Granulomas at initial diagnosis of Crohn’s disease signal a poor outcome

Background. Over time, most patients with Crohn’s disease (CD) develop strictures or fistulas, resulting in hospitalisations and surgery. Timely therapy with immunomodulators and biologicals may alter this natural history, but carries a significant risk of side-effects.Objective. To identify factors to predict poor-outcome severe CD at diagnosis, and thus patients who would benefit most from early, aggressive medical therapies.Methods. CD patients (n=101) with uncomplicated non-stricturing, non-penetrating disease at diagnosis, and with follow-up >5 years, were retrospectively analysed using a predefined definition of severe CD (SCD) over the disease course. Clinical, demographic, laboratory and histological factors at diagnosis associated with SCD and poor outcome were evaluated by univariate and multivariate analysis.Results. Overall 33.7% of the cohort developed SCD, and on multivariate Cox proportional hazard analysis the presence of granulomas on endoscopic biopsy at diagnosis was independently associated with development of SCD (hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.15 - 4.64; p=0.02). Simple perianal disease was also associated with this outcome (HR 2.49; 95% CI 1.14 - 5.41; p=0.02). The presence of these variables had a specificity of 99% and a positive predictive value of 88%.Conclusion. At diagnosis, factors predictive of SCD in our referral centre were the presence of endoscopic biopsy granulomas and perianal disease. Patients with these risk factors should be considered for early, aggressive medical therapy, as benefit will probably outweigh risk. To our knowledge, this is the first study to show that endoscopic biopsy granulomas in patients with uncomplicated (non-stricturing, nonpenetrating) CD predict the subsequent development of SCD

Procedure for prolapsed haemorrhoids vs excisional haemorrhoidectomy: A systematic review and meta-analysis

Background. The procedure for prolapse and haemorrhoids (PPH) was introduced to address the postoperative pain following excisional haemorrhoidectomy (EH). Objective. To assess the efficacy of both procedures to treat haemorrhoids. Data sources. Literature review using MEDLINE. Articles addressing PPH and EH were included. Study selection. RCTs comparing EH and PPH with ≥20 patients. Data extraction. Primary endpoints were pain, operative time, hospital stay, satisfaction with procedure and time to return to normal activity. Secondary endpoints such as recurrence and complications were collated for descriptive analysis. A metaanalysis was performed using the random effects model on studies reporting ‘mean' and SD or SEM. Data synthesis. PPH was associated with less postoperative pain, less operative time, shorter hospital stay and earlier return to normal activities compared with EH. There appears to be no significant difference in satisfaction with the procedure. There was no difference between the two procedures in terms of complications. There were more recurrences after PPH. Conclusion. Compared with EH, PPH is associated with less postoperative pain, reduced operative time and hospital stay and earlier return to normal activity, and a trend towards improved patient satisfaction. The rate of recurrence appears higher with PPH. South African Medical Journal Vol. 99 (1) 2009: pp. 43-5

Self-expanding metal stent placement for oesophageal cancer without fluoroscopy is safe and effective

Background. Self-expanding metal stents (SEMS) are widely used to palliate patients with oesophageal cancer. Placement is usually done under endoscopic and fluoroscopic guidance. We have developed an exclusively endoscopic technique to deploy these stents. This article documents the technique and periprocedural experience.Patients and methods. All patients who had SEMS placement for oesophageal cancer at Grey’s Hospital, Pietermaritzburg, South Africa, over a 5-year period (2007 - 2011) were reviewed. Stenting was performed without radiological guidance using the technique documented in this article. At endoscopy, the oesophageal lesion was identified, dilated over a guidewire if necessary, and a partially covered stent was passed over the wire and positioned and deployed under direct vision. Data were captured from completed procedure forms and included demographics, tumour length, the presence of fistulas, stent size and immediate complications.Results. A total of 480 SEMS were inserted, involving 453 patients, of whom 43 required repeat stenting. There were 185 female patients (40.8%) and 268 male patients (59.2%). The mean age was 60 years (range 38 - 101). There were 432 black patients (95.4%), 15 white patients (3.3%) and 6 Indian patients (1.3%). The reasons for palliative stenting were distributed as follows: age >70 years n=95 patients, tumour >8 cm n=142, tracheo-oesophageal fistula (TOF) n=29, and unspecified n=170. One patient refused surgery, and one stent was placed for a post-oesophagectomy leak. Repeat stenting was for stent migration (n=15), tumour overgrowth (n=26) and a blocked stent and a stricture (n=1 each). Complications were recorded in six cases (1.3%): iatrogenic TOF (n=2), false tracts (n=3) and perforation (n=1). All six were nevertheless successfully stented. There was no periprocedural mortality.Conclusion. The endoscopic placement technique described is a viable and safe option with a low periprocedural complication rate. It is of particular use in situations of restricted access to fluoroscopic guidance

