Overall readmissions and readmissions related to dehydration after creation of an ileostomy: a systematic review and meta-analysis.

BACKGROUND: Hospital readmissions after creation of an ileostomy are common and come with a high clinical and financial burden. The aim of this review with pooled analysis was to determine the incidence of dehydration-related and all-cause readmissions after formation of an ileostomy, and the associated costs. METHODS: A systematic literature search was conducted for studies reporting on dehydration-related and overall readmission rates after formation of a loop or end ileostomy between January 1990 and April 2021. Analyses were performed using R Statistical Software Version 3.6.1. RESULTS: The search yielded 71 studies (n = 82,451 patients). The pooled incidence of readmissions due to dehydration was 6% (95% CI 0.04-0.09) within 30 days, with an all-cause readmission rate of 20% (CI 95% 0.18-0.23). Duration of readmissions for dehydration ranged from 2.5 to 9 days. Average costs of dehydration-related readmission were between $2750 and $5924 per patient. Other indications for readmission within 30 days were specified in 15 studies, with a pooled incidence of 5% (95% CI 0.02-0.14) for dehydration, 4% (95% CI 0.02-0.08) for stoma outlet problems, and 4% (95% CI 0.02-0.09) for infections. CONCLUSIONS: One in five patients are readmitted with a stoma-related complication within 30 days of creation of an ileostomy. Dehydration is the leading cause for these readmissions, occurring in 6% of all patients within 30 days. This comes with high health care cost for a potentially avoidable cause. Better monitoring, patient awareness and preventive measures are required.

Impact of a defunctioning ileostomy and time to stoma closure on bowel function after low anterior resection for rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Impaired bowel function after low anterior resection (LAR) for rectal cancer is a frequent problem with a major impact on quality of life. The aim of this study was to assess the impact of a defunctioning ileostomy, and time to ileostomy closure on bowel function after LAR for rectal cancer. METHODS: We performed a systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Comprehensive literature searches were conducted using PubMed, Embase and Cochrane databases for articles published from 1989 up to August 2019. Analysis was performed using Review Manager (version 5.3) using a random-effects model. RESULTS: The search yielded 11 studies (1400 patients) that reported on functional outcome after LAR with at least 1 year follow-up, except for one study. Five scales were used: the Low Anterior Resection Syndrome (LARS) score, the Wexner score, the Memorial Sloan Kettering Cancer Centre Bowel Function Instrument, the Fecal Incontinence Quality of Life scale, and the Hallbook questionnaire. Based on seven studies, major LARS occurred more often in the ileostomy group (OR 2.84, 95% CI, 1.70-4.75, p < 0.0001: I2 = 60%, X2 = 0.02). Based on six studies, a longer time to stoma closure increased the risk of major LARS with a mean difference in time to closure of 2.39 months (95% CI, 1.28-3.51, p < 0.0001: I2 = 21%, X2 = 0.28) in the major vs. no LARS group. Other scoring systems could not be pooled, but presence of an ileostomy predicted poorer bowel function except with the Hallbook questionnaire. CONCLUSIONS: The risk of developing major LARS seems higher with a defunctioning ileostomy. A prolonged time to ileostomy closure seems to reinforce the negative effect on bowel function; therefore, early reversal should be an important part of the patient pathway.

The management of adult appendicitis during the COVID-19 pandemic: an interim analysis of a UK cohort study.

BACKGROUND: Acute appendicitis (AA) is the most common general surgical emergency. Early laparoscopic appendicectomy is the gold-standard management. SARS-CoV-2 (COVID-19) brought concerns of increased perioperative mortality and spread of infection during aerosol generating procedures: as a consequence, conservative management was advised, and open appendicectomy recommended when surgery was unavoidable. This study describes the impact of the first weeks of the pandemic on the management of AA in the United Kingdom (UK). METHODS: Patients 18 years or older, diagnosed clinically and/or radiologically with AA were eligible for inclusion in this prospective, multicentre cohort study. Data was collected from 23rd March 2020 (beginning of the UK Government lockdown) to 1st May 2020 and included: patient demographics, COVID status; initial management (operative and conservative); length of stay; and 30-day complications. Analysis was performed on the first 500 cases with 30-day follow-up. RESULTS: The patient cohort consisted of 500 patients from 48 sites. The median age of this cohort was 35 [26-49.75] years and 233 (47%) of patients were female. Two hundred and seventy-one (54%) patients were initially treated conservatively; with only 26 (10%) cases progressing to an operation. Operative interventions were performed laparoscopically in 44% (93/211). Median length of hospital stay was significantly reduced in the conservatively managed group (2 [IQR 1-4] days vs. 3 [2-4], p < 0.001). At 30 days, complications were significantly higher in the operative group (p < 0.001), with no deaths in any group. Of the 159 (32%) patients tested for COVID-19 on admission, only 6 (4%) were positive. CONCLUSION: COVID-19 has changed the management of acute appendicitis in the UK, with non-operative management shown to be safe and effective in the short-term. Antibiotics should be considered as the first line during the pandemic and perhaps beyond.

