BACKGROUND The management of high-grade pancreatic trauma is controversial.AIM To review our single-institution experience on the surgical management of blunt and penetrating pancreatic injuries.METHODS A retrospectiv...BACKGROUND The management of high-grade pancreatic trauma is controversial.AIM To review our single-institution experience on the surgical management of blunt and penetrating pancreatic injuries.METHODS A retrospective review of records was performed on all patients undergoing surgical intervention for high-grade pancreatic injuries [American Association for the Surgery of Trauma(AAST) Grade Ⅲor greater] at the Royal North Shore Hospital in Sydney between January 2001 and December 2022. Morbidity and mortality outcomes were reviewed, and major diagnostic and operative challenges were identified.RESULTS Over a twenty-year period, 14 patients underwent pancreatic resection for highgrade injuries. Seven patients sustained AAST Grade Ⅲinjuries and 7 were classified as Grades Ⅳ or Ⅴ. Nine underwent distal pancreatectomy and 5 underwent pancreaticoduodenectomy(PD). Overall, there was a predominance of blunt aetiologies(11/14). Concomitant intra-abdominal injuries were observed in 11 patients and traumatic haemorrhage in 6 patients. Three patients developed clinically relevant pancreatic fistulas and there was one in-hospital mortality secondary to multi-organ failure. Among stable presentations, pancreatic ductal injuries were missed in two-thirds of cases(7/12) on initial computed tomography imaging and subsequently diagnosed on repeat imaging or endoscopic retrograde cholangiopancreatography. All patients who sustained complex pancreaticoduodenal trauma underwent PD without mortality. The management of pancreatic trauma is evolving. Our experience provides valuable and locally relevant insights into future management strategies.CONCLUSION We advocate that high-grade pancreatic trauma should be managed in high-volume hepatopancreato-biliary specialty surgical units. Pancreatic resections including PD may be indicated and safely performed with appropriate specialist surgical, gastroenterology, and interventional radiology support in tertiary centres.展开更多
BACKGROUND Juvenile polyposis syndrome(JPS)is a rare hereditary polyposis disease frequently associated with an autosomal-dominant variant of the SMAD4 or BMPR1A gene.It often manifests with symptoms in children and a...BACKGROUND Juvenile polyposis syndrome(JPS)is a rare hereditary polyposis disease frequently associated with an autosomal-dominant variant of the SMAD4 or BMPR1A gene.It often manifests with symptoms in children and adolescents and is infrequently diagnosed in asymptomatic adults.Establishing the diagnosis is important as patients with JPS have a high risk of developing gastrointestinal cancer and require genetic counselling and close routine follow-up.CASE SUMMARY We report on the case of a 56-year-old female diagnosed with JPS after genetic testing revealed a rare variant of the BMPR1A gene BMPR1A c.1409T>C(p.Met470Thr).She was initially referred for colonoscopy by her general practitioner after testing positive on a screening faecal immunochemical test and subsequently found to have polyposis throughout the entire colorectum on her index screening colonoscopy.The patient was asymptomatic with a normal physical examination and no related medical or family history.Blood tests revealed only mild iron deficiency without anemia.To date,there has only been one other reported case of JPS with the same genetic variant.Subsequent colonoscopies were organised for complete polyp clearance and the patient was returned for surveillance follow-up.CONCLUSION JPS patients can present with no prior symptoms or family history.Genetic testing plays an important diagnostic role guiding management.展开更多
AIM:To describe our own experience with pyogenic liver abscesses over the past 10 years and investigate the risk factors associated with failure of initial percutaneous therapy.METHODS:A retrospective study of records...AIM:To describe our own experience with pyogenic liver abscesses over the past 10 years and investigate the risk factors associated with failure of initial percutaneous therapy.METHODS:A retrospective study of records of 63 PLA patients presenting between 1998 and 2008 to Australian tertiary referral centre,were reviewed.Amoebic and hydatid abscesses were excluded.Demographic,clinical,radiological,and microbiological characteristics,as well as surgical/radiological interventions,were recorded.RESULTS:Sixty-three patients(42 males,21 females) aged 65(±14) years[mean±(SD) ]had prodromal symptoms for a median(interquartile range;IQR) of 7(5-14) d.Only 59%of patients were febrile at presentation;however,the serum C-reactive protein was elevated in all 47 in whom it was measured.Liver function tests were non-specifically abnormal.67%of patients had a solitary abscess,while 32%had>3 abscesses with a median(IQR) diameter of 6.3(4-9) cm.Causative organisms were:Streptococcus milleri 25%,Klebsiella pneumoniae 21%,and Escherichia coli 16%.A presumptive cryptogenic cause was most common (34%).Four patients died in this series:one from sepsis,two from advanced cancer,and one from acute myocardial infarction.The initial procedure was radiological aspiration±drainage in 54 and surgery in two patients.17%underwent surgical management during their hospitalization.Serum hypoalbuminaemia[mean (95%CI) :32(29-35) g/L vs 28(25-31) g/L,P=0.045] on presentation was found to be the only factor related to failure of initial percutaneous therapy on univariate analysis.CONCLUSION:PLA is a diagnostic challenge,because the presentation of this condition is non-specific.Intravenous antibiotics and radiological drainage in the first instance allows resolution of most PLAs;However,a small proportion of patients still require surgical drainage.展开更多
Due to the inherent relationship between the immune system and the hepatitis B virus(HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignanci...Due to the inherent relationship between the immune system and the hepatitis B virus(HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation(HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations' guidelines and the best available evidence to date.展开更多
Gastrointestinal bleeding is a common problem encountered in the emergency department and in the primary care setting. Acute or overt gastrointestinal bleeding is visible in the form of hematemesis, melena or hematoch...Gastrointestinal bleeding is a common problem encountered in the emergency department and in the primary care setting. Acute or overt gastrointestinal bleeding is visible in the form of hematemesis, melena or hematochezia. Chronic or occult gastrointestinal bleeding is notapparent to the patient and usually presents as positive fecal occult blood or iron deficiency anemia. Obscure gastrointestinal bleeding is recurrent bleeding when the source remains unidentified after upper endoscopy and colonoscopic evaluation and is usually from the small intestine. Accurate clinical diagnosis is crucial and guides definitive investigations and interventions. This review summarizes the overall diagnostic approach to gastrointestinal bleeding and provides a practical guide for clinicians.展开更多
