Objective:Sheep are commonly used as large animal pre-clinical models for inves-tigating cardiovascular therapies,interventions,anatomy and physiology.Further,novel small diameter vascular grafts are frequently tested...Objective:Sheep are commonly used as large animal pre-clinical models for inves-tigating cardiovascular therapies,interventions,anatomy and physiology.Further,novel small diameter vascular grafts are frequently tested via implantation into sheep carotid arteries(CAs).This is because,unlike humans,acute occlusion of one or both sheep CAs is not associated with morbidity or mortality and thus provides safer experimental testing,with reduced ethical constraints,animal numbers and costs.However,to date there has been no evidence regarding sheep tolerance of femoral artery(FA)occlusion.Methods:In this study,seven sheep underwent CA graft surgery,with digital subtrac-tion angiography(DSA)of the CAs performed every 2 months via femoral access,for a total of 8 months.Four months into the study,the left FA of two sheep became inac-cessible due to a suspected FA occlusion.Thus,femoral angiography was performed,followed by FA dissection,FA histology and retrospective analysis of both veterinar-ian animal monitoring and pain scores.Results:FA angiography and histology confirmed complete left FA occlusion in two sheep.Retrospective animal monitoring demonstrated sheep with occluded FAs did not display increased pain scores or deleterious effects on their gait or wellbeing.Conclusion:Our data shows that sheep tolerate FA occlusion with no symptoms,similar to their cerebral circulation,making them an appropriate model for assessing small diameter femoral graft interposition studies and testing other cardiovascular interventions.展开更多
Background:Microglia and brain macrophages contribute significantly to the tumor microenvironment in highly malignant glioblastoma where they are considered important drivers of tumor progression.A better understandin...Background:Microglia and brain macrophages contribute significantly to the tumor microenvironment in highly malignant glioblastoma where they are considered important drivers of tumor progression.A better understanding of the role of the brain macrophages present in glioblastoma appears crucial for improving therapeutic outcomes,especially in the context of novel immunotherapeutic approaches.Methods:We investigated the regulation of two well-established markers for microglia and brain macrophages,IBA1 and CD163,in relation to glioblastoma tumor necrosis using immunohistochemistry and modality fusion heatmaps of whole slide images obtained from adjacent tissue sections.Results:IBA1 and CD163 showed remarkable differences in relation to glioblastoma tumor necrosis.Generally,IBA1 immunoreactive cells were far less common in necrotic tissue areas than CD163-expressing cells.We also found extensive and frequently diffuse extracellular CD163 deposition,especially in hypocellular necrobiotic tumor regions where IBA1 was typically absent.Conclusions:Resident microglia seem more likely to be important for the diffuse infiltration of glioma cells in hypercellular tissue areas,whereas myeloid macrophages may be the main macrophage population in the wake of tumor necrosis.Since the necrotic niche with its interactions between microglia,brain macrophages,and glioblastoma/glioma stem cells is increasingly recognised as an important factor in tumor progression,further detailed studies of the macrophage populations in glioblastoma are warranted.展开更多
Background:Much has been written about the loss to follow-up in the transition between pediatric and adult Congenital Heart Disease(CHD)care centers.Much less is understood about the loss to follow-up(LTF)after a succ...Background:Much has been written about the loss to follow-up in the transition between pediatric and adult Congenital Heart Disease(CHD)care centers.Much less is understood about the loss to follow-up(LTF)after a successful transition.This is critical too,as patients lost to specialised care are more likely to experience mor-bidity and premature mortality.Aims:To understand the prevalence and reasons for loss to follow-up(LTF)at a large Australian Adult Congenital Heart Disease(ACHD)centre.Methods:Patients with moderate or highly complex CHD and gaps in care of>3 years(defined as LTF)were identified from a comprehensive ACHD data-base.Structured telephone interviews examined current care and barriers to clinic attendance.Results:Overall,407(22%)of ACHD patients(n=1842)were LTF.The mean age at LTF was 31(SD 11.5)years and 54%were male;311(76%)were uncontactable.Compared to adults seen regularly,lost patients were younger,with a greater socio-economic disadvantage,and had less complex CHD(p<0.05 for all).We interviewed 59 patients(14%).The top 3 responses for care absences were“feeling well”(61%),losing track of time(36%),and not needing fol-low-up care(25%).Conclusions:A large proportion of the ACHD population becomes lost to specialised cardiac care,even after a successful transition.This Australian study reports younger age,moderate complexity defects,and socio-economic disadvantage as predictive of loss to follow-up.This study highlights the need for novel approaches to patient-centered service delivery even beyond the age of transition and resources to maintain patient engagement within the ACHD service.展开更多
Background A medical content-based image retrieval(CBIR)system is designed to retrieve images from large imaging repositories that are visually similar to a user′s query image.CBIR is widely used in evidence-based di...Background A medical content-based image retrieval(CBIR)system is designed to retrieve images from large imaging repositories that are visually similar to a user′s query image.CBIR is widely used in evidence-based diagnosis,teaching,and research.Although the retrieval accuracy has largely improved,there has been limited development toward visualizing important image features that indicate the similarity of retrieved images.Despite the prevalence of 3D volumetric data in medical imaging such as computed tomography(CT),current CBIR systems still rely on 2D cross-sectional views for the visualization of retrieved images.Such 2D visualization requires users to browse through the image stacks to confirm the similarity of the retrieved images and often involves mental reconstruction of 3D information,including the size,shape,and spatial relations of multiple structures.This process is time-consuming and reliant on users'experience.Methods In this study,we proposed an importance-aware 3D volume visualization method.The rendering parameters were automatically optimized to maximize the visibility of important structures that were detected and prioritized in the retrieval process.We then integrated the proposed visualization into a CBIR system,thereby complementing the 2D cross-sectional views for relevance feedback and further analyses.Results Our preliminary results demonstrate that 3D visualization can provide additional information using multimodal positron emission tomography and computed tomography(PETCT)images of a non-small cell lung cancer dataset.展开更多