Safe management of surgical smoke in the age of COVID-19.

BACKGROUND: The COVID-19 global pandemic has resulted in a plethora of guidance and opinion from surgical societies. A controversial area concerns the safety of surgically created smoke and the perceived potential higher risk in laparoscopic surgery. METHODS: The limited published evidence was analysed in combination with expert opinion. A review was undertaken of the novel coronavirus with regards to its hazards within surgical smoke and the procedures that could mitigate the potential risks to healthcare staff. RESULTS: Using existing knowledge of surgical smoke, a theoretical risk of virus transmission exists. Best practice should consider the operating room set-up, patient movement and operating theatre equipment when producing a COVID-19 operating protocol. The choice of energy device can affect the smoke produced, and surgeons should manage the pneumoperitoneum meticulously during laparoscopic surgery. Devices to remove surgical smoke, including extractors, filters and non-filter devices, are discussed in detail. CONCLUSION: There is not enough evidence to quantify the risks of COVID-19 transmission in surgical smoke. However, steps can be undertaken to manage the potential hazards. The advantages of minimally invasive surgery may not need to be sacrificed in the current crisis.

Psychological sequelae of colonic resections.

AIM: The prevalence of anxiety, depression and post-traumatic stress disorder (PTSD) in the general population has been estimated to be 5.9%, 3.3% and 4.4% respectively. The aim of this study was to determine whether psychological problems are more prevalent following colorectal surgery. METHOD: Patients who had undergone colorectal resection in a 2-year period across four centres were asked to complete validated screening questionnaires for anxiety, depression and PTSD (GAD-7, PHQ-9, PCL-5) 12-48 months after surgery. Risk factors were identified using multiple linear regression analysis. RESULTS: After excluding those who had died or received palliative diagnoses, questionnaires were sent to 1150 patients. 371 responded (32.3% response rate); median age 67 (20-99) years; 51% were men. 58% of patients underwent surgery for cancer; 23% had emergency surgery. 28% of patients screened positive for at least one psychological condition, with 20% screening positive for anxiety, 22% for depression and 14% for PTSD. Patients who were younger, women, had surgery as an emergency, for benign conditions, had stomas and had critical care stay were more likely to have poorer psychological outcomes. Multiple linear regression found that only younger age (P = 0.000) and female gender (P = 0.048) were significant risk factors. CONCLUSION: The prevalence of anxiety, depression and PTSD appears to be high in patients who have undergone colorectal surgery. Younger patients and women are particularly at risk. Further work is needed to determine how best to prevent, detect and treat people with adverse psychological outcomes following colorectal surgery.

Altered N-methyl D-aspartate receptor subunit expression causes changes to the circadian clock and cell phenotype in osteoarthritic chondrocytes.