BACKGROUND:Pancreatoduodenectomy offers the only chance of cure for patients with periampullary cancers.This,however,is a major undertaking in most patients and is associated with a significant morbidity and mortality...BACKGROUND:Pancreatoduodenectomy offers the only chance of cure for patients with periampullary cancers.This,however,is a major undertaking in most patients and is associated with a significant morbidity and mortality.A multidisciplinary approach to the workup and follow-up of patients undergoing pancreatoduodenectomy was initiated at our institution to improve the diagnosis,resection rate,mortality and morbidity.We undertook the study to assess the effect of this approach on diagnosis,resection rates and short-term outcomes such as morbidity and mortality.METHODS:A prospective database of patients presenting with periampullary cancers to a single surgeon between April 2004 and April 2010 was reviewed.All cases were discussed at a multidisciplinary meeting comprising surgeons,gastroenterologists,radiologists,oncologists,radiation oncologists,pathologists and nursing staff.A standardized investigation and management algorithm was followed.Complications were graded according to the Clavien-Dindo classification.RESULTS:A total of 295 patients with a periampullary lesion were discussed and 178 underwent pancreatoduodenectomy (resection rate 60%).Sixty-one patients (34%) required either a vascular or an additional organ resection.Eighty-nine patients experienced complications,of which the commonest was blood transfusion (12%).Thirty-four patients (19%) had major complications,i.e.grade 3 or above.There was no in-hospital,30-day or 60-day mortality.CONCLUSIONS:Pancreatoduodenectomy can safely be performed in high-volume centers with very low mortality.The surgeon’s role should be careful patient selection,intensive preoperative investigations,use of a team approach,and an unbiased discussion at a multidisciplinary meeting to optimize the outcome in these patients.展开更多
Intracranial atherosclerotic disease (ICAD) contributes to a significant number of ischemic strokes. There is debate in the recent literature concerning the impact of the location of stenosis in ICAD on outcome. Some ...Intracranial atherosclerotic disease (ICAD) contributes to a significant number of ischemic strokes. There is debate in the recent literature concerning the impact of the location of stenosis in ICAD on outcome. Some reports have suggested that disease processes and outcomes vary by vessel location, potentially altering the natural history and indications for intervention. Here we have performed a comprehensive, critical review of the natural history of ICAD by vessel in an attempt to assess the differences in disease specific to each of the vascular territories. Our assessment concludes that only minor differences exist between patients with different vessels affected in vessel-specific ICAD. We have found that middle cerebral artery disease confers a lower mortality than vessel-specific ICAD in other intracranial vessels, asymptomatic disease follows a more benign course than symptomatic disease, andthat plaque progression or the detection of microemboli on transcranial Doppler may predict poor outcome. Given the expanding indications for treatment of ICAD and rapidly developing endovascular techniques to confront this disease, a thorough understanding of the natural history of ICAD aids the interventional neuroradiologist in determining when to treat and how to predict outcome in this patient population.展开更多
Chronic lymphocytic leukemia(CLL) is the most common leukemia in the western world. Despite significantadvances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemo...Chronic lymphocytic leukemia(CLL) is the most common leukemia in the western world. Despite significantadvances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor(BCR) and cytokine receptors. A better understanding of the pathogenesis of the disease, the underlying biology of the CLL-cell and the roles of the tumour microenvironment has provided the rationale for trials of a range of novel, more targeted therapeutic agents. In particular, clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR signaling pathway respectively, have shown extremely promising results. Here we review the current literature on the key signaling pathways and interactions of CLL cells that mediate the survival and proliferation of the leukemic cells. For each we describe the results of the recent clinical trials and in vitro studies of novel therapeutic agents.展开更多
Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can r...Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary(16%-50%), bile duct(5%-39%), and duodenal cancer(3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival(29-47 mo and 22-54 mo) compared to pancreatic cancer(13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers, KRAS mutation occurs in only approximately a third of ampullary and duodenal cancers. Future clinical trials should group ampullary cancers of intestinal origin and duodenal cancers together given their similarities and their response to fluoropyrimidine therapy in combination with oxaliplatin. The addition of anti-epidermal growth factor receptor therapy in this group warrants study.展开更多
AIM:To compare the prevalence of Functional gastrointestinal disorders(FGIDs)using ROMEⅢand ROMEⅡand to describe predictors of FGIDs among eating disorder(ED)patients.METHODS:Two similar cohorts of female ED inpatie...AIM:To compare the prevalence of Functional gastrointestinal disorders(FGIDs)using ROMEⅢand ROMEⅡand to describe predictors of FGIDs among eating disorder(ED)patients.METHODS:Two similar cohorts of female ED inpatients,aged 17-50 years,with no organic gastrointestinal or systemic disorders,completed either the ROMEⅢ(n=100)or the ROMEⅡ(n=160)questionnaire on admission for ED treatment.The two ROME cohorts were compared on continuous demographic variables(e.g.,age,BMI)using Student’s t-tests,and on categorical variables(e.g.,ED diagnosis)usingχ2-tests.The relationship between ED diagnostic subtypes and FGID categories was explored usingχ2-tests.Age,BMI,and psychological and behavioural predictors of the common(prevalence greater than 20%)ROMEⅢFGIDs were tested using logistic regression analyses.RESULTS:The criteria for at least one FGID were fulfilled by 83%of the ROMEⅢcohort,and 94%of the ROMEⅡcohort.There were no significant differences in age,BMI,lowest ever BMI,ED diagnostic subtypes or ED-related quality of life(QOL)scores between ROMEⅡand ROMEⅢcohorts.The most prevalent FGIDs using ROMEⅢwere postprandial distress syndrome(PDS)(45%)and irritable bowel syndrome(IBS)(41%),followed by unspecified functional bowel disorders(U-FBD)(24%),and functional heartburn(FH)(22%).There was a 29%or 46%increase(depending on presence or absence of cyclic vomiting)in functional gastroduodenal disorders because of the introduction of PDS in ROMEⅢcompared to ROMEⅡ.There was a 35%decrease in functional bowel disorders(FBD)in RomeⅢ(excluding U-FBD)compared to ROMEⅡ.The most significant predictor of PDS was starvation(P=0.008).The predictor of FH(P=0.021)and U-FBD(P=0.007)was somatisation,and of IBS laxative use(P=0.025).Age and BMI were not significant predictors.The addition of the 6-mo duration of symptoms requirement for a diagnosis in ROMEⅢadded precision to many FGIDs.CONCLUSION:ROMEⅢconfers higher precision in diagnosing FGIDs but self-induced vomiting should be excluded from the diagnosis of cyclic vomiting.Psychological factors appear to be more influential in ROMEⅡthan ROMEⅢ.展开更多