Malignant mesothelioma is a highly aggressive neoplasm.The incidence of malignant mesothelioma is increasing worldwide.Diffuse malignant peritoneal mesothelioma(DMPM) represents one-fourth of all mesotheliomas.Associa...Malignant mesothelioma is a highly aggressive neoplasm.The incidence of malignant mesothelioma is increasing worldwide.Diffuse malignant peritoneal mesothelioma(DMPM) represents one-fourth of all mesotheliomas.Association of asbestos exposure with DMPM has been observed,especially in males.The great majority of patients present with abdominal pain and distension,caused by accumulation of tumors and ascitic ? uid.In the past,DMPM was considered a pre-terminal condition;therefore attracted little attention.Patients invariably died from their disease within a year.Recently,several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy.This remarkable improvement in survival has prompted new search into the medical science related to DMPM,a disease previously ignored as uninteresting.This review article focuses on the key advances in the epidemiology,diagnosis,staging,treatments and prognosis of DMPM that have occurred in the past decade.展开更多
AIM:To report the incidence of non-small-bowel bleeding pathologies encountered during double-balloon enteroscopy (DBE) procedures and to analyse their significance.METHODS: A retrospective study of a prospective DBE ...AIM:To report the incidence of non-small-bowel bleeding pathologies encountered during double-balloon enteroscopy (DBE) procedures and to analyse their significance.METHODS: A retrospective study of a prospective DBE database conducted in a tertiary-referral center was conducted. A total of 179 patients with obscure gastrointestinal bleeding (OGIB) referred for DBE from June 2004 to November 2008 were analysed looking for the incidence of non-small-bowel lesions (NSBLs; all and newly diagnosed) encountered during DBE.RESULTS: There were 228 (150 antegrade and 78 retrograde) DBE procedures performed in 179 patients. The mean number of DBE procedures was 1.27 per patient. The mean age (SD) of the patients was 62 ± 16 years old. There were 94 females (52.5%). The positive yield for a bleeding lesion was 65.9%. Of the 179 patients, 44 (24.6%) had NSBLs (19 of them had dual pathology with small-bowel lesions and NSBLs); 27 (15.1%) had lesions not detected by previous endoscopies. The most common type of missed lesions were vascular lesions.CONCLUSION: A significant proportion of patients (24.6%) had lesions within reach of conventional endoscopy. Careful repeat examination with gastroscopy and colonoscopy might be required.展开更多
Perioperative intraperitoneal chemotherapy in combination with cytoreductive surgery has been shown to be of benefit for treating selected patients with peritoneal surface malignancy.It has become a new standard of ca...Perioperative intraperitoneal chemotherapy in combination with cytoreductive surgery has been shown to be of benefit for treating selected patients with peritoneal surface malignancy.It has become a new standard of care in the management of diffuse malignant peritoneal mesothelioma and peritoneal dissemination of appendiceal malignancy.Numerous recent publications on carcinomatosis from colorectal cancer and gastric cancer identify groups of patients that would benef it from this local-regional approach for prevention and treatment of carcinomatosis.This review focuses on pharmacological information regarding intraperitoneal chemotherapeutic agents commonly used in gastrointestinal oncology.展开更多
The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population.We searched PubMed,EMBASE,and Web of Science from inception to the March 1,2018.The studies were...The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population.We searched PubMed,EMBASE,and Web of Science from inception to the March 1,2018.The studies were selected to estimate the prevalence of thyroid nodules in T2DM subjects and to compare the prevalence of thyroid nodules in different glucose tolerance status.The random effects model was used,and the outcome was presented as a pooled prevalence proportion with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI.In the end,9 studies met the inclusion criteria and were included in the analysis.The pooled prevalence of thyroid nodules was 60%(95% CI:0.52,0.68) for T2DM 2 diabetes patients,50%(95% CI:0.4& 0.51) for pre-diabetes,and 43%(95% CI:0.34,0.52) for normal glucose tolerance population.Compared with patients without diabetes,diabetes subjects are more likely to develop thyroid nodules,adjusted OR for thyroid nodule was 1.78 (95% CI:1.25,2.55).Insulin resistance might be involved in thyroid nodule development.展开更多
The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,dise...The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,disease stages and lines of therapy.With this increased use,adverse events including immune checkpoint inhibitor-related hepatotoxicity(ICH)have emerged as an important clinical problem.This along with the introduction of ICI as first-and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists.The incidence of ICH varies between 1%-20%depending on the number,type and dose of ICI received.Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI,corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity.The majority of patients with ICH recover and some may even safely recommence ICI therapy.Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.展开更多
Major advances have been made over the last decade in our understanding of the molecular basis ofseveral cardiac conditions. Hypertrophic cardiomyopathy (HCM) was the first cardiac disorder in whicha genetic basis was...Major advances have been made over the last decade in our understanding of the molecular basis ofseveral cardiac conditions. Hypertrophic cardiomyopathy (HCM) was the first cardiac disorder in whicha genetic basis was identified and as such, has acted as a paradigm for the study of an inherited cardiacdisorder. HCM can result in clinical symptoms ranging from no symptoms to severe heart failure andpremature sudden death. HCM is the commonest cause of sudden death in those aged less than 35 years,including competitive athletes. At least ten genes have now been identified, defects in which cause HCM.All of these genes encode proteins which comprise the basic contractile unit of the heart, i.e. the sarcomere.While much is now known about which genes cause disease and the various clinical presentations, very littleis known about how these gene defects cause disease, and what factors modify the expression of the mutantgenes. Studies in both cell culture and animal models of HCM are now beginning to shed light on thesignalling pathways involved in HCM, and the role of both environmental and genetic modifying factors.Understanding these mechanisms will ultimately improve our knowledge of the basic biology of heart musclefunction, and will therefore provide new avenues for treating cardiovascular disease in man.展开更多