The chondrocyte circadian clock is altered in osteoarthritis. This change is implicated in the disease-associated changes in chondrocyte phenotype and cartilage loss. Why the clock is changed is unknown. N-methyl-D-aspartate receptors (NMDAR) are critical for regulating the hypothalamic clock. Chondrocytes also express NMDAR and the type of NMDAR subunits expressed changes in osteoarthritis. OBJECTIVE: To determine if NMDAR regulate the chondrocyte clock and phenotype. DESIGN: Chondrocytes isolated from macroscopically-normal (MN) and osteoarthritic human cartilage were treated with NMDAR antagonists or transfected with GRIN2A or GRIN2B-targetting siRNA. H5 chondrocytes were transfected with GluN2B-expression plasmids. Clock genes and chondrocyte phenotypic markers were measured by RT-qPCR. RESULTS: PER2 amplitude was higher and BMAL1 amplitude lower in osteoarthritic compared to MN chondrocytes. In osteoarthritic chondrocytes, NMDAR inhibition restored PER2 and BMAL1 expression to levels similar to MN chondrocytes, and resulted in reduced MMP13 and COL10A1. Paradoxically, NMDAR inhibition in MN chondrocytes resulted in increased PER2, decreased BMAL1 and increased MMP13 and COL10A1. Osteoarthritic, but not MN chondrocytes expressed GluN2B NMDAR subunits. GluN2B knockdown in osteoarthritic chondrocytes restored expression of circadian clock components and phenotypic markers to levels similar to MN chondrocytes. Ectopic expression of GluN2B resulted in reduced BMAL1, increased PER2 and altered SOX9, RUNX2 and MMP13 expression. Knockdown of PER2 mitigated the effects of GluN2B on SOX9 and MMP13. CONCLUSIONS: NMDAR regulate the chondrocyte clock and phenotype suggesting NMDAR may also regulate clocks in other peripheral tissues. GluN2B expression in osteoarthritis may contribute to pathology by altering the chondrocyte clock.

Acceptability and benefit of rectal irrigation in patients with Low Anterior Resection Syndrome: a qualitative study.

AIM: Low Anterior Resection Syndrome (LARS) following rectal cancer surgery impairs the patient's quality of life (QoL). Rectal Irrigation has been demonstrated to be effective for anterior resection syndrome but many surgeons do not suggest it as a treatment. This feasibility study aimed to explore treatment acceptability and the benefit of rectal irrigation in patients who developed LARS following an anterior resection for rectal cancer. METHODS: This was a qualitative study, involving semi-structured interviews. Twenty-one patients diagnosed with LARS following anterior resection for rectal cancer in a single tertiary centre were offered rectal irrigation as a treatment option. Qualitative interviews (n=17) were conducted at baseline to explore patient reported impact of LARS on QoL, treatment acceptability and factors influencing the decision to accept/decline treatment. Follow up interviews were carried out at six months for the treatment group only (n=12), to assess its practicality and impact on QoL. RESULTS: Qualitative interview findings suggest rectal irrigation is an acceptable method of treatment for LARS. Participants who perceived their symptoms to be more severe or poorly controlled were most likely to consider rectal irrigation as a treatment option. The patients who completed treatment reported improvements in their QoL, the ability to control the time of defaecation being the key benefit CONCLUSION: Clinicians should consider offering rectal irrigation as a treatment option to patients presenting with bowel dysfunction following anterior resection as it can improve symptoms. Patients who perceive that their symptoms are severe are more likely to consider treatment. This article is protected by copyright. All rights reserved.

Growth hormone deficiency after childhood bone marrow transplantation with total body irradiation: interaction with adiposity and age.

OBJECTIVE: Bone marrow transplantation with total body irradiation (BMT/TBI) has adverse effects on growth, growth hormone status and adiposity. We investigated the GH-IGF-I axis in relation to adiposity. DESIGN: Cross-sectional case control study. PATIENTS: BMT/TBI survivors (n = 22) and short stature control participants (n = 19), all GH-naïve or off GH treatment >3 months. MEASUREMENTS: Auxology, DEXA scans and GH-IGF-I axis investigation: (i) 12-h overnight GH profiles; (ii) insulin tolerance test (ITT); and (iii) IGF-I generation test. ANALYSIS: auto-deconvolution of GH profile data and comparison of quantitative parameters using ANOVA. RESULTS: Eighty-two percent of BMT/TBI survivors had growth hormone deficiency (GHD) using ITT. GH profile area-under-the-curve (GH-AUC) was reduced in BMT/TBI survivors vs short stature control participants [geometric mean (range) 209 (21-825) vs 428 (64-1400) mcg/l/12 h, respectively, P = 0·007]. GHD was more marked in those who had additional cranial irradiation (CRT) [ITT peak 1·4 (0·2-3·0) vs TBI only 4·1 (1·1-14·8) mcg/l, P = 0·036]. GHD was more marked at the end of growth in BMT/TBI survivors vs short stature control participants (GH-AUC 551 (64-2474) vs 1369 (192-4197) mcg/l/12 h, respectively, P = 0·011) and more prevalent (9/11 vs 1/9, respectively, P = 0·005). GH profile data were consistent with ITT results in 80% of participants. IGF-I generation tests were normal. BMT/TBI survivors still demonstrated lower GH levels after adjustment for adiposity (fat-adjusted mean difference for GH-AUC 90·9 mcg/l/12 h, P = 0·025). CONCLUSIONS: GHD was more prevalent in BMT/TBI survivors than expected for the CRT dose in TBI, worsened with time and persisted into adulthood. GHD could not be explained by adiposity. There was no evidence of GH neurosecretory dysfunction or resistance after BMT/TBI.