AIM:To compare the demographic and clinical features of different manometric subsets of ineffective oesophageal motility(IOM;defined as ≥ 30% wet swallows with distal contractile amplitude < 30 mmHg) ,and to deter...AIM:To compare the demographic and clinical features of different manometric subsets of ineffective oesophageal motility(IOM;defined as ≥ 30% wet swallows with distal contractile amplitude < 30 mmHg) ,and to determine whether the prevalence of gastro-oesophageal reflux differs between IOM subsets. METHODS:Clinical characteristics of manometric subsets were determined in 100 IOM patients(73 female,median age 58 years) and compared to those of 100 age-and gender-matched patient controls with oesophageal symptoms,but normal manometry. Supine oesophageal manometry was performed with an eight-channel DentSleeve water-perfused catheter,and an ambulatory pH study assessed gastro-oesophageal reflux. RESULTS:Patients in the IOM subset featuring a majority of low-amplitude simultaneous contractions(LASC) experienced less heartburn(prevalence 26%) ,but more dysphagia(57%) than those in the IOM subset featuring low-amplitude propagated contractions(LAP;heartburn 70%,dysphagia 24%;both P ≤ 0.01) . LASC patients also experienced less heartburn and more dysphagia than patient controls(heartburn 68%,dysphagia 11%;both P < 0.001) . The prevalence of heartburn and dysphagia in IOM patients featuring a majority of non-transmitted sequences(NT) was 54%(P = 0.04 vs LASC) and 36%(P < 0.01 vs controls) ,respectively. No differences inage and gender distribution,chest pain prevalence,acid exposure time(AET) and symptom/reflux association existed between IOM subsets,or between subsets and controls. CONCLUSION:IOM patients with LASC exhibit a different symptom profile to those with LAP,but do not differ in gastro-oesophageal reflux prevalence. These findings raise the possibility of different pathophysiological mechanisms in IOM subsets,which warrants further investigation.展开更多
Cardiovascular magnetic resonance(CMR) represents the reference standard for cardiac morphology and function assessment. Since introduction in 2009, CMR feature tracking(CMR-FT) has become a frequently used tool in th...Cardiovascular magnetic resonance(CMR) represents the reference standard for cardiac morphology and function assessment. Since introduction in 2009, CMR feature tracking(CMR-FT) has become a frequently used tool in the assessment of myocardial deformation and wall motion on the basis of routinely acquired b-SSFP cine images. Extensive validation has led to excellent intra-and inter-observer as well as inter-study reproducibility. CMR-FT derived myocardial deformation indices such as left ventricular(LV) strain have been shown to be impaired in cardiac diseases such as cardiomyopathies as well as myocardial infarction. Although LV ejection fraction(LVEF) is the routinely and frequently utilized parameter for systolic myocardial function assessment and major adverse clinical event(MACE) prediction, it fails to assess regional differences. Recently, LV strain has emerged as a superior measure for risk assessment and MACE prediction as compared to the established markers e.g., LVEF. This editorial aims to elucidate current discussions in the field of strain assessment in myocardial infarction in the light of recent data from a large prospective multicentre CMR study.展开更多
Mucin-like glycoproteins have established roles in epithelial boundary protection and lubricative roles in some tissues.This mini-review illustrates alternative functional roles which rely on keratan sulphate and sial...Mucin-like glycoproteins have established roles in epithelial boundary protection and lubricative roles in some tissues.This mini-review illustrates alternative functional roles which rely on keratan sulphate and sialic acid modifications to mucin glycopolymers which convey charge properties suggestive of novel electroconductive properties not previously ascribed to these polymers.Many tumour cells express mucin-like glycopolymers modified with highly sulphated keratan sulphate and sialic which can be detected using diagnostic biosensors.The mucin-like keratan sulphate glycopolymer present in the ampullae of lorenzini is a remarkable sensory polymer which elasmobranch fish(sharks,rays,skate) use to detect weak electrical fields emitted through muscular activity of prey fish.Information on the proton gradients is conveyed to neuromast cells located at the base of the ampullae and mechanotransduced to neural networks.This ampullae keratan sulphate sensory gel is the most sensitive proton gradient detection polymer known in nature.This process is known as electrolocation,and allows the visualization of prey fish under conditions of low visibility.The bony fish have similar electroreceptors located along their lateral lines which consist of neuromast cells containing sensory hairs located within a cupula which contains a sensory gel polymer which detects distortions in fluid flow in channels within the lateral lines and signals are sent back to neural networks providing information on the environment around these fish.One species of dolphin,the Guiana dolphin,has electrosensory pits in its bill with similar roles to the ampullae but which have evolved from its vibrissal system.Only two terrestrial animals can undertake electrolocation,these are the Duck-billed platypus and long and short nosed Echidna.In this case the electrosensor is a highly evolved innervated mucous gland.The platypus has 40,000 electroreceptors around its bill through which it electrolocates food species.The platypus has poor eyesight,is a nocturnal feeder and closes its eyes,nostrils and ears when it hunts,so electrolocation is an essential sensory skill.Mammals also have sensory cells containing stereocilia which are important in audition in the organ of corti of the cochlea and in olfaction in the olfactory epithelium.The rods and cones of the retina also have an internal connecting cilium with roles in the transport of phototransduced chemical signals and activation of neurotransmitter release to the optic nerve.Mucin-like glycopolymer gels surround the stereocilia of these sensory hair cells but these are relatively poorly characterized however they deserve detailed characterization since they may have important functional attributes.展开更多
Aims: The EORTC-NCI study investigating the addition of temozolomide trial to standard radiation therapy has demonstrated improved duration of survival in patients with Glioblastoma multiforme (GBM). With longer survi...Aims: The EORTC-NCI study investigating the addition of temozolomide trial to standard radiation therapy has demonstrated improved duration of survival in patients with Glioblastoma multiforme (GBM). With longer survival duration, there is the potential for latent RT morbidity, not previously seen in historical patients. This study evaluates the potential dosimetric advantages of utilising IMRT over 3D-conformal RT in such patients. Methods: 10 consecutive patients with GBM formally screened for a clinical study over a two-month period were planned and treated with IMRT utilising daily on-board imaging (OBI). The EORTC protocol dosimetric criteria and constraints were used in target delineation and planning. For each patient, a 3DCRT plan was also produced. Endpoints for dosimetric evaluation analysed related to tumour dose: mean PTV60 dose (mPTV60Dose), Conformity Index (CI);and normal tissue dose: mean normal brain dose (mBrainDose) and V40 Brain (Brainv40). IGRT endpoints were the median isocentre shifts required in 3 axes measured in one direction. The variation between the IMRT and 3DCRT dosimetric endpoints was examined using Wilcoxon analysis. Results: The 10 patients had tumours located in temporal (3), parietal (3), occipital (2) and callosal (2) regions. The median PTV and normal brain volumes were 308.1 cm3 and 1077.5 cm3 respectively. The IMRT dosimetry was significantly improved in all endpoints specifically CI (p = 0.002), mPTV60Dose (p = 0.004), mBrainDose (p = 0.002) and Brainv40 (p = 0.019). OBI directed isocentre measurements in the patient group were available for 230 treatments. The median shifts (and 95% C.I.s) were 0.1 cm vertical (0.1 - 0.2), 0.1 cm longitudinal (0.1 - 0.2) and 0.2 cm lateral (0.2 - 0.2). At a minimum follow-up of 2 years’ post diagnosis, the median survival of the group is 18.0 months (95% CI: 13.4 - 22.6 months). Conclusion: IMRT for GBM produces significant dosimetric advantages in relation to planning target volume and normal tissue dose compared with 3D conformal plans. The data also confirm the accuracy of IMRT technique for CNS with IGRT delivery utilising OBI demonstrating minimal deviation from planned to treated isocentre.展开更多
Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective pr...Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC's function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.展开更多
Pediatric cholesteatoma occurs in one of two forms:congenital cholesteatoma,developing from embryonic epidermal cell rests or acquired cholesteatoma,associated with a focal defect in the tympanic membrane.This disease...Pediatric cholesteatoma occurs in one of two forms:congenital cholesteatoma,developing from embryonic epidermal cell rests or acquired cholesteatoma,associated with a focal defect in the tympanic membrane.This disease has been traditionally managed with the operating microscope,often requiring mastoidectomy for adequate visualization of and access to the middle ear and mastoid cavities.Recently,advances in endoscopic equipment have enabled otologists to manage most cases of pediatric cholesteatoma via a minimally-invasive,transcanal endoscopic approach.This review discusses the current literature relating to the etiopathogenesis,assessment and endoscopic management of pediatric cholesteatoma.Early outcomes of endoscopic treatment,emerging trends and technologies are also reviewed.展开更多
Endoscopic ear surgery(EES) is an exciting, rapidly developing and innovative field of otologic surgery.Technically and conceptually, EES is a significant departure from traditional microscopic transcanal approaches t...Endoscopic ear surgery(EES) is an exciting, rapidly developing and innovative field of otologic surgery.Technically and conceptually, EES is a significant departure from traditional microscopic transcanal approaches to the middle ear and canal that has shown very positive results with respect to patient outcomes. This review serves as a primer for the otologist and otology resident embarking on EES and discusses the theory surrounding the learning process, the optical chain for endoscopic surgery as well as other important underlying principles.展开更多
AIM To determine whether recent evidence-based United States polices on male circumcision(MC) apply to comparable Anglophone countries,Australia and New Zealand.METHODS Articles in 2005 through 2015 were retrieved fro...AIM To determine whether recent evidence-based United States polices on male circumcision(MC) apply to comparable Anglophone countries,Australia and New Zealand.METHODS Articles in 2005 through 2015 were retrieved from PubM ed using the keyword "circumcision" together with 36 relevant subtopics.A further PubM ed search was performed for articles published in 2016.Searches of the EMBASE and Cochrane databases did not yield additional citable articles.Articles were assessed for quality and those rated 2+ and above according to the Scottish Intercollegiate Grading System were studied further.The most relevant andrepresentative of the topic were included.Bibliographies were examined to retrieve further key references.Randomized controlled trials,recent high quality systematic reviews or meta-analyses(level 1++ or 1+ evidence) were prioritized for inclusion.A risk-benefit analysis of articles rated for quality was performed.For efficiency and reliability,recent randomized controlled trials,metaanalyses,high quality systematic reviews and large welldesigned studies were used if available.Internet searches were conducted for other relevant information,including policies and Australian data on claims under Medicare for MC.RESULTS Evidence-based policy statements by the American Academy of Pediatrics(AAP) and the Centers for Disease Control and Prevention(CDC) support infant and later age male circumcision(MC) as a desirable public health measure.Our systematic review of relevant literature over the past decade yielded 140 journal articles that met our inclusion criteria.Together,these showed that early infant MC confers immediate and lifelong benefits by protecting against urinary tract infections having potential adverse long-term renal effects,phimosis that causes difficult and painful erections and "ballooning" during urination,inflammatory skin conditions,inferior penile hygiene,candidiasis,various sexually transmissible infections in both sexes,genital ulcers,and penile,prostate and cervical cancer.Our risk-benefit analysis showed that benefits exceeded procedural risks,which are predominantly minor,by up to 200 to 1.We estimated that more than 1 in 2 uncircumcised males will experience an adverse foreskin-related medical condition over their lifetime.Wide-ranging evidence from surveys,physiological measurements,and the anatomical location of penile sensory receptors responsible for sexual sensation strongly and consistently suggested that MC has no detrimental effect on sexual function,sensitivity or pleasure.United States studies showed that early infant MC is cost saving.The evidence supporting early infant MC has further strengthened since the positive AAP and CDC reviews.CONCLUSION Affirmative MC policies are needed in Australia and New Zealand.Routine provision of accurate,unbiased education,and access in public hospitals,will maximize health and financial benefits.展开更多
Objective. Gastrointestinal symptoms that occur without evidence of structural gastrointestinal disease are a well- recognized feature of patients with eating disorders (EDs). Despite this, the spectrum and predictors...Objective. Gastrointestinal symptoms that occur without evidence of structural gastrointestinal disease are a well- recognized feature of patients with eating disorders (EDs). Despite this, the spectrum and predictors of specific functional gastrointestinal disorders (FGIDs), documented using standardized and validated questionnaires, have received little attention. The aims of the study were to describe the prevalence and type of FGIDs in patients suffering from anorexia nervosa (AN), bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS), and to determine the relationships between psychological features, eating- disordered attitudes and behaviours, demographic characteristics and the type and number of FGIDs present. Material and methods. A total of 101 consecutive female patients admitted to an eating disorder unit (AN 44% , BN 22% , EDNOS 34% , mean age 21 years) completed the Rome II modular questionnaire and a range of other validated self- reported questionnaires detailing illness history, psychological features and eating and exercise behaviour. Results. The criteria for at least one FGID were fulfilled by 98% of the sample. The most prevalent FGIDs were irritable bowel syndrome (IBS: 52% ), functional heartburn (FH: 51% ), functional abdominal bloating (31% ), functional constipation (FC: 24% ), functional dysphagia (23% ) and functional anorectal pain disorder (FAno: 22% ); 52% of the sample satisfied the criteria for at least three coexistent FGIDs. Psychological variables (somatization, neuroticism, state and trait anxiety), age and binge eating were significant predictors of specific, and ≥ 3 coexistent FGIDs. Other disordered eating characteristics, including body mass index, were not predictors. Conclusions. In patients with EDs, specific psychological traits predict FGID type and the presence of multiple coexistent FGIDs. These findings support the role of specific psychological features as important contributors to certain FGIDs.展开更多
基金Research protocol was approved by the Northern Sydney Local Health District ethics committee as a negligible/Low risk project.This study was not a trial or animal study.