AIM To evaluate the therapeutic role of double-balloon enteroscopy(DBE) in small bowel strictures and to propose a standard approach to small bowel strictures.METHODS Systematic review of studies involving DBE in pati...AIM To evaluate the therapeutic role of double-balloon enteroscopy(DBE) in small bowel strictures and to propose a standard approach to small bowel strictures.METHODS Systematic review of studies involving DBE in patients with small bowel strictures. Only studies limited to small bowel strictures were included and those with ileo-colonic strictures were excluded. RESULTS In total 13 studies were included,in which 310 patients were dilated. The average follow-up time was 31.8 mo per patient. The complication rate was 4.8% per patient and 2.6% per dilatation. Surgery was avoided in 80% of patients. After the first dilatation,46% were treated with re-dilatation and only 17% required surgery.CONCLUSION DBE-assisted dilatation avoids surgery in 80% of patients with small bowel strictures and is safe and effective. We propose a standardized approach to small bowel strictures.展开更多
AIM:To investigate the role of osteopontin(OPN) and its splice variants in the proliferation of hepatocellular carcinoma(HCC).METHODS:The expression of OPN variants in HCC cell lines as well as HCC tissue samples and ...AIM:To investigate the role of osteopontin(OPN) and its splice variants in the proliferation of hepatocellular carcinoma(HCC).METHODS:The expression of OPN variants in HCC cell lines as well as HCC tissue samples and nontumour tissue was studied using polymerase chain reaction.OPN variant cDNAs were cloned into a mammalian expression vector allowing both transient expression and the production of stable OPN expressing cell lines.OPN expression was studied in these cells using Western blotting,immunofluoresnce and enzyme linked immunosorbent assay.A CD44 blocking antibody and siRNA targeting of CD44 were used to examine the role of this receptor in the OPN stimulated cell growth observed in culture.Huh-7 cells stably expressing either OPN-A,-B or-C were injected subcutaneously into the flanks of nude mice to observe in vivo tumour growth.Expression of OPN mRNA and protein in these tumours was examined using reverse transcriptionpolymerase chain reaction and immunohistochemistry.RESULTS:OPN is expressed in HCC in 3 forms,the full length OPN-A and 2 splice variants OPN-B and-C.OPN variant expression was noted in HCC tissue as well as cognate surrounding cirrhotic liver tissue.Expression of these OPN variants in the HCC derived cell line Huh-7 resulted in secretion of OPN into the culture medium.Transfer of OPN conditioned media to na ve Huh-7 and HepG2 cells resulted in significant cell growth suggesting that all OPN variants can modulate cell proliferation in a paracrine manner.Furthermore the OPN mediated increase in cellular proliferation was dependent on CD44 as only CD44 positive cell lines responded to OPN conditioned media while siRNA knockdown of CD44 blocked the proliferative effect.OPN expression also increased the proliferation of Huh-7 cells in a subcutaneous nude mouse tumour model,with Huh-7 cells expressing OPN-A showing the greatest proliferative effect.CONCLUSION:This study demonstrates that OPN plays a significant role in the proliferation of HCC through interaction with the cell surface receptor CD44.Modulation of this interaction could represent a novel strategy for the control of HCC.展开更多
AIM: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate. METHODS: This study was a prospective randomized controlled trial conducted from March 2008 to Febr...AIM: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate. METHODS: This study was a prospective randomized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney. The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate. Consecutive cases of total colonoscopy over a 1-year period were recruited. Randomization into either standard colonoscopy (SC) or cap-assisted colonoscopy (CAC) was performed after consent was obtained. For cases randomized to CAC, one of the three sizes of cap was used: D-201-15004 (with a diameter of 15.3 mm), D-201-14304 (14.6 mm) and D-201-12704 (13.0 mm). All of these caps were produced by Olympus Medical Systems, Japan. Independent predictors for faster cecal time and better polyp detection rate were also determined from this study. RESULTS: There were 200 cases in each group. There was no signif icant difference in terms of demographic characteristics between the two groups. CAC, when compared to the SC group, had no signif icant difference in terms of cecal intubation rate (96.0% vs 97.0%, P = 0.40) and time (9.94 ± 7.05 min vs 10.34 ± 6.82 min, P = 0.21), or polyp detection rate (32.8% vs 31.3%, P = 0.75). On the subgroup analysis, there was no significant difference in terms of cecal intubation time by trainees (88.1% vs 84.8%, P = 0.40), ileal intubation rate (82.5% vs 79.0%, P = 0.38) or total colonoscopy time (23.24 ± 13.95 min vs 22.56 ± 9.94 min, P = 0.88). On multivariate analysis, the independent determinants of faster cecal time were consultant-performed procedures (P < 0.001), male patients (P < 0.001), non-usage of hyoscine (P < 0.001) and better bowel preparation (P = 0.01). The determinants of better polyp detection rate were older age (P < 0.001), no history of previous abdominal surgery (P = 0.04), patients not having esophagogastroduodenoscopy in the same setting (P = 0.003), trainee-performed procedures (P = 0.01), usage of hyoscine (P = 0.01) and procedures performed for polyp follow-up (P = 0.01). The limitations of the study were that it was a single-center experience, no blinding was possible, and there were a large number of endoscopists. CONCLUSION: CAC did not signif icantly different from SC in term of cecal intubation time and polyp detection rate.展开更多
BACKGROUND Hemorrhoidal disease is the most common anorectal disorder.Hemorrhoids can be classified as external or internal,according to their relation to the dentate line.External hemorrhoids originate below the dent...BACKGROUND Hemorrhoidal disease is the most common anorectal disorder.Hemorrhoids can be classified as external or internal,according to their relation to the dentate line.External hemorrhoids originate below the dentate line and are managed conservatively unless the patient cannot keep the perianal region clean,or they cause significant discomfort.Internal hemorrhoids originate above the dentate line and can be managed according to the graded degree of prolapse,as described by Goligher.Generally,low-grade internal hemorrhoids are effectively treated conservatively,by non-operative measures,while high-grade internal hemorrhoids warrant procedural intervention.AIM To determine the application of clinical practice guidelines for the current management of hemorrhoids and colorectal surgeon consensus in Australia and New Zealand.METHODS An online survey was distributed to 206 colorectal surgeons in Australia and New Zealand using 17 guideline-based hypothetical clinical scenarios.RESULTS There were 82 respondents(40%)to 17 guideline-based scenarios.Nine(53%)reached consensus,of which only 1(6%)disagreed with the guidelines.This was based on low quality evidence for the management of acutely thrombosed external hemorrhoids.There were 8 scenarios which showed community equipoise(47%)and they were equally divided for agreeing or disagreeing with the guidelines.These topics were based on low and moderate levels of evidence.They included the initial management of grade I internal hemorrhoids,grade III internal hemorrhoids when initial management had failed and the patient had recognised risks factors for septic complications;and finally,the decision-making when considering patient preferences,including a prompt return to work,or minimal post-operative pain.CONCLUSION Although there are areas of consensus in the management of hemorrhoids,there are many areas of community equipoise which would benefit from further research.展开更多