Female infertility following restorative proctocolectomy.

AIM: Females of child-bearing age have been reported to have a two to three-fold increase in infertility after restorative proctocolectomy (RPC). This study aimed to assess aspects of infertility and pregnancy. METHOD: A postal questionnaire was sent to 790 females who had undergone primary RPC in two tertiary centres. Infertility, the number and outcome of pregnancies, delivery method and the use of fertility treatments were determined. RESULTS: Three hundred and six (38.5%) females responded (median age 47.9 years at follow up; 35.3 years at the time of RPC). Eighty-two per cent (n=250) had ulcerative colitis. Forty-five per cent (n=138) had conceived prior to RPC, 5.2% (n=16) conceived both before and after RPC, 5.5% (n=17) conceived after RPC only and 44.1% (n=135) had never conceived. Females delivering before RPC had significantly more vaginal deliveries than those conceiving after (pre-RPC 69.6%, n=96 vs post-RPC 35.3%, n=6; P=0.001). Fifty-seven patients stated they had attempted to conceive after RPC, with 25 (45.5%) being successful. Eighteen females had been referred to a fertility specialist, of whom 16 received in vitro fertilization (IVF). Four (30.7%) females conceived using IVF. CONCLUSION: While RPC is known to be associated with infertility, only a small proportion of patients are referred for fertility management. IVF outcomes and success rates after RPC are similar to the general population. Patients are more likely to have a Caesarean section following RPC.

The National Bowel Cancer Audit Project: what do trusts think of the National Bowel Cancer Audit and how can it be improved?

PURPOSE: The National Bowel Cancer Audit Project (NBOCAP) collects data from hospitals in the UK and aims to improve surgical outcomes and quality of care for patients. The aims of this study were to understand why trusts were/were not participating in the NBOCAP and how to improve the quality of data collected and feedback. METHODS: This was a prospective e-survey on colorectal surgeons' attitudes towards and opinions of the NBOCAP, within trusts in the UK. A questionnaire was emailed to members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI). RESULTS: Of the 171 trusts contacted by email, 66% of trusts (n = 117) had at least 1 consultant respond. Of the 117 trusts that responded, 60 (51.2%) had submitted data to the NBOCAP. A total of 549 consultants received the questionnaire, and 159 (29.0%) consultants responded. Fifty-one per cent (n = 60) of the trusts had submitted data to the NBOCAP. Reasons for data submission included the following: comparison of a units' data with national data (56.8%), a national audit improves outcomes (45.9%) and generation of information for use at a local level (42.6%). The main reasons for non-submission were as follows: lack of technical support (23.6%), lack of funding (19.6%) and lack of dedicated audit time (18.9%). Ninety-six (60.4%) consultants felt that the audit report should identify individual trust results. Fifty-three per cent of consultants (n = 87) rated their trusts' resources for audit as being very poor or poor. CONCLUSION: Consultant members of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) within hospital trusts in the UK feel participation in the National Bowel Cancer Audit improves patients' quality of care and surgical outcomes. Increased awareness of the benefits of the NBOCAP and improved allocation of resources from hospital trusts could improve participation.

The Moondance Bowel Cancer Project schools initiative.