文摘BACKGROUND The management of high-grade pancreatic trauma is controversial.AIM To review our single-institution experience on the surgical management of blunt and penetrating pancreatic injuries.METHODS A retrospective review of records was performed on all patients undergoing surgical intervention for high-grade pancreatic injuries [American Association for the Surgery of Trauma(AAST) Grade Ⅲor greater] at the Royal North Shore Hospital in Sydney between January 2001 and December 2022. Morbidity and mortality outcomes were reviewed, and major diagnostic and operative challenges were identified.RESULTS Over a twenty-year period, 14 patients underwent pancreatic resection for highgrade injuries. Seven patients sustained AAST Grade Ⅲinjuries and 7 were classified as Grades Ⅳ or Ⅴ. Nine underwent distal pancreatectomy and 5 underwent pancreaticoduodenectomy(PD). Overall, there was a predominance of blunt aetiologies(11/14). Concomitant intra-abdominal injuries were observed in 11 patients and traumatic haemorrhage in 6 patients. Three patients developed clinically relevant pancreatic fistulas and there was one in-hospital mortality secondary to multi-organ failure. Among stable presentations, pancreatic ductal injuries were missed in two-thirds of cases(7/12) on initial computed tomography imaging and subsequently diagnosed on repeat imaging or endoscopic retrograde cholangiopancreatography. All patients who sustained complex pancreaticoduodenal trauma underwent PD without mortality. The management of pancreatic trauma is evolving. Our experience provides valuable and locally relevant insights into future management strategies.CONCLUSION We advocate that high-grade pancreatic trauma should be managed in high-volume hepatopancreato-biliary specialty surgical units. Pancreatic resections including PD may be indicated and safely performed with appropriate specialist surgical, gastroenterology, and interventional radiology support in tertiary centres.
文摘BACKGROUND Juvenile polyposis syndrome(JPS)is a rare hereditary polyposis disease frequently associated with an autosomal-dominant variant of the SMAD4 or BMPR1A gene.It often manifests with symptoms in children and adolescents and is infrequently diagnosed in asymptomatic adults.Establishing the diagnosis is important as patients with JPS have a high risk of developing gastrointestinal cancer and require genetic counselling and close routine follow-up.CASE SUMMARY We report on the case of a 56-year-old female diagnosed with JPS after genetic testing revealed a rare variant of the BMPR1A gene BMPR1A c.1409T>C(p.Met470Thr).She was initially referred for colonoscopy by her general practitioner after testing positive on a screening faecal immunochemical test and subsequently found to have polyposis throughout the entire colorectum on her index screening colonoscopy.The patient was asymptomatic with a normal physical examination and no related medical or family history.Blood tests revealed only mild iron deficiency without anemia.To date,there has only been one other reported case of JPS with the same genetic variant.Subsequent colonoscopies were organised for complete polyp clearance and the patient was returned for surveillance follow-up.CONCLUSION JPS patients can present with no prior symptoms or family history.Genetic testing plays an important diagnostic role guiding management.
文摘AIM:To describe our own experience with pyogenic liver abscesses over the past 10 years and investigate the risk factors associated with failure of initial percutaneous therapy.METHODS:A retrospective study of records of 63 PLA patients presenting between 1998 and 2008 to Australian tertiary referral centre,were reviewed.Amoebic and hydatid abscesses were excluded.Demographic,clinical,radiological,and microbiological characteristics,as well as surgical/radiological interventions,were recorded.RESULTS:Sixty-three patients(42 males,21 females) aged 65(±14) years[mean±(SD) ]had prodromal symptoms for a median(interquartile range;IQR) of 7(5-14) d.Only 59%of patients were febrile at presentation;however,the serum C-reactive protein was elevated in all 47 in whom it was measured.Liver function tests were non-specifically abnormal.67%of patients had a solitary abscess,while 32%had>3 abscesses with a median(IQR) diameter of 6.3(4-9) cm.Causative organisms were:Streptococcus milleri 25%,Klebsiella pneumoniae 21%,and Escherichia coli 16%.A presumptive cryptogenic cause was most common (34%).Four patients died in this series:one from sepsis,two from advanced cancer,and one from acute myocardial infarction.The initial procedure was radiological aspiration±drainage in 54 and surgery in two patients.17%underwent surgical management during their hospitalization.Serum hypoalbuminaemia[mean (95%CI) :32(29-35) g/L vs 28(25-31) g/L,P=0.045] on presentation was found to be the only factor related to failure of initial percutaneous therapy on univariate analysis.CONCLUSION:PLA is a diagnostic challenge,because the presentation of this condition is non-specific.Intravenous antibiotics and radiological drainage in the first instance allows resolution of most PLAs;However,a small proportion of patients still require surgical drainage.
文摘Due to the inherent relationship between the immune system and the hepatitis B virus(HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation(HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations' guidelines and the best available evidence to date.