Despite advancements in medical therapy of Crohn's disease(CD), majority of patients with CD will eventually require surgical intervention, with at least a third of patients requiring multiple surgeries. It is imp...Despite advancements in medical therapy of Crohn's disease(CD), majority of patients with CD will eventually require surgical intervention, with at least a third of patients requiring multiple surgeries. It is important to understand the role and timing of surgery, with the goals of therapy to reduce the need for surgery without increasing the odds of emergency surgery and its associated morbidity, as well as to limit surgical recurrence and avoid intestinal failure. The profile of CD patients requiring surgical intervention has changed over the decades with improvements in medical therapy with immunomodulators and biological agents. The most common indication for surgery is obstruction from stricturing disease, followed by abscesses and fistulae. The risk of gastrointestinal bleeding in CD is high but the likelihood of needing surgery for bleeding is low. Most major gastrointestinal bleeding episodes resolve spontaneously, albeit the risk of re-bleeding is high. The risk of colorectal cancer associated with CD is low. While current surgical guidelines recommend a total proctocolectomy for colorectal cancer associated with CD, subtotal colectomy or segmental colectomy with endoscopic surveillance may be a reasonable option. Approximately 20%-40% of CD patients will need perianal surgery during their lifetime. This review assesses the practice parameters and guidelines in the surgical management of CD, with a focus on the indications for surgery in CD(and when not to operate), and a critical evaluation of the timing and surgical options available to improve outcomes and reduce recurrence rates.展开更多
Polymethylmethacrylate(PMMA) bone cement technology has progressed from industrial Plexiglass administration in the 1950 s to the recent advent of nanoparticle additives. Additives have been trialed to address problem...Polymethylmethacrylate(PMMA) bone cement technology has progressed from industrial Plexiglass administration in the 1950 s to the recent advent of nanoparticle additives. Additives have been trialed to address problems with modern bone cements such as the loosening of prosthesis, high post-operative infection rates, and inflammatory reduction in interface integrity. This review aims to assess current additives used in PMMA bone cements and offer an insight regarding future directions for this biomaterial. Low index(< 15%) vitamin E and low index(< 5 g) antibiotic impregnated additives significantly address infection and inflammatory problems, with only modest reductions in mechanical strength. Chitosan(15% w/w PMMA) and silver(1% w/w PMMA) nanoparticles have strong antibacterial activity with no significant reduction in mechanical strength. Future work on PMMA bone cements should focus on trialing combinations of these additives as this may enhance favourable properties.展开更多
AIM: To investigate over-expression of Osteopontin (OPN) pathway expression and mechanisms of action in human alcoholic liver disease (ALD), in vivo and in vitro acute alcohol models.
AIM: To determine the learning curves for antegrade double-balloon enteroscopy (aDBE) and retrograde DBE (rDBE) by analyzing the technical success rates. METHODS: A retrospective analysis in a tertiary referral center...AIM: To determine the learning curves for antegrade double-balloon enteroscopy (aDBE) and retrograde DBE (rDBE) by analyzing the technical success rates. METHODS: A retrospective analysis in a tertiary referral center. This study reviewed all cases from June 2006 to April 2011 with a target lesion in the small-bowel identified by either capsule endoscopy or computed tomography scan posted for DBE examinations. Main outcome measurements were: (1) Technical success of aDBE def ined by f inding or excluding a target lesion after achieving suff icient length of small bowel intubation; and (2) Technical success for rDBE was def ined by either f inding the target lesion or achieving stable overtube placement in the ileum. RESULTS: Two hundred and eighty two procedures fulf illed the inclusion criteria and were analyzed. These procedures were analyzed by blocks of 30 cases. Therewas no distinct learning curve for aDBE. Technical success rates for rDBE continued to rise over time, although on logistic regression analysis testing for trend, there was no signif icance (P = 0.09). The odds of success increased by a factor of 1.73 (95% CI: 0.93-3.22) for rDBE. For these data, it was estimated that at least 30-35 cases of rDBE under supervision were needed to achieve a good technical success of more than 75%. CONCLUSION: There was no learning curve for aDBE. Technical success continued to increase over time for rDBE, although a learning curve could not be proven statistically. Approximately 30-35 cases of rDBE will be required for stable overtube intubation in ileum.展开更多
Postoperative biliary strictures are the most common cause of benign biliary stricture in Western countries, secondary to either operative injury or bile duct anastomotic stricture following orthotopic liver transplan...Postoperative biliary strictures are the most common cause of benign biliary stricture in Western countries, secondary to either operative injury or bile duct anastomotic stricture following orthotopic liver transplantation(OLT).Surgery or endoscopic interventions are the mainstay of treatment for benign biliary strictures.We aim to report the outcome of 2 patients with refractory anastomotic biliary stricture post-OLT,who had successful temporary placement of a prototype removable covered self-expandable metal stent(RCSEMS).These 2 patients(both men,aged 44 and 53 years)were given temporary placement of a prototype RCSEMS (8.5 Fr gauge delivery system,8 mm×40 mm stent dimensions)in the common bile duct across the biliary stricture.There was no morbidity associated with stent placement and removal in these 2 cases.Clinical parameters improved after the RCSEMS placement.Longterm biliary patency was achieved in both the patients. No further biliary intervention was required within 14 and 18 mo follow-up after stent removal.展开更多
基金funded by R.D.H.,P.B.,A.S.W. and Z.W,Heart Foundation Vanguard Grant#107321funded by contributions from The Baird Institute for applied Heart and Lung Research.