BACKGROUND: The 5-year survival rate for bowel cancer in Wales is poor and lags behind the rest of the UK. The aim of the pilot phase of the Moondance Schools Initiative was to develop, deliver and assess a bowel cancer learning module for secondary school students in South Wales. Ultimately, we aim to introduce this programme into the National Curriculum across Wales. METHODS: Two programmes regarding bowel cancer and screening were designed and delivered to a cohort of secondary school pupils in South Wales. This involved interactive teaching with patients and clinicians, practical sessions and live-streamed videos of bowel cancer surgery. Feedback regarding the events and bowel screening was collected from students and their families. RESULTS: The programmes were delivered to 185 secondary school students and feedback was extremely positive. The students delivered a live event at the end of the programme to demonstrate their learning to their families and invited guests. Feedback from family members revealed that 100% of respondents were more likely to take a bowel screening test as a result of attending the event. CONCLUSION: This project established that a pilot to create young bowel screening ambassadors is feasible and was positively received by students, their families and the local community. Future work will disseminate the programme further and correlate changes in bowel screening participation in the local area as a result of these events.

Where have all the appendicectomies gone?

INTRODUCTION: The COVID-19 pandemic stimulated a national lockdown in the UK. The public were advised to avoid unnecessary hospital attendances and health professionals were advised to avoid aerosol-generating procedures wherever possible. The authors hypothesised that these measures would result in a reduction in the number of patients presenting to hospital with acute appendicitis and alter treatment choices. METHODS: A multicentred, prospective observational study was undertaken during April 2020 to identify adults treated for acute appendicitis. Searches of operative and radiological records were performed to identify patients treated during April 2018 and April 2019 for comparison. RESULTS: A total of 190 patients were treated for acute appendicitis pre-lockdown compared with 64 patients treated during lockdown. Patients treated during the pandemic were more likely to have a higher American Society of Anesthesiology (ASA) score (p = 0.049) and to have delayed their presentation to hospital (2 versus 3 days, p = 0.03). During the lockdown, the use of computed tomography (CT) increased from 36.3% to 85.9% (p < 0.001), the use of an antibiotic-only approach increased from 6.2% to 40.6% (p < 0.001) and the rate of laparoscopic appendicectomy reduced from 85.3% to 17.2% (p < 0.001). The negative appendicectomy rate decreased from 21.7% to 7.1% during lockdown (p < 0.001). CONCLUSIONS: The COVID-19 lockdown was associated with a decreased incidence of acute appendicitis and a significant shift in the management approach. The increased use of CT allows the identification of simple appendicitis for conservative treatment and decreases the negative appendicectomy rate.

Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthritis; implications for pathogenesis of erosive disease.

OBJECTIVES: Magnetic resonance imaging (MRI) bone oedema is an important predictor of bone erosion in rheumatoid arthritis (RA). This study aimed to determine the cellular components of MRI bone oedema, and clarify the relationship between bone erosion and MRI bone oedema. METHODS: Twenty-eight bones from 11 patients with RA undergoing orthopaedic surgery were analysed by quantitative and semi-quantitative immunohistochemistry. Pre-operative contrast-enhanced MRI scans were analysed for bone oedema. RESULTS: The density of osteoclasts was higher in those samples with MRI bone oedema than those without MRI bone oedema (p = 0.01). Other cells identified within bone marrow included macrophages and plasma cells, and these were more numerous in samples with MRI bone oedema (p = 0.02 and 0.05 respectively). B cells were present in lower numbers, but B cell aggregates were identified in some samples with MRI bone oedema. There was a trend to increased RANKL expression in samples with MRI bone oedema (p = 0.09). Expression of RANKL correlated with the number of osteoclasts (r = 0.592, p = 0.004). CONCLUSIONS: The increased number of osteoclasts and RANKL expression in samples with MRI bone oedema supports the hypothesis that bone erosion in RA occurs through activation of local bone resorption mechanisms within subchondral bone as well as through synovial invasion into bone.

Measuring sexual and urinary outcomes in women after rectal cancer excision.

