BACKGROUND Liver disease incidence and hence demand on hepatology services is increasing.AIM To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology s...BACKGROUND Liver disease incidence and hence demand on hepatology services is increasing.AIM To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology services.METHODS The registry is populated by International Classification of Diseases-10(ICD-10)code diagnoses for residents derived from mortality data and inpatient/day case activity between 1999-2019.Pseudo-anonymised linkage of:(1)Causative diagnoses;(2)Cirrhosis;(3)Portal hypertension;(4)Decompensation;and(5)Liver cancer diagnoses enabled tracking liver disease progression.RESULTS The population of Wales in 2019 was 3.1 million.Between 1999 and 201973054 individuals were diagnosed with a hepatic disorder,including 18633 diagnosed with cirrhosis,10965 with liver decompensation and 2316 with hepatocellular carcinoma(HCC).Over 21 years the incidence of liver diseases increased 3.6 fold,predominantly driven by a 10 fold increase in non-alcoholic fatty liver disease(NAFLD);the leading cause of liver disease from 2014.The incidence of cirrhosis,decompensation,HCC,and allcause mortality tripled.Liver-related mortality doubled.Alcohol-related liver disease(ArLD),autoimmune liver disease and congestive hepatopathy were associated with the highest rates of decompensation and all-cause mortality.CONCLUSION A 10 fold increase in NAFLD incidence is driving a 3.6 fold increase in liver disease in Wales over 21 years.Liver-related morbidity and mortality rose more slowly reflecting the lower progression rate in NAFLD.Incidence of ArLD remained stable but was associated with the highest rates of liver-related and all-cause mortality.展开更多
Over the last 12 years, the Wales Cancer Biobank (WCB) has consented to more than 2000 patients with colorectal cancer (CRC). From these patients, clinical data has been collected and patients have been followed throu...Over the last 12 years, the Wales Cancer Biobank (WCB) has consented to more than 2000 patients with colorectal cancer (CRC). From these patients, clinical data has been collected and patients have been followed through their cancer journey. Clinical data from these patients have been analyzed to identify any correlation between disease grade and outcome. In a small cohort, consisting of 407 patients, WCB has performed genetic analysis on patient primary tumor samples, identifying and characterizing mutations in the KRAS, NRAS, BRAF, PIK3CA and TP53 genes. The majority of patients with CRC who were consented to WCB were male with a mean age of 69 years and received surgery as the primary treatment for their disease. Pathology and disease-free survival data confirmed worse prognoses associated with more advanced disease. Heterogeneity within the primary tumor was explored in a subgroup of patients. Analysis of the KRAS and TP53 genes confirmed that more than 40% of CRC patients who were tested, harbored a genetic mutation within these genes in their primary tumor. Due to the limited sample size tested, most mutations did not show significant differences in disease-free survival, however, mutation of the BRAF gene did show a decrease in the disease specific survival, in keeping with the published data. Analysis of the patients diagnosed with CRC within the Biobank has provided us with valuable information on the status of CRC disease and treatment within the Welsh population. Over 12 years of consenting, we have witnessed significant changes in the information that researchers are interested in when sourcing samples for translational research. The development of new drugs that are tailored to the genetics of a cancer is emerging and at WCB we are focusing our collections on samples and data that meet the needs of this ever-evolving field.展开更多
The majority of proximal humerus fractures are lowenergy osteoporotic injuries in the elderly and their incidence is increasing in the light of an ageing population. The diversity of fracture patterns encountered rend...The majority of proximal humerus fractures are lowenergy osteoporotic injuries in the elderly and their incidence is increasing in the light of an ageing population. The diversity of fracture patterns encountered renders objective classification of prognostic value challenging. Non-operative management has been associated with good functional outcomes in stable, minimally displaced and certain types of displaced fractures.Absolute indications for surgery are infrequent and comprise compound, pathological, multi-fragmentary head-splitting fractures and fracture dislocations, as well as those associated with neurovascular injury. A constantly expanding range of reconstructive and replacement options however has been extending the indications for surgical management of complex proximal humerus fractures. As a result, management decisions are becoming increasingly complicated, in an attempt to provide the best possible treatment for each indi-vidual patient, that will successfully address their specific fracture configuration, comorbidities and functional expectations. Our aim was to review the management options available for the full range of proximal humerus fractures in adults, along with their specific advantages, disadvantages and outcomes.展开更多
Atrial fibrillation(AF) is the most common cardiac arrhythmia and a huge public health burden associated with significant morbidity and mortality. For decades an increasing number of patients have undergone surgical t...Atrial fibrillation(AF) is the most common cardiac arrhythmia and a huge public health burden associated with significant morbidity and mortality. For decades an increasing number of patients have undergone surgical treatment of AF, mainly during concomitant cardiac surgery. This has sparked a drive for conducting further studies and researching this field. With the cornerstone Cox-Maze III "cut and sew" procedure being technically challenging, the focus in current literature has turned towards less invasive techniques. The introduction of ablative devices has revolutionised the surgical management of AF, moving away from the traditional surgical lesions. The hybrid procedure, a combination of catheter and surgical ablation is another promising new technique aiming to improve outcomes. Despite the increasing number of studies looking at various aspects of the surgical management of AF, the literature would benefit from more uniformly conducted randomised control trials.展开更多
BACKGROUND Achieving a clear resection margins for low rectal cancer is technically challenging.Transanal approach to total mesorectal excision(TME)was introduced in order to address the challenges associated with the...BACKGROUND Achieving a clear resection margins for low rectal cancer is technically challenging.Transanal approach to total mesorectal excision(TME)was introduced in order to address the challenges associated with the laparoscopic approach in treating low rectal cancers.However,previous meta-analyses have included mixed population with mid and low rectal tumours when comparing both approaches which has made the interpretation of the real differences between two approaches in treating low rectal cancer difficult.AIM To investigate the outcomes of transanal TME(TaTME)and laparoscopic TME(LaTME)in patients with low rectal cancer.METHODS A comprehensive systematic review of comparative studies was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards.Intraoperative and postoperative complications,anastomotic leak,R0 resection,completeness of mesorectal excision,circumferential resection margin(CRM),distal resection margin(DRM),harvested lymph nodes,and operation time were the investigated outcome measures.RESULTS We included twelve comparative studies enrolling 969 patients comparing TaTME(n=969)and LaTME(n=476)in patients with low rectal tumours.TaTME was associated with significantly lower risk of postoperative complications(OR:0.74,P=0.04),anastomotic leak(OR:0.59,P=0.02),and conversion to an open procedure(OR:0.29,P=0.002)in comparison with LaTME.Moreover,the rate of R0 resection was significantly higher in the TaTME group(OR:1.96,P=0.03).Nevertheless,TaTME and LaTME were comparable in terms of rate of intraoperative complications(OR:1.87;P=0.23),completeness of mesoractal excision(OR:1.57,P=0.15),harvested lymph nodes(MD:-0.05,P=0.96),DRM(MD:-0.94;P=0.17),CRM(MD:1.08,P=0.17),positive CRM(OR:0.64,P=0.11)and procedure time(MD:-6.99 min,P=0.45).CONCLUSION Our findings indicated that for low rectal tumours,TaTME is associated with better clinical and short term oncological outcomes compared to LaTME.More randomised controlled trials are required to confirm these findings and to evaluate long term oncological and functional outcomes.展开更多
Approximately 1:4 of all cancers in women in develop-ing countries (excluding non-melanoma skin cancer) is a gynaecological cancer. The gynaecological cancer burden in developing countries is huge primarily due to ...Approximately 1:4 of all cancers in women in develop-ing countries (excluding non-melanoma skin cancer) is a gynaecological cancer. The gynaecological cancer burden in developing countries is huge primarily due to the high incidence and mortality of cervical cancer. Cervical cancer accounts for over 60% of the gynaeco-logical cancer burden in developing countries despite being preventable by current technologies. This is due to the absence of effective nationally organized screening programmes in most developing countries. Institution of such programmes, therefore, has the potential to dramatically reduce gynaecological cancer burden in these countries. Subsidized human papil-loma virus (HPV) vaccine and HPV typing as well as cheap screening techniques such as visual inspection aided with acetic acid hold the key to effective preven-tion of cervical cancer in these countries. This is be-cause a signifcant proportion of patients in developing countries are unable to access and avail themselves of the few available preventive, diagnostic and treatment services because of poverty. Although, advocacy and the political will to invest in the development of human resources and healthcare infrastructure appear criti-cal to gynaecological cancer control and reducing the burden of disease in many developing countries, the proposition assumes that resources are truly available for this investment. This may not be true. Many devel-oping countries rely on foreign aids for developmental programmes and these aids have dwindled signifcantly with the current global economic meltdown.展开更多
BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of ...BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library)were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s)of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies)were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84%of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7%of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%)and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75)acid(SeHCAT)scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.展开更多
Sub clinical hyperthyroidism (SCH) is characterized by normal free thyroid hormone concentrations along with a low or undetectable serum TSH (thyrotropin) level. The increased use of TSH as a screening measure and imp...Sub clinical hyperthyroidism (SCH) is characterized by normal free thyroid hormone concentrations along with a low or undetectable serum TSH (thyrotropin) level. The increased use of TSH as a screening measure and improved assay sensitivity is contributing to the diagnosis of sub clinical hyperthyroidism more frequently than ever in our clinical practise leading to the increased prevalence of the disease. The significance of SCH remains uncertain for most patients as some will revert to normal thyroid status over time whereas others will either remain static or progress to overt thyroid disease in the future. The detrimental effects of a persistently suppressed TSH has now been extensively studied and its effect on the cardiovascular system, the skeleton, mood disturbance, quality of life is quite significant leading to considerable morbidity and mortality. Majority of the patients are asymptomatic and lack overt features but the relevance of treatment is more focussed in elderly patients where the risk of developing cardiac arrhythmia and loss of bone mineral density is much more than young people in whom a conservative approach is usually preferred. The issue is contentious, the situation is challenging and the benefits of treatment are debatable. The consensus for who, when and how to treat is growing but still hasn’t been universally accepted. We attempt to review the recent literature available for sub clinical hyperthyroidism and suggest an analytical approach to its investigations and management.展开更多
BACKGROUND Hajibandeh index(HI),derived from combined levels of C-reactive protein,lactate,neutrophils,lymphocytes and albumin,is a modern predictor of peritoneal contamination and mortality in patients with acute abd...BACKGROUND Hajibandeh index(HI),derived from combined levels of C-reactive protein,lactate,neutrophils,lymphocytes and albumin,is a modern predictor of peritoneal contamination and mortality in patients with acute abdominal pathology.AIM To validate the performance of HI in predicting the presence and nature of peritoneal contamination in patients with acute abdominal pathology in a larger cohort study and to synthesis evidence in a systematic review and meta-analysis.METHODS The STROBE guidelines and the PRISMA statement standards were followed to conduct a cohort study(ChiCTR2200056183)and a meta-analysis(CRD420-22306018),respectively.All adult patients undergoing emergency laparotomy for acute abdominal pathology were eligible.The accuracy of the HI was evaluated using receiver operating characteristic(ROC)curve analysis in the cohort study and using weighted summary area under the curve(AUC)under the fixed and random effects modelling in the meta-analysis.The Quality Assessment of Diagnostic Accuracy Studies 2 criteria were used for methodological quality assessment of the included studies.RESULTS A total of 1437 patients were included(700 from the cohort study and 737 from the literature search).ROC curve analysis of the cohort study showed that the AUC of HI for presence of contamination,purulent contamination and feculent contamination were 0.79[95%confidence interval(CI):0.76-0.82,P<0.0001],0.76(95%CI:0.72-0.80,P<0.0001),and 0.83(95%CI:0.79-0.86,P<0.0001),respectively.The meta-analysis showed that the pooled AUC of HI for presence of contamination,purulent contamination and feculent contamination were 0.79(95%CI:0.75-0.83),0.78(95%CI:0.74-0.81),and 0.80(95%CI:0.77-0.83),respectively.CONCLUSION The HI is a strong and accurate predictor of intraperitoneal contamination.Although the available evidence is robust,it is limited to the studies conducted by our evidence synthesis group.We encourage other researchers to validate performance of HI in predicting the presence of intraperitoneal contamination and more importantly in predicting mortality following emergency laparotomy.展开更多