文摘Objective:Sheep are commonly used as large animal pre-clinical models for inves-tigating cardiovascular therapies,interventions,anatomy and physiology.Further,novel small diameter vascular grafts are frequently tested via implantation into sheep carotid arteries(CAs).This is because,unlike humans,acute occlusion of one or both sheep CAs is not associated with morbidity or mortality and thus provides safer experimental testing,with reduced ethical constraints,animal numbers and costs.However,to date there has been no evidence regarding sheep tolerance of femoral artery(FA)occlusion.Methods:In this study,seven sheep underwent CA graft surgery,with digital subtrac-tion angiography(DSA)of the CAs performed every 2 months via femoral access,for a total of 8 months.Four months into the study,the left FA of two sheep became inac-cessible due to a suspected FA occlusion.Thus,femoral angiography was performed,followed by FA dissection,FA histology and retrospective analysis of both veterinar-ian animal monitoring and pain scores.Results:FA angiography and histology confirmed complete left FA occlusion in two sheep.Retrospective animal monitoring demonstrated sheep with occluded FAs did not display increased pain scores or deleterious effects on their gait or wellbeing.Conclusion:Our data shows that sheep tolerate FA occlusion with no symptoms,similar to their cerebral circulation,making them an appropriate model for assessing small diameter femoral graft interposition studies and testing other cardiovascular interventions.
基金funding but aspects of this work(computer analysis)were supported by an Australian Research Council(ARC)grant,DP150104472(MBG)The Australian Genomics and Outcomes of Glioma project was funded by a Cancer Council NSW Strategic Research Partnership Grant.
文摘Background:Microglia and brain macrophages contribute significantly to the tumor microenvironment in highly malignant glioblastoma where they are considered important drivers of tumor progression.A better understanding of the role of the brain macrophages present in glioblastoma appears crucial for improving therapeutic outcomes,especially in the context of novel immunotherapeutic approaches.Methods:We investigated the regulation of two well-established markers for microglia and brain macrophages,IBA1 and CD163,in relation to glioblastoma tumor necrosis using immunohistochemistry and modality fusion heatmaps of whole slide images obtained from adjacent tissue sections.Results:IBA1 and CD163 showed remarkable differences in relation to glioblastoma tumor necrosis.Generally,IBA1 immunoreactive cells were far less common in necrotic tissue areas than CD163-expressing cells.We also found extensive and frequently diffuse extracellular CD163 deposition,especially in hypocellular necrobiotic tumor regions where IBA1 was typically absent.Conclusions:Resident microglia seem more likely to be important for the diffuse infiltration of glioma cells in hypercellular tissue areas,whereas myeloid macrophages may be the main macrophage population in the wake of tumor necrosis.Since the necrotic niche with its interactions between microglia,brain macrophages,and glioblastoma/glioma stem cells is increasingly recognised as an important factor in tumor progression,further detailed studies of the macrophage populations in glioblastoma are warranted.
文摘Background:Much has been written about the loss to follow-up in the transition between pediatric and adult Congenital Heart Disease(CHD)care centers.Much less is understood about the loss to follow-up(LTF)after a successful transition.This is critical too,as patients lost to specialised care are more likely to experience mor-bidity and premature mortality.Aims:To understand the prevalence and reasons for loss to follow-up(LTF)at a large Australian Adult Congenital Heart Disease(ACHD)centre.Methods:Patients with moderate or highly complex CHD and gaps in care of>3 years(defined as LTF)were identified from a comprehensive ACHD data-base.Structured telephone interviews examined current care and barriers to clinic attendance.Results:Overall,407(22%)of ACHD patients(n=1842)were LTF.The mean age at LTF was 31(SD 11.5)years and 54%were male;311(76%)were uncontactable.Compared to adults seen regularly,lost patients were younger,with a greater socio-economic disadvantage,and had less complex CHD(p<0.05 for all).We interviewed 59 patients(14%).The top 3 responses for care absences were“feeling well”(61%),losing track of time(36%),and not needing fol-low-up care(25%).Conclusions:A large proportion of the ACHD population becomes lost to specialised cardiac care,even after a successful transition.This Australian study reports younger age,moderate complexity defects,and socio-economic disadvantage as predictive of loss to follow-up.This study highlights the need for novel approaches to patient-centered service delivery even beyond the age of transition and resources to maintain patient engagement within the ACHD service.