PURPOSE: This study was designed to investigate sexual and urinary dysfunction in women who underwent rectal cancer excision, and the influence of tumor and treatment variables on long-term outcomes. METHODS: Data were prospectively collected on 295 women who underwent rectal cancer excision at a tertiary referral colorectal center from 1998 to 2006. Sexual and urinary function was assessed preoperatively and at intervals up to five years after surgery. Functional outcomes were assessed by using univariate and multivariate regression analysis, chi-squared test for trend, or Kruskal-Wallis test. RESULTS: The mean age of the patients was 60.9 years. Anterior resection was performed in 222 patients (75.2 percent) and abdominoperineal resection in 73 patients (24.7 percent). Patients who underwent abdominoperineal resection were less sexually active (25 vs. 50 percent; P = 0.02) and had a lower frequency of intercourse than anterior resection patients at one year after surgery (anterior resection, 3 (0-5) (median interquartile range); abdominoperineal resection 0 (0-4); P = 0.029). The frequency of intercourse improved over time for abdominoperineal resection (4 months, 0 (0-0) median interquartile range; 5 years, 3 (0.25-4) median interquartile range; P = 0.028). Abdominoperineal resection was associated with increased dyspareunia (odds ratio, 5.75; 95 percent confidence interval (CI), 1.87-17.6; P = 0.002), urinary urgency (odds ratio, 8.52; 95 percent CI, 2.81-25.8; P < 0.001), incontinence (odds ratio, 2.41; 95 percent CI, 1.11-5.26; P = 0.026), poor stream (odds ratio, 5.64, 95 percent CI, 2.55-12.5; P

The role of peptides and receptors of the calcitonin family in the regulation of bone metabolism.

The 'calcitonin family' is a group of peptide hormones that share structural similarities with calcitonin, and includes calcitonin gene-related peptide (CGRP), amylin, adrenomedullin and adrenomedullin 2 (intermedin). These hormones are produced by different tissues, with calcitonin being produced in thyroid C cells, alphaCGRP predominantly in neural tissue, amylin in beta-islet cells of the pancreas and adrenomedullin in many tissues and cell types. Bone appears to be a common target for all the peptides of the calcitonin family, although the specific bone effects of the peptides vary. Administration of calcitonin produces rapid lowering of serum calcium levels, mainly through inhibition of bone resorption by osteoclasts. In vitro and in a number of animal experimental models, amylin and CGRP are also effective in inhibiting osteoclast activity and bone resorption. Amylin, adrenomedullin and CGRP can also affect cells of the osteoblast lineage, inducing osteoblast proliferation and promoting bone formation. Receptors for the peptides of the calcitonin family are formed by heterodimerization of the calcitonin receptor (CTR) or calcitonin receptor-like receptor (CLR) with receptor activity modifying proteins (RAMPs). Although the different combinations of these proteins create receptors with distinct ligand specificities, there is a degree of cross-reactivity and the receptors are able to bind other ligands from the family, usually with lower affinity. Analysis of the expression of the receptors for the calcitonin family in 16 samples of human osteoblasts showed high levels of CLR and RAMP1, low levels of RAMP2 and no expression of RAMP3 or CTR. Recent studies of the bone phenotype of knockout animals lacking the calcitonin, alphaCGRP or amylin gene indicated that in this experimental system the main physiological role of amylin in bone is the inhibition of bone resorption, that of CGRP is the activation of bone formation, while calcitonin, unexpectedly appears to be inhibiting bone formation without affecting bone resorption. Further investigations will be required to determine the mechanisms of action of calcitonin peptides in bone and their significance to human bone physiology.

Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials.

The definition of indications for allogeneic SCT in children with high-risk (HR) ALL in the first remission or after the first or subsequent relapse depends on biological features, response to treatment and survival after chemotherapy alone. As the results of frontline and relapse protocols are improving over time, there is a strong need for prospective SCT trials, ensuring a well-standardized procedure regarding all relevant components that are potentially responsible for heterogeneity in post-SCT outcome. Therefore, in 2003, the ALL-BFM and the ALL-REZ BFM Study Group initiated a prospective, international, multicenter trial (ALL-SCT-BFM 2003). This trial will now be extended to a larger consortium, trial ALL-SCT-BFM-international (ALL-SCT-BFMi). Strict rules define HLA-typing, donor selection, conditioning regimen, GvHD prophylaxis and therapy as well as standards of supportive care to reduce treatment-related mortality and establish an early GVL effect. Moreover, comprehensive and closely reviewed documentation and serious adverse event reporting shall ensure high study quality. Case-by-case discussions of any fatal or critical course during annual meetings will improve the culture of failure management and lead to modifications of guidelines of supportive care. Finally, the results of these prospective trials will determine the current potential of the different SCT procedures in HR or relapsed childhood ALL.