BACKGROUND:CA19-9 is a carbohydrate tumor-associated antigen which is frequently upregulated in pancreatobiliary neoplasia.However,it may also be elevated in patients with jaundice in the absence of a tumor due to bil...BACKGROUND:CA19-9 is a carbohydrate tumor-associated antigen which is frequently upregulated in pancreatobiliary neoplasia.However,it may also be elevated in patients with jaundice in the absence of a tumor due to biliary obstruction,and in other non-hepato-pancreatico-biliary conditions.This study aimed to evaluate whether CA19-9 levels could accurately differentiate between benign and malignant pancreatobiliary disease.METHODS:All patients referred to a single surgeon for investigation of pancreaticobiliary disease in 2003 in whom a firm diagnosis had been established were included.For malignant disease,a histological diagnosis was required but for benign disease a firm radiological diagnosis was deemed adequate.The patients were divided into 4 categories:pancreatic adenocarcinoma(PCa);cholangiocarcinoma(CCa);chronic pancreatitis(CP)and biliary calculous disease(Calc).Bilirubin and alkaline phosphatase levels corresponding to the point of assessment of CA19-9 were also noted.RESULTS:Final diagnoses were made of pancreatic adenocarcinoma(PCa,n=73),cholangiocarcinoma(CCa,n=19),ampullary carcinoma(Amp,n=7),neuroendocrine carcinoma(Neu,n=4),duodenal carcinoma(Duo,n=3),chronic pancreatitis(CP,n=115),and biliary calculous disease(Calc,n=27).Median CA19-9 levels(U/ml)were:PCa,653;CCa,408;Duo,403;Calc,27;CP,19;Neu,10.5;Amp,8(reference range:0-37).The CA19-9 levels were significantly greater for malignant than for benign disease,could differentiate PCa from CCa/Duo,and were significantly higher in unresectable than in resectable PCa.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)for CA19-9 were 84.9%,69.7%,67.7%and 86.1%,respectively.A ROC analysis provided an area under the curve for CA19-9 of 0.871(0.820-0.922),giving an optimal CA19-9 of 70.5 U/ml for differentiating benign from malignant pathology.Using this cut-off,the sensitivity was 82.1%,while specificity,PPV and NPV improved to 85.9%,81.3%and 86.5%,respectively.When standard radiology was included(US/ CT/MRCP)in the decision process,the results improved to 97.2%,88.7%,86.6%,and 97.7%.For benign disease,the CA19-9 correlated directly with the serum bilirubin,but for malignant disease,CA19-9 levels were elevated independent of the bilirubin level.CONCLUSIONS:CA19-9 is useful in the differentiation of pancreatobiliary disease and when using an optimized cut-off and combining with routine radiology,the diagnostic yield is improved significantly,thus stressing the importance of a multi-disciplinary approach to pancreatobiliary disease.展开更多
BACKGROUND Mixed neuroendocrine non-neuroendocrine neoplasm(MiNEN)is a rare diagnosis,mainly encountered in the gastro-entero-pancreatic tract.There is limited knowledge of its epidemiology,prognosis and biology,and t...BACKGROUND Mixed neuroendocrine non-neuroendocrine neoplasm(MiNEN)is a rare diagnosis,mainly encountered in the gastro-entero-pancreatic tract.There is limited knowledge of its epidemiology,prognosis and biology,and the best management for affected patients is still to be defined.AIM To investigate clinical-pathological characteristics,treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN.METHODS Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European centres.Patient data were retrospectively collected from medical records.Pathological samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of MiNEN.Tumour responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours 1.1.Kaplan-Meier analysis was applied to estimate survival outcomes.Associations between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions(univariate)and Cox-regression analysis(multivariable).RESULTS Sixty-nine consecutive patients identified;Median age at diagnosis:64 years.Males:63.8%.Localised disease(curable):53.6%.Commonest sites of origin:colon-rectum(43.5%)and oesophagus/oesophagogastric junction(15.9%).The neuroendocrine component was;predominant in 58.6%,poorly differentiated in 86.3%,and large cell in 81.25%,of cases analysed.Most distant metastases analysed(73.4%)were occupied only by a poorly differentiated neuroendocrine component.Ninety-four percent of patients with localised disease underwent curative surgery;53%also received perioperative treatment,most often in line with protocols for adenocarcinomas from the same sites of origin.Chemotherapy was offered to most patients(68.1%)with advanced disease,and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal proportion.In localised cases,median recurrence free survival(RFS);14.0 months(95%CI:9.2-24.4),and median overall survival(OS):28.6 months(95%CI:18.3-41.1).On univariate analysis,receipt of perioperative treatment(vs surgery alone)did not improve RFS(P=0.375),or OS(P=0.240).In advanced cases,median progression free survival(PFS);5.6 months(95%CI:4.4-7.4),and median OS;9.0 months(95%CI:5.2-13.4).On univariate analysis,receipt of palliative active treatment(vs best supportive care)prolonged PFS and OS(both,P<0.001).CONCLUSION MiNEN is most commonly driven by a poorly differentiated neuroendocrine component,and has poor prognosis.Advances in its biological understanding are needed to identify effective treatments and improve patient outcomes.展开更多
Magnetic resonance imaging(MRI)in rectal cancer was first investigated in 1999 and has become almost mandatory in planning rectal cancer treatment.MRI has a high accuracy in predicting circumferential resection margin...Magnetic resonance imaging(MRI)in rectal cancer was first investigated in 1999 and has become almost mandatory in planning rectal cancer treatment.MRI has a high accuracy in predicting circumferential resection margin involvement and is used to plan neoadjuvant therapy.The accuracy of MRI in assessing mesorectal lymph nodes remains moderate,as there are no reliable criteria to assess nodal involvement.MRI seems to be good in assessing peritoneal involvement in upper rectal cancer;this however has been assessed in only a few studies and needs further research.For low rectal cancers,mesorectum is thin at the level of levator ani especially in relation to prostate;so predicting circumferential resection margin involvement is not easy.However high spatial resolution coronal imaging shows levator muscles,sphincter complex and intersphincteric plane accurately.This is used to stage low rectal tumors and plan plane of surgery(standard surgery,intersphincteric resection,Extralevator abdominoperineal resection).While most centres perform MRI post chemoradiotherapy,its role in accurate staging post neoadjuvant therapy remains debatable.THe role of Diffusion weighted MRI post neoadjuvant therapy is being evaluated in research settings.展开更多
AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples...AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included.Cancer cases were diagnosed between April 2007 and June 2010.HER2 over expression was assessed using immunohistochemistry,those that scored "0" and "+1" were considered "negative" for HER2;those that scored "+3" were considered "Positive".Cases that were scored "+2" on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colourin situ hybridisations(HER B DISH) assay and either came back to be positive or negative for HER2 over expression.Overall survival was measured from date of histological diagnosis until date of death.93% of the cases were followed up till five years or death,and all were followed up till two years.Cases of gastro-oesophageal junctional tumours were excluded.RESULTS:The median age of our sample was 66 years(range:38-91 years).Eighty one were male and 19 female.Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma.The anatomical distribution of the tumours was;upper oesophagus 2,middle oesophagus 11,and 87 were in the lower oesophagus.Operative resection was completed in 15 cases;seven cases had attempted surgical resections,i.e.,open and close,33 patients received definitive chemo-radiation and 52 had palliative treatment.Twenty-five of the cancers showed evidence of HER2 over expression,all were adenocarcinomas.Of the 25 cases that showed evidence of HER2 over expression,21(84%) were located in the lower third of the oesophagus.On staging,24 out of the 25 HER2 positive cases were at stage 3 or more(13 at stage 3 and 11 at stage 4),For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4.Seventeen out of twenty five cases(68%) with HER2 over expression received palliative therapy,in comparison to thirty five out of seventy five(46.7%) in tumours not expressing HER2.No significant difference in overall survival was demonstrated between patients whose cancers showed evidence of HER2 over expression and those who did not;median overall survival for HER2 positive tumours was 15 mo(95%CI,11-19 mo) compared to 13 mo(95%CI,9-17 mo) for HER2 negative ones.Two years cumulative survival for cases with HER2 over expression was 33.7% compared to 31.6% in cases without HER2 over expression(P = 0.576).Only cancer's stage significantly affected overall survival on both univariant and multivariable analysis(P = 0.034 and P = 0.009 respectively).None of the patients included in this study received Trastuzumab.CONCLUSION:Twenty-seven point five percent of oesophageal adenocarcinomas showed evidence of HER2 over expression.Routine testing for human HER2 in oesophageal adenocarcinomas can have significant implication on treatments offered to patients that may potentially affect their prognosis.展开更多
Background: We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ. Method...Background: We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ. Methods: In all, 31 patients with biopsy-proven cutaneous SCC in situ were randomly assigned to placebo (vehicle) (n = 16) or imiquimod 5% cream (n = 15) daily for 16 weeks. Patients were assessed at week 28 for the primary end point, resolution of cutaneous SCC in situ. Results: Of the 31 patients enrolled, 3 dropped out. Intention-to-treat analysis revealed 11 of the 15 patients (73% ) in the imiquimod group achieved resolution of cutaneous SCC in situ, with no relapse during the 9-month follow-up period; none in the placebo group achieved resolution (P < .001). Imiquimod 5% cream was generally well tolerated and there were no serious adverse events. Limitations: Topical imiquimod 5% cream has proven to be an effective treatment for cutaneous SCC in situ. However, studies to define the ideal dosing regimen and cost-effectiveness are required before it can be accepted as a recognized therapy. Conclusions: In this controlled trial, patients with cutaneous SCC in situ receiving topical imiquimod 5% cream as monotherapy experienced a high degree of clinical benefit compared with placebo.展开更多
Objective: To evaluate the influence of gestational age on uterine scar rupture. Methods: This was a population-based study of data from Cardiff Births Survey over a 10- year (1990- 1999) period. Women with only one p...Objective: To evaluate the influence of gestational age on uterine scar rupture. Methods: This was a population-based study of data from Cardiff Births Survey over a 10- year (1990- 1999) period. Women with only one previous lower segment caesarean section with singleton uncomplicated pregnancy of 37 or more week’s gestation, undergoing trial of vaginal delivery were included. SPSS version 10 was used for statistical analysis. Mann-Whitney, Fisher’s exact test and Chi-square tests were used wherever appropriate. Odds ratio (OR) with confidence intervals (CI) was used to quantify the risk. Potential confounding by other factors was controlled using logistic regression and corrected odds ratios with 95% confidence intervals were calculated. The data was analysed separately for induced and spontaneous labours. Primary outcome measure assessed was uterine scar rupture rate. Secondary outcome measures were repeat caesarean section rates, maternal and perinatal mortality and morbidity. Results:Total sample number was 1620. Eighty percent (n = 1301) of the population went into spontaneous labour and 20% (n = 319) were induced. Successful trial of vaginal birth was accomplished in 60% and trial of scar after estimated date of delivery did not alter this outcome significantly (39.1% versus 43.6% , p > 0.05). We noted an overall scar rupture rate of 0.9% (n = 14) and caesarean section rate of 40.4% (n = 654). Scar rupture rates significantly increased in women who underwent trial of labour after estimated date of delivery (p < 0.001, OR 6.3, CI 1.9- 20.2) without a corresponding increase in caesarean section, maternal and perinatal morbidity figures. The influence of gestational age on scar rupture persisted even after controlling for other confounding factors such as birth weight, induction of labour and BMI (corrected OR 1.9, CI 1.1- 3.5). Conclusions: The overall incidence of scar rupture and success of trial of scar after previous caesarean section in our population was similar to that quoted in the literature. Previous evidence has suggested that it is safe for these women to exceed 40 weeks gestation but our data do not support this.展开更多
Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regim...Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regimen (RCVP and RICE) consisting of rituximab before bone marrow transplantation went on to develop cy- tomegalovirus enterocolitis. This supports evidence from previously described cases that rituximab may be associ- ated with cytomegalovirus enterocolitis.展开更多
Mycoplasma hominis is a member of the genus mycoplasma and has only been isolated from humans. It is most frequently isolated from the urogenital tract in the absence of symptoms, but has been isolated from wounds, br...Mycoplasma hominis is a member of the genus mycoplasma and has only been isolated from humans. It is most frequently isolated from the urogenital tract in the absence of symptoms, but has been isolated from wounds, brain abscess, inflamed joints, blood and placenta from pregnancy with adverse outcomes (especially preterm birth and occasionally term stillbirth). Controversy surrounds whether this organism is a commensal or a pathogen;however, Mycoplasma hominis has been shown to induce preterm birth and foetal lung injury in an experimental primate model as a sole pathogen. These bacteria are known to exist as a parasitic infection, due to a number of missing synthetic and metabolism pathway enzymes from their minimal genome;therefore, the ability to adhere to host cells is important. Here we provide a review that clarifies the different nomenclature (variable adherence-associated antigen and P50) that has been used to investigate the major surface adhesin for this organism, as well as reported mechanisms responsible for turning off its expression. Variation in the structure of this protein can be used to separate strains into six categories, a method that we were able to use to distinguish and characterise 12 UK strains isolated from between 1983 and 2012. We propose that the Vaa should be used in further investigations to determine if commensal populations and those that are associated with disease utilise different forms of this adhesin, as this is under-studied and identification of pathogenic determinants is overdue for this organism.展开更多