文摘Background A medical content-based image retrieval(CBIR)system is designed to retrieve images from large imaging repositories that are visually similar to a user′s query image.CBIR is widely used in evidence-based diagnosis,teaching,and research.Although the retrieval accuracy has largely improved,there has been limited development toward visualizing important image features that indicate the similarity of retrieved images.Despite the prevalence of 3D volumetric data in medical imaging such as computed tomography(CT),current CBIR systems still rely on 2D cross-sectional views for the visualization of retrieved images.Such 2D visualization requires users to browse through the image stacks to confirm the similarity of the retrieved images and often involves mental reconstruction of 3D information,including the size,shape,and spatial relations of multiple structures.This process is time-consuming and reliant on users'experience.Methods In this study,we proposed an importance-aware 3D volume visualization method.The rendering parameters were automatically optimized to maximize the visibility of important structures that were detected and prioritized in the retrieval process.We then integrated the proposed visualization into a CBIR system,thereby complementing the 2D cross-sectional views for relevance feedback and further analyses.Results Our preliminary results demonstrate that 3D visualization can provide additional information using multimodal positron emission tomography and computed tomography(PETCT)images of a non-small cell lung cancer dataset.
文摘Malignant mesothelioma is a highly aggressive neoplasm.The incidence of malignant mesothelioma is increasing worldwide.Diffuse malignant peritoneal mesothelioma(DMPM) represents one-fourth of all mesotheliomas.Association of asbestos exposure with DMPM has been observed,especially in males.The great majority of patients present with abdominal pain and distension,caused by accumulation of tumors and ascitic ? uid.In the past,DMPM was considered a pre-terminal condition;therefore attracted little attention.Patients invariably died from their disease within a year.Recently,several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy.This remarkable improvement in survival has prompted new search into the medical science related to DMPM,a disease previously ignored as uninteresting.This review article focuses on the key advances in the epidemiology,diagnosis,staging,treatments and prognosis of DMPM that have occurred in the past decade.
文摘AIM:To report the incidence of non-small-bowel bleeding pathologies encountered during double-balloon enteroscopy (DBE) procedures and to analyse their significance.METHODS: A retrospective study of a prospective DBE database conducted in a tertiary-referral center was conducted. A total of 179 patients with obscure gastrointestinal bleeding (OGIB) referred for DBE from June 2004 to November 2008 were analysed looking for the incidence of non-small-bowel lesions (NSBLs; all and newly diagnosed) encountered during DBE.RESULTS: There were 228 (150 antegrade and 78 retrograde) DBE procedures performed in 179 patients. The mean number of DBE procedures was 1.27 per patient. The mean age (SD) of the patients was 62 ± 16 years old. There were 94 females (52.5%). The positive yield for a bleeding lesion was 65.9%. Of the 179 patients, 44 (24.6%) had NSBLs (19 of them had dual pathology with small-bowel lesions and NSBLs); 27 (15.1%) had lesions not detected by previous endoscopies. The most common type of missed lesions were vascular lesions.CONCLUSION: A significant proportion of patients (24.6%) had lesions within reach of conventional endoscopy. Careful repeat examination with gastroscopy and colonoscopy might be required.
文摘Perioperative intraperitoneal chemotherapy in combination with cytoreductive surgery has been shown to be of benefit for treating selected patients with peritoneal surface malignancy.It has become a new standard of care in the management of diffuse malignant peritoneal mesothelioma and peritoneal dissemination of appendiceal malignancy.Numerous recent publications on carcinomatosis from colorectal cancer and gastric cancer identify groups of patients that would benef it from this local-regional approach for prevention and treatment of carcinomatosis.This review focuses on pharmacological information regarding intraperitoneal chemotherapeutic agents commonly used in gastrointestinal oncology.
基金This project was supported by the National Natural Science Foundation of China (No.81300642).
文摘The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population.We searched PubMed,EMBASE,and Web of Science from inception to the March 1,2018.The studies were selected to estimate the prevalence of thyroid nodules in T2DM subjects and to compare the prevalence of thyroid nodules in different glucose tolerance status.The random effects model was used,and the outcome was presented as a pooled prevalence proportion with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI.In the end,9 studies met the inclusion criteria and were included in the analysis.The pooled prevalence of thyroid nodules was 60%(95% CI:0.52,0.68) for T2DM 2 diabetes patients,50%(95% CI:0.4& 0.51) for pre-diabetes,and 43%(95% CI:0.34,0.52) for normal glucose tolerance population.Compared with patients without diabetes,diabetes subjects are more likely to develop thyroid nodules,adjusted OR for thyroid nodule was 1.78 (95% CI:1.25,2.55).Insulin resistance might be involved in thyroid nodule development.
文摘The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,disease stages and lines of therapy.With this increased use,adverse events including immune checkpoint inhibitor-related hepatotoxicity(ICH)have emerged as an important clinical problem.This along with the introduction of ICI as first-and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists.The incidence of ICH varies between 1%-20%depending on the number,type and dose of ICI received.Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI,corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity.The majority of patients with ICH recover and some may even safely recommence ICI therapy.Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.
文摘Major advances have been made over the last decade in our understanding of the molecular basis ofseveral cardiac conditions. Hypertrophic cardiomyopathy (HCM) was the first cardiac disorder in whicha genetic basis was identified and as such, has acted as a paradigm for the study of an inherited cardiacdisorder. HCM can result in clinical symptoms ranging from no symptoms to severe heart failure andpremature sudden death. HCM is the commonest cause of sudden death in those aged less than 35 years,including competitive athletes. At least ten genes have now been identified, defects in which cause HCM.All of these genes encode proteins which comprise the basic contractile unit of the heart, i.e. the sarcomere.While much is now known about which genes cause disease and the various clinical presentations, very littleis known about how these gene defects cause disease, and what factors modify the expression of the mutantgenes. Studies in both cell culture and animal models of HCM are now beginning to shed light on thesignalling pathways involved in HCM, and the role of both environmental and genetic modifying factors.Understanding these mechanisms will ultimately improve our knowledge of the basic biology of heart musclefunction, and will therefore provide new avenues for treating cardiovascular disease in man.
文摘AIM To evaluate the therapeutic role of double-balloon enteroscopy(DBE) in small bowel strictures and to propose a standard approach to small bowel strictures.METHODS Systematic review of studies involving DBE in patients with small bowel strictures. Only studies limited to small bowel strictures were included and those with ileo-colonic strictures were excluded. RESULTS In total 13 studies were included,in which 310 patients were dilated. The average follow-up time was 31.8 mo per patient. The complication rate was 4.8% per patient and 2.6% per dilatation. Surgery was avoided in 80% of patients. After the first dilatation,46% were treated with re-dilatation and only 17% required surgery.CONCLUSION DBE-assisted dilatation avoids surgery in 80% of patients with small bowel strictures and is safe and effective. We propose a standardized approach to small bowel strictures.
文摘AIM:To investigate the role of osteopontin(OPN) and its splice variants in the proliferation of hepatocellular carcinoma(HCC).METHODS:The expression of OPN variants in HCC cell lines as well as HCC tissue samples and nontumour tissue was studied using polymerase chain reaction.OPN variant cDNAs were cloned into a mammalian expression vector allowing both transient expression and the production of stable OPN expressing cell lines.OPN expression was studied in these cells using Western blotting,immunofluoresnce and enzyme linked immunosorbent assay.A CD44 blocking antibody and siRNA targeting of CD44 were used to examine the role of this receptor in the OPN stimulated cell growth observed in culture.Huh-7 cells stably expressing either OPN-A,-B or-C were injected subcutaneously into the flanks of nude mice to observe in vivo tumour growth.Expression of OPN mRNA and protein in these tumours was examined using reverse transcriptionpolymerase chain reaction and immunohistochemistry.RESULTS:OPN is expressed in HCC in 3 forms,the full length OPN-A and 2 splice variants OPN-B and-C.OPN variant expression was noted in HCC tissue as well as cognate surrounding cirrhotic liver tissue.Expression of these OPN variants in the HCC derived cell line Huh-7 resulted in secretion of OPN into the culture medium.Transfer of OPN conditioned media to na ve Huh-7 and HepG2 cells resulted in significant cell growth suggesting that all OPN variants can modulate cell proliferation in a paracrine manner.Furthermore the OPN mediated increase in cellular proliferation was dependent on CD44 as only CD44 positive cell lines responded to OPN conditioned media while siRNA knockdown of CD44 blocked the proliferative effect.OPN expression also increased the proliferation of Huh-7 cells in a subcutaneous nude mouse tumour model,with Huh-7 cells expressing OPN-A showing the greatest proliferative effect.CONCLUSION:This study demonstrates that OPN plays a significant role in the proliferation of HCC through interaction with the cell surface receptor CD44.Modulation of this interaction could represent a novel strategy for the control of HCC.
文摘AIM: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate. METHODS: This study was a prospective randomized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney. The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate. Consecutive cases of total colonoscopy over a 1-year period were recruited. Randomization into either standard colonoscopy (SC) or cap-assisted colonoscopy (CAC) was performed after consent was obtained. For cases randomized to CAC, one of the three sizes of cap was used: D-201-15004 (with a diameter of 15.3 mm), D-201-14304 (14.6 mm) and D-201-12704 (13.0 mm). All of these caps were produced by Olympus Medical Systems, Japan. Independent predictors for faster cecal time and better polyp detection rate were also determined from this study. RESULTS: There were 200 cases in each group. There was no signif icant difference in terms of demographic characteristics between the two groups. CAC, when compared to the SC group, had no signif icant difference in terms of cecal intubation rate (96.0% vs 97.0%, P = 0.40) and time (9.94 ± 7.05 min vs 10.34 ± 6.82 min, P = 0.21), or polyp detection rate (32.8% vs 31.3%, P = 0.75). On the subgroup analysis, there was no significant difference in terms of cecal intubation time by trainees (88.1% vs 84.8%, P = 0.40), ileal intubation rate (82.5% vs 79.0%, P = 0.38) or total colonoscopy time (23.24 ± 13.95 min vs 22.56 ± 9.94 min, P = 0.88). On multivariate analysis, the independent determinants of faster cecal time were consultant-performed procedures (P < 0.001), male patients (P < 0.001), non-usage of hyoscine (P < 0.001) and better bowel preparation (P = 0.01). The determinants of better polyp detection rate were older age (P < 0.001), no history of previous abdominal surgery (P = 0.04), patients not having esophagogastroduodenoscopy in the same setting (P = 0.003), trainee-performed procedures (P = 0.01), usage of hyoscine (P = 0.01) and procedures performed for polyp follow-up (P = 0.01). The limitations of the study were that it was a single-center experience, no blinding was possible, and there were a large number of endoscopists. CONCLUSION: CAC did not signif icantly different from SC in term of cecal intubation time and polyp detection rate.
文摘BACKGROUND Hemorrhoidal disease is the most common anorectal disorder.Hemorrhoids can be classified as external or internal,according to their relation to the dentate line.External hemorrhoids originate below the dentate line and are managed conservatively unless the patient cannot keep the perianal region clean,or they cause significant discomfort.Internal hemorrhoids originate above the dentate line and can be managed according to the graded degree of prolapse,as described by Goligher.Generally,low-grade internal hemorrhoids are effectively treated conservatively,by non-operative measures,while high-grade internal hemorrhoids warrant procedural intervention.AIM To determine the application of clinical practice guidelines for the current management of hemorrhoids and colorectal surgeon consensus in Australia and New Zealand.METHODS An online survey was distributed to 206 colorectal surgeons in Australia and New Zealand using 17 guideline-based hypothetical clinical scenarios.RESULTS There were 82 respondents(40%)to 17 guideline-based scenarios.Nine(53%)reached consensus,of which only 1(6%)disagreed with the guidelines.This was based on low quality evidence for the management of acutely thrombosed external hemorrhoids.There were 8 scenarios which showed community equipoise(47%)and they were equally divided for agreeing or disagreeing with the guidelines.These topics were based on low and moderate levels of evidence.They included the initial management of grade I internal hemorrhoids,grade III internal hemorrhoids when initial management had failed and the patient had recognised risks factors for septic complications;and finally,the decision-making when considering patient preferences,including a prompt return to work,or minimal post-operative pain.CONCLUSION Although there are areas of consensus in the management of hemorrhoids,there are many areas of community equipoise which would benefit from further research.
文摘Despite advancements in medical therapy of Crohn's disease(CD), majority of patients with CD will eventually require surgical intervention, with at least a third of patients requiring multiple surgeries. It is important to understand the role and timing of surgery, with the goals of therapy to reduce the need for surgery without increasing the odds of emergency surgery and its associated morbidity, as well as to limit surgical recurrence and avoid intestinal failure. The profile of CD patients requiring surgical intervention has changed over the decades with improvements in medical therapy with immunomodulators and biological agents. The most common indication for surgery is obstruction from stricturing disease, followed by abscesses and fistulae. The risk of gastrointestinal bleeding in CD is high but the likelihood of needing surgery for bleeding is low. Most major gastrointestinal bleeding episodes resolve spontaneously, albeit the risk of re-bleeding is high. The risk of colorectal cancer associated with CD is low. While current surgical guidelines recommend a total proctocolectomy for colorectal cancer associated with CD, subtotal colectomy or segmental colectomy with endoscopic surveillance may be a reasonable option. Approximately 20%-40% of CD patients will need perianal surgery during their lifetime. This review assesses the practice parameters and guidelines in the surgical management of CD, with a focus on the indications for surgery in CD(and when not to operate), and a critical evaluation of the timing and surgical options available to improve outcomes and reduce recurrence rates.
文摘Polymethylmethacrylate(PMMA) bone cement technology has progressed from industrial Plexiglass administration in the 1950 s to the recent advent of nanoparticle additives. Additives have been trialed to address problems with modern bone cements such as the loosening of prosthesis, high post-operative infection rates, and inflammatory reduction in interface integrity. This review aims to assess current additives used in PMMA bone cements and offer an insight regarding future directions for this biomaterial. Low index(< 15%) vitamin E and low index(< 5 g) antibiotic impregnated additives significantly address infection and inflammatory problems, with only modest reductions in mechanical strength. Chitosan(15% w/w PMMA) and silver(1% w/w PMMA) nanoparticles have strong antibacterial activity with no significant reduction in mechanical strength. Future work on PMMA bone cements should focus on trialing combinations of these additives as this may enhance favourable properties.
基金Supported by Philanthropic Anonymous Sourcethe University of Sydney Bridging Support Grant,in part for Honours ProjectSupported by the National Health and Medical Research Council,No.NHMRC Practitioner Research Fellowship for PH support
文摘AIM: To investigate over-expression of Osteopontin (OPN) pathway expression and mechanisms of action in human alcoholic liver disease (ALD), in vivo and in vitro acute alcohol models.
文摘AIM: To determine the learning curves for antegrade double-balloon enteroscopy (aDBE) and retrograde DBE (rDBE) by analyzing the technical success rates. METHODS: A retrospective analysis in a tertiary referral center. This study reviewed all cases from June 2006 to April 2011 with a target lesion in the small-bowel identified by either capsule endoscopy or computed tomography scan posted for DBE examinations. Main outcome measurements were: (1) Technical success of aDBE def ined by f inding or excluding a target lesion after achieving suff icient length of small bowel intubation; and (2) Technical success for rDBE was def ined by either f inding the target lesion or achieving stable overtube placement in the ileum. RESULTS: Two hundred and eighty two procedures fulf illed the inclusion criteria and were analyzed. These procedures were analyzed by blocks of 30 cases. Therewas no distinct learning curve for aDBE. Technical success rates for rDBE continued to rise over time, although on logistic regression analysis testing for trend, there was no signif icance (P = 0.09). The odds of success increased by a factor of 1.73 (95% CI: 0.93-3.22) for rDBE. For these data, it was estimated that at least 30-35 cases of rDBE under supervision were needed to achieve a good technical success of more than 75%. CONCLUSION: There was no learning curve for aDBE. Technical success continued to increase over time for rDBE, although a learning curve could not be proven statistically. Approximately 30-35 cases of rDBE will be required for stable overtube intubation in ileum.
文摘Postoperative biliary strictures are the most common cause of benign biliary stricture in Western countries, secondary to either operative injury or bile duct anastomotic stricture following orthotopic liver transplantation(OLT).Surgery or endoscopic interventions are the mainstay of treatment for benign biliary strictures.We aim to report the outcome of 2 patients with refractory anastomotic biliary stricture post-OLT,who had successful temporary placement of a prototype removable covered self-expandable metal stent(RCSEMS).These 2 patients(both men,aged 44 and 53 years)were given temporary placement of a prototype RCSEMS (8.5 Fr gauge delivery system,8 mm×40 mm stent dimensions)in the common bile duct across the biliary stricture.There was no morbidity associated with stent placement and removal in these 2 cases.Clinical parameters improved after the RCSEMS placement.Longterm biliary patency was achieved in both the patients. No further biliary intervention was required within 14 and 18 mo follow-up after stent removal.