文摘Gastrointestinal bleeding is a common problem encountered in the emergency department and in the primary care setting. Acute or overt gastrointestinal bleeding is visible in the form of hematemesis, melena or hematochezia. Chronic or occult gastrointestinal bleeding is notapparent to the patient and usually presents as positive fecal occult blood or iron deficiency anemia. Obscure gastrointestinal bleeding is recurrent bleeding when the source remains unidentified after upper endoscopy and colonoscopic evaluation and is usually from the small intestine. Accurate clinical diagnosis is crucial and guides definitive investigations and interventions. This review summarizes the overall diagnostic approach to gastrointestinal bleeding and provides a practical guide for clinicians.
文摘BACKGROUND:Pancreatoduodenectomy offers the only chance of cure for patients with periampullary cancers.This,however,is a major undertaking in most patients and is associated with a significant morbidity and mortality.A multidisciplinary approach to the workup and follow-up of patients undergoing pancreatoduodenectomy was initiated at our institution to improve the diagnosis,resection rate,mortality and morbidity.We undertook the study to assess the effect of this approach on diagnosis,resection rates and short-term outcomes such as morbidity and mortality.METHODS:A prospective database of patients presenting with periampullary cancers to a single surgeon between April 2004 and April 2010 was reviewed.All cases were discussed at a multidisciplinary meeting comprising surgeons,gastroenterologists,radiologists,oncologists,radiation oncologists,pathologists and nursing staff.A standardized investigation and management algorithm was followed.Complications were graded according to the Clavien-Dindo classification.RESULTS:A total of 295 patients with a periampullary lesion were discussed and 178 underwent pancreatoduodenectomy (resection rate 60%).Sixty-one patients (34%) required either a vascular or an additional organ resection.Eighty-nine patients experienced complications,of which the commonest was blood transfusion (12%).Thirty-four patients (19%) had major complications,i.e.grade 3 or above.There was no in-hospital,30-day or 60-day mortality.CONCLUSIONS:Pancreatoduodenectomy can safely be performed in high-volume centers with very low mortality.The surgeon’s role should be careful patient selection,intensive preoperative investigations,use of a team approach,and an unbiased discussion at a multidisciplinary meeting to optimize the outcome in these patients.
文摘Intracranial atherosclerotic disease (ICAD) contributes to a significant number of ischemic strokes. There is debate in the recent literature concerning the impact of the location of stenosis in ICAD on outcome. Some reports have suggested that disease processes and outcomes vary by vessel location, potentially altering the natural history and indications for intervention. Here we have performed a comprehensive, critical review of the natural history of ICAD by vessel in an attempt to assess the differences in disease specific to each of the vascular territories. Our assessment concludes that only minor differences exist between patients with different vessels affected in vessel-specific ICAD. We have found that middle cerebral artery disease confers a lower mortality than vessel-specific ICAD in other intracranial vessels, asymptomatic disease follows a more benign course than symptomatic disease, andthat plaque progression or the detection of microemboli on transcranial Doppler may predict poor outcome. Given the expanding indications for treatment of ICAD and rapidly developing endovascular techniques to confront this disease, a thorough understanding of the natural history of ICAD aids the interventional neuroradiologist in determining when to treat and how to predict outcome in this patient population.
文摘Chronic lymphocytic leukemia(CLL) is the most common leukemia in the western world. Despite significantadvances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor(BCR) and cytokine receptors. A better understanding of the pathogenesis of the disease, the underlying biology of the CLL-cell and the roles of the tumour microenvironment has provided the rationale for trials of a range of novel, more targeted therapeutic agents. In particular, clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR signaling pathway respectively, have shown extremely promising results. Here we review the current literature on the key signaling pathways and interactions of CLL cells that mediate the survival and proliferation of the leukemic cells. For each we describe the results of the recent clinical trials and in vitro studies of novel therapeutic agents.
文摘Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary(16%-50%), bile duct(5%-39%), and duodenal cancer(3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival(29-47 mo and 22-54 mo) compared to pancreatic cancer(13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers, KRAS mutation occurs in only approximately a third of ampullary and duodenal cancers. Future clinical trials should group ampullary cancers of intestinal origin and duodenal cancers together given their similarities and their response to fluoropyrimidine therapy in combination with oxaliplatin. The addition of anti-epidermal growth factor receptor therapy in this group warrants study.
文摘AIM:To compare the prevalence of Functional gastrointestinal disorders(FGIDs)using ROMEⅢand ROMEⅡand to describe predictors of FGIDs among eating disorder(ED)patients.METHODS:Two similar cohorts of female ED inpatients,aged 17-50 years,with no organic gastrointestinal or systemic disorders,completed either the ROMEⅢ(n=100)or the ROMEⅡ(n=160)questionnaire on admission for ED treatment.The two ROME cohorts were compared on continuous demographic variables(e.g.,age,BMI)using Student’s t-tests,and on categorical variables(e.g.,ED diagnosis)usingχ2-tests.The relationship between ED diagnostic subtypes and FGID categories was explored usingχ2-tests.Age,BMI,and psychological and behavioural predictors of the common(prevalence greater than 20%)ROMEⅢFGIDs were tested using logistic regression analyses.RESULTS:The criteria for at least one FGID were fulfilled by 83%of the ROMEⅢcohort,and 94%of the ROMEⅡcohort.There were no significant differences in age,BMI,lowest ever BMI,ED diagnostic subtypes or ED-related quality of life(QOL)scores between ROMEⅡand ROMEⅢcohorts.The most prevalent FGIDs using ROMEⅢwere postprandial distress syndrome(PDS)(45%)and irritable bowel syndrome(IBS)(41%),followed by unspecified functional bowel disorders(U-FBD)(24%),and functional heartburn(FH)(22%).There was a 29%or 46%increase(depending on presence or absence of cyclic vomiting)in functional gastroduodenal disorders because of the introduction of PDS in ROMEⅢcompared to ROMEⅡ.There was a 35%decrease in functional bowel disorders(FBD)in RomeⅢ(excluding U-FBD)compared to ROMEⅡ.The most significant predictor of PDS was starvation(P=0.008).The predictor of FH(P=0.021)and U-FBD(P=0.007)was somatisation,and of IBS laxative use(P=0.025).Age and BMI were not significant predictors.The addition of the 6-mo duration of symptoms requirement for a diagnosis in ROMEⅢadded precision to many FGIDs.CONCLUSION:ROMEⅢconfers higher precision in diagnosing FGIDs but self-induced vomiting should be excluded from the diagnosis of cyclic vomiting.Psychological factors appear to be more influential in ROMEⅡthan ROMEⅢ.