Aims: To compare prevalence, reasons, motivations, initiation, perceived helpfulness, and communication of complementary and alternative medicine (CAM) use between two tertiary children’ s hospitals. Methodology: A s...Aims: To compare prevalence, reasons, motivations, initiation, perceived helpfulness, and communication of complementary and alternative medicine (CAM) use between two tertiary children’ s hospitals. Methodology: A study, using a face-to-face questionnaire, of 500 children attending the University Hospital of Wales, Cardiff, UK was compared to an identical study of 503 children attending the Royal Children’ s Hospital, Melbourne, Australia. Results: One year CAM use in Cardiff was lower than Melbourne (41% vs 51% ; OR = 0.67, 95% CI 0.52-0.85), reflected in non-medicinal use (OR = 0.41, 95% CI 0.29-0.58) and general paediatric outpatients (OR = 0.38, 95% CI 0.21-0.67). Compared to Melbourne, factors associated with lower CAM use in Cardiff included families born locally (father: OR=0.58, 95% CI 0.44-0.77) or non-tertiary educated parents (mother: OR = 0.54, 95% CI 0.38-0.77). Cardiff participants used less vitamin C (OR = 0.31, 95% CI 0.18-0.51) and herbs (OR= 0.49, 95% CI 0.34-0.71), attended less chiropractors (OR = 0.25, 95% CI 0.06-0.37) and naturopaths (OR = 0.08, 95% CI 0.02-0.33), but saw more reflexologists (OR = 3.33, 95% CI 1.08-10.29). In Cardiff, CAM was more popular for relaxation (OR = 1.92, 95% CI 1.03-3.57) but less for colds/coughs (OR = 0.4, 95% CI 0.27-0.73). Most CAM was self-initiated (by parent) in Cardiff and Melbourne (74% vs 70% ), but Cardiff CAM users perceived it less helpful (OR = 0.46, 95% CI 0.31-0.68). Non-disclosure of CAM use was high in Cardiff and Melbourne (66% vs 63% ); likewise few doctors/nurses documented recent medicinal CAM use in inpatient notes (0/21 vs 2/22). Conclusions: The differences in CAM use may reflect variation in sociocultural factors influencing reasons, motivations, attitudes, and availability. The regional variation in use and poor communication highlights the importance of local policy development.展开更多
A 54 year old man presented with numerous cutaneous schwannomas, cranial nerve lesions, and spinal cord lesions, but no evidence of vestibular nerve involvement. There was no family history of neurocutaneous lesions. ...A 54 year old man presented with numerous cutaneous schwannomas, cranial nerve lesions, and spinal cord lesions, but no evidence of vestibular nerve involvement. There was no family history of neurocutaneous lesions. To help discriminate between the various possible diagnoses in this patient, molecular analysis of two cutaneous schwannomas was undertaken. An identical point mutation in the NF2 gene in the two anatomically distinct tumours was found, confirming this as a case of NF2 mosaicism.展开更多
文摘BACKGROUND Liver disease incidence and hence demand on hepatology services is increasing.AIM To describe trends in incidence and natural history of liver diseases in Wales to inform effective provision of hepatology services.METHODS The registry is populated by International Classification of Diseases-10(ICD-10)code diagnoses for residents derived from mortality data and inpatient/day case activity between 1999-2019.Pseudo-anonymised linkage of:(1)Causative diagnoses;(2)Cirrhosis;(3)Portal hypertension;(4)Decompensation;and(5)Liver cancer diagnoses enabled tracking liver disease progression.RESULTS The population of Wales in 2019 was 3.1 million.Between 1999 and 201973054 individuals were diagnosed with a hepatic disorder,including 18633 diagnosed with cirrhosis,10965 with liver decompensation and 2316 with hepatocellular carcinoma(HCC).Over 21 years the incidence of liver diseases increased 3.6 fold,predominantly driven by a 10 fold increase in non-alcoholic fatty liver disease(NAFLD);the leading cause of liver disease from 2014.The incidence of cirrhosis,decompensation,HCC,and allcause mortality tripled.Liver-related mortality doubled.Alcohol-related liver disease(ArLD),autoimmune liver disease and congestive hepatopathy were associated with the highest rates of decompensation and all-cause mortality.CONCLUSION A 10 fold increase in NAFLD incidence is driving a 3.6 fold increase in liver disease in Wales over 21 years.Liver-related morbidity and mortality rose more slowly reflecting the lower progression rate in NAFLD.Incidence of ArLD remained stable but was associated with the highest rates of liver-related and all-cause mortality.
文摘Over the last 12 years, the Wales Cancer Biobank (WCB) has consented to more than 2000 patients with colorectal cancer (CRC). From these patients, clinical data has been collected and patients have been followed through their cancer journey. Clinical data from these patients have been analyzed to identify any correlation between disease grade and outcome. In a small cohort, consisting of 407 patients, WCB has performed genetic analysis on patient primary tumor samples, identifying and characterizing mutations in the KRAS, NRAS, BRAF, PIK3CA and TP53 genes. The majority of patients with CRC who were consented to WCB were male with a mean age of 69 years and received surgery as the primary treatment for their disease. Pathology and disease-free survival data confirmed worse prognoses associated with more advanced disease. Heterogeneity within the primary tumor was explored in a subgroup of patients. Analysis of the KRAS and TP53 genes confirmed that more than 40% of CRC patients who were tested, harbored a genetic mutation within these genes in their primary tumor. Due to the limited sample size tested, most mutations did not show significant differences in disease-free survival, however, mutation of the BRAF gene did show a decrease in the disease specific survival, in keeping with the published data. Analysis of the patients diagnosed with CRC within the Biobank has provided us with valuable information on the status of CRC disease and treatment within the Welsh population. Over 12 years of consenting, we have witnessed significant changes in the information that researchers are interested in when sourcing samples for translational research. The development of new drugs that are tailored to the genetics of a cancer is emerging and at WCB we are focusing our collections on samples and data that meet the needs of this ever-evolving field.
文摘The majority of proximal humerus fractures are lowenergy osteoporotic injuries in the elderly and their incidence is increasing in the light of an ageing population. The diversity of fracture patterns encountered renders objective classification of prognostic value challenging. Non-operative management has been associated with good functional outcomes in stable, minimally displaced and certain types of displaced fractures.Absolute indications for surgery are infrequent and comprise compound, pathological, multi-fragmentary head-splitting fractures and fracture dislocations, as well as those associated with neurovascular injury. A constantly expanding range of reconstructive and replacement options however has been extending the indications for surgical management of complex proximal humerus fractures. As a result, management decisions are becoming increasingly complicated, in an attempt to provide the best possible treatment for each indi-vidual patient, that will successfully address their specific fracture configuration, comorbidities and functional expectations. Our aim was to review the management options available for the full range of proximal humerus fractures in adults, along with their specific advantages, disadvantages and outcomes.
文摘Atrial fibrillation(AF) is the most common cardiac arrhythmia and a huge public health burden associated with significant morbidity and mortality. For decades an increasing number of patients have undergone surgical treatment of AF, mainly during concomitant cardiac surgery. This has sparked a drive for conducting further studies and researching this field. With the cornerstone Cox-Maze III "cut and sew" procedure being technically challenging, the focus in current literature has turned towards less invasive techniques. The introduction of ablative devices has revolutionised the surgical management of AF, moving away from the traditional surgical lesions. The hybrid procedure, a combination of catheter and surgical ablation is another promising new technique aiming to improve outcomes. Despite the increasing number of studies looking at various aspects of the surgical management of AF, the literature would benefit from more uniformly conducted randomised control trials.