The efficacy of endoscopic therapy in bleeding peptic ulcer patients

Background. Endotherapy is the primary modality for the control ofbleeding from peptic ulceration.Objective. To assess the efficacy of endoscopic intervention for high-risk bleeding peptic ulcer disease and to benchmark our surgical and mortality rates.Methods. Two hundred and twenty-seven patients with pepticulcers stratified by Rockall and Forrest scores as being at high risk for rebleeding underwent therapeutic intervention (adrenalin injection) between January 2004 and December 2009. The median age of the patients was 57 years (range 19 - 87 years); 60% were males.Results. Primary endoscopic haemostasis failed in 51/227 patients (22.5%); 18 patients (7.9%) required surgery for bleeding not controlled at initial or second endoscopy; and 29 patients (12.8%) died, 12 by day 3 and 17 by day 30. Fifteen patients, all with significant medical co-morbidity, died after successful primary endotherapy, and 4 died after surgery. Surgical patients required more blood (odds ratio (OR) 1.45, p=0.0001) than those not undergoing surgery, but had similar mortality. Rebleeding was the only predictor of death in patients who died by day 3 (OR 18.77). A high Rockall score was the only predictor of death by day 30 (OR 1.98).Conclusion. The overall surgical and mortality rates were 7.9% and 12.8%, respectively. Over half the deaths resulted from medical co-morbidity, despite successful primary endotherapy. This finding is supported by the use of the Rockall score as a predictor of mortality at day 30. Improving the technical success of primary endoscopic haemostasis, currently 77.5%, has the potential to reduce rebleeding after primary endotherapy, a predictor of death at day 3 in this study

Cushing's syndrome caused by ectopic ACTH secretion from pulmonary tumourlets

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Oesophageal cancer in Area 2 of Kwazulu-Natal: predictors of late presentation.

BACKGROUND: There are limited prospective data sets on clinical characteristics, stage of presentation and treatment of patients with Oesophageal Squamous Cell Carcinoma (OSCC) in South Africa. This study aimed to assess the frequency and severity of clinical characteristics associated with late presentation of patients with OSCC presenting to a cancer referral centre in KwaZulu-Natal, South Africa. METHODS: A prospective consecutive series of patients presenting with confirmed OSCC treated at Greys Hospital in 2016/2017 were enrolled. Data collected included: age, gender, home language, referral centre, clinical and laboratory characteristics: dysphagia score, Eastern Cooperative Oncology Group (ECOG) performance status, body mass index (BMI), serum albumin, tumour pathology and treatment administered. RESULTS: One hundred patients were analysed. Ninety four percent spoke isiZulu. The mean age was 61 with a male to female ratio of 1.5:1 Ninety percent had palliative treatment as their overall assessment precluded curative treatment. Five patients underwent curative treatment. The age standardised incidence (ASR) was 25.2 per 100 000. The factors associated with late presentation and their frequency were: advanced dysphagia grade ( </=2 in 68%), malnutrition (BMI <18.5kg/m2 in 49%), hypoalbuminaemia (serum albumin < 35 g/l in 70%), poor performance status (ECOG</=2 in 50% ) and moderate to poor tumour differentiation in 95% of patients. CONCLUSION: OSCC in Kwazulu-Natal has double the ASR of South Africa and places a significant burden on the region's health care system. Factors associated with late presentation occur in the majority and alone or in combination preclude curative therapies. The frequency of these factors serve as a benchmark for comparison, and reduction in their frequency may indicate effectiveness of interventions designed to improve awareness and access to proper care

Hitting the Target: Developing High-quality Evidence for Proton Beam Therapy Through Randomised Controlled Trials

The National Health Service strategy for the delivery of proton beam therapy (PBT) in the UK provides a unique opportunity to deliver high-quality evidence for PBT through randomised controlled trials (RCTs). We present a summary of three UK PBT RCTs in progress, including consideration of their key design characteristics and outcome assessments, to inform and support future PBT trial development. The first three UK multicentre phase III PBT RCTs (TORPEdO, PARABLE and APPROACH), will compare PBT with photon radiotherapy for oropharyngeal squamous cell carcinoma, breast cancer and oligodendroglioma, respectively. All three studies were designed by multidisciplinary teams, which combined expertise from clinicians, clinical trialists and scientists with strong patient advocacy and guidance from national radiotherapy research networks and international collaborators. Consistent across all three studies is a focus on the reduction of long-term radiotherapy-related toxicities and an evaluation of patient-reported outcomes and health-related quality of life, which will address key uncertainties regarding the clinical benefits of PBT. Innovative translational components will provide insights into mechanisms of toxicity and help to frame the key future research questions regarding PBT. The UK radiotherapy research community is developing and delivering an internationally impactful PBT research portfolio. The combination of data from RCTs with prospectively collected data from a national PBT outcomes registry will provide an innovative, high-quality repository for PBT research and the platform to design and deliver future trials of PBT

The impact of xerostomia on oral-health-related quality of life among younger adults

BACKGROUND: Recent research has suggested that chronic dry mouth affects the day-to-day lives of older people living in institutions. The condition has usually been considered to be a feature of old age, but recent work by our team produced the somewhat surprising finding that 10% of people in their early thirties are affected. This raises the issue of whether dry mouth is a trivial condition or a more substantial threat to quality of life among younger people. The objective of this study was to examine the association between xerostomia and oral-health-related quality of life among young adults while controlling for clinical oral health status and other potential confounding factors. METHODS: Cross-sectional analysis of data from a longstanding prospective observational study of a Dunedin (New Zealand) birth cohort: clinical dental examinations and questionnaires were used at age 32. The main measures were xerostomia (the subjective feeling of dry mouth, measured with a single question) and oral-health-related quality of life (OHRQoL) measured using the short-form Oral Health Impact Profile (OHIP-14). RESULTS: Of the 923 participants (48.9% female), one in ten were categorised as 'xerostomic', with no apparent gender difference. There was a strong association between xerostomia and OHRQoL (across all OHIP-14 domains) which persisted after multivariate analysis to control for clinical characteristics, gender, smoking status and personality characteristics (negative emotionality and positive emotionality). CONCLUSION: Xerostomia is not a trivial condition; it appears to have marked and consistent effects on sufferers' day-to-day lives

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA