urinary symptom distress, and higher severity and frequency of urinary incontinence post-treatment. Older age was associated with higher levels of self-reported urinary frequency and severity post-treatment. Finally, the severity of pre-treatment incontinence impact was associated with worse incontinence impact post-treatment. Findings from this thesis will assist clinicians in the selection of urethral bulking agents. It will also assist clinicians in the selection of patients most likely to benefit from polyacrylamide hydrogel (Bulkamid) urethral bulking agents injection treatment, and in the counselling of expected long-term efficacy and safety outcomes.
-
ItemFocused ultrasound as an adjunct to clinical evaluation for patients admitted to general medicine units( 2021)General internal medicine physicians have started to incorporate point-of-care ultrasound (POCUS) into their clinical practices. Limited data is available on POCUS use in internal medicine. This thesis aimed to evaluate the clinical impact of adding POCUS to the initial assessment of patients hospitalised in internal medicine units through three main research projects. First, a systematic review was conducted to investigate POCUS' clinical impact on hospitalised internal medicine patients. Five previous studies have addressed this question differing in their design, intervention, and outcomes reported. Two observational studies described the influence of POCUS on the diagnosis formulation. POCUS use changed in the principal diagnosis and added relevant new diagnoses occurred in up to 18% and 24 % of the cases, respectively. Impact on the management plan was reported in 37% to 52% of the participants as a composite outcome including change in medications, additional testing, change in prognosis or change in discharge time. Two randomised controlled trials (RCTs) addressed the effect of POCUS on the length of hospital stay. One study reported no difference between the groups, and the other study found a reduction of one day using serial lung ultrasound in patients admitted with heart failure. These studies were assessed as having moderate to severe risk of bias, which highlights the need for high-quality studies investigating the effect of POCUS on clinical outcomes. Subsequently, an RCT was conducted at the Royal Melbourne Hospital, Victoria, Australia that tested the impact of adding a multiorgan POCUS exam to the initial assessment of cardiopulmonary admissions on the length of hospital stay, clinical decision-making process, readmissions and health costs. Two hundred fifty participants were enrolled and randomised to intervention or control group. The intervention was a POCUS exam of the heart, lungs, and lower extremities (2-point venous compression) performed in the first 24 hours of admission to the unit. POCUS identified new pathology in 70% and changed the primary diagnosis in 28 %, medical treatment in 28%, and imaging tests in 60% of the subjects. However, there was no significant difference between the POCUS and control groups in the hospital length of stay, (POCUS 113 hours vs. control 125 hours, p=0.53), readmission rates (POCUS 16 % vs. control 12%, p=0.43) and total hospital costs ($7.8K vs. $7.9K, p=0.79). Finally, this thesis reports a prospective observational study assessing the feasibility and effectiveness of a heart and lung POCUS training program delivered to internal medicine physicians. The study identified the potential barriers of implementing POCUS' training programs in Australian hospitals. Moreover, it showed that a combination of electronic learning material, ultrasound simulators and supervised clinical rounds effectively improved participant's knowledge, image acquisition and interpretation skills. Overall, this thesis has generated substantial data on the impact of using POCUS on the clinical decision-making process performed by the treating physician and on patient's outcome, such as the length of hospital stays. Moreover, it has explored a POCUS training program for general internal medicine physicians in Australian hospitals.