文摘AIM:To compare the demographic and clinical features of different manometric subsets of ineffective oesophageal motility(IOM;defined as ≥ 30% wet swallows with distal contractile amplitude < 30 mmHg) ,and to determine whether the prevalence of gastro-oesophageal reflux differs between IOM subsets. METHODS:Clinical characteristics of manometric subsets were determined in 100 IOM patients(73 female,median age 58 years) and compared to those of 100 age-and gender-matched patient controls with oesophageal symptoms,but normal manometry. Supine oesophageal manometry was performed with an eight-channel DentSleeve water-perfused catheter,and an ambulatory pH study assessed gastro-oesophageal reflux. RESULTS:Patients in the IOM subset featuring a majority of low-amplitude simultaneous contractions(LASC) experienced less heartburn(prevalence 26%) ,but more dysphagia(57%) than those in the IOM subset featuring low-amplitude propagated contractions(LAP;heartburn 70%,dysphagia 24%;both P ≤ 0.01) . LASC patients also experienced less heartburn and more dysphagia than patient controls(heartburn 68%,dysphagia 11%;both P < 0.001) . The prevalence of heartburn and dysphagia in IOM patients featuring a majority of non-transmitted sequences(NT) was 54%(P = 0.04 vs LASC) and 36%(P < 0.01 vs controls) ,respectively. No differences inage and gender distribution,chest pain prevalence,acid exposure time(AET) and symptom/reflux association existed between IOM subsets,or between subsets and controls. CONCLUSION:IOM patients with LASC exhibit a different symptom profile to those with LAP,but do not differ in gastro-oesophageal reflux prevalence. These findings raise the possibility of different pathophysiological mechanisms in IOM subsets,which warrants further investigation.
文摘Cardiovascular magnetic resonance(CMR) represents the reference standard for cardiac morphology and function assessment. Since introduction in 2009, CMR feature tracking(CMR-FT) has become a frequently used tool in the assessment of myocardial deformation and wall motion on the basis of routinely acquired b-SSFP cine images. Extensive validation has led to excellent intra-and inter-observer as well as inter-study reproducibility. CMR-FT derived myocardial deformation indices such as left ventricular(LV) strain have been shown to be impaired in cardiac diseases such as cardiomyopathies as well as myocardial infarction. Although LV ejection fraction(LVEF) is the routinely and frequently utilized parameter for systolic myocardial function assessment and major adverse clinical event(MACE) prediction, it fails to assess regional differences. Recently, LV strain has emerged as a superior measure for risk assessment and MACE prediction as compared to the established markers e.g., LVEF. This editorial aims to elucidate current discussions in the field of strain assessment in myocardial infarction in the light of recent data from a large prospective multicentre CMR study.
基金supported by the National Health and Medical Research Council Project,No.1004032
文摘Mucin-like glycoproteins have established roles in epithelial boundary protection and lubricative roles in some tissues.This mini-review illustrates alternative functional roles which rely on keratan sulphate and sialic acid modifications to mucin glycopolymers which convey charge properties suggestive of novel electroconductive properties not previously ascribed to these polymers.Many tumour cells express mucin-like glycopolymers modified with highly sulphated keratan sulphate and sialic which can be detected using diagnostic biosensors.The mucin-like keratan sulphate glycopolymer present in the ampullae of lorenzini is a remarkable sensory polymer which elasmobranch fish(sharks,rays,skate) use to detect weak electrical fields emitted through muscular activity of prey fish.Information on the proton gradients is conveyed to neuromast cells located at the base of the ampullae and mechanotransduced to neural networks.This ampullae keratan sulphate sensory gel is the most sensitive proton gradient detection polymer known in nature.This process is known as electrolocation,and allows the visualization of prey fish under conditions of low visibility.The bony fish have similar electroreceptors located along their lateral lines which consist of neuromast cells containing sensory hairs located within a cupula which contains a sensory gel polymer which detects distortions in fluid flow in channels within the lateral lines and signals are sent back to neural networks providing information on the environment around these fish.One species of dolphin,the Guiana dolphin,has electrosensory pits in its bill with similar roles to the ampullae but which have evolved from its vibrissal system.Only two terrestrial animals can undertake electrolocation,these are the Duck-billed platypus and long and short nosed Echidna.In this case the electrosensor is a highly evolved innervated mucous gland.The platypus has 40,000 electroreceptors around its bill through which it electrolocates food species.The platypus has poor eyesight,is a nocturnal feeder and closes its eyes,nostrils and ears when it hunts,so electrolocation is an essential sensory skill.Mammals also have sensory cells containing stereocilia which are important in audition in the organ of corti of the cochlea and in olfaction in the olfactory epithelium.The rods and cones of the retina also have an internal connecting cilium with roles in the transport of phototransduced chemical signals and activation of neurotransmitter release to the optic nerve.Mucin-like glycopolymer gels surround the stereocilia of these sensory hair cells but these are relatively poorly characterized however they deserve detailed characterization since they may have important functional attributes.
文摘Aims: The EORTC-NCI study investigating the addition of temozolomide trial to standard radiation therapy has demonstrated improved duration of survival in patients with Glioblastoma multiforme (GBM). With longer survival duration, there is the potential for latent RT morbidity, not previously seen in historical patients. This study evaluates the potential dosimetric advantages of utilising IMRT over 3D-conformal RT in such patients. Methods: 10 consecutive patients with GBM formally screened for a clinical study over a two-month period were planned and treated with IMRT utilising daily on-board imaging (OBI). The EORTC protocol dosimetric criteria and constraints were used in target delineation and planning. For each patient, a 3DCRT plan was also produced. Endpoints for dosimetric evaluation analysed related to tumour dose: mean PTV60 dose (mPTV60Dose), Conformity Index (CI);and normal tissue dose: mean normal brain dose (mBrainDose) and V40 Brain (Brainv40). IGRT endpoints were the median isocentre shifts required in 3 axes measured in one direction. The variation between the IMRT and 3DCRT dosimetric endpoints was examined using Wilcoxon analysis. Results: The 10 patients had tumours located in temporal (3), parietal (3), occipital (2) and callosal (2) regions. The median PTV and normal brain volumes were 308.1 cm3 and 1077.5 cm3 respectively. The IMRT dosimetry was significantly improved in all endpoints specifically CI (p = 0.002), mPTV60Dose (p = 0.004), mBrainDose (p = 0.002) and Brainv40 (p = 0.019). OBI directed isocentre measurements in the patient group were available for 230 treatments. The median shifts (and 95% C.I.s) were 0.1 cm vertical (0.1 - 0.2), 0.1 cm longitudinal (0.1 - 0.2) and 0.2 cm lateral (0.2 - 0.2). At a minimum follow-up of 2 years’ post diagnosis, the median survival of the group is 18.0 months (95% CI: 13.4 - 22.6 months). Conclusion: IMRT for GBM produces significant dosimetric advantages in relation to planning target volume and normal tissue dose compared with 3D conformal plans. The data also confirm the accuracy of IMRT technique for CNS with IGRT delivery utilising OBI demonstrating minimal deviation from planned to treated isocentre.