Recent improvement in outcome of unrelated donor transplantation for aplastic anemia.

The aim was to determine whether outcome of unrelated donor transplantation for severe aplastic anemia has improved in recent years and whether this is due to patient selection or better transplant technology. We analyzed 498 patients transplanted during 1990-2005. By running univariate regression models dichotomizing year of transplantation we defined 1998 as the year of the most significant change in survival. Five-year survival increased from 32+/-8% before 1998 to 57+/-8% after 1998 (P<0.0001). When comparing the cohort before (n=149) and after 1998 (n=349), there were no differences except for older age, and more frequent use of PBSCs, after 1998. High-resolution HLA typing data were unavailable. After 1998, there was less graft failure (11 vs 26%, P<0.0001), less acute GvHD (cumulative incidence 28 vs 37%, P=0.02) and less chronic GvHD (22 vs 38%, P=0.004). In multivariate analyses adjusting for differences in age, HLA-mismatch, performance score and time to transplantation, there was no change in the year of transplant effect (relative risk of death in transplants after 1998: 0.44 (95% confidence interval 0.33-0.59)). There is no evidence for patient selection to explain significantly improved survival in patients transplanted after 1998. We speculate that this is due to better donor matching.

Surgical strategies for faecal incontinence--a decision analysis between dynamic graciloplasty, artificial bowel sphincter and end stoma.

BACKGROUND: Artificial bowel sphincter (ABS) and dynamic graciloplasty (DG) are surgical treatments for faecal incontinence (FI). FI may affect quality of life (QOL) so severely that patients are often willing to consider a permanent end stoma (ES). It is unclear which is the more cost-effective strategy. METHOD: Probability estimates for patients with FI were obtained from published data (ABS, n = 319; DG, n = 301), supplemented by expert opinion. The primary outcome was quality-adjusted life years (QALYs) gained from each strategy. Factors considered were the risk of failure of the primary and redo operation and the consequent risk of permanent stoma. Results were assessed as incremental cost-effectiveness ratio (ICER). RESULTS: Over the 5-year time horizon, ES gave a QALY gain of 3.45 for 16,280 pounds sterling, giving an ICER of 4719 pounds sterling/QALY. ABS produced a gain of 4.38 QALYs for 23,569 pounds sterling, giving an ICER of 5387 pounds sterling/QALY. DG produced a gain of 4.00 QALYs for 25,035 pounds sterling, giving an ICER of 6257 pounds sterling/QALY. With the willingness-to-pay threshold set at 30,000 pounds sterling/QALY, ES was the most cost-effective intervention. The ABS was most cost-effective after 10 years. CONCLUSION: All three procedures were found to be cost-effective. The ES was most cost-effective over 5 years, while the ABS was most cost-effective in excess of 10. DG maybe considered as an alternative in specialist centres.

Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget's disease of bone.

Paget's disease is characterized by highly localized areas of increased osteoclast (OCL) activity. This suggests that the microenvironment in pagetic lesions is highly osteoclastogenic, or that OCL precursors in these lesions are hyperresponsive to osteoclastogenic factors (or both). To examine these possibilities, we compared RANK ligand (RANKL) mRNA expression in a marrow stromal cell line developed from a pagetic lesion (PSV10) with that in a normal stromal cell line (Saka), and expression in marrow samples from affected bones of Paget's patients with that in normal marrow. RANKL mRNA was increased in PSV10 cells and pagetic marrow compared with Saka cells and normal marrow, and was also increased in marrow from affected bones compared with uninvolved bones from Paget's patients. Furthermore, pagetic marrow cells formed OCLs at much lower RANKL concentrations than did normal marrow. Anti-IL-6 decreased the RANKL responsivity of pagetic marrow to normal levels, whereas addition of IL-6 to normal marrow enhanced RANKL responsivity. Thus, RANKL expression and responsivity is increased in pagetic lesions, in part mediated by IL-6. These data suggest that the combination of enhanced expression of RANKL in affected bones and increased RANKL sensitivity of pagetic OCL precursors may contribute to the elevated numbers of OCLs in Paget's disease.