文摘BACKGROUND Achieving a clear resection margins for low rectal cancer is technically challenging.Transanal approach to total mesorectal excision(TME)was introduced in order to address the challenges associated with the laparoscopic approach in treating low rectal cancers.However,previous meta-analyses have included mixed population with mid and low rectal tumours when comparing both approaches which has made the interpretation of the real differences between two approaches in treating low rectal cancer difficult.AIM To investigate the outcomes of transanal TME(TaTME)and laparoscopic TME(LaTME)in patients with low rectal cancer.METHODS A comprehensive systematic review of comparative studies was performed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards.Intraoperative and postoperative complications,anastomotic leak,R0 resection,completeness of mesorectal excision,circumferential resection margin(CRM),distal resection margin(DRM),harvested lymph nodes,and operation time were the investigated outcome measures.RESULTS We included twelve comparative studies enrolling 969 patients comparing TaTME(n=969)and LaTME(n=476)in patients with low rectal tumours.TaTME was associated with significantly lower risk of postoperative complications(OR:0.74,P=0.04),anastomotic leak(OR:0.59,P=0.02),and conversion to an open procedure(OR:0.29,P=0.002)in comparison with LaTME.Moreover,the rate of R0 resection was significantly higher in the TaTME group(OR:1.96,P=0.03).Nevertheless,TaTME and LaTME were comparable in terms of rate of intraoperative complications(OR:1.87;P=0.23),completeness of mesoractal excision(OR:1.57,P=0.15),harvested lymph nodes(MD:-0.05,P=0.96),DRM(MD:-0.94;P=0.17),CRM(MD:1.08,P=0.17),positive CRM(OR:0.64,P=0.11)and procedure time(MD:-6.99 min,P=0.45).CONCLUSION Our findings indicated that for low rectal tumours,TaTME is associated with better clinical and short term oncological outcomes compared to LaTME.More randomised controlled trials are required to confirm these findings and to evaluate long term oncological and functional outcomes.
文摘Approximately 1:4 of all cancers in women in develop-ing countries (excluding non-melanoma skin cancer) is a gynaecological cancer. The gynaecological cancer burden in developing countries is huge primarily due to the high incidence and mortality of cervical cancer. Cervical cancer accounts for over 60% of the gynaeco-logical cancer burden in developing countries despite being preventable by current technologies. This is due to the absence of effective nationally organized screening programmes in most developing countries. Institution of such programmes, therefore, has the potential to dramatically reduce gynaecological cancer burden in these countries. Subsidized human papil-loma virus (HPV) vaccine and HPV typing as well as cheap screening techniques such as visual inspection aided with acetic acid hold the key to effective preven-tion of cervical cancer in these countries. This is be-cause a signifcant proportion of patients in developing countries are unable to access and avail themselves of the few available preventive, diagnostic and treatment services because of poverty. Although, advocacy and the political will to invest in the development of human resources and healthcare infrastructure appear criti-cal to gynaecological cancer control and reducing the burden of disease in many developing countries, the proposition assumes that resources are truly available for this investment. This may not be true. Many devel-oping countries rely on foreign aids for developmental programmes and these aids have dwindled signifcantly with the current global economic meltdown.
文摘BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library)were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s)of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies)were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84%of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7%of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%)and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75)acid(SeHCAT)scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.
文摘Sub clinical hyperthyroidism (SCH) is characterized by normal free thyroid hormone concentrations along with a low or undetectable serum TSH (thyrotropin) level. The increased use of TSH as a screening measure and improved assay sensitivity is contributing to the diagnosis of sub clinical hyperthyroidism more frequently than ever in our clinical practise leading to the increased prevalence of the disease. The significance of SCH remains uncertain for most patients as some will revert to normal thyroid status over time whereas others will either remain static or progress to overt thyroid disease in the future. The detrimental effects of a persistently suppressed TSH has now been extensively studied and its effect on the cardiovascular system, the skeleton, mood disturbance, quality of life is quite significant leading to considerable morbidity and mortality. Majority of the patients are asymptomatic and lack overt features but the relevance of treatment is more focussed in elderly patients where the risk of developing cardiac arrhythmia and loss of bone mineral density is much more than young people in whom a conservative approach is usually preferred. The issue is contentious, the situation is challenging and the benefits of treatment are debatable. The consensus for who, when and how to treat is growing but still hasn’t been universally accepted. We attempt to review the recent literature available for sub clinical hyperthyroidism and suggest an analytical approach to its investigations and management.
文摘BACKGROUND Hajibandeh index(HI),derived from combined levels of C-reactive protein,lactate,neutrophils,lymphocytes and albumin,is a modern predictor of peritoneal contamination and mortality in patients with acute abdominal pathology.AIM To validate the performance of HI in predicting the presence and nature of peritoneal contamination in patients with acute abdominal pathology in a larger cohort study and to synthesis evidence in a systematic review and meta-analysis.METHODS The STROBE guidelines and the PRISMA statement standards were followed to conduct a cohort study(ChiCTR2200056183)and a meta-analysis(CRD420-22306018),respectively.All adult patients undergoing emergency laparotomy for acute abdominal pathology were eligible.The accuracy of the HI was evaluated using receiver operating characteristic(ROC)curve analysis in the cohort study and using weighted summary area under the curve(AUC)under the fixed and random effects modelling in the meta-analysis.The Quality Assessment of Diagnostic Accuracy Studies 2 criteria were used for methodological quality assessment of the included studies.RESULTS A total of 1437 patients were included(700 from the cohort study and 737 from the literature search).ROC curve analysis of the cohort study showed that the AUC of HI for presence of contamination,purulent contamination and feculent contamination were 0.79[95%confidence interval(CI):0.76-0.82,P<0.0001],0.76(95%CI:0.72-0.80,P<0.0001),and 0.83(95%CI:0.79-0.86,P<0.0001),respectively.The meta-analysis showed that the pooled AUC of HI for presence of contamination,purulent contamination and feculent contamination were 0.79(95%CI:0.75-0.83),0.78(95%CI:0.74-0.81),and 0.80(95%CI:0.77-0.83),respectively.CONCLUSION The HI is a strong and accurate predictor of intraperitoneal contamination.Although the available evidence is robust,it is limited to the studies conducted by our evidence synthesis group.We encourage other researchers to validate performance of HI in predicting the presence of intraperitoneal contamination and more importantly in predicting mortality following emergency laparotomy.
文摘BACKGROUND:CA19-9 is a carbohydrate tumor-associated antigen which is frequently upregulated in pancreatobiliary neoplasia.However,it may also be elevated in patients with jaundice in the absence of a tumor due to biliary obstruction,and in other non-hepato-pancreatico-biliary conditions.This study aimed to evaluate whether CA19-9 levels could accurately differentiate between benign and malignant pancreatobiliary disease.METHODS:All patients referred to a single surgeon for investigation of pancreaticobiliary disease in 2003 in whom a firm diagnosis had been established were included.For malignant disease,a histological diagnosis was required but for benign disease a firm radiological diagnosis was deemed adequate.The patients were divided into 4 categories:pancreatic adenocarcinoma(PCa);cholangiocarcinoma(CCa);chronic pancreatitis(CP)and biliary calculous disease(Calc).Bilirubin and alkaline phosphatase levels corresponding to the point of assessment of CA19-9 were also noted.RESULTS:Final diagnoses were made of pancreatic adenocarcinoma(PCa,n=73),cholangiocarcinoma(CCa,n=19),ampullary carcinoma(Amp,n=7),neuroendocrine carcinoma(Neu,n=4),duodenal carcinoma(Duo,n=3),chronic pancreatitis(CP,n=115),and biliary calculous disease(Calc,n=27).Median CA19-9 levels(U/ml)were:PCa,653;CCa,408;Duo,403;Calc,27;CP,19;Neu,10.5;Amp,8(reference range:0-37).The CA19-9 levels were significantly greater for malignant than for benign disease,could differentiate PCa from CCa/Duo,and were significantly higher in unresectable than in resectable PCa.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)for CA19-9 were 84.9%,69.7%,67.7%and 86.1%,respectively.A ROC analysis provided an area under the curve for CA19-9 of 0.871(0.820-0.922),giving an optimal CA19-9 of 70.5 U/ml for differentiating benign from malignant pathology.Using this cut-off,the sensitivity was 82.1%,while specificity,PPV and NPV improved to 85.9%,81.3%and 86.5%,respectively.When standard radiology was included(US/ CT/MRCP)in the decision process,the results improved to 97.2%,88.7%,86.6%,and 97.7%.For benign disease,the CA19-9 correlated directly with the serum bilirubin,but for malignant disease,CA19-9 levels were elevated independent of the bilirubin level.CONCLUSIONS:CA19-9 is useful in the differentiation of pancreatobiliary disease and when using an optimized cut-off and combining with routine radiology,the diagnostic yield is improved significantly,thus stressing the importance of a multi-disciplinary approach to pancreatobiliary disease.
文摘BACKGROUND Mixed neuroendocrine non-neuroendocrine neoplasm(MiNEN)is a rare diagnosis,mainly encountered in the gastro-entero-pancreatic tract.There is limited knowledge of its epidemiology,prognosis and biology,and the best management for affected patients is still to be defined.AIM To investigate clinical-pathological characteristics,treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN.METHODS Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European centres.Patient data were retrospectively collected from medical records.Pathological samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of MiNEN.Tumour responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours 1.1.Kaplan-Meier analysis was applied to estimate survival outcomes.Associations between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions(univariate)and Cox-regression analysis(multivariable).RESULTS Sixty-nine consecutive patients identified;Median age at diagnosis:64 years.Males:63.8%.Localised disease(curable):53.6%.Commonest sites of origin:colon-rectum(43.5%)and oesophagus/oesophagogastric junction(15.9%).The neuroendocrine component was;predominant in 58.6%,poorly differentiated in 86.3%,and large cell in 81.25%,of cases analysed.Most distant metastases analysed(73.4%)were occupied only by a poorly differentiated neuroendocrine component.Ninety-four percent of patients with localised disease underwent curative surgery;53%also received perioperative treatment,most often in line with protocols for adenocarcinomas from the same sites of origin.Chemotherapy was offered to most patients(68.1%)with advanced disease,and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal proportion.In localised cases,median recurrence free survival(RFS);14.0 months(95%CI:9.2-24.4),and median overall survival(OS):28.6 months(95%CI:18.3-41.1).On univariate analysis,receipt of perioperative treatment(vs surgery alone)did not improve RFS(P=0.375),or OS(P=0.240).In advanced cases,median progression free survival(PFS);5.6 months(95%CI:4.4-7.4),and median OS;9.0 months(95%CI:5.2-13.4).On univariate analysis,receipt of palliative active treatment(vs best supportive care)prolonged PFS and OS(both,P<0.001).CONCLUSION MiNEN is most commonly driven by a poorly differentiated neuroendocrine component,and has poor prognosis.Advances in its biological understanding are needed to identify effective treatments and improve patient outcomes.
文摘Magnetic resonance imaging(MRI)in rectal cancer was first investigated in 1999 and has become almost mandatory in planning rectal cancer treatment.MRI has a high accuracy in predicting circumferential resection margin involvement and is used to plan neoadjuvant therapy.The accuracy of MRI in assessing mesorectal lymph nodes remains moderate,as there are no reliable criteria to assess nodal involvement.MRI seems to be good in assessing peritoneal involvement in upper rectal cancer;this however has been assessed in only a few studies and needs further research.For low rectal cancers,mesorectum is thin at the level of levator ani especially in relation to prostate;so predicting circumferential resection margin involvement is not easy.However high spatial resolution coronal imaging shows levator muscles,sphincter complex and intersphincteric plane accurately.This is used to stage low rectal tumors and plan plane of surgery(standard surgery,intersphincteric resection,Extralevator abdominoperineal resection).While most centres perform MRI post chemoradiotherapy,its role in accurate staging post neoadjuvant therapy remains debatable.THe role of Diffusion weighted MRI post neoadjuvant therapy is being evaluated in research settings.
文摘AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included.Cancer cases were diagnosed between April 2007 and June 2010.HER2 over expression was assessed using immunohistochemistry,those that scored "0" and "+1" were considered "negative" for HER2;those that scored "+3" were considered "Positive".Cases that were scored "+2" on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colourin situ hybridisations(HER B DISH) assay and either came back to be positive or negative for HER2 over expression.Overall survival was measured from date of histological diagnosis until date of death.93% of the cases were followed up till five years or death,and all were followed up till two years.Cases of gastro-oesophageal junctional tumours were excluded.RESULTS:The median age of our sample was 66 years(range:38-91 years).Eighty one were male and 19 female.Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma.The anatomical distribution of the tumours was;upper oesophagus 2,middle oesophagus 11,and 87 were in the lower oesophagus.Operative resection was completed in 15 cases;seven cases had attempted surgical resections,i.e.,open and close,33 patients received definitive chemo-radiation and 52 had palliative treatment.Twenty-five of the cancers showed evidence of HER2 over expression,all were adenocarcinomas.Of the 25 cases that showed evidence of HER2 over expression,21(84%) were located in the lower third of the oesophagus.On staging,24 out of the 25 HER2 positive cases were at stage 3 or more(13 at stage 3 and 11 at stage 4),For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4.Seventeen out of twenty five cases(68%) with HER2 over expression received palliative therapy,in comparison to thirty five out of seventy five(46.7%) in tumours not expressing HER2.No significant difference in overall survival was demonstrated between patients whose cancers showed evidence of HER2 over expression and those who did not;median overall survival for HER2 positive tumours was 15 mo(95%CI,11-19 mo) compared to 13 mo(95%CI,9-17 mo) for HER2 negative ones.Two years cumulative survival for cases with HER2 over expression was 33.7% compared to 31.6% in cases without HER2 over expression(P = 0.576).Only cancer's stage significantly affected overall survival on both univariant and multivariable analysis(P = 0.034 and P = 0.009 respectively).None of the patients included in this study received Trastuzumab.CONCLUSION:Twenty-seven point five percent of oesophageal adenocarcinomas showed evidence of HER2 over expression.Routine testing for human HER2 in oesophageal adenocarcinomas can have significant implication on treatments offered to patients that may potentially affect their prognosis.
文摘Background: We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ. Methods: In all, 31 patients with biopsy-proven cutaneous SCC in situ were randomly assigned to placebo (vehicle) (n = 16) or imiquimod 5% cream (n = 15) daily for 16 weeks. Patients were assessed at week 28 for the primary end point, resolution of cutaneous SCC in situ. Results: Of the 31 patients enrolled, 3 dropped out. Intention-to-treat analysis revealed 11 of the 15 patients (73% ) in the imiquimod group achieved resolution of cutaneous SCC in situ, with no relapse during the 9-month follow-up period; none in the placebo group achieved resolution (P < .001). Imiquimod 5% cream was generally well tolerated and there were no serious adverse events. Limitations: Topical imiquimod 5% cream has proven to be an effective treatment for cutaneous SCC in situ. However, studies to define the ideal dosing regimen and cost-effectiveness are required before it can be accepted as a recognized therapy. Conclusions: In this controlled trial, patients with cutaneous SCC in situ receiving topical imiquimod 5% cream as monotherapy experienced a high degree of clinical benefit compared with placebo.
文摘Objective: To evaluate the influence of gestational age on uterine scar rupture. Methods: This was a population-based study of data from Cardiff Births Survey over a 10- year (1990- 1999) period. Women with only one previous lower segment caesarean section with singleton uncomplicated pregnancy of 37 or more week’s gestation, undergoing trial of vaginal delivery were included. SPSS version 10 was used for statistical analysis. Mann-Whitney, Fisher’s exact test and Chi-square tests were used wherever appropriate. Odds ratio (OR) with confidence intervals (CI) was used to quantify the risk. Potential confounding by other factors was controlled using logistic regression and corrected odds ratios with 95% confidence intervals were calculated. The data was analysed separately for induced and spontaneous labours. Primary outcome measure assessed was uterine scar rupture rate. Secondary outcome measures were repeat caesarean section rates, maternal and perinatal mortality and morbidity. Results:Total sample number was 1620. Eighty percent (n = 1301) of the population went into spontaneous labour and 20% (n = 319) were induced. Successful trial of vaginal birth was accomplished in 60% and trial of scar after estimated date of delivery did not alter this outcome significantly (39.1% versus 43.6% , p > 0.05). We noted an overall scar rupture rate of 0.9% (n = 14) and caesarean section rate of 40.4% (n = 654). Scar rupture rates significantly increased in women who underwent trial of labour after estimated date of delivery (p < 0.001, OR 6.3, CI 1.9- 20.2) without a corresponding increase in caesarean section, maternal and perinatal morbidity figures. The influence of gestational age on scar rupture persisted even after controlling for other confounding factors such as birth weight, induction of labour and BMI (corrected OR 1.9, CI 1.1- 3.5). Conclusions: The overall incidence of scar rupture and success of trial of scar after previous caesarean section in our population was similar to that quoted in the literature. Previous evidence has suggested that it is safe for these women to exceed 40 weeks gestation but our data do not support this.
文摘Rituximab has been associated with the development of cytomegalovirus enterocolitis in immunosuppressed patients. A 51-year-old patient with diffuse large B-cell lymphoma who received a conditioning chemotherapy regimen (RCVP and RICE) consisting of rituximab before bone marrow transplantation went on to develop cy- tomegalovirus enterocolitis. This supports evidence from previously described cases that rituximab may be associ- ated with cytomegalovirus enterocolitis.
文摘Mycoplasma hominis is a member of the genus mycoplasma and has only been isolated from humans. It is most frequently isolated from the urogenital tract in the absence of symptoms, but has been isolated from wounds, brain abscess, inflamed joints, blood and placenta from pregnancy with adverse outcomes (especially preterm birth and occasionally term stillbirth). Controversy surrounds whether this organism is a commensal or a pathogen;however, Mycoplasma hominis has been shown to induce preterm birth and foetal lung injury in an experimental primate model as a sole pathogen. These bacteria are known to exist as a parasitic infection, due to a number of missing synthetic and metabolism pathway enzymes from their minimal genome;therefore, the ability to adhere to host cells is important. Here we provide a review that clarifies the different nomenclature (variable adherence-associated antigen and P50) that has been used to investigate the major surface adhesin for this organism, as well as reported mechanisms responsible for turning off its expression. Variation in the structure of this protein can be used to separate strains into six categories, a method that we were able to use to distinguish and characterise 12 UK strains isolated from between 1983 and 2012. We propose that the Vaa should be used in further investigations to determine if commensal populations and those that are associated with disease utilise different forms of this adhesin, as this is under-studied and identification of pathogenic determinants is overdue for this organism.
文摘Aims: To compare prevalence, reasons, motivations, initiation, perceived helpfulness, and communication of complementary and alternative medicine (CAM) use between two tertiary children’ s hospitals. Methodology: A study, using a face-to-face questionnaire, of 500 children attending the University Hospital of Wales, Cardiff, UK was compared to an identical study of 503 children attending the Royal Children’ s Hospital, Melbourne, Australia. Results: One year CAM use in Cardiff was lower than Melbourne (41% vs 51% ; OR = 0.67, 95% CI 0.52-0.85), reflected in non-medicinal use (OR = 0.41, 95% CI 0.29-0.58) and general paediatric outpatients (OR = 0.38, 95% CI 0.21-0.67). Compared to Melbourne, factors associated with lower CAM use in Cardiff included families born locally (father: OR=0.58, 95% CI 0.44-0.77) or non-tertiary educated parents (mother: OR = 0.54, 95% CI 0.38-0.77). Cardiff participants used less vitamin C (OR = 0.31, 95% CI 0.18-0.51) and herbs (OR= 0.49, 95% CI 0.34-0.71), attended less chiropractors (OR = 0.25, 95% CI 0.06-0.37) and naturopaths (OR = 0.08, 95% CI 0.02-0.33), but saw more reflexologists (OR = 3.33, 95% CI 1.08-10.29). In Cardiff, CAM was more popular for relaxation (OR = 1.92, 95% CI 1.03-3.57) but less for colds/coughs (OR = 0.4, 95% CI 0.27-0.73). Most CAM was self-initiated (by parent) in Cardiff and Melbourne (74% vs 70% ), but Cardiff CAM users perceived it less helpful (OR = 0.46, 95% CI 0.31-0.68). Non-disclosure of CAM use was high in Cardiff and Melbourne (66% vs 63% ); likewise few doctors/nurses documented recent medicinal CAM use in inpatient notes (0/21 vs 2/22). Conclusions: The differences in CAM use may reflect variation in sociocultural factors influencing reasons, motivations, attitudes, and availability. The regional variation in use and poor communication highlights the importance of local policy development.
文摘A 54 year old man presented with numerous cutaneous schwannomas, cranial nerve lesions, and spinal cord lesions, but no evidence of vestibular nerve involvement. There was no family history of neurocutaneous lesions. To help discriminate between the various possible diagnoses in this patient, molecular analysis of two cutaneous schwannomas was undertaken. An identical point mutation in the NF2 gene in the two anatomically distinct tumours was found, confirming this as a case of NF2 mosaicism.