基金Supported by Ulysses Club Arthritis Research Fellowshipand Henry Langley Arthritis Research Fellowship respectively,to McKelvey K and Xue M
文摘Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC's function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.
文摘Pediatric cholesteatoma occurs in one of two forms:congenital cholesteatoma,developing from embryonic epidermal cell rests or acquired cholesteatoma,associated with a focal defect in the tympanic membrane.This disease has been traditionally managed with the operating microscope,often requiring mastoidectomy for adequate visualization of and access to the middle ear and mastoid cavities.Recently,advances in endoscopic equipment have enabled otologists to manage most cases of pediatric cholesteatoma via a minimally-invasive,transcanal endoscopic approach.This review discusses the current literature relating to the etiopathogenesis,assessment and endoscopic management of pediatric cholesteatoma.Early outcomes of endoscopic treatment,emerging trends and technologies are also reviewed.
文摘Endoscopic ear surgery(EES) is an exciting, rapidly developing and innovative field of otologic surgery.Technically and conceptually, EES is a significant departure from traditional microscopic transcanal approaches to the middle ear and canal that has shown very positive results with respect to patient outcomes. This review serves as a primer for the otologist and otology resident embarking on EES and discusses the theory surrounding the learning process, the optical chain for endoscopic surgery as well as other important underlying principles.
文摘AIM To determine whether recent evidence-based United States polices on male circumcision(MC) apply to comparable Anglophone countries,Australia and New Zealand.METHODS Articles in 2005 through 2015 were retrieved from PubM ed using the keyword "circumcision" together with 36 relevant subtopics.A further PubM ed search was performed for articles published in 2016.Searches of the EMBASE and Cochrane databases did not yield additional citable articles.Articles were assessed for quality and those rated 2+ and above according to the Scottish Intercollegiate Grading System were studied further.The most relevant andrepresentative of the topic were included.Bibliographies were examined to retrieve further key references.Randomized controlled trials,recent high quality systematic reviews or meta-analyses(level 1++ or 1+ evidence) were prioritized for inclusion.A risk-benefit analysis of articles rated for quality was performed.For efficiency and reliability,recent randomized controlled trials,metaanalyses,high quality systematic reviews and large welldesigned studies were used if available.Internet searches were conducted for other relevant information,including policies and Australian data on claims under Medicare for MC.RESULTS Evidence-based policy statements by the American Academy of Pediatrics(AAP) and the Centers for Disease Control and Prevention(CDC) support infant and later age male circumcision(MC) as a desirable public health measure.Our systematic review of relevant literature over the past decade yielded 140 journal articles that met our inclusion criteria.Together,these showed that early infant MC confers immediate and lifelong benefits by protecting against urinary tract infections having potential adverse long-term renal effects,phimosis that causes difficult and painful erections and "ballooning" during urination,inflammatory skin conditions,inferior penile hygiene,candidiasis,various sexually transmissible infections in both sexes,genital ulcers,and penile,prostate and cervical cancer.Our risk-benefit analysis showed that benefits exceeded procedural risks,which are predominantly minor,by up to 200 to 1.We estimated that more than 1 in 2 uncircumcised males will experience an adverse foreskin-related medical condition over their lifetime.Wide-ranging evidence from surveys,physiological measurements,and the anatomical location of penile sensory receptors responsible for sexual sensation strongly and consistently suggested that MC has no detrimental effect on sexual function,sensitivity or pleasure.United States studies showed that early infant MC is cost saving.The evidence supporting early infant MC has further strengthened since the positive AAP and CDC reviews.CONCLUSION Affirmative MC policies are needed in Australia and New Zealand.Routine provision of accurate,unbiased education,and access in public hospitals,will maximize health and financial benefits.
文摘Objective. Gastrointestinal symptoms that occur without evidence of structural gastrointestinal disease are a well- recognized feature of patients with eating disorders (EDs). Despite this, the spectrum and predictors of specific functional gastrointestinal disorders (FGIDs), documented using standardized and validated questionnaires, have received little attention. The aims of the study were to describe the prevalence and type of FGIDs in patients suffering from anorexia nervosa (AN), bulimia nervosa (BN) and eating disorders not otherwise specified (EDNOS), and to determine the relationships between psychological features, eating- disordered attitudes and behaviours, demographic characteristics and the type and number of FGIDs present. Material and methods. A total of 101 consecutive female patients admitted to an eating disorder unit (AN 44% , BN 22% , EDNOS 34% , mean age 21 years) completed the Rome II modular questionnaire and a range of other validated self- reported questionnaires detailing illness history, psychological features and eating and exercise behaviour. Results. The criteria for at least one FGID were fulfilled by 98% of the sample. The most prevalent FGIDs were irritable bowel syndrome (IBS: 52% ), functional heartburn (FH: 51% ), functional abdominal bloating (31% ), functional constipation (FC: 24% ), functional dysphagia (23% ) and functional anorectal pain disorder (FAno: 22% ); 52% of the sample satisfied the criteria for at least three coexistent FGIDs. Psychological variables (somatization, neuroticism, state and trait anxiety), age and binge eating were significant predictors of specific, and ≥ 3 coexistent FGIDs. Other disordered eating characteristics, including body mass index, were not predictors. Conclusions. In patients with EDs, specific psychological traits predict FGID type and the presence of multiple coexistent FGIDs. These findings support the role of specific psychological features as important contributors to certain FGIDs.